{"_id": "cardio$$$8c8ab993-ee48-4ae5-8847-bcbf32f47061", "text": "The process by which atherosclerotic plaques form is\u00a0summarized in figure 7.1, but there are four fundamental stages:"}
{"_id": "cardio$$$9d4e0880-9f21-484f-b9ac-c6ff8fb556de", "text": "Types of Myocardial Ischemia and Infarction"}
{"_id": "cardio$$$64d10d2a-fd9c-41bb-b48e-727607b9ad2b", "text": "The degree of occlusion caused by the plaque and the oxygen demand of the myocardium determine the degree of ischemia that can develop. Arterial occlusion tends not to be a significant factor until the\u00a0lumen is occluded by about 70 percent. Vascular occlusion may also be masked by formation of anastomoses\u00a0(new vessels that bypass the occlusion). Rupture of the plaque and formation of a thrombus can drastically and quickly reduce the lumen and blood flow.\u00a0The degree and duration of ischemia\u00a0determine the type of acute coronary syndrome that occurs and the clinical impact. Mild or brief ischemia can lead to angina pectoris with no permanent tissue damage, but when ischemia is prolonged then myocardial infarction becomes more likely, and significant changes in ECG and release of cardiac enzymes are seen."}
{"_id": "cardio$$$24600c4f-2ccc-4588-8d18-94cee47e02d5", "text": "Stable and unstable angina pectoris"}
{"_id": "cardio$$$693aa8ee-fda5-45f0-873f-67576411c6e8", "text": "While not considered an acute coronary syndrome, stable angina is pain associated with periods of myocardial ischemia, usually associated with exertion and an increase in myocardial oxygen demand that is unmeet because of insufficient tissue perfusion. The inadequate perfusion is most commonly caused by coronary artery disease (vessel occlusion). Stable angina is predictable and\u00a0regular, and\u00a0resolves when\u00a0the myocardial oxygen demand is reduced\u00a0(i.e., cessation of exercise)."}
{"_id": "cardio$$$ee5d9eca-b1b8-42c6-9ff8-03bb70da5bec", "text": "Unstable angina is more serious and may be an unpredictable exacerbation of anginal pain that\u00a0had previously\u00a0been stable. It may occur at rest\u00a0or lower than usual levels of exertion. Unstable angina is part of the acute coronary syndrome spectrum and may reflect rupture of a plaque that has led\u00a0to thrombosis. The ECG in unstable angina may show hyperacute T-waves, flattening of the T-waves, inverted T-waves, and ST depression.\u00a0Without the presence of myocardial damage, unstable angina is not associated with elevated cardiac enzymes (e.g.,\u00a0troponin). Continued or worsening stenosis of the coronary artery leads to tissue\u00a0infarction and\u00a0more clinically significant elements of acute coronary syndrome."}
{"_id": "cardio$$$fff7764f-ceb1-4df7-bcb2-42206013871e", "text": "Non-ST segment elevation myocardial infarction"}
{"_id": "cardio$$$2395eb07-d28a-4e14-983c-126fe6e1985e", "text": "With non-ST segment elevation myocardial infarction (NSTEMI), there is necrosis of the myocardium. Although, as the name suggests, there is no consistent\u00a0ST segment elevation in a NSTEMI, other ECG\u00a0changes may be seen. These include\u00a0transient ST elevation, ST depression, or new T-wave inversions.\u00a0The lysing myocytes release their contents including enzymes that can be used as biomarkers of the necrotic event. Presence of elevated\u00a0cardiac enzymes distinguishes NSTEMI from unstable angina, but denotes myocardial damage\u00a0and a poorer prognosis. There are several cardiac enzymes that can be detected (myoglobin, creatine kinase, and troponin I), and each has a different timeline from onset of infarction (figure 7.3). But because of improvements in test sensitivity, the test\u00a0enzyme of choice is troponin I."}
{"_id": "cardio$$$e88f6f73-35ba-4543-850d-bde4573e3e48", "text": "Troponin"}
{"_id": "cardio$$$4f0f9ab6-657f-4aef-89da-6fd69fe98608", "text": "Troponin I is a\u00a0normal protein important in the contractile apparatus of the cardiac myocyte. It is\u00a0released into the circulation about three to four\u00a0hours after MI and are still detectable for ten\u00a0days afterward.\u00a0The long half-life allows for the late diagnosis of MI but makes it difficult to detect reinfarction (a\u00a0major complication associated with new thrombus formation during\u00a0stent placement). Although\u00a0there are a number causes for troponin elevation unrelated to MI, troponin elevation is much more sensitive and specific than myoglobin and even creatine kinase."}
{"_id": "cardio$$$4c70078b-6929-461d-a32c-5da9ed2e8626", "text": "ST segment elevation myocardial infarction"}
{"_id": "cardio$$$3cf60f09-5ee1-4aaa-9b08-339066533313", "text": "ST segment elevation myocardial infarction (STEMI) most often results from complete occlusion of a major epicardial vessel. The resultant myocardial infarction raises cardiac enzymes measured in the blood (as with NSTEMI), but is accompanied by\u00a0an\u00a0ST segment elevation on the 12-lead ECG. This is the most serious of the acute coronary syndromes."}
{"_id": "cardio$$$e78b3de3-d87d-4158-9f50-e4a2516402ca", "text": "Pathophysiology of a STEMI"}
{"_id": "cardio$$$0f262d19-ab49-437d-87c8-88681d2af370", "text": "The most common cause of a STEMI is rupture of an atherosclerotic plaque. The continued degradation and calcification of the fibrous cap results in it breaking and spilling its contents into the bloodstream. Tissue factor within the necrotic core instigates the coagulation cascade when it is exposed to the blood and a thrombus is formed and the vessel\u00a0is occluded. Plaques rupture most frequently at their \u201cshoulder,\u201d\u00a0the thin peripheral edges where proteolytic and apoptotic activity are highest and mechanical forces are most effective. The tissue downstream\u00a0from the occlusion experiences ischemia and then infarcts. The impact on cardiac function and output depends on the site and extent of the infarcted tissue. For example, if a significant section of the left ventricular wall is involved,\u00a0then the fall in cardiac output may be catastrophic, or if the papillary muscles of a valve are included, the valve may become incompetent and allow regurgitation."}
{"_id": "cardio$$$92596e8c-cd79-4c33-9b0f-18249fb0c967", "text": "Physical Exam of a STEMI"}
{"_id": "cardio$$$99654ea9-1084-45f3-8c5b-2479b32f7b8e", "text": "The physical examination findings may include elevated\u00a0heart rate and blood pressure due to increased sympathetic tone. However, if cardiac function is severely impacted because of the size or location of the infarction,\u00a0cardiogenic shock may result with a fall in blood pressure. The insufficient\u00a0ATP\u00a0production in the ischemic region means the interaction of actin and myosin in the cardiac myocytes cannot be broken and the muscle cannot relax. An S4 heart sound\u00a0(figure 7.4)\u00a0occurs when the noncompliant, stiffened left ventricle\u00a0vibrates\u00a0when blood enters from the atrium. The S4 sound is also known as an atrial gallop\u2014not because\u00a0the sound comes from the ventricle, but because\u00a0it is associated with atrial contraction (and ventricular filling).\u00a0If the infarction involves an\u00a0impact\u00a0of the\u00a0papillary muscle function, the associated valve will fail and the\u00a0regurgitation\u00a0will cause\u00a0a holosystolic murmur. A STEMI in the left ventricle sufficient to cause congestion and a rise in left-ventricular and end-diastolic pressure can lead to rises in left atrial and pulmonary pressure; this may be heard\u00a0on the lung exam as rales due to the transient pulmonary edema."}
{"_id": "cardio$$$a75a7fe1-ec08-4354-b08d-c7acfbfd7914", "text": "Diagnosis of a STEMI"}
{"_id": "cardio$$$d23a054f-12c2-4916-b9b0-6ca0f924a9fa", "text": "As mentioned above the two most important tools for diagnosing a STEMI are the ECG and the presence of cardiac enzymes that have been released into the bloodstream. Figure 7.4 shows the time line of myoglobin, creatine kinase, and troponin elevations after an infarction. Using the values of all three enzymes\u00a0allowed the history of an infarction to be generated, but amazing\u00a0improvements in the sensitivity of the troponin I\u00a0test\u00a0have allowed it to become the gold standard because of its specificity to the myocardium."}
{"_id": "cardio$$$ba2ac968-c97b-41e2-b754-9f1afe1b868d", "text": "Changes in ECG"}
{"_id": "cardio$$$72ffb72c-4a64-4cc6-873f-de27f4b99bc8", "text": "The first ECG sign to arise during a STEMI are\u00a0\u201chyperacute T-waves\u201d (figure 7.5). These T-waves are taller than normal and caused by the release of intracellular potassium from lysing cells and the consequent hyperkalemia in the surrounding tissue. Hyperacute T-waves are not often seen clinically because they occur so early in the event and prior to the patient\u2019s arrival in the hospital. Subsequent ECG stages are more commonly observed, and these include the ST elevation."}
{"_id": "cardio$$$88db4132-68ca-4549-89a2-924cf9f900ea", "text": "Determining which ECG\u00a0leads show the ST elevation allow for the\u00a0location of the infarcted tissue to be determined\u00a0and provide insight into which coronary vessel is effected. How the leads of a twelve-lead ECG\u00a0relate to the coronary vessels is summarized in figure 7.6. The following looks at the characteristic ECG changes in relation to location in a bit more detail (tip: relate back to figure 7.6\u00a0as you read the next sections)."}
{"_id": "cardio$$$6d68f09a-8787-48f2-b06c-14d0b66cf653", "text": "Anterior wall myocardial infarctions (AWMI)"}
{"_id": "cardio$$$49edadfd-c220-471a-a2a7-98961115d828", "text": "The anterior wall is affected when the left anterior descending coronary artery becomes occluded. Additional involvement of\u00a0lateral and septal regions is indicative of the left main coronary artery being involved. Inclusion of these regions is termed an extensive anterior infarction. The ECG shows\u00a0ST segment elevation\u00a0in\u00a0leads V3 and V4\u00a0(the anterior leads), seen as a raised\u00a0J-point (see figure 7.7).\u00a0A\u00a0reciprocal ST depression will be seen in leads\u00a0II, III, and aVF (the inferior leads). If the extent of the infarction is large, the elevated ST segment may been seen in\u00a0the lateral and septal leads.\u00a0The elevated ST segment is also associated in a change in shape of the T-wave as it becomes broader and loses its concave shape on the downward section. This broad\u00a0T-wave can be higher as well as the ST elevation progresses, and its height can surpass the R-wave. These morphological changes result in a T-wave that looks like a tombstone (see figure 7.7)."}
{"_id": "cardio$$$986cf8b1-e6e2-4571-8ae3-2049c903e560", "text": "Inferior wall myocardial infarction (IWMI)"}
{"_id": "cardio$$$6bffe156-b418-440d-b656-519ab719029a", "text": "Occlusion of the right coronary artery is the usual culprit for an inferior wall myocardial infarction (IWMI), which may be severe enough to extend to posterior regions. \u00a0The ECG findings of an acute inferior myocardial infarction (figure 7.9) will be an\u00a0ST segment elevation in leads\u00a0II, III, and aVF\u00a0(the inferior leads) and reciprocal depression in lead\u00a0aVL\u00a0(a\u00a0lateral lead); without the reciprocal depression in aVL,\u00a0alternative causes of ST segment elevation in the inferior leads\u00a0should be considered (e.g., pericarditis). Because the right coronary artery\u00a0perfuses the SA node, bradycardia may occur.\u00a0An inferior MI can have multiple potential complications, including cardiogenic shock, atrioventricular block, or ventricular fibrillation, and can be fatal."}
{"_id": "cardio$$$2aecae86-a90c-4fa9-8f1e-b688c1a0e472", "text": "Posterior wall myocardial infarction (PWMI)"}
{"_id": "cardio$$$efe18db6-82d6-407b-ac2b-58efb88e6c6d", "text": "Most posterior myocardial infarctions occur with occlusion of the posterior descending artery (which in most people is a branch of the right coronary artery); because of the shared supply, a posterior infarction is often accompanied by an IWMI. The ECG findings include ST segment elevation in V7\u2013V9 (the posterior leads that are placed on the posterior axillary line, not shown in figure 7.11) and ST depression in V1\u2013V4 (the septal and anterior leads, shown in\u00a0figure 7.10). If an IWMI\u00a0is also present then there will be an ST elevation in leads II, III, and aVF (the inferior leads). A\u00a0twelve-lead ECG showing a posterior wall infarction is shown in figure 7.11."}
{"_id": "cardio$$$c3555430-b628-4c1d-a1b4-ea3410d63415", "text": "The location of the infarction, leads showing ST elevation\u00a0and depression, and the involved coronary artery are summarized in table 7.1."}
{"_id": "cardio$$$fad9a2c1-10a1-4b64-b8df-f054450efa3c", "text": "Table 7.1: Location of the infarction, leads showing ST elevation and depression, and the involved coronary artery."}
{"_id": "cardio$$$2651f059-9715-43df-b265-f410f3408493", "text": "Text"}
{"_id": "cardio$$$8c6e0429-e47f-4997-a67a-ddf069d958f5", "text": "Rhee, June-Wha, Sabatine, Marc S., and Leonard S. Lilly. \u201cIschemic Heart Disease.\u201d In Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty, 5e, edited by Leonard S. Lilly, Chapter 6. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer Business, 2010."}
{"_id": "cardio$$$f418f90a-4b61-47fe-9986-92500c9a8db6", "text": "Rhee, June-Wha, Sabatine, Marc S., and Leonard S. Lilly. \u201cAcute Coronary Syndromes.\u201d In Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty, 5e, edited by Leonard S. Lilly, Chapter 7. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer Business, 2010."}
{"_id": "cardio$$$0d5c9a9d-0b35-43ee-a67d-f78f5b489c22", "text": "Surawicz, Borys, Rory Childers, Barbara J. Deal, and Leonard S. Gettes. \u201cAHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram.\u201d Circulation 119, no. 10 (2009): e235\u2013e240."}
{"_id": "cardio$$$60ff9e9a-c126-471e-99f6-c12310ca27fc", "text": "Surawicz, Borys, and Timothy Knilans. Chou\u2019s Electrocardiography in Practice, 6th ed. Philadelphia: Saunders, 2008."}
{"_id": "cardio$$$70a5d101-5e2a-46e9-a9a1-78aa0dd2d4fa", "text": "Embryology"}
{"_id": "cardio$$$9f0f09d4-e613-43c5-b0c4-d88febf2b828", "text": "The most common atrial septal defects arise from:"}
{"_id": "cardio$$$ac320655-8631-40bf-a7c4-44003a642f6f", "text": "A patent foramen ovale (20 percent of the population) is not a true ASD as no tissue is missing and the remaining tissue acts as a one-way valve, so a PFO does not have the same pathophysiology as a true ASD. ASDs are common in infants with Down syndrome, as are VSDs."}
{"_id": "cardio$$$ff7507ba-bb5b-4c42-b863-bdd165e96c8d", "text": "Pathophysiology"}
{"_id": "cardio$$$0ca2e9a4-4235-43f9-ab0c-905df40a4de4", "text": "ASDs allow blood flow between the atria. As the pressure in the left atria is higher than that in the left, blood flows from left to right (figure 6.1). This causes volume overload of the right side of the heart. This excessive load may lead to right ventricular compliance being reduced as remodeling takes place. The reduced compliance can elevate right-side pressure and thereby reduce the left\u2013right shunt."}
{"_id": "cardio$$$199d8a5e-d915-41f5-9d3d-5eea4c8dd85e", "text": "Ventricular Septal Defect (VSD)"}
{"_id": "cardio$$$2207e1e4-c6bd-4d7f-942d-aba1814d1dac", "text": "Most ventricular septal defects arise from membraneous portion of the septum (70 percent), while others form in the muscular portion (20 percent); less frequently they occur near the aortic or AV valves."}
{"_id": "cardio$$$905a0d96-2952-42f9-8fba-fd4f61c9a889", "text": "The manifestations of a VSD depend on the VSD size and the relative resistance of the pulmonary and systemic circulations\u2014all of which will determine the direction of blood flow. During fetal development, the pulmonary and systemic circulations have equivalent resistances, so there may be very little shunting through the VSD, particularly if it is small. After birth, however, the resistance of the pulmonary system falls dramatically, so right ventricular pressure is lower and below left ventricular pressure (which still has to contend with systemic resistance)\u2014consequently a left\u2013right shunt is established. If this shunt is large (depending on the size of the defect), then blood returning from the pulmonary circulation to the left atrium can pass into the left ventricle, through the VSD into the right ventricle and head back into pulmonary circulation to start this loop again (figure 6.2)."}
{"_id": "cardio$$$aa70f67a-58aa-47d6-848c-2372e6335b6d", "text": "When a large VSD is present, the recirculated blood causes volume overload of the\u00a0right ventricle and\u00a0the pulmonary circulation and subsequently\u00a0both chambers of the left heart (figure 6.2). This can eventually cause chamber dilation and lead to heart failure. The extra volume load in the pulmonary circulation can also lead to early onset of pulmonary vascular disease."}
{"_id": "cardio$$$9b0b34e2-c605-4829-b940-b7778129ea5f", "text": "Coarctation of the Aorta"}
{"_id": "cardio$$$baf51c4b-f19b-4d5a-97c8-2f134e75f7fc", "text": "Coarctation of the aorta (figure 6.3) is a constriction of the aortic lumen, usually close to the ductus. The cause is unclear, but low flow through the left heart and aorta flow during development may cause the defect (no flow, no grow)."}
{"_id": "cardio$$$2b7ddeef-3daa-4e16-996a-9128398cd540", "text": "The diminished lumen causes increased afterload on the left ventricle. Vessels branching off the aorta before the coarctation can receive normal blood flow, so the head (carotid) and upper extremities (subclavian) are usually properly perfused whereas branching arteries after the coarctation may be underperfused. Consequently, differential cyanosis is a possible manifestation."}
{"_id": "cardio$$$10718bcf-894c-46c4-a78a-b6ea3eb0a184", "text": "Tetralogy of Fallot (ToF)"}
{"_id": "cardio$$$7a4760f4-973c-4a6a-8a2b-28a1f5d1c029", "text": "In Tetralogy of Fallot (ToF) the outflow tract (infundibular) portion of the interventricular septum is displaced. This single defect leads to four defects:"}
{"_id": "cardio$$$93e3f0c6-c5f9-413c-b352-7115cb701e96", "text": "Other defects can be associated with ToF, but the defects listed above lead this to be the most common form of cyanotic congenital heart disease."}
{"_id": "cardio$$$af60813e-aa12-41db-9727-78873b12e12e", "text": "The high resistance of the stenosed pulmonic valve (#1, figure 6.4) causes the blood in the right ventricle to exit through VSD (#3, figure 6.4) and enter the left ventricle forming a right-left shunt, bypassing the pulmonary circulation. Consequently blood with venous PO2 enters the systemic circulation and hypoxemia/cyanosis results. The degree of hypoxemia/cyanosis that occurs\u00a0depends\u00a0on the degree of pulmonic stenosis."}
{"_id": "cardio$$$122179b7-183d-407d-9568-e9c309c64fd0", "text": "Transposition of the Great Arteries"}
{"_id": "cardio$$$236b9e5b-579c-4497-81b7-5d66ab40a6f8", "text": "Although not completely understood, it is thought that failure of the aortic-pulmonary septum to spiral during development results in the great vessels coming off the wrong ventricles\u2014the aorta exits the right, and the pulmonary artery exits the left. Other theories exist."}
{"_id": "cardio$$$895cbe7b-7f2f-4641-a6fa-539f64d1cd91", "text": "The placement of the pulmonary artery on the left means left ventricular blood is pumped up to pulmonary circulation, only to return to the left side of the heart via the pulmonary veins. Similarly, the aorta on the right forms a closed-system with the right ventricle pumping into the systemic circulation, only for it to return to the right atrium via the vena cava (see figure 6.5). So how is this compatible with life? In short, it is not. Embryonic development can continue because the two looped circulations can mix at the ductus arteriosus and foramen ovale of the fetal circulation. But after birth these shunts between the two circulations MUST be artificially maintained, or the patient must be \u201cfortunate\u201d enough to also have a VSD for mixing to take place."}
{"_id": "cardio$$$8d03a6dc-6832-47fb-953e-5f9cf307cb01", "text": "Patent Ductus Arteriosus"}
{"_id": "cardio$$$cb3ec1c2-1b92-4d52-a7bf-705e9bf6c4ef", "text": "The ductus arteriosus is part of the fetal circulation allowing blood in the pulmonary artery to bypass the nonfunctional, high resistance lungs and instead traverse into the aorta and systemic circulation. The ductus should close at birth, and failure to do so leaves a patent ductus arteriosus (PDA)."}
{"_id": "cardio$$$d331685f-470c-41e0-978f-1aeb22b0fb60", "text": "In utero, the high resistance of the pulmonary circulation ensures that blood is diverted through the ductus arteriosis into the aorta. However, at birth there is a dramatic fall in the resistance of the pulmonary circulation as the lungs inflate. The pressure gradient across the ductus is consequently reversed (low on the pulmonary side, high on the systemic), so if the ductus remains open blood will flow from the aorta to the pulmonary artery (i.e., the opposite direction to fetal circulation) (figure 6.6)."}
{"_id": "cardio$$$e3219b6e-0643-4242-8ce2-be68ebbccf30", "text": "The consequences of this are that a greater volume of blood reenters the pulmonary circulation, the left atria, and the left ventricle. Consequently the compartments of the left heart can eventually fail through volume overload. When the left heart fails, the shunt through the PDA can be reversed, and desaturated blood destined for the pulmonary circulation can end up passing through the PDA to the aorta instead\u2014this reversal later in life is called Eisenmenger syndrome. In Eisenmenger\u2019s the upper extremities receive uncontaminated, saturated blood, as their branching arteries are upstream of the desaturated blood entering the aorta at the PDA. Not so for the lower extremities whose arteries branch after the PDA and so receive low oxygen blood. Hence in Eisenmenger syndrome patients, only the feet are cyanosed."}
{"_id": "cardio$$$ed277b4c-0a9c-4b8c-bde1-40bf8aeb7a07", "text": "Atrioventricular Canal"}
{"_id": "cardio$$$c2876a14-af63-464b-bdaf-f313627386d0", "text": "Complete AV canal defect is a result of complete failure of fusion between endocardial cushions. It is characterized by a primum atrial septal defect (#1, figure 6.7) that is contiguous with a ventricular septal defect (#4 in figure 6.7) and a malformed or common AV valve. Although several forms of this defect exist, this complete form is effectively a single chambered heart."}
{"_id": "cardio$$$974946a0-a10f-48d8-b255-5854625a572b", "text": "The malformed valves allow regurgitation, and the unrestricted interventricular communication allow a profound left\u2013right shunt. This leads to volume overload in the pulmonary circulation, and heart failure will be produced if there is no correction. Pulmonary artery hypertension (PAH) and premature development of pulmonary vascular obstructive disease are other common outcomes."}
{"_id": "cardio$$$38784677-a607-48ec-990d-f6a502eae531", "text": "Truncus Arteriosus"}
{"_id": "cardio$$$38f7669b-8f52-4a28-859d-6bcf408a76ba", "text": "Failed development of the truncoconal septum that normally leads to separation of the pulmonary artery and aorta leads to truncus arteriosus (TA). This condition leads to a single vessel with a single (often incompetent) valve positioned above the ventricular septum (see figure 6.8)."}
{"_id": "cardio$$$a4208a50-27fd-43a0-abb7-f887dba520fb", "text": "The underlying issues with TA are 1) mixing of blood from the left (saturated) and right heart (unsaturated), and 2) the common valve can allow regurgitation. In utero the high pulmonary vascular resistance means most blood exiting the heart goes through the aorta and cardiac output is rarely affected. At birth mild cyanosis can be produced by the mixing of blood from the left and right heart, but as pulmonary vascular resistance remains high in the first few days of life, cardiac output my be maintained. As pulmonary vascular resistance continues to fall in the first few weeks of life, a significant left\u2013right shunt can become established as more left ventricular blood finds it \u201ceasier\u201d to ascend up the pulmonary artery. Similar to a VSD, this leads to volume overload in the pulmonary circulation and eventually heart failure. The heart failure has a more rapid onset in TA than VSD if the common valve allows regurgitation. The regurgitation lowers end-diastolic ventricular volumes, so cardiac work to maintain cardiac output increases and promotes myocardial ischemia. Add to this the left\u2013right shunt (as seen in VSD) and heart failure is more likely."}
{"_id": "cardio$$$338365cf-229f-462a-a031-98082c43433e", "text": "Bhansali, Suneet, and Colin Phoon.\u00a0Truncus Arteriosis. Treasure Island, FL: StatPearls Publishing, 2022.\u00a0https://www.ncbi.nlm.nih.gov/books/NBK534774/,\u00a0CC BY 4.0."}
{"_id": "cardio$$$995ee375-aece-4390-b26d-9b4c9f312271", "text": "Cunningham, Jonathan W., and David W. Brown. \u201cCongenital Heart Disease.\u201d In\u00a0Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty, edited by Leonard S. Lilly, Chapter 16. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer Business, 2012."}
{"_id": "cardio$$$840aca0a-c487-491a-b695-a8457d2cbc98", "text": "Dakkak, Wael, and Tony I. Oliver.\u00a0Ventricular Septal Defect.\u00a0Treasure Island, FL: StatPearls Publishing, 2022.\u00a0https://www.ncbi.nlm.nih.gov/books/NBK470330/,\u00a0CC BY 4.0."}
{"_id": "cardio$$$51d7dd59-efef-49b1-b87a-858bd257fe67", "text": "Diaz-Frias, Josua, and Melissa Guillaume.\u00a0Tetralogy of Fallot. Treasure Island, FL: StatPearls Publishing, 2022.\u00a0https://www.ncbi.nlm.nih.gov/books/NBK513288/,\u00a0CC BY 4.0."}
{"_id": "cardio$$$c7943f22-f9f3-4d59-b486-0d892d7fc01d", "text": "Gillam-Krakauer, Maria, and Kunal Mahajan.\u00a0Patent Ductus Ateriosus. Treasure Island, FL: StatPearls Publishing, 2022.\u00a0https://www.ncbi.nlm.nih.gov/books/NBK430758/,\u00a0CC BY 4.0."}
{"_id": "cardio$$$eb6a5536-2fab-49e9-8fea-fb6dfd90ac7e", "text": "Law, Mark A., and Vijai\u00a0 S. Tivakaran.\u00a0Coarctation of the Aorta. Treasure Island, FL: StatPearls Publishing, 2022.\u00a0https://www.ncbi.nlm.nih.gov/books/NBK430913/,\u00a0CC BY 4.0."}
{"_id": "cardio$$$7dab3894-5603-4e66-a595-a4a501477845", "text": "Menillo, Alexandra M., Lawrence S. Lee, and Anthony L. Pearson-Shaver.\u00a0Atrial Septal Defect.\u00a0Treasure Island, FL: StatPearls Publishing, 2022.\u00a0https://www.ncbi.nlm.nih.gov/books/NBK535440/,\u00a0CC BY 4.0."}
{"_id": "cardio$$$477bb241-ffa8-4452-b076-05fd90b9111e", "text": "Szymanski, Michael W., Sheila M. Moore, Stacy M. Kritzmire, and Amandeep Goyal.\u00a0Transposition of the Great Arteries. Treasure Island, FL: StatPearls Publishing, 2022.\u00a0https://www.ncbi.nlm.nih.gov/books/NBK430758/,\u00a0CC BY 4.0."}
{"_id": "cardio$$$740f1bed-fa6b-4651-a963-90a31353aa51", "text": "Umapathi, Krishna Kishore, and Pradyumna Agasthi.\u00a0Atrioventricular Canal Defects.\u00a0Treasure Island, FL: StatPearls Publishing, 2022.\u00a0https://www.ncbi.nlm.nih.gov/books/NBK557511/,\u00a0CC BY 4.0."}
{"_id": "cardio$$$d8d591c3-619a-4016-9b13-b8fdb39f286b", "text": "unintrusive"}
{"_id": "cardio$$$5ffbc2bb-1935-4280-878f-182fffd98c9a", "text": "The first and second sounds (S1 and S2) are the fundamental heart sounds."}
{"_id": "cardio$$$334f25ea-7306-46ac-9e69-58e46df94d20", "text": "S1 occurs at the beginning of isovolumetric contraction. The ventricle is beginning to contract, so ventricular pressure quickly rises above atrial pressure and the atrioventricular (tricuspid and mitral) valves close,\u00a0producing the S1 sound. The mitral valve normally closes slightly (0.04 seconds) before the tricuspid, causing S1 to be \u201csplit\u201d\u00a0(i.e., actually being two sounds, M1 and T1 (figure 5.1)), but the time gap is too short with a normal heart to be detectable with a stethoscope. The reasons for M1 preceding T1 are not clear, but may be due to the force generation of the left ventricle being slightly faster than that of the right ventricle.\u00a0The splitting of S1 can be more pronounced and audible in the presence of a right bundle branch block (figure 5.1) that causes left ventricular contraction (and mitral valve closure) to markedly precede contraction of the right ventricle. Conversely, in the case of a left bundle branch block, the normal splitting of S1 may be absent (figure 5.1) as M1 is delayed and so occurs in synchrony with T1."}
{"_id": "cardio$$$724a9152-0b3a-4764-ba81-4c3120c38cff", "text": "S2 is caused by closure of the aortic and pulmonic valves at the beginning of isovolumetric ventricular relaxation when ventricular pressure falls below pulmonary and aortic pressure. As aortic pressure (80 mmHg) is far greater than pulmonary artery pressure (10 mmHg), S2 is normally split with two components (A2 and P2) relating to the closure of the aortic and pulmonic valves, respectively. How split A2 and P2 are depend on physiological conditions, primarily the phase of breathing that influences the pulmonary artery pressure. In expiration pulmonary artery pressure is higher, so the pulmonic valve closes earlier and P2 occurs closer to A2. Conversely, during inspiration pulmonary artery pressure falls, so pulmonic valve closing occurs later and A2 and P2 occur further apart (figure 5.2). This physiological splitting can be heard with a stethoscope, but can be further influenced by diseases as listed in table 5.1."}
{"_id": "cardio$$$4d7c531a-16ee-4653-afbd-f021fd27c395", "text": "Table 5.1: Changes in S2 splitting and possible underlying causes."}
{"_id": "cardio$$$b85a54b0-6aea-444b-b9c5-1b982105fbc8", "text": "S3 is associated with the rapid filling phase of the ventricle (when the AV valves open), about 0.14 to 0.16 seconds after S2 (closure of the aortic and pulmonic valves). The exact cause of the sound is unclear, but a normal S3 occurs as a brief, low-frequency vibration. Previously thought to be an intracardiac sound arising from vibrations in the valve cusps or ventricular wall, more recent studies suggest the sound may be due to the filling ventricular wall hitting the inner chest wall, or it may arise from the ventricular apex as it hits a limitation of its longitudinal expansion."}
{"_id": "cardio$$$41134bf7-67fa-419e-b65e-355eba0c75ce", "text": "Table 5.2: Common causes of abnormal S3."}
{"_id": "cardio$$$b6f4bdf6-2cdb-4402-978e-0d2c0f12ef68", "text": "As S3 is a filling sound, an abnormal S3 (higher pitch and referred to as a ventricular gallop) is an important clue to heart failure or volume overload (see table 5.2). The absence of an abnormal S3 does not rule out heart failure, but its presence is a sensitive indicator of ventricular dysfunction. Constriction around the heart (e.g., constrictive pericarditis) may cause an early S3, or \u201cpericardial knock.\u201d"}
{"_id": "cardio$$$8e78b9d6-934e-48c2-8d8e-2a605bc52c8b", "text": "S4 is abnormal and is associated with poor ventricular compliance (e.g., ventricular hypertrophy). It occurs during atrial contraction and is associated with the atrial pressure pulse. The sound is thought to be caused by reverberation of the stiffened ventricular wall as blood is propelled into the ventricle from the atrium (hence it is also known as an atrial gallop). S4 and raised end-diastolic ventricular pressure (EDVP)\u00a0commonly occur together as both are\u00a0caused by poor ventricular compliance, so S4 tends to be associated with conditions that cause pressure overload (see table 5.3)."}
{"_id": "cardio$$$862d6bb6-963f-4074-bc42-16be655a662e", "text": "Table 5.3: Common causes of abnormal S4."}
{"_id": "cardio$$$c8f90997-4325-48ec-9369-c2c8ff8c3cdb", "text": "Ejection Sounds (Clicks)"}
{"_id": "cardio$$$1f6b22d4-bf70-4b81-afa4-729a627cdae7", "text": "As S1 and S2 occur during closure of heart valves, pathological conditions can lead to the valves producing a high-frequency \u201cclicking\u201d\u00a0sound when they open during chamber ejection\u2014hence they can be referred to as ejection sounds and they are pathological."}
{"_id": "cardio$$$a2f5be91-51f5-4d63-bf3e-f8125ee88346", "text": "Aortic ejection sounds usually occur 0.12\u20130.14 seconds after the Q-wave of the ECG (i.e., after ventricular pressure has risen to exceed aortic pressure). Because of its timing, the \u201cclick\u201d produced can be misinterpreted as a split S1. The abnormal opening of the aortic valve is usually caused by a deformed but mobile valve leaflet or aortic root dilation that may be caused by the conditions listed in table 5.4."}
{"_id": "cardio$$$7e8d8d0a-4d81-4e44-982a-bcec6f5b34c6", "text": "Pulmonary ejection sounds occur a little earlier (0.09\u20130.11 seconds) after the Q-wave as the pulmonary valve opens a little earlier (figure 5.1). It can also be distinguished by the fact that its\u00a0intensity is diminished during inspiration as increased venous return during inspiration augments the effect of atrial contraction and causes a \u201cgentler\u201d opening of the valve. As with the aortic ejection sounds, pulmonary ejection sounds are associated with deformed valves or pulmonary arterial dilation."}
{"_id": "cardio$$$1b153493-e775-4028-9b43-5efb5d11fad0", "text": "A click occurring in diastole is associated with abnormal opening of either the mitral or tricuspid valve. Similar to systolic clicks, a diastolic click can be misinterpreted as a split S2. The most common cause of diastolic clicks is valvular stenosis of an AV valve."}
{"_id": "cardio$$$1615eacf-7f87-43a8-b7b5-a3cb428b9d53", "text": "Table 5.4: Common causes of ejection \"clicks.\""}
{"_id": "cardio$$$6d7f8ae7-bcc3-4cd4-b369-87408b0ec793", "text": "Heart Murmurs"}
{"_id": "cardio$$$9c3bb02c-fc73-48a6-b44b-aeaa0ac2089e", "text": "A murmur is the sound of turbulence associated with abnormal blood flow through a valve or chamber. The turbulent flow produces low-frequency audible sounds that are distinct from heart sounds associated with valve closures. Murmurs can be divided into those caused by valvular defects and those caused by abnormal interchamber flow. Depending on the defect involved, the murmur may occur during diastole and systole, hence distinguishing whether a murmur is diastolic or systolic is a useful first diagnostic step."}
{"_id": "cardio$$$6946a7b2-cc20-4f01-8124-e43277e1447a", "text": "Classification of a murmur includes the intensity (Grades 1\u20136, faintest to loudest), the pitch (high or low), configuration, location, and timing. The timing refers to the onset and duration of the murmur, and the classifications are shown in table 5.5 with some common causes listed there and below."}
{"_id": "cardio$$$4787b84f-230c-41ed-a33c-e809c93db364", "text": "Table 5.5: Classifications of heart murmurs."}
{"_id": "cardio$$$ade10988-52d5-40bb-a747-06d819e62b55", "text": "Dornbush, Sean, and Andre E. Turnquest. Physiology, Heart Sounds. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK541010, CC BY 4.0."}
{"_id": "cardio$$$1d13203a-5404-4ba4-abaa-6b5f3df36f97", "text": "Kulkarni, Vivek T., and Leonard S. Lilly. \u201cThe Cardiac Cycle: Mechanisms of Heart Sounds and Murmurs.\u201d In Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty, 5e edited by Leonard S. Lilly, Chapter 2. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer Business, 2010."}
{"_id": "cardio$$$3f337c79-9677-4c2d-8bca-e53e383a902f", "text": "Thomas, Seth L., Joseph Heaton, and Amgad N. Makaryus. Physiology, Cardiovascular Murmurs. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK525958, CC BY 4.0."}
{"_id": "cardio$$$79ed1809-c439-4208-b3fb-eabdea6a3c5c", "text": "Table 5.5: Classifications of heart murmurs. Grey, Kindred. 2022. CC BY 4.0. https://archive.org/details/5.5_20220113"}
{"_id": "cardio$$$0d9a3874-61bf-4706-bc3b-cd7d9ea2021c", "text": "Abnormalities of valvular structure and/or function can either be congenital or acquired. Acquired valvular disease is by far the most common and is most prevalent in the elderly. The high blood flow and pressures that valves are exposed to make them particularly susceptible to other risk factors that promote valvular damage (see table 4.1). Congenital valvular defects arise from disrupted heart development, about 50 percent\u00a0of which involve the valves. The impact of congenital defects has diminished with the advent of advanced detection techniques.\u00a0What we will spend time on in this chapter is the main instigating factors and pathologies that result\u00a0in acquired valvular defects."}
{"_id": "cardio$$$ccc9c78e-3005-40ab-baac-35ac9036e771", "text": "Table 4.1: Risk factors for acquired valvular damage."}
{"_id": "cardio$$$9098edeb-f4b5-4b10-aa41-7ecc7e039310", "text": "The constant stress of facing high flow and pressure over thirty to forty\u00a0million cardiac contractions a year is not without its consequences, and the most common valvular disorder is calcification that comes with \u201cwear-and-tear\u201d\u00a0and aging. The presence of other factors such as hyperlipidemia, hypertension, and inflammation accelerate this process and promote the deposition of hydroxyapatite (a form of calcium phosphate), and the valve structure contains cells that resemble osteoblasts (figure 4.1)."}
{"_id": "cardio$$$8e9c7284-ff78-4170-bdb5-1bb9aa034b4b", "text": "As they face the most pressure, the aortic and mitral valves are more prone to calcification. The most common pattern of calcification in the aortic valve is mounded masses within the cusps of the valve (see table\u00a04.2) that eventually fuse and stop the valve from opening fully.\u00a0Calcification in the mitral valve\u00a0tends to start in the fibrous annulus, which does not\u00a0impact valvular function to the same extent, but in exceptional cases can cause regurgitation or stenosis, or even arrhythmias as calcium deposits impinge on the atrioventricular conduction system (see table\u00a04.2)."}
{"_id": "cardio$$$56ee9369-4764-475a-bf47-8192d06fa092", "text": "Table 4.2: Location of calcium deposits on aortic and mitral valves and their pathological consequences."}
{"_id": "cardio$$$d0b0605b-9171-49cc-a037-2b1824b6be14", "text": "Mitral Valve Prolapse (MVP)"}
{"_id": "cardio$$$25e1bb25-ef77-49ee-becc-697b567b01d0", "text": "A prolapsed mitral valve is one where one or both leaflets have become floppy and\u00a0capable of ballooning back into the left atrium during systole (figure 4.2). The condition is more common in women, affects 2\u20133 percent of adults in the United States,\u00a0and can be a secondary effect of mitral valve regurgitation."}
{"_id": "cardio$$$83ad3463-bd48-4a5d-9550-96ee5e4586ac", "text": "The causes of MVP are usually unidentified, but a few cases can be attributed to inherited connective tissue disorders such as Marfan syndrome. The prolapsed valve leaflet composition is enlarged and thickened with deposition of myxomatous material rich in proteoglycans, and a reduction in the structurally critical fibrosa layer where a higher prevalence of type III collagen (a more stretchy than structural form of collagen) is found."}
{"_id": "cardio$$$3830bcdf-10ca-46bc-b1c6-da084e9eb154", "text": "The flapping valve structure can cause secondary fibrosis on the structures it strikes, such as the leaflet edges or the endocardium where the abnormally elongated cords rub. The agitation may also promote thrombus formation in the atrium."}
{"_id": "cardio$$$071facc2-9ef2-4958-bb2d-ef391a7e20cf", "text": "The resultant floppy leaflet can be detected by a midsystolic click,\u00a0and any associated incompetence may produce a late-systolic murmur (summary in figure 4.2). MVP is usually asymptomatic, but potential complications include:"}
{"_id": "cardio$$$7bb51be0-96d8-496d-8012-70b75e35f133", "text": "Rheumatic Heart Disease"}
{"_id": "cardio$$$2093f797-eecd-4860-b20e-322f80a0b697", "text": "Rheumatic heart disease (RHD) is virtually the only cause of mitral valve stenosis. It arises after a group A streptococcal infection that often originates in the upper airway and leads to rheumatic fever (a multisystem, immune-mediated disease). The incidence in developed countries is relatively low because of rapid diagnosis and treatment of the instigating pharyngitis, but in poor, crowed, urban areas RHD remains an important health issue."}
{"_id": "cardio$$$360fb267-07a9-402e-9a7e-438c6986ea70", "text": "The acute results of rheumatic fever occur days to weeks after the streptococcal infection, and while the initial pharyngeal infection may have cleared and the test results have become\u00a0negative, the antibodies to the streptococcal enzymes (Streptolysin O and DNase B) can still be detected. The initial cardiac effects include carditis, pericardial rubs, tachycardia, and arrhythmias. However, the chronic effects may arise years or even decades later."}
{"_id": "cardio$$$e933abed-192e-441f-b157-fbf11ce31326", "text": "The chronic effects involve an immune cross-reaction between the antibodies and CD4+ T-cells directed against the streptococcal M proteins and cardiac self-antigens. Antibody binding and T-cell activity toward the cardiac antigens activate complement and recruit neutrophils and macrophages toward\u00a0the valve tissue. The damage they produce includes histologically distinct lesions called Aschoff bodies (figure 4.3), and plump activated macrophages called Anitschkow cells (or caterpillar cells) appear in the effected areas (figure 4.3). All layers of the myocardium can be effected, but the valves can show leaflet thickening and fusion as well as shortened, thickened cords. Vegetative verrucae are associated with the necrotic fibrinoid foci,\u00a0making RHD one\u00a0of the vegetative forms of valvular disease."}
{"_id": "cardio$$$fabf8aa6-13d8-4527-8773-5aaca4242bc6", "text": "As the valve thickens it can become calcified as well, and the adhered leaflets produce a \u201cfish-mouth\u201d\u00a0or \u201cbutton hole\u201d\u00a0appearance \u00a0that causes the valve to narrow. The damage is cumulative with the increased turbulence through a stenosed valve perpetuating the fibrotic process (see summary in figure 4.3)."}
{"_id": "cardio$$$0ebbe1a6-cda0-4ef4-aaf0-d105344147e7", "text": "Infective Endocarditis"}
{"_id": "cardio$$$4d708ee1-4455-43f5-bbcf-2b98b7d02e96", "text": "Infective endocarditis (IE) is divided into acute and subacute forms, depending on the virulence of the causal pathogen. Acute IE is rapid in onset and involves highly destructive pathogens that cause necrosis and significant lesions that can lead to death in a matter of days. Subacute IE, alternatively,\u00a0can deform the valves over weeks to months and generally involves a much less destructive pathogen."}
{"_id": "cardio$$$b4efabae-c886-41e7-afdd-30e3c3e1fde1", "text": "Acute cases tend to involve healthy individuals and are responsible for 20 to 30 percent\u00a0of cases, whereas the less virulent pathogens that cause subacute IE tend to need a foothold and only affect previously damaged or deformed valves."}
{"_id": "cardio$$$208863b0-d700-491e-a56c-57d15fcf0459", "text": "Most incidence of IE start with fever, but it can also manifest as nonspecific fatigue, weight loss, or flu-like symptoms in older adults.\u00a0The infection leads to vegetations on the valve that are the hallmark of IE (figure 4.4). These lesions contain fibrin, inflammatory cells, and bacteria."}
{"_id": "cardio$$$04cf7a1f-a0b1-4e9c-bb8a-d473cd9f1098", "text": "The risk is twofold as the vegetations can:"}
{"_id": "cardio$$$2ada3b7c-1dd9-4458-a070-a1cf8b01ba05", "text": "After a few weeks, complications arise that are the product of immune complex deposition or emboli. They can include glomerulonephritis as immune complexes become embedded in the glomerular basement membrane. Other later complications are now rare due to early detection and effective treatment but can include microthromboemboli that produce splinter or subungual lesions. Other hemorrhagic signs include Janeway lesions on the palms or soles, Osler nodes on the fingers, or Roth spots on the retina (figure 4.5)."}
{"_id": "cardio$$$99aa4115-b5d2-4ffa-967a-744f26be09fc", "text": "Noninfective Vegetations"}
{"_id": "cardio$$$d7a40cbf-0c72-4cc8-9b48-8f359276ee39", "text": "Some vegetations are sterile\u00a0(i.e., occur in the absence of infection). There are two main examples of this\u2014nonbacterial thrombotic endocarditis (NBTE) and the systemic lupus erythematosus (SLE)."}
{"_id": "cardio$$$9735b804-9384-4972-8801-65b4137d8a8a", "text": "Often coinciding with emboli in other sites, NBTE occurs in states of hypercoagulability, such as in cancer or sepsis. The small thrombi (1\u20135 mm) bind to the valve leaflets (figure 4.6), but do not illicit an inflammatory response nor are they invasive. Often the local consequences are trivial, but they can be the source of emboli that lead to\u00a0infarcts in the brain, heart, or elsewhere."}
{"_id": "cardio$$$fc5b8240-74d4-4363-8ff2-89da75b67d46", "text": "In SLE, the vegetations are again sterile and small (1\u20134\u00a0mm) with a pink, wart-like appearance that are composed of eosinophilic material, granular material, and cellular debris. They tend to adhere to the undersurfaces of the atrioventricular valves, the valvular endocardium, and the cords (figure 4.7). Unlike NBTE, the vegetations can instigate complement and Fc-bearing cells that cause intense valvulitis. The end product of this is referred to as Libman Sacks disease."}
{"_id": "cardio$$$1a5ae73c-60e1-4608-842e-4bd4e79ff4cb", "text": "Carcinoid Heart Disease"}
{"_id": "cardio$$$4951a27c-fe47-412b-a160-ced605a85c96", "text": "Lastly, carcinoid heart disease is the cardiac manifestation of carcinoid syndrome. Carcinoid tumors are neuroendocrine tumors that usually arise in the gastrointestinal\u00a0tract or lungs, and they secrete a number of mediators (figure 4.8) that can give rise to carcinoid heart disease."}
{"_id": "cardio$$$f5fc14dc-e762-4dc2-9c28-aefe679a91e4", "text": "The liver normally metabolizes these circulating mediators, but when the metastatic burden overwhelms hepatic clearance, the right heart is exposed to their effects (the left heart is somewhat protected by the degradation performed by the pulmonary circulation)."}
{"_id": "cardio$$$66efaec5-1124-469a-b63e-a04259cca668", "text": "Of all these released mediators, serotonin is the most likely candidate for causing cardiac effects, although the mechanism is not\u00a0clear. Once established, carcinoid lesions are distinctive white intimal thickenings (figure 4.8) composed of smooth muscle cells and collagen embedded in a mucopolysaccharide matrix. The most common manifestations are tricuspid insufficiency and pulmonary stenosis."}
{"_id": "cardio$$$87a6622f-680a-4032-acf2-22d1a3d06a57", "text": "Dass, Clarissa, and Arun Kanmanthareddy. Rheumatic Heart Disease. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK538286/, CC BY 4.0."}
{"_id": "cardio$$$01571255-0baf-4ad1-abdb-c3c38901b4f1", "text": "Douedi, Steven, and Hani Douedi. Mitral Regurgitation. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK553135/, CC BY 4.0."}
{"_id": "cardio$$$7f9e8792-d353-4380-b72b-10095d2e32d2", "text": "Lopez, Diana M., Patrick T. O\u2019Gara, and Leonard S. Lilly. \u201cValvular Heart\u00a0 Disease.\u201d In Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty, 5e edited by Leonard S. Lilly, Chapter 8. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer Business, 2010."}
{"_id": "cardio$$$0b92e173-7511-4e4f-a01c-46a261d63327", "text": "Wenn, Peter, and Roman Zeltser. Aortic Valve Disease. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK542205/, CC BY 4.0."}
{"_id": "cardio$$$1ae0ec16-694d-4b2e-9c46-4f16ca1187bc", "text": "Table 4.1: Location of calcium deposits on aortic and mitral valves and their pathological consequences. Grey, Kindred. 2022. CC BY 4.0. https://archive.org/details/4.2a_20220113"}
{"_id": "cardio$$$36cfa87f-cb4a-40da-be59-3fe09efefb82", "text": "The current guidelines (JNC 8, 2017) list the following pressures and categories to define hypertension:"}
{"_id": "cardio$$$ca95c35a-0b57-45d0-9703-1d6bb256020a", "text": "JNC"}
{"_id": "cardio$$$17c3cb39-d548-4da3-b59e-211a3acb1f40", "text": "Hypertension can be categorized as either essential or secondary. Secondary is much less common and a consequence of another condition (e.g., renal or endocrine disease). Essential hypertension (EH), despite being the prevalent form, is poorly understood but can be attributed to a problem\u00a0with\u00a0either cardiac output or peripheral resistance (i.e., the components of blood pressure regulation). Because\u00a0multiple factors contribute to these components AND there is evidence of some genetic component to hypertension AND due to the contribution from environmental factors, essential hypertension can be considered a \u201cdescription\u201d\u00a0rather than a \u201cdiagnosis.\u201d Primary abnormalities that may contribute to essential hypertension are shown in figure 3.1."}
{"_id": "cardio$$$bd8f6ac2-ffb9-44cd-b02f-17ae00fcf21a", "text": "Genetic components of essential hypertension"}
{"_id": "cardio$$$4184d91a-cb44-49b4-bcbc-cdd7b0e4adff", "text": "No single loci has been identified as causing hypertension, but strong familial histories suggest polygenic causes (i.e., multiple loci are involved). Much attention has been paid to genes involved with enzymes and receptor production within the Renin-Angiotensin-Aldosterone (RAA)\u00a0system because of its critical role in blood pressure control through sodium and volume regulation. Similarly genes involved with renal regulation of sodium have been studied. Our inability to demonstrate a genetic basis to hypertension is also consistent with\u00a0significant environmental causes."}
{"_id": "cardio$$$b7e052e3-654a-4a17-87a7-6db87f0f5912", "text": "Systemic abnormalities and EH"}
{"_id": "cardio$$$ade4db08-4c80-4062-a00a-d762ac4f1a0f", "text": "Since Blood Pressure\u00a0= Cardiac Output\u00a0x Peripheral Resistance, it should be easy to imagine why aberrant rises in cardiac output (e.g., increased sympathetic tone) or peripheral resistance (e.g., low levels of vasodilators) would cause a rise in blood pressure (BP). Some of those aberrations of the acute BP control mechanisms are in figure 3.1, but this is clearly half the story as there are chronic control mechanisms that should surely compensation for loss of acute control. What this means is, for hypertension to be sustained, the kidney must be \u201cin on the hypertension act.\u201d\u00a0While the kidney itself can be responsible for volume-based hypertension (dysregulated renal blood flow, ion channels defects, etc.), there are deficits in renal control in hypertension. Renin levels are normal or high in 70 to 75 percent\u00a0of EH patients\u2014and of course they should be low as elevated\u00a0BP should suppress renin secretion. So while this begins a chicken-and-egg scenario, for hypertension to be sustained, both acute and chronic control mechanisms must\u00a0fail."}
{"_id": "cardio$$$c3b6d65d-b3fa-495f-9a7c-8e790f15aac0", "text": "Diabetes, obesity, and EH"}
{"_id": "cardio$$$d3b69c04-1d15-4424-af89-f77f1666b7c6", "text": "The linkage between diabetes and EH, and obesity and EH, appears strong and direct. Because\u00a0insulin is a dietary-induced mediator of sympathetic activity, the elevated insulin levels in insulin-resistant diabetes can directly promote hypertension. Insulin can also lead to an increase in peripheral resistance via its mitogenic effect on vascular smooth muscle that causes hypertrophy in the medial vascular layers and a decrease in lumen size."}
{"_id": "cardio$$$0aa43dbb-2668-4efb-a242-208f5a95abc7", "text": "Obesity can also induce hypertension through release of angiotensinogen from more abundant adipocytes, thus providing more substrate for the RAA system. The increase in body mass is also accompanied by an increase in blood volume, and that blood may be more viscous as the large population of adipocytes release coagulative proteins, including prothrombin."}
{"_id": "cardio$$$75060c42-4a07-43bd-b3d8-76a55bb39a88", "text": "Secondary Hypertension"}
{"_id": "cardio$$$2668fb3a-6fdd-45e9-8cf6-051e1d037aa6", "text": "Although not as common, there are numerous causes of secondary hypertension. There are some distinguishing features that are clinically useful to distinguish it from EH. Your first heads-up is if the patient is younger and not in the typical range for EH (> fifty years old). Secondary hypertension\u00a0also tends to be more severe, and BP can rise dramatically; EH does not have a rapid onset. While\u00a0EH often comes with family history,\u00a0secondary hypertension is more sporadic."}
{"_id": "cardio$$$c91ed7c1-a706-4945-a2c5-4c0b8a9b5695", "text": "Suspicion of secondary hypertension can usually be confirmed by urinalysis that reveals the underlying issue (see table 3.1 for some common causes and cues for diagnosis). Disturbances in electrolytes and creatinine accompany the renal and mineralocorticoid-based diseases. Pheochromocytoma is rare and accounts for 0.2 percent\u00a0of secondary hypertension cases (however, it is much more common in exam questions than it is in the clinic!)."}
{"_id": "cardio$$$54d3be50-bfae-46a9-a39c-282c93b69103", "text": "Drugs that disrupt the angiotensinogen pathways (e.g., estrogens), are sympathomimetic\u00a0(e.g., over-the-counter cold remedies), or promote sodium and water retention (e.g., NSAIDS) can all produce secondary hypertension."}
{"_id": "cardio$$$8d5e0d50-b1e4-47bb-bee9-8a863d69af60", "text": "Consequences of Hypertension"}
{"_id": "cardio$$$af882988-7ccc-462e-9505-98fd0bd3263c", "text": "As most hypertensive patients are asymptomatic, the condition can be left unmanaged and allowed to produce significant chronic effects. Most of these effects are caused by the extra work placed on the heart with the increased afterload and the damage to the interior of the vasculature."}
{"_id": "cardio$$$d283f412-2185-450b-9f1e-c9490be56efa", "text": "The excess afterload can lead to systolic dysfunction and eventually heart failure with reduced ejection fraction (HFREF). In response to the excessive afterload the left ventricle can hypertrophy, causing a loss of compliance diastolic dysfunction and eventually heart failure with normal ejection fraction (HFNEF). The increased workload and muscle mass also increase\u00a0the myocardial oxygen demand. This increase in demand often occurs at the same time that blood supply is diminished by concurrent atherosclerosis that is accelerated by the hypertension-induced\u00a0arterial damage. Consequently,\u00a0with high demand and low supply, the patient is prone to ischemia and myocardial infarction."}
{"_id": "cardio$$$c1ed34a9-7d84-4ac5-9417-1199bdbf9872", "text": "The arterial damage will also promote thrombosis and atheroemboli, so risk of embolic stroke is raised. Risk of hemorrhagic stroke is also increased as the vessel ways become weak. The large vessels are also at risk of being unable to counteract raised pressure\u00a0(remember Laplace\u2019s\u00a0law?), so aortic aneurysm and dissection can also occur."}
{"_id": "cardio$$$a8286b9f-39dc-4ddd-a8c6-737c69993a46", "text": "High pressures entering the renal circulation can lead to nephrosclerosis. As renal function declines,\u00a0a vicious cycle forms with renal failure exacerbating hypertension that exacerbates renal failure."}
{"_id": "cardio$$$020ddd29-fe19-4942-a12e-51cb278a5826", "text": "The retinal circulation\u00a0provides a direct window into the state of the vasculature. Rapid onset and severe hypertension may burst small retinal vessels and produce local infarctions. In more chronic cases, arterial narrowing and medial hypertrophy of the retinal vessel can be seen. As the chronic hypertension worsens,\u00a0arterial sclerosis is evident. While\u00a0these chronic effects may not produce functional issues, they are at least an accessible indicator of the vascular status. The consequences of hypertension are summarized in figure 3.2."}
{"_id": "cardio$$$96a5472c-9338-4294-b65a-0fdb83b57265", "text": "Hypertensive Crisis"}
{"_id": "cardio$$$73d9b885-aa84-4b56-81a7-5ed3c181505c", "text": "Most commonly caused by a hemodynamic insult overlaid on chronic hypertension, a hypertensive crisis is a severe elevation of blood pressure that can become life threatening through raising intracranial pressure. The rise in intracranial pressure produces severe\u00a0headache, blurred vision, confusion, or even coma and is referred to as hypertensive encephalopathy. Funduscopy reveals retinal hemorrhages, exudates, and sometimes papilledema. The massive afterload on the left ventricle can precipitate angina.\u00a0Therapy must be rapid to prevent permanent vascular consequences, and if administered in time the acute changes are usually reversed. However, the underlying cause of the crisis (usually renal failure) will persist."}
{"_id": "cardio$$$043d0a6c-c109-49d3-864d-1049ae0bab92", "text": "Brown, Jenifer M., Gordon H. Williams, and Leonard S. Lilly. \u201cHypertension.\u201d In Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty, 5e edited by Leonard S. Lilly, Chapter 13. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer Business, 2010."}
{"_id": "cardio$$$6a1b6fe6-83fe-406c-9e01-1a06a4791350", "text": "Hajar, Rachel. \u201cFramingham Contribution to Cardiovascular Disease.\u201d Heart Views 17, no. 2 (April\u2013June 2016): 78\u201381. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966216."}
{"_id": "cardio$$$b09e6339-ed87-40ae-b475-924c98e1a575", "text": "Iqbal, Arshad Muhammad, and Syed F. Jaml. Essential Hypertension. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK539859/, CC BY 4.0."}
{"_id": "cardio$$$df8f6825-cd8d-4f33-a3b6-3aa95e2b7231", "text": "Page, Michael R. \u201cThe JNC 8 Hypertension Guidelines: An In-Depth Guide.\u201d Evidence-Based Diabetes Management 20, no. SP1\u00a0 (January 2014). https://www.ajmc.com/view/the-jnc-8-hypertension-guidelines-an-in-depth-guide."}
{"_id": "cardio$$$542c40cb-0157-4bdb-8e18-253f38324396", "text": "For whichever reason the end effect of the failure is a decline in blood flow out of the heart, and consequently congestion on the way in."}
{"_id": "cardio$$$7793dbfa-5e5b-4555-9631-e10c6b1d4a99", "text": "Table 2.1: Changes in cardiac function in different disease states."}
{"_id": "cardio$$$810dee93-c004-4109-b99d-0c58c90f8bc4", "text": "Impediments to emptying the heart during systole (i.e., a reduced contractility or increased afterload) were\u00a0referred to as systolic heart failure. Similarly, problems with filling the ventricle during diastole were referred to as diastolic heart failure (figure 2.1)."}
{"_id": "cardio$$$9d443965-9456-4656-a0f9-1e1e37fce404", "text": "In reality there is a great deal of overlap between these forms of heart failure, and elements of both can be present in the same patient. Similarly, as both forms result in congestion before the heart and reduced flow after it, they are hard to immediately distinguish. Consequently the type and degree of failure is now categorized by the effect on ejection fraction that can help distinguish the source of the problem."}
{"_id": "cardio$$$33c5d98f-6bcc-40b2-9a97-f4a5cf465f1c", "text": "Let us quickly remind ourselves of what ejection fraction is. Ejection fraction is the proportion of blood volume that the left ventricle ejects in one beat. It is mathematically described as the starting volume (i.e., end-diastolic volume, EDV) minus the finishing volume (i.e., end-systolic volume, ESV) as a proportion of the starting volume (figure 2.2)\u2014in simpler terms, what percentage of the ventricular blood volume was pushed out during a contraction."}
{"_id": "cardio$$$20622c34-1a4f-473e-973b-176ee18cd7b4", "text": "Ejection Fraction in Systolic Failure"}
{"_id": "cardio$$$8313e09f-8062-4d5c-992f-418a2f86e873", "text": "Let us\u00a0first relate this to systolic failure by looking at what happens when the contractility of the myocardium is reduced. In systolic failure, there is a problem getting blood out of the heart, so the volume of blood coming out of the heart per beat (EDV-ESV) is reduced. However, the end diastolic volume will remain the same, or more likely rise. So our ejection fraction is reduced. Consequently, if you have a reduced ejection fraction you know you have a systolic failure. So to improve diagnosis, systolic failure is now referred to as heart failure with a reduced ejection fraction (HFREF)."}
{"_id": "cardio$$$bb4d5498-c998-405e-bfe2-bdc0fdb98ee3", "text": "Let us\u00a0look at the pathophysiological consequences of HFREF. With a poor ejection fraction blood will begin to accumulate in the ventricle, and EDV will begins to rise and consequently so will the ventricular pressure. The raised pressure will impede venous return\u00a0and promote venous congestion as blood struggles to enter the heart, and in the case of left ventricular\u00a0failure the congestion will occur first in the left atrium and then in the pulmonary system (figure 2.3)."}
{"_id": "cardio$$$a6ecac52-4f7f-4f9a-959c-73163b2c45e2", "text": "So systolic failure is referred to as HFREF, but what started as a problem emptying the heart has led to congestion and has produced a problem getting blood into the heart. Let us compare this with diastolic failure."}
{"_id": "cardio$$$94108388-5e0d-4c37-bf0b-ca7771e3c675", "text": "Ejection Fraction in Diastolic Failure"}
{"_id": "cardio$$$4a4369ee-b8dd-4481-b713-a6c69f9c6ce7", "text": "Remember that in diastolic failure there is a problem relaxing/filling the ventricle. Consequently EDV tends to be lower than normal, and this lower volume of blood in the chamber is relatively easy for the heart to expel. So proportionately, the ejection fraction can be maintained, even if the absolute stroke volume may be low. This is now classified as heart failure with a normal ejection fraction (HFNEF)."}
{"_id": "cardio$$$3c7cd1cb-4846-4b2e-a25f-4cab6021fbc9", "text": "The pathophysiological consequences of HFNEF stem from the poor relaxation of the ventricle and/or ability to accept blood. When the ventricle is noncompliant during diastole (i.e., does not relax properly), it does not\u00a0take much blood volume to enter the chamber before the ventricle pressure begins to rise. This rise in ventricular pressure opposes the entry of more blood, so it accumulates in the atrium. Atrial pressure rises and venous return is impeded, so blood becomes congested in the venous system."}
{"_id": "cardio$$$41492948-d42e-48d2-8d92-5f2fa12f7f3f", "text": "If you compare this sequence of events in HFREF\u00a0and HFNEF\u00a0in figure 2.3 the end point is the same\u2014congestion in the venous system, hence the difficulty in distinguishing \u201csystolic\u201d and \u201cdiastolic\u201d failure and the need to measure ejection fraction and the newer categories of HFREF and HFNEF.\u00a0In summary, HFREF starts with a problem getting blood out, that leads to a problem getting blood in, whereas HFNEF starts with a problem getting blood in that leads to a problem getting blood out. Both produce congestion, and both result in a diminished cardiac output."}
{"_id": "cardio$$$7c1b6d8d-ee1a-4cfe-be3e-3be6c7664e69", "text": "Acute Responses to Reduced Cardiac Output in Heart Failure: Good or Bad?"}
{"_id": "cardio$$$e63043fd-51c9-4f41-a0c6-e96a7748fc36", "text": "Initial responses to the diminished cardiac output include the acute compensatory responses to low blood pressure, myocardial stretch, or changes in renal perfusion. Let us\u00a0do a quick review."}
{"_id": "cardio$$$2457bc27-6e6b-4146-8364-866cf6245fb9", "text": "The reduced cardiac output leads to a reduced arterial blood pressure, which, in combination with low volume exiting the heart, results in lower blood flow. With less blood exiting the heart, more remains in the chamber, particularly with systolic failure, so the myocardium is stretched. These three factors (pressure, flow, and myocardial stretch) elicit mechanical, neural, and hormone responses intended to correct the fall in pressure, resume flow, and clear the heart of congestion\u2014but these responses are intended for a normal heart, not one undergoing failure."}
{"_id": "cardio$$$827a6f0f-2995-441d-a84f-1326feff6ad8", "text": "First, the extended myocardium elicits the Frank-Starling mechanism to increase contractility, while the release of ANP and BNP induces sodium and fluid loss at the kidney. Conversely, reduced renal blood flow instigates the RAAS system to cause salt and fluid retention and vasoconstriction aided by the release of Endothelin-1 from the endothelium of flow-deprived vessels. Finally, the reduced arterial pressure prompts the baroreceptor reflex that increases\u00a0sympathetic tone to increase rate and contractility, and antidiuretic hormone causes fluid retention. See the summary in figure 2.4."}
{"_id": "cardio$$$f4564ed9-680a-4eb9-98a0-9300621443d8", "text": "These compensatory effects are all attempts to improve cardiac output and blood pressure, but the failing heart is being forced to work harder against an increased afterload and move more volume. Consequently, but for the natriuretic peptides, these responses are maladaptive in the long term, and chronic changes to the heart are instigated."}
{"_id": "cardio$$$e31b68ab-dffc-4c91-8adf-bc3c6dfa5449", "text": "Chronic Remodeling and Hypertrophy"}
{"_id": "cardio$$$38a6b3ec-f8b6-41bd-a4dc-855ba9398345", "text": "The long-term structural changes begin with additional wall stress in the failing heart interacting with neurohormonal and cytokine alterations, but the wall stress seems to be an important instigator of hypertrophy and remodeling.\u00a0Stress can be placed on the chamber walls in two major ways."}
{"_id": "cardio$$$3d505d61-d695-4456-81c2-16b0858e0ef1", "text": "But the two forms of overload (volume and pressure) lead to different patterns of hypertrophy. In volume overload the myocytes add more sarcomeres in series, so they elongate and contribute to the dilation of the chamber while there is a proportional increase in wall thickness. This is referred to as eccentric hypertrophy (figure 2.5)."}
{"_id": "cardio$$$cf5247ca-13e8-49ce-a929-e13d964bdeee", "text": "Pressure loading, on the other hand, leads to the synthesis of new sarcomeres that are formed in parallel to the old ones, causing an increase in wall thickness\u00a0without any dilation of the chamber. This is referred to as concentric hypertrophy (figure 2.5)."}
{"_id": "cardio$$$af81a211-a1f5-4981-aeb8-b5e176b28af0", "text": "These adaptations are accompanied by increased deposition of connective tissue that may have conductive or contractive ramifications. The difference in myocytic arrangement and presence of connective tissue is clear in the histological views of normal myocardium and myocardium chronically exposed\u00a0to valvular disease in figure 2.6."}
{"_id": "cardio$$$1688bd5c-bfae-42ba-abd9-825ce316194a", "text": "Myocytes may also be lost through either apoptosis or necrosis. As hypertrophy occurs the blood supply to the thickening wall becomes inadequate so infarction and consequent necrosis are more likely. Factors that promote myocyte apoptosis are all present during heart failure and include\u00a0elevated catecholamines, Angiotensin II, inflammatory cytokines, and wall stress."}
{"_id": "cardio$$$bb79e7cd-ae7b-4e7e-9b25-d6a2a2fa57c2", "text": "These same factors also disrupt gene expression in myocytes and cause intracellular deficits, including loss of Ca++\u00a0homeostasis and production of high-energy phosphates. While the mechanisms of these intracellular effects is still being heavily researched, the inability to control calcium or regulate high-energy phosphates obviously has implications of excitation\u2013contraction coupling."}
{"_id": "cardio$$$384bc000-79c1-4a05-be16-e91fa7cc8b07", "text": "So while hypertrophy may seem a sensible response in the failing heart, the patterns and inflammation and stress-driven changes are eventually maladaptive and lead to a progressive decline in cardiac function."}
{"_id": "cardio$$$b96a14b3-90c1-46d9-85a7-3d8097f1cc0b", "text": "Clinical Manifestations of Heart Failure"}
{"_id": "cardio$$$8eedeb9c-8875-4207-8dc0-63d9714411a6", "text": "The clinical manifestations arise as fluid begins to move from the blood to the interstitium due to congestion (see summary in figure 2.7)."}
{"_id": "cardio$$$cd53d0f7-ff4a-4644-bb06-f1b12dd8d8d7", "text": "If the right heart fails, there is a rise in systemic venous pressure and peripheral edema arises. There may be abdominal discomfort as the liver becomes engorged and a loss of appetite or nausea as gastrointestinal edema arises. If the left heart fails, then the pulmonary circulation is exposed to the congestion and pulmonary edema arises."}
{"_id": "cardio$$$f01b9785-90a8-4f1f-9af6-b2abdb605faa", "text": "Low cardiac output\u00a0reduces renal filtration, so urine formation maybe impaired. Similarly cerebral blood flow may be compromised, causing dulled mental status."}
{"_id": "cardio$$$aae92405-fd79-4bad-b17c-3704ca13b242", "text": "Orthopnea\u00a0arises when the patient lays down and venous return toward the failing left ventricle increases, compounding the pulmonary congestion. Patients often sleep propped up on pillows to elevate the heart and lungs. In severe cases the patient may only be able to sleep upright in a chair."}
{"_id": "cardio$$$0dade292-7120-4fea-a845-e26eeb3159a3", "text": "Eberly, Lauren A., Eldrin F. Lewis, and Leonard S. Lilly. \u201cHeart Failure.\u201d In Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty, 5e, edited by Leonard S. Lilly, Chapter 9. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer Business, 2010."}
{"_id": "cardio$$$d3239a6f-3c3d-4562-9ca8-835f21d500e2", "text": "Malik, Ahmad, Daniel Brito, Sarosh Vaqar, and Lovely Chhabra. Congestive Heart Failure. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK430873/, CC BY 4.0."}
{"_id": "cardio$$$6c46f5ba-cd4b-46df-be9b-4a6f16ed3be2", "text": "USMLE"}
{"_id": "cardio$$$77eb1c38-43b0-47d4-96c7-3a2c17c4056c", "text": "Atrial fibrillation is the most common cardiac arrhythmia and is\u00a0caused by rapidly firing\u00a0potentials in the atrial myocardium. These aberrant depolarizations are often the result of myocardial remodeling and frequently\u00a0originate within the muscular sleeves that extend into the pulmonary veins from the atria. Causes include hypertension, valvular and ischemic heart disease, and genetics (e.g., mutation of\u00a010q22\u2013q24 on chromosome 10).\u00a0The rapid depolarizations result in a very fast atrial rate from 400 to 600 bpm. Because the atrial rate is so fast, the ECG shows \u201ccoarse fibrillatory waves\u201d\u00a0(figure 1.1);\u00a0the action potentials produced are\u00a0low amplitude, and P-waves will not be seen."}
{"_id": "cardio$$$f46b72ef-06f9-4563-bda4-c278a237fa2f", "text": "10q22"}
{"_id": "cardio$$$b8793902-7452-426b-96d7-a119cd75ef71", "text": "q24"}
{"_id": "cardio$$$7027c49e-bf8b-4d34-9d4f-0a51df267154", "text": "fibrillatory"}
{"_id": "cardio$$$3aee9c75-9844-4eed-9724-f09cc605c6ca", "text": "The rapid atrial depolarizations are transmitted to the atrioventricular (AV) node, but far from all are conducted through to the ventricle because of the node\u2019s long refractory period. This means the ventricular rate does not rise to 400\u2013600 bpm (which would be catastrophic), but some of the atrial fibrillation activity can be \u201clucky\u201d and reach the AV node when it is not in a refractory period. When this occurs, the ventricular rate rises to 100\u2013200 bpm, and QRS complexes can be \u201cirregularly irregular\u201d with a varying R-R interval (left panel, figure 1.2)."}
{"_id": "cardio$$$639d540a-0158-4f7d-9820-e67b5789ff80", "text": "Table 1.1: Atrial fibrillation summary."}
{"_id": "cardio$$$178f8b4b-2f2d-47c8-a4d9-92fe0b874e4f", "text": "Atrial Flutter"}
{"_id": "cardio$$$818acd74-546e-4e12-9767-de1f0f024d58", "text": "Atrial flutter is caused by a macroreentrant current, rather than the\u00a0multiple sites of aberrant depolarization seen in fibrillation. The cavotricuspid isthmus (CTI) usually provides the circuit for the slower reentrant current to become established (typical atrial flutter), but other sites of reentry and slow conducting circuits are possible (atypical atrial flutter) and are usually associated with structural heart disease or sites of previous surgical or ablations procedures. The slower reentry current produces an atrial rate of 250\u2013350 bpm (compared to the 400\u2013600 of atrial flutter), and P-waves are present but have a characteristic \u201csawtooth\u201d pattern (figure 1.3 and middle panel figure 1.2)."}
{"_id": "cardio$$$7901f6d3-4a4f-47c1-b2f3-ed60b1bcaab5", "text": "macroreentrant"}
{"_id": "cardio$$$3082a6e8-a32b-486c-84f2-37181b801cfa", "text": "cavotricuspid"}
{"_id": "cardio$$$f7916563-e0d7-45f6-801c-c44dbb0572db", "text": "As with atrial fibrillation, the AV node\u2019s refractory period prevents most of the P-waves from progressing to the ventricle, but commonly the AV conduction will be 2-to-1, so with an atrial rate of 300 bpm the ventricular rate will be 150 bpm. Parasympathetic stimulation or changes in AV node refractoriness can modify how many P-waves pass into the ventricle, but the the resultant rhythm is \u201cregularly irregular.\u201d When the heart rate is elevated, then distinguishing flutter from fibrillation becomes challenging and slowing ventricular rate pharmaceutically (adenosine) helps the flutter waves reemerge for a definitive diagnosis to be made."}
{"_id": "cardio$$$ae040685-4088-4ccd-b7e7-8ae11993a0e8", "text": "Table 1.2: Atrial flutter summary."}
{"_id": "cardio$$$6af9e4b1-ef83-4de9-923d-7c09cba52590", "text": "Multifocal Atrial Tachycardia"}
{"_id": "cardio$$$af0d299e-2b3f-4089-b62a-9764b4a18f71", "text": "Multifocal atrial tachycardia (MAT)\u00a0is caused by the presence of\u00a0multiple\u00a0ectopic foci. The multiple foci result in\u00a0P-waves with multiple morphologies and irregular intervals (see figure 1.4).\u00a0The pathophysiology of MAT is not clear, although several\u00a0theories exists (e.g., triggered activity,\u00a0reentry,\u00a0or abnormal automaticity). The multiple\u00a0foci\u00a0within the atrium generate consecutive action potentials that are all conducted to the ventricles. Thus, each QRS complex will be preceded by a P-wave; however, each P-wave will have a different morphology because they originate from different areas. By definition, MAT\u00a0must have at least three distinctly different P-wave morphologies (figure 1.4) and a ventricular rate of greater than 100 bpm."}
{"_id": "cardio$$$69d51e67-954b-4217-ad36-a22a50989d54", "text": "MAT\u00a0frequently occurs in the setting of severe lung disease and, more specifically, during an exacerbation of lung disease. This rhythm is benign, and once the underlying lung disease is treated, it should resolve."}
{"_id": "cardio$$$98afd1fa-85df-4d62-a0c1-9e9c898401fe", "text": "Table 1.3: MAT summary."}
{"_id": "cardio$$$4cba9425-2ae2-4564-b06d-4dbc63fd3b2d", "text": "Premature Atrial Contraction"}
{"_id": "cardio$$$8bb9a3f4-eda3-41e3-bdac-aecaedc793cd", "text": "A premature atrial contraction (PAC) is generated by a depolarization instigated outside of the SA node. This produces an extra P-wave, and consequently\u00a0a shortening from previous P-P intervals is seen. The aberrant P-wave also has a different morphology from\u00a0a sinus P-wave because of its different anatomical origin."}
{"_id": "cardio$$$7d84a37a-b966-4fe7-808c-348e93346e99", "text": "The premature complex may also upset the timing of the SA\u00a0node,\u00a0placing it back into a\u00a0refractory period when it should be depolarizing for its next scheduled beat. This means that a PAC\u00a0may cause a \u201ccompensatory pause\u201d as the SA node restarts its pacemaker depolarization. Consequently the ECG can show \u201catrial bigeminy\u201d\u00a0where complexes appear to be in pairs with a normal complex followed by a complex driven by the atrial ectopic activity, then a pause while the SA node begins\u00a0its depolarization again (see figure 1.5)."}
{"_id": "cardio$$$37713deb-c7b3-4fbc-b01c-3eb0aaa9d84c", "text": "If a PAC occurs when the AV node has not yet recovered from its refractory period, the PAC will fail to conduct to the ventricles; meaning the PAC will not be followed by a QRS complex or the ectopic P-R interval will be prolonged. The ECG will show a premature, ectopic P-wave and then no QRS complex afterward. When this occurs along with bigeminy, the ECG can appear as if there is sinus bradycardia."}
{"_id": "cardio$$$2b9aed14-4aa1-4521-9f3c-275cf0a91144", "text": "Table 1.4: PAC summary."}
{"_id": "cardio$$$10e603ab-8f39-46fa-b0bf-7d92fc3221e0", "text": "Sinus Bradycardia"}
{"_id": "cardio$$$c51217b8-d2af-458e-9418-7fbedc1cfabc", "text": "Sinus bradycardia denotes a sinus rhythm below 60 bpm. Otherwise the\u00a0ECG waveform is normal\u00a0on an ECG with an\u00a0upright P-wave in lead II\u00a0preceding every QRS complex. There are many intrinsic causes associated with the heart\u00a0itself, as well\u00a0as\u00a0extrinsic causes, some of which are listed table 1.5. Sinus bradycardia is usually asymptomatic as\u00a0rates of 40\u201350\u00a0bpm can maintain hemodynamic stability. Rates below this can produce symptoms of fatigue,\u00a0dizziness, and dyspnea on exertion."}
{"_id": "cardio$$$971cfd9a-1095-4b66-9155-ceda21053890", "text": "Table 1.5: Intrinsic and extrinsic causes associated with the heart."}
{"_id": "cardio$$$fd17df84-794f-4519-a7eb-53390b52b442", "text": "Table 1.6: Sinus bradycardia summary."}
{"_id": "cardio$$$9effc782-cdd4-42f2-8f31-d6b9d6ee0ed2", "text": "Premature Ventricular Contractions"}
{"_id": "cardio$$$dc9ee840-69de-4976-87b6-7abde5e38a90", "text": "Similar to a PAC, a premature ventricular contraction (PVC) occurs when a focus in the ventricle generates an action potential before the pacemaker cells in the SA node\u00a0depolarize.\u00a0This early depolarization\u00a0is out of rhythm with the normal R-R interval, and because it starts outside of the normal conduction pathways, it has a very different shape from\u00a0a normal, scheduled QRS complex (figure 1.6). The PVC is wider as it has to travel from myocyte to myocyte, so it is much slower than a normal SA node\u2013driven depolarization that travels through the faster conduction network fibers. There is also a compensatory pause following the PVC as the unscheduled depolarization puts the ventricular myocardium into refractory state, forcing it to \u201cskip a beat\u201d (figure 1.6)."}
{"_id": "cardio$$$23079878-bc12-424c-9e14-a9826f400b5b", "text": "Table 1.7: PVC summary."}
{"_id": "cardio$$$28557e1f-119f-4244-815b-027c7e462e4f", "text": "Ventricular Tachycardia"}
{"_id": "cardio$$$0ee66a98-cebd-476f-99fb-3bd440a76037", "text": "Ventricular tachycardia (VT) is caused by reentry currents being established in the ventricular myocardium or groups of ventricular myocytes that have aberrant electrical behavior. As such, VT is usually caused by underlying cardiac disease."}
{"_id": "cardio$$$c446e254-69fd-477f-b95e-d85d69a4a7bc", "text": "Like a PVC, the aberrant depolarizations do not follow the normal conduction pathways so are wide (>120 msecs), but unlike a PVC, VT involves a ventricular rate >100 bpm. With disorganized contractility and reduced filling time, VT can lead to hemodynamic instability and severe hypotension\u2014hence it is life threatening."}
{"_id": "cardio$$$740e2583-adaa-4879-9900-42e40e3469ca", "text": "The QRS morphology in VT is highly variable between patients and depends on where the arrhythmia originates. Consequently there are several ways to classify VT based on duration, symptoms, QRS morphology, rate, and origin."}
{"_id": "cardio$$$c3cb9d9f-2d2b-4cfe-8810-58f2fa676d70", "text": "Sustained VT is any VT\u00a0that lasts for more than 30 seconds or is symptomatic. Nonsustained VT lasts for less than 30 seconds and is asymptomatic."}
{"_id": "cardio$$$404d4366-865a-4d38-8585-bbc56474a36d", "text": "VT can be monomorphic or polymorphic (figure 1.7). The QRS complexes in monomorphic VT have the same shape and are symmetrical because they start in the same place in the myocardium. Polymorphic VT has a variable QRS shape because the depolarizations are instigated at multiple points. An electrophysiologist\u00a0can describe the location(s) within the ventricles from where the VT originates\u00a0using the shape(s) of the QRS complexes."}
{"_id": "cardio$$$4e92395d-61e7-40e7-b3bd-de21c9a0c006", "text": "Torsades de pointes (twist of peaks) is a form of VT with multiple QRS morphologies. The twist references\u00a0the undulating amplitude of the QRS complexes that twist around the isoelectric line, giving the ECG the appearance of a twisted ribbon (figure 1.8)."}
{"_id": "cardio$$$4165fe0e-c783-42fb-9b63-edc7c4a8c906", "text": "Torsades de pointes is associated with a prolonged QT interval (>600 msecs) that helps distinguish it from other forms of polymorphous VT. The longer QT interval can be caused by ionic abnormalities that reduce the repolarizing current of Phase 3 of the cardiac action potential. This makes the myocardium susceptible to early after-depolarizations\u2014the trigger for torsades de pointes. These after-depolarizations do not happen uniformly across the myocardium and are more common in endocardial tissue where the repolarization currents are slower. So torsades de pointes arises from the after-depolarizations causing reentry currents in neighboring tissue."}
{"_id": "cardio$$$44532f18-cc77-412b-9a9f-8e896baa0e7c", "text": "Both common garden variety VTs\u00a0and torsades de pointes can progress to ventricular fibrillation."}
{"_id": "cardio$$$f04b8ce2-30d4-4391-bb46-71176695b350", "text": "Table 1.8: VT summary."}
{"_id": "cardio$$$05c698a0-3c11-49f2-9b45-f762a4ecdd4c", "text": "Ventricular Fibrillation"}
{"_id": "cardio$$$33e8af1d-efa7-4fd2-98e0-85c264cccead", "text": "Ventricular fibrillation (VF) occurs when the ventricular rate exceeds 400 bpm. The disorganized and uncoordinated contraction of the myocardium causes cardiac output to fall to catastrophic levels. Rates of survival for out-of-hospital VF are low."}
{"_id": "cardio$$$01764ee2-2aa5-4abb-899c-572d11954a23", "text": "There are a number of instigating events, but coronary artery disease and resultant myocardial ischemia or tissue scarring are the most common. The onset of VF may be preceded by other changes in the myocardial rhythmicity, such as PVCs, ST changes, VT, or QT prolongation. The tissue damage allows formation of reentry patterns that cause the chaotic ventricular depolarization. These reentry patterns break up into multiple smaller wavelets that cause high-frequency activation of the myocytes. The result is an ECG that is chaotic (figure 1.9) and consequently a heart that has little output."}
{"_id": "cardio$$$21fd698f-b39d-40ea-9c6a-ae7c5d2c7faf", "text": "Table 1.9: VF summary."}
{"_id": "cardio$$$9b4f91e0-801b-4631-ba6d-d02525b927e8", "text": "First-Degree Atrioventricular Block"}
{"_id": "cardio$$$26fd284b-1d08-488e-addc-2f1d278c835d", "text": "A first-degree atrioventricular node block results from slow action potential conduction through the\u00a0AV node\u00a0conduction. The slowing can be due to changes in vagal tone or structural changes associated with damage or disease affecting the conductive tissue of the atria, AV node (most common), bundle of His or bundle branches, and Purkinje system. It\u00a0takes longer for the action potential\u00a0to reach the ventricles, so P and R appear further apart. The P-R interval is normally between 0.12 and 0.20 seconds, but in first-degree block\u00a0it exceeds\u00a00.20 seconds (>5 small boxes;\u00a0figure 1.10)."}
{"_id": "cardio$$$c0c80220-7953-4f14-aa25-f18009fc23d1", "text": "In first-degree block each P-wave is accompanied by a QRS complex\u00a0(i.e.,\u00a0\u201cthey all get through\u201d) (figure 1.10), which is not the case in second-degree and third-degree blocks (see below). Generally a first-degree block is asymptomatic and does not require any treatment, but long-term monitoring for worsening conduction is advisable."}
{"_id": "cardio$$$c743fff8-73b7-4075-a969-1feae0d8a568", "text": "Table 1.10: First-degree block summary."}
{"_id": "cardio$$$de2cec40-73b4-4f8d-91b4-f9ef35abdaa2", "text": "Second-Degree Atrioventricular Block"}
{"_id": "cardio$$$df09dbda-3d2e-4c9b-8b12-c7c7c05b4acb", "text": "A second-degree atrioventricular block also has changes in P-R interval, but it starts to show failure of the P-wave to propagate a QRS complex every time (i.e., intermittently the depolarization fails to reach the ventricles). The pattern of missed ventricular depolarizations, or blocked P-waves, is often very regular and described as a ratio of P-waves to QRS complex. The way in which the P-R interval changes in relation to the blocked P-waves produces subclassifications of second-degree blocks, Mobitz I and II."}
{"_id": "cardio$$$f9d26c65-3284-41a0-b2ad-4b66547da199", "text": "Mobitz I (or Wenckebach)\u2014The P-R interval progressively lengthens until a P-wave is missed and then goes back to its original length (figure 1.11).\u00a0So P-R is longest before the dropped QRS complex and shortest immediately after it. This progressive difficulty in traversing the AV node is reflective of the node becoming increasingly refractory."}
{"_id": "cardio$$$48fe1443-e99b-4d7a-ad87-78d36e7557b0", "text": "Mobitz II has blocked P-waves as well, but the P-R interval remains unchanged, and the P:QRS ratio\u00a0appears in a fixed pattern (figure 1.12). This is a rarer and more serious condition and usually involves problems with the conduction system below the AV node, most commonly in the bundle branches. What can frequently been seen is a widening of the QRS complex that are generated."}
{"_id": "cardio$$$a1642ccd-4cff-4d8a-9308-edf4c700436d", "text": "Table 1.11: Second-degree block summary."}
{"_id": "cardio$$$a4608bf3-06e9-47e8-8006-55d25793936f", "text": "Third-Degree Atrioventricular Block"}
{"_id": "cardio$$$61b944f1-ad84-4652-aadc-89ed8cf18352", "text": "A third-degree atrioventricular block is where\u00a0no action potentials\u00a0pass\u00a0through the AV node, hence it is often called \u201ccomplete heart block\u201d. This is usually because of damage (e.g., ischemia) or disease (e.g., Lyme disease, sarcoidosis) affecting the AV node. In a third-degree atrioventricular\u00a0block, no P-waves have associated QRS complexes. Without any descending control by the SA node pacemakers, the ventricular pacemaker cells\u00a0are finally free to rule the ventricles\u00a0(insert maniacal laughter). Consequently P-waves and QRS complexes are completely unrelated to each other, and this is termed \u201cAV dissociation.\u201d\u00a0The ECG (figure 1.13) reflects this with P-waves occurring at an SA node rate (~75 bpm with parasympathetic tone) and the ventricles depolarizing at between thirty and fifty\u00a0times per minute, depending on which ventricular tissue acts as pacemaker."}
{"_id": "cardio$$$190d3598-0b72-47c6-9ef7-0547c20cfca4", "text": "Table 1.12: Third-degree block summary."}
{"_id": "cardio$$$4bc7df69-7264-4d65-a3f7-76203dcef9ca", "text": "Left Bundle Branch Block"}
{"_id": "cardio$$$7d8c7572-df90-4f8b-9ce4-756804698c77", "text": "A left bundle branch block (LBBB) is generated when the conductivity of the His-Purkinje system in the left ventricle is compromised, either through damage or disease. The ECG changes, and criteria for LBBB relate to these changes in conductivity and the left-side\u00a0location."}
{"_id": "cardio$$$d816de31-6a21-4de3-a05e-28301d77ae86", "text": "Because the normal route through conductive tissue is impaired or blocked, the depolarization has to travel through myocytes,\u00a0which takes more time. Consequently, the QRS complex is wider (figure 1.14) (i.e., has a duration >120 msecs, with 80\u2013100 msecs being normal).\u00a0The slower conduction through the left ventricle means the right ventricle depolarizes first and the left last. This means the depolarization has a prominent right-then-left direction and will be moving away from lead V1, causing that lead to have a deep downward S-wave\u00a0(figure 1.14)."}
{"_id": "cardio$$$ea861933-f312-44a7-b370-ce8f7bcfde6d", "text": "The lateral leads (I, V5, and V6) normally show a downward deflecting Q-wave as normal septal deflection initially occurs left-to-right (i.e., away from the lateral leads). In LBBB the change in direction to right-to-left, plus the longer duration, eliminates the Q-wave from the lateral leads, and Q-waves will be small in aVL."}
{"_id": "cardio$$$2080c0ff-56d1-4e29-8db3-51cc8f868100", "text": "The R-wave in the lateral leads may also change morphology when there is a distinct separation of right and then left ventricular depolarization. This manifests as an M-shaped R-wave (figure 1.15) or a notched R-wave in the lateral leads (figure 1.14)."}
{"_id": "cardio$$$a1da0307-b435-4784-be2c-4eac84a16ecc", "text": "Conversely a W-shaped R-wave may occur in leads facing the opposite direction\u00a0(e.g., aVR) (figure 1.14)."}
{"_id": "cardio$$$e92edea7-e190-4049-ba98-e1f1633e591f", "text": "Table 1.13: LBBB summary."}
{"_id": "cardio$$$051c8ca1-b15e-42d1-8361-5aed91faa6da", "text": "Right Bundle Branch Block"}
{"_id": "cardio$$$205b49ac-17ce-43c1-aacd-68e3d026a96b", "text": "The causes and manifestations of a right bundle branch block (RBBB) bear some similarities to those described for LBBB, but of course this time its depolarization of the right ventricle\u00a0is\u00a0delayed. Causes of RBBB include ischemic heart disease again as well as other myocardial diseases, but pulmonary issues such as pulmonary embolism and cor pulmonale can be added to the list."}
{"_id": "cardio$$$421580b1-f84f-4e74-96ce-fc2031991d9d", "text": "Again the QRS complex becomes broad (>120 msecs) because of the slower conduction through ventricular myocytes. However, the delayed activation of the right ventricle causes a secondary R-wave (RSR\u2019) to occur in the right precordial leads (V1\u2013V3) and a slurred S-wave in the lateral leads (I, aVL, and frequently V5 and V6) (figure 1.16)."}
{"_id": "cardio$$$fe029546-fd85-41f4-8858-24dfa01f1d67", "text": "Table 1.14: RBBB summary."}
{"_id": "cardio$$$f1574f5a-6c63-4d63-b842-e538a4fe50a7", "text": "Wolff-Parkinson-White Syndrome"}
{"_id": "cardio$$$330caca1-1db9-4ae4-9ff4-9452e5516814", "text": "Normally the only electrical connection between the atria and the ventricles is the AV node. Otherwise the fibrous skeleton of the heart electrically\u00a0insulates the atria from the ventricles. In Wolff-Parkinson-White (WPW)\u00a0syndrome, that insulation is incomplete, and an \u201caccessory pathway\u201d connects the electrical system of the atria directly to the ventricles. If you think of the AV node as a\u00a0bridge over the fibrous wall with regulated\u00a0access, the accessory pathway is like a pathological tunnel under it with no regulation."}
{"_id": "cardio$$$2e85d51e-4ad4-4591-8ff6-5d386e5cced4", "text": "The accessory pathway provides a second route (figure 1.17) for normal sinus rhythm to pass from atrium to ventricle much more quickly (there is\u00a0no AV node\u00a0delay), thus the P-R interval is shortened. Because of this \u201cpreexcitation\u201d through the accessory pathway, the ECG\u00a0shows a slurring of the onset of the QRS complex, referred to as a delta wave because of its triangular shape (figure 1.18)."}
{"_id": "cardio$$$cb95c23f-df1f-4ad6-9ae3-5dcf0a4ade4d", "text": "WPW syndrome is often asymptomatic, and patients do not require immediate treatment. However, if atrial fibrillation occurs in a WPW\u00a0patient, the accessory pathway can allow the atrial\u00a0fibrillation waves through to the ventricle (with no AV\u00a0nodal refractory period to prevent them).\u00a0Consequently a high ventricular rate is seen, and the risk of ventricular fibrillation being established means immediate clinical attention is required."}
{"_id": "cardio$$$3035e5d9-c887-40f5-aedc-3082e70604f6", "text": "Hyper- and Hypocalcemia"}
{"_id": "cardio$$$38c72953-09f5-4d7b-8d42-b09066da831a", "text": "Moderate rises in extracellular levels of Ca++ (3.0\u20133.4 mmol/L, normal = 2.1\u20132.6 mmol/L) block the\u00a0movement of sodium\u00a0through voltage-gated sodium channels. This results in a reduced depolarization of myocytes, and consequently repolarization time is\u00a0less. Raised extracellular\u00a0Ca++\u00a0also\u00a0changes the\u00a0closing kinetics of the L-type Ca++ channels such that the plateau phase of the cardiac action potential\u00a0is shortened and repolarization occurs earlier.\u00a0These two\u00a0effects manifest as the most common ECG finding of short QT intervals,\u00a0mainly through shortening of the ST segment (figure 1.19)."}
{"_id": "cardio$$$63b671b1-8b99-4cdb-b28f-24b3e8fc25b8", "text": "If hypercalcemia becomes severe (>3.4 mmol/L) then Osborne waves (or J-waves) may be seen\u2014an extra wave seen at the J-point of the ECG (the R-ST junction). The pathophysiology of the J-wave (figure 1.20) is poorly understood, but it is likely caused by an early repolarization of the epicardium\u2014think of it as a chunk of early T-wave. (The other common cause of J-waves is hypothermia.)\u00a0During hypocalcemia (<2.2 mmol/L) the opposite changes are seen in the ECG\u2014the QT interval is prolonged, primarily due to a lengthened ST segment (figure 1.19)."}
{"_id": "cardio$$$fefcffa4-b8dc-4ef8-a8c2-701e5e9afbe3", "text": "Table 1.16: Hyper- and hypocalcemia summary."}
{"_id": "cardio$$$61c5760f-25de-49b1-b522-3dece56df2cc", "text": "Hyper- and Hypokalemia"}
{"_id": "cardio$$$a06e32f7-e9ee-43af-9582-869eb8490ff4", "text": "The pathophysiology is not as simple as changes in extracellular K+ changing the electrochemical gradient for K+. Because of potassium\u2019s role in maintaining the resting membrane potential, shifts in extracellular potassium can also influence the activity of Na+ and Ca++ channels."}
{"_id": "cardio$$$2667f29a-a755-4a38-985d-d706f37adaba", "text": "Your intuition may lead you to think that hypokalemia (<2.7 mmol/L) would increase K+ conductances because there is a greater gradient from inside to outside the cell, but that is not the case. Instead hypokalemia suppresses K+ channel conductances by destabilizing K+ channels. With low K+ conductance, the ECG changes reflect problems with repolarization. The T-wave is flattened and can be inverted, and a prominent U-wave may be seen in the precordial leads (figure 1.21). ST depression may also be apparent."}
{"_id": "cardio$$$37c842fb-78a5-4e08-a063-339d8ef14949", "text": "As hypokalemia also inhibits Na+-K+ ATPase, Na+ accumulates inside the cell. This in turn leads to an accumulation of Ca++ because of a subsequent failure of the Na+-Ca++ exchanger. Extended presence of these two positive ions inside the myocyte\u00a0prolongs the\u00a0action potential\u00a0and may manifest as an increased width and amplitude of the P-wave."}
{"_id": "cardio$$$76f1e8bf-2c73-4b0a-89b6-b9ba772253a5", "text": "As hypokalemia worsens, the problems with K+ conductance and repolarization increase, and the myocardium becomes susceptible to early after-depolarization (EAD) arrhythmias."}
{"_id": "cardio$$$a52d120f-fd2e-4cd2-b407-63069bdc1796", "text": "As K+\u00a0is retained in the myocyte (due to the poor K+ conductance)\u00a0and elevated\u00a0intracellular\u00a0Na+ and Ca++ results in\u00a0the myocyte\u00a0being\u00a0more capable of depolarizing again.\u00a0\u00a0Because these after-depolarizations (figure 1.22) may not be uniform across the whole myocardium, an arrhythmia can be established. Potential arrhythmias include life-threatening forms, such as VT, VF, or torsades de pointes."}
{"_id": "cardio$$$fbfd6120-fe57-4551-99a2-1931c696dee2", "text": "Hyperkalaemia produces different changes in myocardial excitability depending on the degree of excess potassium. Again the changes in excitability do not\u00a0necessarily follow an intuitive logic of the change in the electrochemical gradient of K+.\u00a0Mild hyperkalemia (5.5\u20136.5 mEq/L) causes peaked T-waves (figure 1.23)\u2014the first sign of raised extracellular potassium. The excess potassium allosterically interferes with K+ channels\u00a0and, inverse to hypokalemia, causes an increase in K+ conductance (despite the lower transmembrane gradient)."}
{"_id": "cardio$$$b8e21e93-ae09-4953-9220-de2a123f5fc4", "text": "Moderate hyperkalemia (5.5\u20136.5 mEq/L) raises the membrane potential closer to the threshold of voltage-gated Na+ channels (-70 mV) and voltage-gated Ca++channels. Consequently these channels are more likely to fire and cause depolarization, hence the myocardium is initially more excitable. However, this persistent depolarization leaves the slow deactivation (h)\u00a0gates on Na+ channels closed for longer, and the ECG manifestations soon reflect a decreased excitability. The P-wave is longer but has low amplitude (and may eventually disappear), the QT interval is prolonged, and there is a decreased R-wave amplitude (figure 1.24). In simpler terms, the overstimulation of Na+ channels causes them to \u201clock up.\u201d"}
{"_id": "cardio$$$97d5700a-306c-4745-90d8-94d723590dea", "text": "Severe hyperkalemia (>7.0 mEq/L) sees a worsening of the unresponsiveness of the myocardium, and the SA node rhythm is slowed, producing sinus bradycardia until there is no P-wave. Conductive issues arise, and a high-grade atrioventricular\u00a0block is likely, allowing ventricular pacemakers to take over, but the ventricular myocardium is also unresponsive, so the QRS complex becomes broad and sine wave\u2013like on the ECG (figure 1.25); this is\u00a0a preterminal rhythm. At this point cardiovascular collapse and death are imminent, often through a VF finale."}
{"_id": "cardio$$$2f0edb5d-c677-4289-bf39-55bb65e19c52", "text": "Table 1.17: Hypo- and hyperkalemia summary."}
{"_id": "cardio$$$db70c622-ab24-4c25-ae89-2675ffd7083d", "text": "References,\u00a0resources, and further reading"}
{"_id": "cardio$$$25e09e1a-9d83-488d-ad5f-1fbe028f8fb0", "text": "Burns, Ed, and Robert Buttner. Hypercalcaemia. Lift in the Fast Lane, 2021. https://litfl.com/hypercalcaemia-ecg-library/, CC BY 4.0."}
{"_id": "cardio$$$98b0eb2b-328b-4f37-95d0-4a1d717348c2", "text": "Burns, Ed, and Robert Buttner. Hypocalcaemia. Life in the Fast Lane, 2021. https://litfl.com/hypocalcaemia-ecg-library/, CC BY 4.0."}
{"_id": "cardio$$$924eb71e-f15c-45cf-a207-17b43a28255e", "text": "Buttner, Robert, and Ed Burns. Hyperkalaemia. Life in the Fast Lane. https://litfl.com/hyperkalaemia-ecg-library/, CC BY 4.0."}
{"_id": "cardio$$$3f6b51a5-0594-4ad0-aff0-def446f6da9d", "text": "Buttner, Robert, and Ed Burns. Hypokalaemia. Life in the Fast Lane, 2021. https://litfl.com/hypokalaemia-ecg-library/, CC BY 4.0."}
{"_id": "cardio$$$c2ec9ebd-39e6-4027-8d33-99309d013968", "text": "Chhabra, Lovely, Amandeep Goyal, and Michael D. Benham. Wolff Parkinson White Syndrome. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK554437/, CC BY 4.0."}
{"_id": "cardio$$$de0f5e7f-54b2-4ef7-80ca-92553b8b6171", "text": "Custer, Adam M., Varun S. Yelamanchili, and Sarah L. Lappin. Multifocal Atrial Tachycardia. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK459152/, CC BY 4.0."}
{"_id": "cardio$$$3e262579-d93b-409b-983d-96ddc6f0517c", "text": "Farzam, Khashayar, and John R. Richards. Premature Ventricular Contraction. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK532991/, CC BY 4.0."}
{"_id": "cardio$$$7328f663-c5ef-4e2f-ade4-a4211caf5868", "text": "Foth, Christopher, Manesh Kumar Gangwani, and Heidi Alvey. Ventricular Tachycardia. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK532954/, CC BY 4.0."}
{"_id": "cardio$$$fc065c88-8e7e-4e26-a309-85650123fb33", "text": "Hafeez, Yamama, and Shamai A. Grossman. Sinus Bradycardia. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK493201/, CC BY 4.0."}
{"_id": "cardio$$$f1595d60-c9c3-4d6b-ba3b-44af48991758", "text": "Harkness, Weston T., and Mary Hicks. Right Bundle Branch Block. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK507872/, CC BY 4.0."}
{"_id": "cardio$$$d2624d0f-ba5a-421e-b634-e2a663b7ab7e", "text": "Heaton, Joseph, and Srikanth Yandrapalli. Premature Atrial Contractions. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK559204/, CC BY 4.0."}
{"_id": "cardio$$$dcf93591-9453-4b52-a6ad-1aca2b965dd9", "text": "Kashou, Anthony H., Amandeep Goyal, Tran Nguyen, and Lovely Chhabra. Atrioventricular Block. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK459147/, CC BY 4.0."}
{"_id": "cardio$$$54fd1955-7dcf-474e-a1c7-48be82daaf68", "text": "\u201cLearn the Heart.\u201d Healio. https://www.healio.com/cardiology/learn-the-heart."}
{"_id": "cardio$$$d631c93d-f5f0-400a-84c4-7fbe032819dc", "text": "Ludhwani, Dipesh, Amandeep Goyal, and Mandar Jagtap. Ventricular Fibrillation. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK537120/, CC BY 4.0."}
{"_id": "cardio$$$23d28e5a-2755-4f59-a997-fe25fb642627", "text": "Nesheiwat, Zeid, Amandeep Goyal, and Mandar Jagtap. Atrial Fibrillation. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK526072/, CC BY 4.0."}
{"_id": "cardio$$$c652c067-fadb-4dcb-b5b7-c4507437ffd4", "text": "Pipilas, Daniel C., Bruce A. Koplan, and Leonard S. Lilly. \u201cThe Electrocardiogram.\u201d In Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty, 5e edited by Leonard S. Lilly, Chapter 4. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer Business, 2010."}
{"_id": "cardio$$$7c80cf5c-7fd6-4813-bb3d-279ddffa421e", "text": "Rodriguez Ziccardi, Mary, Amandeep Goyal, and Christopher V. Maani. Atrial Flutter. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK540985/, CC BY 4.0."}
{"_id": "cardio$$$9c33cea2-2522-4f34-b5de-1bb5ae1c0182", "text": "Scherbak, Dmitriy, and Gregory J. Hicks. Left Bundle Branch Block. Treasure Island, FL: StatPearls Publishing, 2022. https://www.ncbi.nlm.nih.gov/books/NBK482167/, CC BY 4.0."}
{"_id": "myocardial_clean$$$corpus_1", "text": "The myocytes here are hypertrophied, marked by the large, dark nuclei, and there is interstitial fibrosis. This is an example of cardiomyopathy. In this case, long-standing, severe occlusive atherosclerosis led to \"ischemic\" cardiomyopathy.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_2", "text": "The wall of the aneurysm is thin, as seen here in cross section, but it is formed of dense collagenous tissue, so it does not rupture. However, the aneurysm is formed of non-functional tissue that does not contract, so the ejection fraction and stroke volume of the heart are reduced. In addition, mural thrombus can form in the aneurysm, and is seen here as the dark red layers extending inward from the thin aneurysmal wall. Portions of the mural thrombus could break off and embolize to the systemic circulation.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_3", "text": "A complication of infarction is aneurysm formation, which is the bulge seen here in the left ventricular wall. Note the very thin white wall of the aneurysm toward the apex.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_4", "text": "Grossly, a remote myocardial infarction is evidenced by white collagenous scar.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_5", "text": "The remote myocardial infarction is evidenced by a collagenous scar with some residual red surviving myocardial fibers. This stage is reached about 2 months following the initial ischemic event. This scar tissue is nonfunctional, and the reduction in ejection fraction is related to the extent of scarring.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_6", "text": "Healing is well under way 3 weeks after the ischemic event, and there is more extensive collagen deposition in the region of myocardium that was infarcted.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_7", "text": "Toward the end of the first week, healing of a myocardial infarction becomes more prominent. Seen here is ingrowth of capillaries along with fibroblasts and macrophages filled with hemosiderin. The granulation tissue seen here is found in abundance from 10 days to 3 weeks following onset of infarction, with a peak around 1 to 2 weeks. Cardiac troponin markers may still be present in the blood up to weeks following the initial ischemic event.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_8", "text": "Rupture (at the arrow) into the pericardial sac can produce a life-threatening cardiac tamponade, as seen here. The septum may also rupture.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_9", "text": "When the infarction is 3 to 5 days old, the necrosis and inflammation are most extensive, and the myocardium is the softest, so that transmural infarctions may be complicated by rupture. A papillary muscle may rupture as well to produce sudden valvular insufficiency. Rupture through the septum results in a left-to-right shunt and right heart failure.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_10", "text": "This is an acute myocardial infarction of the anterior left ventricular free wall and septum in cross section. Note that the infarction is nearly transmural. There is a yellowish center with necrosis and inflammation surrounded by a hyperemic border.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_11", "text": "This is an acute myocardial infarction in the septum. After several days, there is a yellowish center with necrosis and inflammation surrounded by a hyperemic border.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_12", "text": "This is an acute myocardial infarction of several days' duration. There is a more extensive neutrophilic infiltrate along with the prominent necrosis and hemorrhage.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_13", "text": "This is an acute myocardial infarction. There is loss of cross striations, and the nuclei are not present. There is extensive hemorrhage here at the border of the infarction, which accounts for the grossly apparent hyperemic border.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_14", "text": "This is an early acute myocardial infarction. There is increasing loss of cross striations, and some contraction bands are also seen, and the nuclei are undergoing karyolysis. Some neutrophils are beginning to infiltrate the myocardium.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_15", "text": "This is an early acute myocardial infarction. Note the prominent pink contraction bands.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_16", "text": "Here are two views of very early ischemic changes, with beginning loss of cross-striations within myocardial fibers, but the cardiac fiber nuclei are still present and there is not yet an inflammatory infiltrate. This represents an evolving infarction less than 12 hours old.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_17", "text": "This is normal myocardium. There are cross striations and central nuclei. Pale pink intercalated disks are also present.In this condition, there may be previous myocardial infarction, but the disease results from severe coronary atherosclerosis involving all major branches. The result is an inadequate vascular supply which leads to myocyte loss. The myocyte loss coupled with fibrosis in the form of interstitial collagen deposition results in decreased compliance, which along with the accompanying cardiac dilation, results in overload of remaining myocytes. This keeps the process going, with compensation by continuing myocyte hypertrophy. There may even be compensation through hyperplasia as well as hypertrophy, which can explain the enormous size (2 to 3 times normal size) of the resulting heart. Eventually, the heart can no longer compensate, and cardiac failure ensues with arrhythmias and/or ischemic events. There is slow, progressive heart failure with or without a history of a previous MI or anginal pain. Ischmic cardiomyopathy is responsible for as much as 40% of the mortality in IHD. (Anversa et al, 1995)"}
{"_id": "myocardial_clean$$$corpus_18", "text": "The atheromatous plaque around this thrombus in a coronary artery has many cholesterol clefts and foam cells as well as fibrin and hemorrhage.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_19", "text": "This severely narrowed coronary artery has the remaining lumen filled by thrombus.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_20", "text": "This is thrombosis in a coronary artery. Such a thrombus severely narrows or occludes the lumen and can produce a sudden ischemic event. \"Sudden death\" as well as infarction can occur.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_21", "text": "This is thrombosis in the anterior interventricular (left anterior descending) coronary artery opened longitudinally here over the surface of the heart. This is another complication of atherosclerosis. The purpose of thrombolytic therapy (as with streptokinase or with tissue plasminogen activator, or TPA) is to dissolve recently formed thrombi and re-establish circulation before irreversible myocardial damage has been done, or at least to prevent additional myocardial injury.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_22", "text": "There is a fibrin cap at the right with disruption in this atheromatous plaque in a coronary artery. Note the many \"foam\" cells (pale because of lipid) and cholesterol clefts.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_23", "text": "There is hemorrhage into a coronary artery plaque, one complication of atherosclerosis, seen here grossly.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_24", "text": "This cross section of coronary artery demonstrates nearly complete lumenal occlusion. If this occurs slowly, there is time for collateral circulation to develop.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_25", "text": "This cross section of coronary artery demonstrates >75% narrowing, which would be associated with angina.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_26", "text": "This cross section of coronary artery demonstrates occlusive atherosclerosis complicated by calcification (the blue material in this section).Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_27", "text": "This cross section of coronary artery demonstrates the extent of the intimal plaque at the right above the internal elastic lamina.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_28", "text": "This composite picture demonstrates cross sections of coronary artery with  atherosclerosis. At the left the lumen is about 50% occluded. At the right, there has been thrombosis with organization and recanalization to leave three small remaining lumens.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_29", "text": "This coronary artery opened longitudinally demonstrates severe atherosclerosis.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_30", "text": "This coronary artery demonstrates yellowish atherosclerotic plaques grossly.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_31", "text": "These serial sections of a coronary artery demonstrate grossly the appearance of lumenal narrowing with atherosclerosis.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "myocardial_clean$$$corpus_32", "text": "This is a normal coronary artery with a nice, big, unobstructed lumen for supplying plenty of blood to the myocardium.Ischemic heart disease is caused by an imbalance between the myocardial blood flow and the metabolic demand of the myocardium. Reduction in coronary blood flow is mosst often related to progressive atherosclerosis with increasing occlusion of coronary arteries. Blood flow can be further decreased by superimposed events such as vasospasm, thrombosis, or circulatory changes leading to hypoperfusion. (Bergmark et al, 2022). Coronary artery perfusion depends upon the pressure differential between the ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure). Coronary blood flow is reduced during systole because of Venturi effects at the coronary orifices and compression of intramuscular arteries during ventricular contraction. Factors reducing coronary blood flow include: Decreased aortic diastolic pressure, Increased intraventricular pressure and myocardial contraction. Coronary artery stenosis, which can be further subdivided into the following etiologies: Fixed coronary stenosis, Acute plaque change (rupture, hemorrhage), Coronary artery thrombosis, Vasoconstriction, Aortic valve stenosis and regurgitation. Increased right atrial pressure 40 micron collateral vessels are present in all hearts with pressure gradients permitting flow, despite occlusion of major vessels. In general, the cross-sectional area of the coronary artery lumen must be reduced by more than 75% to significantly affect perfusion. Coronary atherosclerosis is diffuse (involving more than one major arterial branch) but is often segmental, and typically involves the proximal 2 cm of arteries (epicardial). (Anversa et al, 1995). Percutaneous coronary intervention (PCI) following coronary angiography can aid in re-establishing myocardial perfusion. \"Thrombolytic therapy\" with agents such as streptokinase or tissue plasminogen activators (TPA) such as alteplase is often used following onset of symptoms and to try and lyse a recently formed thrombus. Such therapy with lysis of the thrombus can re-establish blood flow in a majority of cases. This helps to prevent significant myocardial injury, if early in the course of events, and can at least help to reduce further damage. Anti-platelet therapy can also be used. (Kumar and Cannon, Part II, 2009) (Bergmark et al, 2022)"}
{"_id": "WikiPedia_Cardio$$$corpus_1", "text": "The  lipid hypothesis  (also known as the  cholesterol  hypothesis ) is a  medical theory  postulating a link between  blood cholesterol  levels and the occurrence of  cardiovascular disease . A summary from 1976 described it as: \"measures used to lower the plasma lipids in patients with  hyperlipidemia  will lead to reductions in new events of  coronary heart disease \". [ 1 ]  It states, more concisely, that \"decreasing blood cholesterol [...] significantly reduces coronary heart disease\". [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2", "text": "As of 2023, there is international clinical acceptance of the lipid hypothesis. [ 3 ] [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3", "text": "In 1856, the German  pathologist   Rudolf Virchow  first described  lipid  accumulation in arterial walls. [ 7 ]  However, the initial connection between  arteriosclerosis  and dietary cholesterol would not be established until the research of Russian pathologist  Nikolay Anichkov , prior to  World War I . [ 8 ]  In 1913, a study by Anichkov showed that rabbits fed on  cholesterol  developed lesions in their arteries similar to  atherosclerosis , suggesting a role for cholesterol in  atherogenesis . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4", "text": "Dutch physician  Cornelis de Langen  noted the correlation between nutritional cholesterol intake and incidence of  gallstones  in   Javanese  people in 1916. [ 10 ] [ 11 ]  de Langen showed that the traditional Javanese diet, poor in cholesterol and other lipids, was associated with a low level of blood cholesterol and low incidence of  cardiovascular disease  (CVD), while the prevalence of CVD in Europeans living in Java on a Western diet was higher. [ 10 ]  Since de Langen published his results only in Dutch, his work remained unknown to most of the international scientific community until the 1940s and 1950s. [ 10 ]  By 1951, it was accepted that, although the causes of  atheroma  were still unknown, fat deposition was a major feature of the disease process. \"The so-called fatty flecks or streaks of arteries are the early lesions of atherosclerosis and... may develop into the more advanced lesions of the disease.\" [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5", "text": "With the emergence of CVD as a major cause of death in the Western world in the middle of the 20th century, the lipid hypothesis received greater attention. In the 1940s, a University of Minnesota researcher,  Ancel Keys , postulated that the apparent epidemic of  heart attacks  in middle-aged American men was related to their mode of life and possibly modifiable physical characteristics. He first explored this idea in a group of Minnesota business and professional men that he recruited into a prospective study in 1947, the first of many cohort studies eventually mounted internationally. The first major report appeared in 1963 and the men were followed through until 1981. [ 13 ]  After fifteen years follow-up, the study confirmed the results of larger studies that reported earlier on the predictive value for heart attack of several risk factors: blood pressure, blood cholesterol level, and cigarette smoking. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6", "text": "Keys presented his diet-lipid-heart disease hypothesis at a 1955 expert meeting of the  World Health Organization  in Geneva. [ 14 ]  In response to criticism at the conference, Keys recruited collaborating researchers in seven countries to mount the first cross-cultural comparison, the years-long  Seven Countries Study , which is still under observation today. This was to compare the heart attack risk in populations of men engaged in traditional occupations and being from cultures with different diets, especially in the proportion of fat calories of different composition. [ 15 ]  There was also criticism before the study began: Yerushalmy and Hilleboe pointed out that Keys had selected for the study the countries that would give him the results he wanted, while leaving out data from sixteen countries that would not; they also pointed out that Keys was studying a \"tenuous association\" rather than any possible proof of  causality . [ 16 ]  Keys then joined the nutrition committee of the  American Heart Association  (AHA), successfully promulgated his idea, and in 1961, the AHA became the first group anywhere in the world to advise cutting back on saturated fat (and dietary cholesterol) to prevent heart disease. [ 17 ]  This historic recommendation was reported on the cover of  Time Magazine  in that same year. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_7", "text": "The Seven Countries Study was formally started in fall 1958 in  Yugoslavia . In total, 12,763 males, 40\u201359 years of age, were enrolled in seven countries, in four regions of the world (United States, Northern Europe, Southern Europe, Japan). One cohort is in the United States, two cohorts in Finland, one in the Netherlands, three in Italy, five in Yugoslavia (two in Croatia, and three in Serbia), two in Greece, and two in Japan. The entry examinations were performed between 1958 and 1964 with an average participation rate of 90%, lowest in the US, with 75%, and highest in one of the Japanese cohorts, with 100%. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_8", "text": "Keys' book  Eat Well and Stay Well \u200a [ 20 ]  popularized the idea that reducing the amount of  saturated fat  in the diet would reduce cholesterol levels and the risks of serious diseases due to atheroma. [ 21 ]  Keys was followed during the rest of the 20th century by an accumulation of work that repeatedly demonstrated associations between cholesterol levels (and other modifiable risk factors including smoking and exercise) and risks of heart disease. These led to the acceptance of the lipid hypothesis as orthodoxy by much of the medical community. [ 22 ]  By the end of the 1980s, there were widespread academic statements that the lipid hypothesis was proven beyond reasonable doubt, [ 23 ] [ 24 ] [ 25 ]  or, as one article stated,  \"universally recognized as a law.\" \u200a [ 26 ] [ 27 ] [ 28 ] [ 29 ] [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_9", "text": "The medical consensus supports the lipid hypothesis as evidence from separate  meta-analyses ,  prospective  epidemiologic studies and  randomized clinical trials  have demonstrated that elevated levels of  LDL  blood cholesterol are a significant risk factor for cardiovascular disease. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_10", "text": "The  National Lipid Association  have stated that by 2012, a wealth of evidence including numerous clinical trials examined by the Cholesterol Treatment Trialists' Collaboration has confirmed the lipid hypothesis. [ 31 ]  Too much LDL (called \"bad cholesterol\") can lead to fatty deposits building up in the arteries, which increases the risk of cardiovascular disease. A 2017 consensus statement from the  European Atherosclerosis Society  concluded that \"consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.\" [ 3 ]  The consensus statement noted:"}
{"_id": "WikiPedia_Cardio$$$corpus_11", "text": "Most publications that question the causal effect of LDL on the development of ASCVD tend to cite evidence from individual studies or a small group of highly selected studies, often without a quantitative synthesis of the presented evidence. Therefore, to avoid this type of selection bias, we have based our conclusions on the totality of evidence from separate meta-analyses of genetic studies, prospective epidemiologic studies, Mendelian randomization studies, and randomized clinical trials. This evidence base includes over 200 studies involving over 2 million participants with over 20 million person-years of follow-up and more than 150 000 cardiovascular events. Together these studies provide remarkably consistent and unequivocal evidence that LDL causes ASCVD. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_12", "text": "A review from the  Journal of the American College of Cardiology  in 2018 concluded:"}
{"_id": "WikiPedia_Cardio$$$corpus_13", "text": "The causal effect of LDL and other apo B\u2013containing lipoproteins on the risk of cardiovascular disease is determined by both the magnitude and the cumulative duration of exposure to these lipoproteins. The goal of maintaining optimal lipid levels throughout life is to keep the concentration of circulating LDL and other apo B\u2013containing lipoproteins low to minimize the number of particles that become retained in the arterial wall and thereby minimize the rate of progression of atherosclerotic plaques. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_14", "text": "The 2021  Canadian Cardiovascular Society  Guidelines say \"We recommend that for any patient with triglycerides > 1.5 mmol/L, non- HDL-C  or  ApoB  be used instead of LDL-C as the preferred lipid parameter for screening (Strong Recommendation, High-Quality Evidence)\". [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_15", "text": "The  European Society of Cardiology  have noted:"}
{"_id": "WikiPedia_Cardio$$$corpus_16", "text": "For almost a century, evidence has been overwhelming that lipids and diet are related and have a negative impact on CVD. It is also clear that lipids, and especially LDL, play a crucial role in atherosclerosis. However, groups of \u201cnon-believers\u201d decelerated developments and clinical progress, sometimes for decades. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_17", "text": "In 2023, the  World Heart Federation  published a report which stated that high levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for cardiovascular diseases and that elevated LDL cholesterol contributed to 3.8 million deaths in 2021. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_18", "text": "The  National Lipid Association  (NLA) is an American non-profit multidisciplinary medical society that aims to enhance the practice of lipid management in  clinical medicine . The NLA focuses on the prevention of  cardiovascular disease  and other lipid-related disorders. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_19", "text": "The National Lipid Association was formed in 1997 and has over 2,000 members. [ 2 ] [ 3 ]  It provides medical education for healthcare professionals and physicians to advance knowledge and certification in clinical  lipidology . [ 2 ]  Joseph Saseen is the current president of NLA. [ 4 ] [ 5 ]  In 2014, the NLA proposed a working definition of  statin  intolerance and made general recommendations for health professionals. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_20", "text": "The NLA have stated that by 2012, a wealth of evidence including numerous clinical trials examined by the Cholesterol Treatment Trialists' Collaboration has confirmed the  lipid hypothesis . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_21", "text": "The NLA publishes the  Journal of Clinical Lipidology . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_22", "text": "In 2019, the NLA's Nutrition and Lifestyle Task Force published a scientific statement based on a comprehensive review of recent clinical evidence on the effects of low and very- low-carbohydrate diets  on the management of body weight and other cardiometabolic risk factors. [ 10 ] [ 11 ]  The statement concluded that low and very-low-carbohydrate die are not superior to other dietary approaches for weight loss and are difficult to maintain in the long term. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_23", "text": "In 2021, the NLA published a scientific statement on lipid measurements in the management of cardiovascular diseases. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_24", "text": "In 2022, the NLA published a scientific statement on statin intolerance, updating the definition which now classifies statin intolerance as either partial or complete. [ 13 ]  The 2022 statement recommends different strategies to help patients stay on statin medications, and alternative medications to those who cannot tolerate statins. [ 1 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_25", "text": "The  Seven Countries Study  is an  epidemiological   longitudinal study  directed by  Ancel Keys  at what is today the  University of Minnesota  Laboratory of Physiological Hygiene & Exercise Science (LPHES). Begun in 1956 with a yearly grant of US$200,000 from the  U.S. Public Health Service , the study was first published in 1978 and then followed up on its subjects every five years thereafter."}
{"_id": "WikiPedia_Cardio$$$corpus_26", "text": "As the world's first multicountry epidemiological study, it systematically examined the relationships between lifestyle, diet,  coronary heart disease  and  stroke  in different populations from different regions of the world. It directed attention to the causes of coronary heart disease and stroke, but also showed that an individual\u2019s risk can be changed."}
{"_id": "WikiPedia_Cardio$$$corpus_27", "text": "Writing in 1975, project officer Henry Blackburn identified two \"strikingly polar attitudes\", characterising them as persisting \"academic\" and \"pragmatic\" views with \"much talk from each and little listening between.\" [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_28", "text": "In the 1940s, a University of Minnesota researcher,  Ancel Keys , postulated that the apparent epidemic of heart attacks in middle-aged American men was related to their mode of life and possibly modifiable physical characteristics. He first explored this idea in a group of Minnesota business and professional men (executives aged 45 to 55) that he recruited into a prospective study in 1947, the first of many  cohort studies  eventually mounted internationally. The U.S. Public Health Service agreed to fund the study (and then set up and proceeded to fund the  Framingham Heart Study  on a larger scale). The Minnesota men were followed through 1981 and the first major report appeared in 1963 after the fifteen-year follow-up study. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_29", "text": "The study contributed much to survey methods and confirmed larger studies that reported earlier on the predictive value for heart attack of several characteristics, the now-traditional risk factors of  blood pressure  and blood  cholesterol  level and cigarette  smoking . Keys traveled widely with his wife Margaret who tested people's serum cholesterol. They sent their samples back to Minnesota for analysis. In 1952, Keys's hypothesis that coronary heart disease could be related to diet was first published in  Voeding  in The Netherlands. [ 4 ]  His work in post-wartime  Naples  led him to seek organization and funding for studies of different populations, as did his subsequent work in  Uganda ;  Cape Town , South Africa;  Sardinia ;  Bologna ; and  Ilomantsi , Finland; and with Japanese men living in  Hawaii  and in  Japan . He decided to concentrate on men living in  villages , rather than those in cities where the population moved around frequently. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_30", "text": "In the mid-1950s, with improved methods and design, Keys recruited collaborating researchers in seven countries to mount the first cross-cultural comparison of heart attack risk in populations of men engaged in traditional occupations in cultures contrasting in diet, especially in the proportion of fat calories of different composition, the Seven Countries Study still under observation today."}
{"_id": "WikiPedia_Cardio$$$corpus_31", "text": "The Seven Countries Study was formally started in fall 1958 in  Yugoslavia . In total, 12,763 males, 40\u201359 years of age, were enrolled as 16 cohorts, in seven countries, in four regions of the world (United States, Northern Europe, Southern Europe, Japan). One cohort is in the United States, two cohorts in Finland, one in the Netherlands, three in Italy, five in Yugoslavia (two in  Croatia , and three in  Serbia ), two in Greece, and two in Japan. The entry examinations were performed between 1958 and 1964 with an average participation rate of 90%, lowest in the US, with 75% and highest in one of the Japanese cohorts, with 100%. [ 5 ]  The study has continued for more than 50 years."}
{"_id": "WikiPedia_Cardio$$$corpus_32", "text": "The Seven Countries Study suggested that the risk and rates of  heart attack and stroke  (CVR), both at the population level and at the individual level,  correlated  directly and independently to the level of total serum cholesterol, in seven sampled out countries. It demonstrated that the correlation between blood cholesterol level and coronary heart disease (CHD) risk from 5 to 40 years follow-up is found consistently across different specially selected cultures in these seven countries. Cholesterol and obesity correlated with increased mortality from cancer. [ 6 ] [ 7 ] [ 8 ]  The Seven Countries Study suggested that elevated blood pressure ( hypertension ) was correlated with risk of coronary heart disease and stroke. It showed that the  mortality rate  after a coronary heart disease event or stroke was associated with the level of hypertension. In several cohorts of the study, stroke deaths exceeded deaths from coronary heart disease. [ 9 ] [ 10 ]  It hinted that differences in overall mortality between the different regions of the seven countries are largely associated with variation in cardiovascular mortality. [ 11 ]  Coronary deaths in the United States and Northern Europe greatly exceeded those in Southern Europe, even when controlled for age, cholesterol, blood pressure, smoking, physical activity, and weight."}
{"_id": "WikiPedia_Cardio$$$corpus_33", "text": "The Seven Countries Study was investigated further in regard to an eating pattern loosely characterized as the  Mediterranean Diet . [ 12 ] [ 13 ] [ 14 ] [ 11 ] [ 15 ]  What exactly is meant by \"Mediterranean Diet\" today, was detailed by  Antonia Trichopoulou  (wife of  Dimitrios Trichopoulos ), [ 16 ]  and Anna Ferro-Luzzi. [ 17 ]  The diet was publicized and popularized by Greg Drescher of the Oldways Preservation and Exchange Trust and by  Walter Willett  of the  Harvard School of Public Health . [ 18 ] [ 19 ] [ 20 ] [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_34", "text": "The Seven Countries Study also showed that the slowly changing habits of a population in the Mediterranean region, from a healthy, active lifestyle and diet, to a less active lifestyle and a diet influenced by the  Western pattern diet , significantly correlated with increased risk of heart disease. [ 23 ] [ 24 ]  Meanwhile, it has been confirmed by other researchers that there is an inverse association between adherence to the  Mediterranean Diet  and the incidence of fatal and non- fatal heart disease in initially healthy middle-aged adults in the Mediterranean region. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_35", "text": "The Seven Countries Study, along with other studies, e.g., the  Framingham Heart Study  and the  Nurses' Health Study , showed the importance of  overweight ,  obesity  and regular  exercise  as health issues. [ 26 ] [ 27 ] [ 28 ] [ 29 ]  It showed a correlation between good cardiovascular health and dementia in the general population. It also showed that cardiovascular risk factors in mid life are significantly associated with increased risk of dementia death later in life. [ 30 ]  It indicated that cigarette smoking is a highly significant predictor of the development of coronary heart disease, leading to excess rates of  angina pectoris ,  myocardial infarction  (MI) and coronary death, along with other studies about smoking, e.g., the Framingham Heart Study and the  British Doctors Study . [ 31 ] [ 32 ] [ 33 ] [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_36", "text": "Initial results from the Seven Countries Study in North Karelia (Finland) prompted public pressure for the authorities to act to reduce historically high levels of chronic disease in the region. The results influenced a subsequent public health program, the  North Karelia Project , which ran from 1972 until 1997, and which had among its aims a reduction in levels of peoples' saturated fat intake. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_37", "text": "Charles Antzelevitch  is an American cardiovascular research scientist in the fields of cardiac electrophysiology and cardiac arrhythmia syndromes. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_38", "text": "Antzelevitch graduated from  Queens College, City University of New York  with a BA in biology. He earned a  PhD  in  pharmacology  from  State University of New York Upstate Medical University  in 1978. [ 1 ]  From 1977 to 1980, he held a postdoctoral fellowship in the department of experimental cardiology at the Masonic Medical Research Laboratory (MMRL) in  Utica , New York. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_39", "text": "After his fellowship, he joined the staff of the  MMRL as a research scientist. In 1984, he was named executive director and director of research at the MMRL and was appointed the Gordon K. Moe Scholar, an endowed chair in experimental cardiology, in 1987. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_40", "text": "Antzelevitch was a member of the faculty at  State University of New York Upstate Medical University  in  Syracuse ,  New York , from 1980 until 2015. In 1980, he received an appointment as assistant professor in the department of pharmacology there. In 1983, he was promoted to associate professor and then in 1986, to research professor. He became professor of pharmacology in 1995. [ 2 ] [ 3 ]  In 2015, Antzelevitch moved to the Lankenau Institute for Medical Research (LIMR), where he was appointed professor and executive director of cardiovascular research and director of research at the Lankenau Heart Institute. In 2020, he was designated as distinguished professor emeritus at LIMR. [ 4 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_41", "text": "Antzelevitch was president of the  International Cardiac Electrophysiology Society  from 1996 to 1998 [ 5 ]  and has served as secretary/treasurer since 1998. [ 6 ]  He serves as Associate Editor of  Heart Rhythm  journal as well as on the editorial board of several other peer-reviewed medical publications, including  Journal of Electrocardiology [ 7 ]  and  Journal of the American College of Cardiology . [ 8 ]  He received the Distinguished Scientist Award from the North American Society of Pacing and Electrophysiology (NASPE), currently the  Heart Rhythm Society  (HRS 2002), [ 9 ]  Excellence in Cardiovascular Science Award from the NE Affiliate of the  American Heart Association  (AHA 2003), [ 10 ]  Carl J. Wiggers Award from the  American Physiological Society  (2007), [ 11 ] [ 12 ]  Distinguished Scientist Award from the  American College of Cardiology  (ACC 2011), [ 9 ] [ 13 ]  Distinguished Service Award from the Cardiac Electrophysiology Society (2015), [ 14 ]  the Douglas P. Zipes Lecture Award from the  Heart Rhythm Society  (2016) [ 10 ]  and the Lifetime Achievement Award from the  American College of Cardiology  (ACC 2020). [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_42", "text": "Deepak L. Bhatt  is a US  interventional cardiologist , researcher, and educator. He is known for novel clinical trials in cardiovascular prevention, intervention, and heart failure. As of 2024, he is the director of  Mount Sinai Fuster Heart Hospital  in  New York City  and the Dr.  Valentin Fuster  Professor of  Cardiovascular Medicine  at the  Icahn School of Medicine at Mount Sinai  Health System. [ 1 ] [ 2 ]  Prior, he served as the executive director of Interventional Cardiovascular programs at  Brigham and Women\u2019s Hospital  Heart and Vascular Center and a professor of medicine at  Harvard Medical School . [ 3 ] [ 4 ]  He was given the  American College of Cardiology 's Distinguished Mentor Award in 2018, and in 2019, the  American Heart Association  presented him with its Distinguished Scientist award. [ 5 ]  As of 2024,  Google Scholar  reports that he has been cited 294,036  times, has an  h-index  of 201, and an  i10-index  of 1,261."}
{"_id": "WikiPedia_Cardio$$$corpus_43", "text": "Bhatt graduated  Boston Latin School , earned his science degree as a  National Merit Scholar  from  MIT , an MD from  Cornell  and an MPH from  Harvard . [ 6 ]  He received his Executive MBA from the  University of Oxford  in 2024. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_44", "text": "He trained in internal medicine and cardiology at the  University of Pennsylvania  and  Cleveland Clinic , completing fellowships in interventional cardiology and cerebral and peripheral vascular intervention. He served as chief interventional fellow at Cleveland Clinic [ 8 ]  where he worked as an interventional cardiologist, associate professor of medicine, director of the interventional cardiology fellowship, associate director of the cardiovascular medicine fellowship, and associate director of the cardiovascular coordinating center. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_45", "text": "Later, he became the Chief of Cardiology at the  VA Boston Healthcare System  and, subsequently, the Interventional Cardiovascular Programs executive director at Brigham and Women\u2019s Hospital. Additionally, he was a Senior Investigator in the  TIMI  Study Group and Editor-in-Chief of the Harvard Heart Letter. [ 8 ]  In 2012, he was appointed a professor of medicine at  Harvard Medical School . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_46", "text": "As of 2024, Bhatt serves on the Board of Directors and Science and Technology Committee of  Bristol Myers Squibb . [ 11 ]  He is on the cardiovascular advisory board for  McKinsey  and is a consultant to Broadview Ventures. He had previously served on the Board of Directors of the Boston VA Research Institute and as a Trustee of the  American College of Cardiology . [ 7 ]   He serves on the Board of Directors of the American Heart Association New York City chapter. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_47", "text": "Bhatt focuses on several areas of cardiology, including interventional cardiology, heart attacks, stroke, prevention, and heart failure, as well as related areas such as high cholesterol, diabetes, and obesity. [ 13 ]  AD Scientific Index ranks him as one of the top 3% of scientists worldwide in his field. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_48", "text": "Recent trials as of 2024 include:"}
{"_id": "WikiPedia_Cardio$$$corpus_49", "text": "Brigham and Women\u2019s Hospital chose Bhatt in 2014 as the Eugene Braunwald Scholar and in 2016 presented him with the Research Mentor Award, and in 2017 he was awarded the Eugene Braunwald Teaching Award for Excellence in the Teaching of Clinical Cardiology. [ 6 ]  He was given the American College of Cardiology\u2019s Distinguished Mentor Award in 2018, [ 20 ]  and in 2019, the American Heart Association\u2019s Distinguished Scientist Award. [ 5 ] [ 21 ]  He received  NLA \u2019s Honorary Lifetime Membership Award in 2021, and the Society for Cardiovascular Angiography and Interventions\u2019 Master Designation in 2022. [ 2 ]  Also in 2022, Research.com recognized him with its Best Scientists award. [ 13 ]  He was listed by the  Web of Science Group  as a Highly Cited Researcher from 2014 to 2024. [ 12 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_50", "text": "Bhatt is the Editor of the first and second editions of  Cardiovascular Intervention: A Companion to Braunwald\u2019s Heart Disease [ 23 ]  and of  Opie's Cardiovascular Drugs: A Companion to Braunwald's Heart Disease . [ 24 ]  He is one of the co-editors of  Braunwald\u2019s Heart Disease . [ 25 ]   Elsevier  credits him with a total of 11 titles as an author, chapter contributor, and editor. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_51", "text": "Bhatt was Senior Associate Editor for News and Clinical Trials for  ACC .org, member of the Healio | Cardiology Today Editorial Board, [ 27 ]  and Editor-in-Chief of the  Journal of Invasive Cardiology,  which also lists him as: [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_52", "text": "As of 2024,  Google Scholar  reports that he has been cited 294,036 times, has an h-index of 201  and an i10-index of 1,261. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_53", "text": "Bhatt has authored or co-authored over 2,000 publications [ 33 ]  and has been listed by the Web of Science Group as a highly cited researcher from 2014 to 2024. [ 34 ] [ 35 ] [ 36 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_54", "text": "Bhatt's most cited, peer-reviewed articles include:"}
{"_id": "WikiPedia_Cardio$$$corpus_55", "text": "Javed Butler  is an  American   cardiologist  and  academic , recognized for his contributions to  cardiovascular medicine , particularly in  heart failure  research. He serves as the Maxwell A. and Gayle H. Clampitt Endowed Chair, president, and chief research executive at Baylor Scott & White Research Institute, and senior vice president at  Baylor Scott & White Health  in  Dallas, Texas . He is a fellow of  Heart Failure Society of America ,  European Society of Cardiology ,  American College of Cardiology , and  American Heart Association . [ 1 ] [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_56", "text": "Born in  Karachi ,  Pakistan , Butler completed his higher secondary education at  Adamjee Science College  and received his  MBBS  from  Aga Khan University  in 1990. He moved to the  United States  for further medical training, earning a  MPH  from the  Harvard T.H. Chan School of Public Health  in 1998 and a  MBA  from  Emory University 's  Goizueta Business School  in 2015. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_57", "text": "Butler completed his residency in  primary care   internal medicine  at  Yale University , where he also served as Chief Resident. His specialization in cardiovascular disease was further developed through fellowships in Cardiovascular Disease and Heart Failure & Transplantation at  Vanderbilt University . He pursued additional specialization in  cardiac imaging  at  Massachusetts General Hospital ,  Harvard University . [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_58", "text": "Butler began as an instructor of medicine at  Yale University  (1994\u20131995) and later served as assistant professor at  Vanderbilt University  (1999\u20132006), where he was medical director of both the  Heart Transplant  and  heart-lung transplant  programs. In 2007, he joined  Emory University  as a full professor of medicine and director of the Heart Failure Research Program. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_59", "text": "At  Stony Brook University , Butler served as Director of Cardiovascular Medicine and co-director of the Heart Institute (2014\u20132017), where he held the Charles A. Gargano Chair in Cardiology. [ 9 ]  From 2018 to 2022, he chaired the Department of Medicine at the  University of Mississippi Medical Center , where he was also a professor of Physiology and Biophysics and held the Patrick H. Lehan Chair in Cardiovascular Research. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_60", "text": "Butler has combined clinical work with research, education, and leadership, directing heart failure and transplant programs at Vanderbilt and Tennessee Valley Healthcare systems. He served as Deputy Chief Science Officer for the  American Heart Association  (AHA) from 2009 to 2016. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_61", "text": "He has chaired committees for the Heart Failure Society of America and the  American College of Cardiology , and represented the U.S. on the  European Society of Cardiology  Heart Failure Guidelines panel. Butler is a  Fellow  of the AHA, ACC, HFSA, and ESC. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_62", "text": "Butler chairs the U.S. Food and Drug Administration's Cardio-Renal Advisory Committee, co-chairs the NIH-funded HeartShare study on heart failure progression, and serves as principal investigator for several international cardiovascular trials. He is ranked as one of the top cardiovascular experts globally. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_63", "text": "Butler is a heart failure expert, with research spanning prevention to advanced therapies, including  cardiac transplantation  and  ventricular assist devices . He has led or participated in over 100 clinical trials, developed the Atlanta Cardiomyopathy Consortium, and helped establish the NIH-funded Heart Failure Network at Emory University. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_64", "text": "Butler is an associate editor for the  European Heart Journal , section editor for the  Journal of the American College of Cardiology: Heart Failure , guest editor for the  European Journal of Heart Failure , and serves on the editorial board of  Circulation . He has also peer-reviewed for journals, including the  New England Journal of Medicine ,  Journal of the American Medical Association  (JAMA), and  Lancet . [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_65", "text": "Arthur DeBoer , (July 2, 1917-July 31, 2007), was an American  cardiologist  specializing in  cardiac surgery  at  Northwestern University 's  Feinberg School of Medicine . DeBoer was one of the pioneer cardiac surgeons in  Chicago  and was on staff at Wesley Memorial Hospital (later called  Northwestern University Hospital ).  DeBoer was the hospital's first chief of cardiothoracic surgery, and performed the first  open heart operation  at Wesley Memorial Hospital in 1958. [ citation needed ]  He served as Chair of Northwestern's Department of Cardiovascular Surgery until 1975.  [ 1 ]  He was also a pioneer in research on  congenital heart defects ."}
{"_id": "WikiPedia_Cardio$$$corpus_66", "text": "He was born to John and Lucy DeBoer in  Gallatin County, Montana , and was a graduate of Montana Normal School (now  University of Montana Western ) earning his B.E. Degree in 1938.  He earned a B.S. Degree from  University of Montana  while teaching school. He graduated from  Northwestern University Medical School  in 1946 and after serving his internship at Wesley Hospital he served in the U.S. Army Medical Corps in Asia. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_67", "text": "This biographical article related to a physician in the United States is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_68", "text": "Ying Ge  is a Chinese-American chemist who is a Professor of Cell and Regenerative Biology at the  University of Wisconsin\u2013Madison . Her research considers the molecular mechanisms that underpin cardiac disease. She has previously served on the board of directors of the  American Society for Mass Spectrometry . In 2020 Ge was named on the Analytical Scientist Power List."}
{"_id": "WikiPedia_Cardio$$$corpus_69", "text": "Ge was born in  China . She attended  Peking University  for her undergraduate studies, where she studied chemistry. [ 1 ]  After graduating in 1997 Ge moved to the  United States , where she joined  Cornell University  as a doctoral student. [ 1 ]  Here she started to work on mass spectrometry, using  electron-capture dissociation  to study proteins. [ 2 ]  She worked under the supervision of  Tadhg Begley  and  Fred McLafferty . After completing her doctorate, Ge worked as a research scientist at  Wyeth . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_70", "text": "Ge joined the  University of Wisconsin\u2013Madison  as an assistant scientist, where she oversaw the  mass spectrometry  programme. She became an Associate Professor in 2015, and full Professor in 2019. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_71", "text": "Ge develops high-resolution mass spectrometry  proteomics  to better understand cardiac disease.  To image the very large proteins of human heart tissue, Ge combines  fourier-transform ion cyclotron resonance  (FT\u2013ICR) mass spectrometry with  electron-capture dissociation . [ 4 ]  She has worked to create a top-down disease proteomic platform that allows for the separation, detection and characterisation of the biomarkers of heart damage."}
{"_id": "WikiPedia_Cardio$$$corpus_72", "text": "Nanoproteomics, a technique developed by Ge and co-workers, makes use of nanoparticles and high resolution mass spectrometry to capture and characterise cardiac  troponins , including  troponin I . [ 5 ] [ 6 ]  Being able to test for and characterise troponin I would help with the early detection and diagnosis of heart disease. [ 7 ]  The peptide-functionalised superparamagnetic nanoparticles are combined with top-down mass spectrometry to identify the molecular fingerprints of troponins. [ 7 ]  Rather than just detecting cardiac troponins, which is possible using  ELISA -based antibody testing, this higher level of characterisation will allow Ge to identify various forms of modified troponins, allowing a  personalised  understanding of cardiac disease. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_73", "text": "Ge served on the board of the Top-Down Proteomics Consortium, [ 8 ]  on the editorial board of the Journal of Muscle Research and Cell Motility, [ 9 ]  as treasurer for the  American Society for Mass Spectrometry  (2016-2018). [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_74", "text": "Ying Ge  publications indexed by  Google Scholar ."}
{"_id": "WikiPedia_Cardio$$$corpus_75", "text": "Renata Gomes  is a  cardiovascular  specialist who focusses her work on the use of  molecular biology , imaging and  nanotechnology  applications for  regeneration  purposes. [ 1 ] [ 2 ]  She is a Professor of Veteran's Health and Biomedical Research and the Chief Scientific Officer of veteran health charity BRAVO VICTOR. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_76", "text": "Renata Gomes (born in 1985) was born in  Barcelos ,  Portugal . At a young age she was dissecting birds that had been shot by hunters in her village. In her choice of career, she was also influenced by an uncle who was a forensic doctor at the Institute of Legal Medicine at the  University of Minho  in the northern Portuguese town of  Braga . Her academic training was in the United Kingdom, where she received a Forensic Medicine and Forensic Sciences Degree from the  University of Bradford , before doing post-graduate research and training in  Cardiovascular  Biochemistry and Medicine at  University College London  and an international PhD on Cardiovascular Regeneration and  Nanotechnology  with  University of Coimbra  in Portugal, the  University of Oxford  and the  University of Eastern Finland  (Kupio). Her work with the Universities of Coimbra, Oxford and Kupio on a  nanoparticle  that can contribute to cardiovascular  regeneration  placed her first in the 2011 Science-Image Competition organised by the  British Heart Foundation . [ 1 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_77", "text": "Among the people with whom she has worked was the  Nobel Prize  winner, Professor  Oliver Smithies . In Bradford, she worked over the holidays with Professor  Karin Schallreuter  on plastic surgery. While working with Professor Lino Ferreira at the  Centre for Neuroscience and Cell Biology  at Coimbra University, they had an idea to combine  stem cell  technology with nanotechnology. The research took place between 2008 and 2012. After the results were published, Gomes was nominated for and won the  Science, Engineering and Technology for Britain 2012  award, given annually by the British Parliament. In 2013 her home town of Barcelos awarded her the title of Professional of the Year. [ 2 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_78", "text": "Part of her time is devoted to community and humanitarian causes. She has worked with the  Small Scientists Network , based in her home town of Barcelos, which is aimed at promoting scientific curiosity among young people. Although having been treated for cancer, Gomes ran the  London Marathon  to raise money for the British Heart Foundation. While on a visit to Israel she contributed to a vaccination campaign among  Bedouins . In Israel she met  Henrique Cymerman , an Israeli journalist of Portuguese descent, with whom she decided to set up a Task Force called  Knowledge for the Benefit of Mankind , to bring together religious leaders of various faiths and other influential thinkers and young people, to find realistic solutions in favour of peace. [ 2 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_79", "text": "Based in London, she then worked as Head of Research and Innovation for the charity Blind Veterans UK (formerly St Dunstan's), seeking to find regenerative-medicine solutions to benefit blind veterans. In 2020 she became its Chief Scientific Officer, before the Directorate became BRAVO VICTOR. [ 2 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_80", "text": "Roberta Anne Gottlieb  is an American  oncologist , academic, and researcher. She is a Professor, and Vice-Chair of Translational Medicine in the Department of  Biomedical Sciences  at  Cedars-Sinai Medical Center , and a Professor of Medicine at the  University of California, Los Angeles . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_81", "text": "Gottlieb published over 150 papers and has 6 patents awarded. [ 2 ]  Her research primarily focuses on the molecular basis of myocardial ischemia/ reperfusion injury  and on developing ways to mitigate damage. She has given over 200 invited talks both at scientific conferences, professional organizations and for the general public. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_82", "text": "Gottlieb is a Fellow of the  International Society for Heart Research  (FISHR), [ 4 ]  and the  American Heart Association  (FAHA), and was the Founder and CEO of Radical Therapeutix, from 2005 till 2014, and Co-Founder and Scientific Advisory Board Co-Chair, TissueNetix, from 2011 till 2018."}
{"_id": "WikiPedia_Cardio$$$corpus_83", "text": "Gottlieb received her B.A. degree from the  Johns Hopkins University  in 1980, and her M.D. degree from  The Johns Hopkins University School of Medicine  in 1984. She completed her Residency in Pediatrics at the  University of Texas Health Science Center  in 1987, and her Fellowship in  Pediatric Hematology & Oncology  at the  University of Texas M.D. Anderson Cancer Center  in 1990. Following this, she became a Postdoctoral Fellow in Michael Karin\u2019s lab at the  University of California San Diego School of Medicine  until 1992, and at  The Scripps Research Institute  in the lab of Bernard Babior until 1995. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_84", "text": "Gottlieb began her career as a Research Biochemist in the Department of Veterans Affairs Medical Center, San Diego in 1994. During this appointment, she also held concurrent appointments at Scripps Research Institute as an Assistant Member in the Department of Molecular and Experimental Medicine in 1995, and as an Associate Member from 1997 till 1998. In 1997, she was appointed as an Adjunct Assistant Professor in the Department of Medicine University of California San Diego School of Medicine, and from 1999 to 2006, she served at Scripps Research Institute as an Associate Professor in the Department of Molecular and Experimental Medicine. Gottlieb was appointed as the Director of San Diego State University BioScience Center from 2007 till 2013. Since 2013, she has been serving as a Research Scientist IV, and a Professor of Cardiology and Biomedical Sciences at Cedars-Sinai Medical Center, and as a Professor of Medicine at the University of California Los Angeles. [ 1 ]  At Cedars-Sinai Medical Center, she serves as the Director of Metabolism and Mitochondrial Research Core, as Curriculum Director for CSMC Clinical Scholars Program, and as Vice-Chair of Translational Medicine in the Department of Biomedical Sciences. Gottlieb retired from full-time research in March, 2022, but remains involved in several ongoing collaborations. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_85", "text": "Gottlieb leads ongoing research focused on  autophagy , [ 7 ]  mitophagy and biogenesis, with particular attention to the molecular basis of myocardial ischemia/reperfusion injury and in developing ways to mitigate damage. Her current projects are focused on the development of small-molecular cardioprotective agents for the treatment of reperfusion injury,  mitochondria  and stem cells in anthracycline-induced heart failure, rescue and role of complex I in myocardial ischemic injury, and microbial basis of cardiovascular disease. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_86", "text": "In 1994, Gottlieb described the occurrence of programmed cell death (apoptosis) in the ischemic and reperfused heart, and highlighted that programmed cell death taking place during reperfusion is a regulated process that might be blocked to salvage myocardium. [ 9 ]  Her subsequent work has explored the role of proteases and mitochondrial dysfunction in ischemia/reperfusion injury, [ 10 ]  and most recently, the importance of autophagy in mitigating reperfusion injury. [ 11 ]  She has developed tools and techniques in her lab for studying autophagy in cells and in ex vivo and in vivo models. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_87", "text": "Gottlieb was the first to suggest that autophagy served a protective role in the setting of myocardial stress. These concepts, tools, and approaches have extended beyond the cardiac field and have led to novel findings in the fields of infectious disease, diabetes, and neurology. [ 13 ]  Current efforts in her lab are focused on autophagic clearance of mitochondria and mitochondrial biogenesis as essential elements of cardioprotection; efficient removal of damaged mitochondria is important for limiting inflammation mediated by damage associated molecular pattern receptors. [ 14 ] [ 15 ]  In another study, she examined the effect of impaired autophagy on cardioprotection, [ 16 ]  and the Program Project Grant was focused on the impacts of age and obesity. [ 17 ]  Her current work is focused on mitophagy and mitochondrial biogenesis as linked processes that are tightly controlled in the heart. In 2018, she with the collaboration of Jennifer Van Eyk, developed polysome profiling and azidohomoalanine labeling to interrogate the newly-synthesized proteome. [ 18 ]  They also developed advanced proteomic methods to interrogate mitochondria (Mitoplex) [ 19 ]  and to image mitochondrial turnover (MitoTimer). [ 20 ]  In 2017, her research identified a new potential way to help cardiac muscle recover from procedures, and revealed that cardiomyocytes can be damaged by the process of stopping and starting the heart during surgeries that use cardiopulmonary bypass machines to take over the heart's functions. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_88", "text": "Gottlieb has been at the leading edge of research on mitochondria in cardiac homeostasis, which led her into the study of autophagy and mitophagy including being the first to demonstrate the critical role of  Parkin  in clearing damaged mitochondria during ischemic stress. [ 22 ]  Her work, in collaboration with cardiac surgeon Robert M. Mentzer, Jr., has extended to human studies, further validating the importance of Parkin in the human heart. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_89", "text": "Gottlieb has worked to determine the role of autophagy and mitophagy in pancreatitis. She initially studied cerulein-induced pancreatitis and now has expanded the focus to pancreatitis induced by ethanol and cigarette smoke. This work is done in collaboration with Honit Piplani and Stephen Pandol. In 2019, she highlighted how simvastatin induces autophagic flux to restore cerulein-impaired phagosome-lysosome fusion in acute pancreatitis, and also discussed the role of simvastatin in enhancing autophagic flux to prevent pancreatic cell injury and pancreatitis. [ 24 ]  She also contributed to a SEER-Medicare analysis focusing on the association of statin use after cancer diagnosis with survival in pancreatic cancer patients, and found out that statin treatment after cancer diagnosis is associated with enhanced survival in patients with low-grade, resectable PDAC. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_90", "text": "Mukesh K. Jain  is an American  physician-scientist  specializing in  cardiovascular medicine . [ 1 ]  Since March 2022 he has served as Dean of Biological Sciences at  Brown University  and Dean of Medicine at the  Warren Alpert Medical School . [ 2 ]  Jain previously served as Chief Scientific Officer at  University Hospitals Health System  and Vice-Dean for Medical Sciences at  Case Western Reserve University . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_91", "text": "Jain was born in the 1960s. [ 1 ]  He received a bachelor of science in biochemistry from the  University of Buffalo  in 1987. He earned his M.D. from the University of Buffalo's  Jacobs School of Medicine and Biomedical Sciences  in 1991. Jain completed his residency in internal medicine at  Beth Israel Deaconess Medical Center  in  Boston, Massachusetts . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_92", "text": "He subsequently completed fellowships at the  Harvard T.H. Chan School of Public Health  and at  Brigham and Women's Hospital / Harvard Medical School . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_93", "text": "Jain worked at Harvard from 1998 to 2006, serving as an Instructor of Medicine, Assistant Professor, and later Director of the Cardiovascular Transcriptional Biology Program at Brigham and Women's Hospital. Jain joined Case Western in 2006 as the founding Director of the Case Cardiovascular Research Institute, Professor of Medicine, and Ellery Sedgwick Jr. Chair and Distinguished Scientist. He was appointed Vice Dean for Medical Sciences at the university in 2016. [ 5 ]  In August 2021 he was appointed Distinguished University Professor. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_94", "text": "In October 2021, Jain was appointed Dean of Medicine and Biological Sciences at Brown University. He began as dean in March 2022, succeeding  Jack A. Elias . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_95", "text": "Jain is a vocal supporter of physician-scientists and advocate for increasing their ubiquity in the field. [ 7 ] [ 1 ]  In a 2020 article in  The Washington Post  Jain, Paul J. Utz, and Vivian G. Cheung wrote \"we need a well-trained group of readied physician-scientists who can be deployed at any time to meet our nation\u2019s medical needs, whether a  coronavirus pandemic  or other health emergencies.\" [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_96", "text": "Marlys Laverne Koschinsky  (born 1959)  OOnt   FCAHS  is a Canadian cardiovascular researcher. As of 2015 [update] , she is the executive director at the  University of Western Ontario 's  Robarts Research Institute . Koschinsky formally served as Dean of the Faculty of Science at the  University of Windsor ."}
{"_id": "WikiPedia_Cardio$$$corpus_97", "text": "Koschinsky was born in 1959. [ 1 ]  She graduated with her  Bachelor of Science  degree in 1982 from the  University of Winnipeg  and was subsequently awarded the Chancellor's gold medal for highest standing in the 4-year science program. Following this, Koschinsky completed her PhD in biochemistry at the  University of British Columbia . In 1988, Koschinsky began her postdoctoral research in the Cardiovascular Research Group at  Genentech  in San Francisco. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_98", "text": "Following her post-doctoral work, Koschinsky became the first female research professor at  Queen's University at Kingston  in biochemistry. [ 3 ]  During the 1996\u201397 academic year, she was the co-recipient of the Mihran and Mary Rasmajian Award for excellence in research. [ 4 ]  Throughout her tenure at Queen's, Koschinsky accepted a 5-year scholarship from the  Heart and Stroke Foundation of Canada  and a 10-year Career Investigator award from the Heart and Stroke Foundation of Ontario. [ 2 ]  Prior to leaving Queen's, Koschinsky served as director of the Cardiac, Circulatory & Respiratory Research Program and Head of the Department of Physiology. [ 5 ]  She eventually left to become the Dean of the Faculty of Science at the  University of Windsor . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_99", "text": "During her tenure at the University of Windsor, Koschinsky became involved in outside organizations around the city including serving as vice-chair of the board of directors for WEtech Alliance and Chair of the Windsor-Essex Mission Committee. She was also a member of the steering committee for the South West Academic Health Network. Koschinsky remained as Dean of the Faculty of Science until 2015 when she accepted the position of executive director at the  University of Western Ontario 's Robarts Research Institute. [ 5 ]  As a result of her research into cardiovascular disease and the study of related risk factors, she was named a 2020 Fellow of the  Canadian Academy of Health Sciences . [ 7 ]  The following year, Koschinsky was named a Member of the  Order of Ontario . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_100", "text": "Koschinsky is married to Michael Boffa. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_101", "text": "Bruce B. Lerman  is a  cardiologist . He is the Hilda Altschul Master Professor of Medicine at  Weill Cornell Medical College , and was chief of the Division of Cardiology and director of the Cardiac Electrophysiology Laboratory at  Weill Cornell Medicine  and the  New York Presbyterian Hospital ."}
{"_id": "WikiPedia_Cardio$$$corpus_102", "text": "Lerman received a BA at  Clark University  in 1972, an MD medical degree from  Loyola University  -  Stritch School of Medicine  in 1977, was an  intern  and  medical resident  in  internal medicine  at  Northwestern University , and completed a  fellowship  in  cardiovascular disease  at the  Johns Hopkins School of Medicine . [ 1 ] [ 2 ] [ 3 ]   He trained in  cardiac electrophysiology  at the  Perelman School of Medicine at the University of Pennsylvania . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_103", "text": "Lerman is a  cardiologist  in New York City, with specialties in adult  congenital heart disease  and  cardiac electrophysiology . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_104", "text": "Lerman is the Hilda Altschul Master Professor of Medicine at  Weill Cornell Medical College , and chief of the Division of Cardiology and director of the Cardiac  Electrophysiology Laboratory at  Weill Cornell Medicine  and the  New York Presbyterian Hospital . [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_105", "text": "He has focused in his research on clarifying the  electrophysiologic  mechanisms of the  nucleoside   adenosine , current-based  defibrillation , and determining the role of mechanoelectrical feedback as a stimulus for causing malignant  ventricular arrhythmias . [ 2 ]   He has been issued 4  patents . [ 2 ]  Lerman has focused in his clinical work on the diagnosis and treatment by  ablation  of complicated atrial and ventricular  arrhythmias , and treating life-threatening arrhythmias with implantable devices. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_106", "text": "Lerman received the Established Investigator Award from the  American Heart Association , and had received a number of grants from the  National Institutes of Health . [ 2 ]   He is on the editorial boards of a number of medical and scientific journals, including  Circulation  and   Heart Rhythm . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_107", "text": "Lerman has written or co-written over 200 medical articles, 60 book chapters, and two books. [ 8 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_108", "text": "Among his publications are: [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_109", "text": "Merry L. Lindsey  is an American cardiac physiologist. In 2022 she was named the Dean of the School of Graduate Studies at Meharry Medical College. In 2019 she was named the Stokes-Shackleford Professor and Chair of the  University of Nebraska Medical Center  Department of Cellular and Integrative Physiology and the director of the Center for Heart and Vascular Research. In 2021, Lindsey was appointed  editor-in-chief  of the  American Journal of Physiology. Heart and Circulatory Physiology."}
{"_id": "WikiPedia_Cardio$$$corpus_110", "text": "Lindsey was born Stuart, Florida in 1970 [ 1 ] [ 2 ]  and raised in  South Florida , [ 3 ]  where she attended South Fork High School. [ 4 ]  Following high school, Lindsey earned her undergraduate degree in biology from  Boston University  and her PhD in cardiovascular sciences from  Baylor College of Medicine . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_111", "text": "Upon completing her PhD, Lindsey worked at the  Medical University of South Carolina  as an  assistant professor  before joining the faculty at the  University of Texas Health Science Center . In 2019, she left the Mississippi Center for Heart Research to accept an appointment as the Stokes-Shackleford Professor and Chair of the Department of Cellular and Integrative Physiology at the  University of Nebraska Medical Center . [ 3 ]  Upon joining the department, Lindsey also became the founding director of the Center for Heart and Vascular Research. [ 5 ]  She joined  Meharry Medical College  as the dean of the School of Graduate Studies and Research. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_112", "text": "In 2021, Lindsey was appointed  editor-in-chief  of the  American Journal of Physiology. Heart and Circulatory Physiology , a journal published by the  American Physiological Society . [ 7 ]  She received the Vincenzo Panagia Distinguished Lecture Award from the Institute of Cardiovascular Sciences at St-Boniface Hospital Research in 2021, [ 8 ]  and the Distinguished Investigator Award from the British Society for Cardiovascular Research in 2022. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_113", "text": "Joseph Randall Moorman  (born April 4, 1953) is an American physician-scientist. He is bicentennial Professor of Advanced Medical Analytics at the  University of Virginia School of Medicine ."}
{"_id": "WikiPedia_Cardio$$$corpus_114", "text": "Moorman is the younger son of Ruth, classicist and professor at the University of Southern Mississippi, and  Charles W. Moorman III , medievalist and dean at the University of Southern Mississippi. His brother is former Norfolk Southern and Amtrak CEO  Charles Moorman . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_115", "text": "Moorman grew up in Hattiesburg, Mississippi. He received his undergraduate degree from the  University of Mississippi  and his M.D. from  University of Mississippi School of Medicine . In 1978, Moorman began his medical internship at  Duke University Medical Center , [ 2 ]   where he served as Chief Resident from 1982-1983 and Cardiology Fellow from 1983-1985. He then finished his post-doctoral research training in membrane biophysics and molecular electrophysiology at  Baylor University . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_116", "text": "From 1985-1990, Moorman was Assistant Professor of Medicine at the  University of Texas Medical Branch  and worked in the laboratory of Arthur M. Brown at  Baylor College of Medicine . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_117", "text": "In 1990, he joined the faculty of the University of Virginia School of Medicine. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_118", "text": "From 2014 to 2019, he was Editor-in-Chief of  Physiological Measurement.   [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_119", "text": "From 2014 to 2021, he was Chief Medical Officer of AMP3D (Advanced Medical Predictive Devices, Diagnostics, and Displays) [ 6 ]  before the company's acquisition by Nihon Kohden. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_120", "text": "In 2014, he and DE Lake were named Edlich-Henderson\u00a0 Innovators of the Year by the University of Virginia Licensing and Ventures Group.\u00a0 [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_121", "text": "In 2017, he was keynote speaker for the  Association for the Advancement of Medical Instrumentation  Annual Conference. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_122", "text": "While at Baylor College of Medicine, Moorman studied the biophysical properties of cloned ion channel proteins expressed in heterologous systems. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_123", "text": "At the University of Virginia, Moorman and coworkers discovered a unique channel activity for the molecule phospholemman (PLM, also  FXYD1 ). [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_124", "text": "In 2000, Moorman and JS Richman introduced  sample entropy  as a measure of complexity in dynamical systems. [ 14 ]  This method has been successfully used to test for non-linear dynamics and temporal predictability in many systems. [ 15 ] [ 16 ] [ 17 ]  In 2011, he and DE Lake developed the\u00a0 coefficient of sample entropy for use in detecting atrial fibrillation. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_125", "text": "In 2001, he and MP Griffin demonstrated unique changes in heart rate characteristics (HRC) prior to the diagnosis of sepsis in premature infants. [ 19 ]  They and their coworkers devised the HRC Index, the relative risk of illness in the next 24 hours, and showed 22% relative reduction in death rates in one of the largest randomized trials in neonatology. This work was the first effective use of Big Data and Machine Learning to save lives, [ 20 ] [ 21 ] [ 22 ]  and was recognized as one of the top 12 scientific discoveries in the past 50 years at the University of Virginia. [ 23 ] [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_126", "text": "[ 26 ]   Moorman and coworkers went on to develop and validate multiple Machine Learning models for early detection of illness throughout the hospital.\u00a0 [ 27 ]  Advanced Medical Predictive Devices, Diagnostics and Devices (AMP3D), [ 28 ] [ 29 ]  a Charlottesville, VA, small business, licensed the intellectual property from the University of Virginia Licensing and Ventures Group, developed and implemented the Continuous Monitoring of Event Trajectories (CoMET)  [ 30 ]  display, and was acquired in 2021 by Nihon Kohden Digital Health Solutions in Irvine, CA, a subsidiary of Nihon Kohden Corporation, Japan-based maker of medical devices."}
{"_id": "WikiPedia_Cardio$$$corpus_127", "text": "According to ResearchGate, Moorman has written and co-written 229 peer-reviewed publications."}
{"_id": "WikiPedia_Cardio$$$corpus_128", "text": "Kiran Musunuru  is an American cardiologist who is a Professor of Medicine at the  University of Pennsylvania Perelman School of Medicine . [ 1 ]  He researches the genetics and genomics of cardiovascular and metabolic diseases. Musunuru is a leading expert in the field of  gene-editing ."}
{"_id": "WikiPedia_Cardio$$$corpus_129", "text": "Musunuru is the son of Rao and Prameela Musunuru; he was born in  New York City  and grew up in  Florida . [ 2 ]  His father is a renowned cardiologist who moved to the US from India in 1976. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_130", "text": "Musunuru obtained a degree in Biochemical Sciences from  Harvard College  in 1997. [ 1 ]  He later obtained a PhD in Biomedical Sciences from  Rockefeller University  in 2003, and an MD from  Weill-Cornell Medical College  in 2004. [ 1 ]  Musunuru also graduated with a Masters of Public Health (MPH) in Epidemiology from the  Johns Hopkins Bloomberg School of Public Health  in 2009, and an ML in Law from the  University of Pennsylvania Law School  in 2019. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_131", "text": "Musunuru was interested in heart disease early in his medical career, first training in Internal Medicine at  Brigham and Women's Hospital  and then in Cardiovascular Medicine at  Johns Hopkins Hospital . [ 3 ] [ 4 ]  He also undertook postdoctoral work at the  Massachusetts General Hospital , as well as the  Broad Institute . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_132", "text": "Musunuru's researches the genetics and genomics of cardiovascular and metabolic diseases, and is a leading expert in genome-editing techniques, particularly  CRISPR-Cas9 . His lab was the first to develop an efficient technique to genetically modify human pluripotent stem cells, and differentiate them to model disease. [ 5 ]  He discovered two novel genes involved in  coronary artery disease : SORT1 and ANGPTL3. [ 5 ]  His research aims to find genetic variants which affect the course of disease and could be used to develop protective therapies. [ 3 ]  Musunuru ultimately hopes to create a one-shot \"vaccination\" against heart attacks, which would introduce a complementary, loss-of-function mutation in a gene such as ANGPTL3 to lower the risk of developing cardiovascular disease in at-risk populations. [ 2 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_133", "text": "Musunuru has pioneered the use of genome-editing tools as therapies for heart disease. For example, some people with a variant of the PCSK9 gene have lower levels of low-density lipoprotein (LDL) cholesterol levels, and therefore have a reduced risk of heart attack. [ 4 ]  Research from Musunuru's laboratory has shown that the levels of the PCSK9 gene expression could be altered in the liver of mice using CRISPR-Cas9 gene editing technology, drastically reducing the mice's cholesterol levels. [ 4 ] [ 7 ]  Musunuru has also led research into prenatal gene editing of PCSK9 or HPD using both CRISPR-Cas9 and base editor 3 (BE3), offering a proof-of-concept for a potential new therapeutic approach for congenital genetic disorders. [ 8 ] [ 9 ]  Musunuru cofounded  Verve Therapeutics  to develop gene editing techniques for treat cholesterol altering congenital genetic disorders."}
{"_id": "WikiPedia_Cardio$$$corpus_134", "text": "In 2019, Musunuru was among a team of researchers at the University of Pennsylvania to develop a stem cell-based test for the effect of genetic variants on heart muscle cells. [ 10 ] [ 11 ]  They used the test to determine that a 65-year-old woman's specific variant of TNNT2, a gene which has been associated with cardiomyopathy, was not pathogenic. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_135", "text": "He was an Associate Professor of Cardiovascular Medicine and Genetics at the Perelman School of Medicine at the University of Pennsylvania, as well as the scientific director of the Center for Inherited Cardiovascular Disease. [ 3 ] [ 12 ]  He is now a Professor of Medicine at the University of Pennsylvania Perelman School of Medicine. [ 1 ]  As of 2021, he serves on the board of directors of the American Society of Human Genetics, in addition to serving on its Diversity and Inclusion Task force. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_136", "text": "Musunuru is the author of The CRISPR Generation: The Story of the World's First Gene-Edited Babies, in which he delves into the scientific breakthroughs that enabled  He Jiankui  to create the world's first  gene-edited babies , a scandal Musunuru describes as a \"historic ethical fiasco, a deeply flawed experiment\". [ 14 ] [ 2 ]  He was one of the independent experts who reviewed He's manuscript. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_137", "text": "He has an  h-index  of 57 according to  Semantic Scholar . [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_138", "text": "Frits F.W. Prinzen  is an expert on  cardiac pacing  therapies, both for  bradycardia  and for heart failure ( cardiac resynchronisation therapy , CRT)."}
{"_id": "WikiPedia_Cardio$$$corpus_139", "text": "He was born July 2, 1954, in  Hilversum .  He earned a master's degree in medical biology from  Utrecht University  in 1978, and a PhD in physiology from  Maastricht University  in 1982. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_140", "text": "Prinzen works on cardiac  pacing therapies , both for  bradycardia  and for  heart failure  ( cardiac resynchronisation therapy , CRT). His main research topic is cardiac mechanics and long-term structural and functional adaptations to various conditions, with emphasis on asynchronous electrical activation and cardiac resynchronisation. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_141", "text": "In 1995, he took a sabbatical year during which he worked at the  Johns Hopkins University  in Baltimore, MD, USA, where he dove into the world of MRI tagging of the heart. This work was published in a well-cited article in the  Journal of the American College of Cardiology . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_142", "text": "His work led to improved cardiological treatments, especially in the field of cardiac pacing. Together with cardiologists and industrial partners he improved and developed pacemakers, pacing wires, and implantation methods. [ 4 ]  An  example is published in NEJM in 2007, [ 5 ]  describing the case of a child with heart failure who directly benefited by changing the site of the pacemaker wire. This theory was later confirmed in a large clinical trial, published in 2013 in Circulation. [ 6 ]  In his lab of it was shown for the first time that pacing the left side of the interventricular septum maintained cardiac function. [ 7 ] [ 8 ]  This pacing strategy has been adopted in clinical practice. [ 9 ]  Frits was awarded the CARIM commitment award in 2016. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_143", "text": "Frits Prinzen is co-author of over 280 scientific articles, with over 16,000 citations and an all time H-index of 70. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_144", "text": "He contributed to  Clinical Cardiac Pacing, Defibrillation and Resynchronization Therapy . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_145", "text": "Harvard Medical School"}
{"_id": "WikiPedia_Cardio$$$corpus_146", "text": "Massachusetts General Hospital"}
{"_id": "WikiPedia_Cardio$$$corpus_147", "text": "Toronto General Hospital"}
{"_id": "WikiPedia_Cardio$$$corpus_148", "text": "John D. Puskas  is an American researcher, author, inventor and cardiovascular surgeon. As of 2022, he is Professor,  Cardiovascular  Surgery,  Icahn School of Medicine  at Mount Sinai, [ 1 ]  and chairman, Department of Cardiovascular Surgery at  Mount Sinai Morningside ,  Mount Sinai Beth Israel  and  Mount Sinai West . He holds 11 U.S. patents and co-founded the International Coronary Congress and the International Society for Coronary Artery Surgery. [ 2 ]  He is credited by  ResearchGate  with 330 publications and 15,234 citations [ 3 ]  and as of 2022  Scopus  reports an  h-index  of  62. [ 4 ]  Puskas is known for advancing  coronary artery bypass  ( CABG ) surgery by refining surgical techniques for all-arterial, off-pump CABG and inventing finer instruments to be used for advanced coronary bypass surgical procedures. [ 5 ]  He is credited with performing the first totally thoracoscopic bilateral  pulmonary vein isolation  procedure. [ 6 ]  He is the co-editor of  State of the Art Surgical Coronary  Revascularization , [ 7 ] [ 8 ]  the first textbook solely devoted to coronary artery surgery. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_149", "text": "In 2021, Puskas ran the  New York City Marathon  with his patient who, in 2018, suffered cardiac arrest and was clinically dead for five minutes, but recovered after all-arterial CABG. [ 10 ]  Their trainer, John Garlepp was another CABG patient of Puskas. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_150", "text": "Born in 1960, Puskas received his MD at  Harvard Medical School  in 1986 and in 1991, a Master of Science in Surgical Science ( MSc ) at the  University of Toronto . Post-graduate training included a general surgery internship and residency, department of surgery,  Massachusetts General Hospital ; fellowship in  cardiothoracic surgery  at  Emory University Hospitals ,  Atlanta ,  a  lung transplantation  research fellowship, division of  thoracic  surgery,  Toronto General Hospital ; and an advanced fellowship in  tracheal  surgery,  Massachusetts General Hospital , Division of General  Thoracic Surgery . [ 1 ] [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_151", "text": "Puskas research concentrations include arterial bypass grafting, robotic and hybrid coronary bypass grafting, novel designs and materials for artificial heart valves, mitral and aortic valve repair and replacement, surgical and medical treatments for people with atrial fibrillation and surgical instruments for adult cardiac surgery. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_152", "text": "He founded the  Emory University   Cardiothoracic  Clinical Research Unit in 2005 and was a founding investigator in the creation of the  NIH  Cardiothoracic Surgery Trials Network in 2007; he has served on the steering committee of that NIH Network since that time.\u00a0As of 2022, he has served as the  principal investigator  (PI) of five multi-center  FDA  investigatory drug/device exemption trials in cardiovascular surgery. At  Mount Sinai Health System , he founded and directs the Cardiovascular Clinical Research Unit at Mount Sinai Morningside and Mount Sinai Beth Israel Hospitals to create a multidisciplinary collaborative clinical research infrastructure allowing clinical cardiologists and surgeons to enroll patients in multiple trials. He led 47 clinical sites nationwide to conduct the first  RCT  of hybrid coronary revascularization. [ 15 ]  He is listed on NIH RePORTER with 12 NHLBI PI roles. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_153", "text": "Puskas performs cardiovascular surgical procedures including all-arterial coronary bypass grafting, minimally invasive robotic coronary bypass surgery, hybrid coronary  revascularization ,  off-pump  coronary artery bypass surgery,  ablation  surgery for the treatment of  atrial fibrillation ,  mitral valve  repair/replacement,  aortic valve  replacement, valve-sparing aortic root replacement and surgery for  aortic dissection . [ 17 ]  He performed the first triple off-pump bypass surgery using minimally invasive coronary artery bypass graft instrumentation in 1997. [ 18 ]  Between 1996 and 2022, he performed approximately 300 cardiac surgical cases annually, specializing in multiple arterial  CABG  and robotic CABG. [ 18 ]  In 2019, Puskas, with Gianluca Torregrossa, MD, successfully performed two totally endoscopic coronary arterial bypass surgeries ( TECABs ) making Mount Sinai the only New York State health system qualified to make the procedure available. [ 19 ]  As of 2022, Puskas has served as President of the International Society for Minimally Invasive Cardiothoracic Surgery (2009) and the International Society for Coronary Artery Surgery."}
{"_id": "WikiPedia_Cardio$$$corpus_154", "text": "*Present indicates 2022"}
{"_id": "WikiPedia_Cardio$$$corpus_155", "text": "As of 2022, Puskas is a reviewer and editorial contributor to nine journals, including  The Annals of Thoracic Surgery ,  Journal of Thoracic and Cardiovascular Surgery , Heart Surgery Forum, The  Lancet , The  Journal of Cardiac Surgery ,  Circulation ,  Innovations ,  American College of Cardiology ,  European Association for Cardiothoracic Surgery ."}
{"_id": "WikiPedia_Cardio$$$corpus_156", "text": "PubMed lists 320 publications as of 2022. [ 20 ]  A short list ranked by citations include:"}
{"_id": "WikiPedia_Cardio$$$corpus_157", "text": "Smith, P. K., Puskas, J. D., Ascheim, D. D., Voisine, P., Gelijns, A. C., Moskowitz, A. J., ... & Michler, R. E. (2014).  Surgical treatment of moderate ischemic mitral regurgitation .  New England Journal of Medicine ,  371 (23), 2178\u20132188; 273 citations [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_158", "text": "Puskas, J. D., Thourani, V. H., Marshall, J. J., Dempsey, S. J., Steiner, M. A., Sammons, B. H., ... & Guyton, R. A. (2001).  Clinical outcomes, angiographic patency, and resource utilization in 200 consecutive off-pump coronary bypass patients .  The Annals of thoracic surgery ,  71 (5), 1477\u20131484; 324 citations [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_159", "text": "Gaudino, M., Benedetto, U., Fremes, S., Biondi-Zoccai, G., Sedrakyan, A., Puskas, J. D., ... & Taggart, D. P. (2018).  Radial-artery or saphenous-vein grafts in coronary-artery bypass surgery .  New England Journal of Medicine ,  378 (22), 2069\u20132077; 295 citations [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_160", "text": "Gillinov, A. M., Gelijns, A. C., Parides, M. K., DeRose Jr, J. J., Moskowitz, A. J., Voisine, P., ... & Argenziano, M. (2015).  Surgical ablation of atrial fibrillation during mitral-valve surgery .  New England Journal of Medicine ,  372 (15), 1399\u20131409; 261 citations [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_161", "text": "El-Chami, M. F., Kilgo, P., Thourani, V., Lattouf, O. M., Delurgio, D. B., Guyton, R. A., ... & Puskas, J. D. (2010).  New-onset atrial fibrillation predicts long-term mortality after coronary artery bypass graft .  Journal of the American College of Cardiology ,  55 (13), 1370\u20131376; 338 citations [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_162", "text": "State of the Art Surgical Coronary Revascularization .  ISBN \u00a0 0198758782"}
{"_id": "WikiPedia_Cardio$$$corpus_163", "text": "Winston AD and Puskas JD. \" Techniques for Multivessel OPCAB \". Minimally Invasive Cardiac Surgery. 2ndEdition, edited by Oz MC and Goldstein DJ, Humana Press, 2003. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_164", "text": "Sharoni E and Puskas JD. \" Techniques in Multivessel OPCAB \". Operative Cardiac Surgery, edited by Gardner T J and Spray TL, Arnold Publishers, 2004."}
{"_id": "WikiPedia_Cardio$$$corpus_165", "text": "Thourani VH and Puskas JD. \" Coronary Artery Bypass Procedures\u00b7Medical Management of the Surgical Patient .\" Fourth Edition, edited by Lubin MF, Walker HK, Smith RB III, 2006. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_166", "text": "Song HK and Puskas JD. \" Off-pump Coronary Artery Bypass Surgery \". Mastery of Cardiothoracic Surgery, 2nd Edition, Lippincott Williams and Wilkins, New York, 2007. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_167", "text": "Richard J. Myung and John D. Puskas. \" Off-Pump Coronary Artery Bypass Grafting for Repeat Coronary Revascularization \", Redo Cardiac Surgery in Adults, 2nd Edition, Edited by Venkat R. Machiraju, Hartzell V. Schaff and Lars G. Svensson. Springer. 2011. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_168", "text": "Michael E. Halkos, John D. Puskas. \" Minimally Invasive Coronary Artery Bypass Graft to Cardiac Surgery: Recent Advances and Techniques \", 2012. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_169", "text": "Yanagawa B and Puskas JD. \u201c Off-Pump Coronary Artery Bypass Grafting \u201d, in Mastery of Techniques in Cardiac Surgery, 2016."}
{"_id": "WikiPedia_Cardio$$$corpus_170", "text": "Michael E. Halkos, Emmanuel Moss, and John D. Puskas. \u201c Chapter 2 Off-pump versus on-pump coronary artery bypass grafting \u201d, in Core Concepts in Cardiac Surgery, Edited by David Taggart and Yasir Abu-Omar, Oxford University Press, 2018."}
{"_id": "WikiPedia_Cardio$$$corpus_171", "text": "Bobby Yanagawa, Michael E. Halkos, John D. Puskas. \u201c Chapter 21: Myocardial Revascularization Without Cardiopulmonary Bypass \u201d, in Cardiac Surgery in the Adult, 5e, Edited by Lawrence H. Cohn, David H. Adams, Cenveo\u00ae Publisher Services, 2018."}
{"_id": "WikiPedia_Cardio$$$corpus_172", "text": "Tom J. Quinn  was the UK's first Professor of  cardiac nursing , and is a Fellow of the  Royal College of Nursing  (RCN) for his outstanding contribution to research and practice of cardiac nursing. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_173", "text": "He currently [ when? ]  works at the  Kingston University  covering research, development and consultancy in cardiovascular care issues, particularly emergency and critical cardiac care and policy. [ 3 ]  He was previously Professor of Cardiac Nursing at  Coventry University . [ 4 ]  His NHS experience over almost three decades included periods at  St Bartholomew's Hospital , the  National Heart Hospital  and  York Hospital  and at regional office, Strategic Health Authority, the Department of Health [ 5 ]  and NHS Modernisation Agency, and the ambulance service. He is clinical lead in the National Library for Health covering the cardiovascular, stroke and vascular specialist libraries. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_174", "text": "He was instrumental in developing and writing the  Department of Health's  National Service Framework on heart disease and is a fellow of the  European Society of Cardiology ."}
{"_id": "WikiPedia_Cardio$$$corpus_175", "text": "He has also published more than 60 papers focusing on the care of patients with cardiac disease or developing nursing practice. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_176", "text": "Naveed Amjid Sattar  is a Scottish medical researcher and Professor of Metabolic Medicine at the  Institute of Cardiovascular & Medical Sciences  at the  University of Glasgow , as well as an Honorary Consultant in Metabolic Medicine at the  Glasgow Royal Infirmary . [ 1 ]  He was described by the  BBC  as \"a leading expert in  diabetes  and  cardio-vascular disease  research\". [ 2 ]  He has been an  ISI Highly Cited Researcher  since 2014. [ 1 ]  In 2016, he was elected a fellow of the  Academy of Medical Sciences . [ 3 ]  He is also a Fellow of the  Royal College of Pathologists , the  Royal College of Physicians and Surgeons of Glasgow , and the  Royal Society of Edinburgh . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_177", "text": "This biography of a Scottish academic is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_178", "text": "Katja Schenke-Layland  (born  Eisenach, Germany , March 21, 1977) is the Professor of Medical Technologies and Regenerative Medicine, Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine at the  University of T\u00fcbingen . [ 1 ]  She is the Director of the NMI Natural and Medical Sciences Institute at the University T\u00fcbingen in Reutlingen, [ 2 ]  Study Dean of Medical Technologies at the University of T\u00fcbingen, and Founding Director of the Institute of Biomedical Engineering at the Medical Faculty of the University T\u00fcbingen. She is also the Founding Director of the 3R Center for In Vitro Models and Alternatives to Animal Testing T\u00fcbingen."}
{"_id": "WikiPedia_Cardio$$$corpus_179", "text": "Katja Schenke-Layland began her doctoral work in the area of heart valve  tissue engineering  and non-invasive imaging at the  University of Jena , Germany. Her specific interest was the effect of cryopreservation, decellularization/recellularization and biomechanical forces on heart valve extracellular matrix (ECM) structures and cells. [ 3 ] [ 4 ] [ 5 ]  She helped develop the use of multiphoton laser-based confocal microscopy and second harmonic generation as non-invasive tissue imaging tools. [ 6 ]  For her post-doctoral work, she focused on cardiac stem cell biology and biomaterials. Here, her seminal work was to be the first scientist to demonstrate that  induced pluripotent stem cells  (iPSCs) differentiate towards the cardiovascular and hematopoietic lineages, showing that beating cardiomyocytes could be derived from iPSCs. [ 7 ] [ 8 ]  She then returned to Germany to join the Fraunhofer IGB in Stuttgart, Germany as a group leader, which was then followed by her appointment as Professor in the Medical Faculty of the University of T\u00fcbingen, and promotion to Department Head and later Director of the Fraunhofer IGB. She remained focused on cardiovascular development [ 9 ] [ 10 ]  and biomaterials, [ 11 ]  and moved into the areas of in vitro test systems [ 12 ] [ 13 ]  and Raman microspectroscopy, [ 14 ] [ 15 ]  with a focus on ECM proteins."}
{"_id": "WikiPedia_Cardio$$$corpus_180", "text": "Currently, her research lab at the University T\u00fcbingen focuses on the translation of human development into clinically relevant biomaterials and regenerative therapies, and the development of diagnostic tools to assess (stem) cell states, discover therapeutic candidates and diagnose diseases. [ 24 ]  She leverages her appointments to bridge the gaps between science and industry to drive viable health care solutions, particularly at the NMI where they focus on supporting local SMEs [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_181", "text": "Katja Schenke-Layland is currently the Co-Editor-In-Chief of Tissue Engineering Part B (Mary Ann Liebert) and Executive Editor of  Advanced Drug Delivery Reviews [ 26 ]  ( Elsevier ), as well as on the editorial boards of  Matrix Biology (journal) [ 27 ]  (Elsevier), Current Opinion in Biomedical Engineering (Elsevier),  Journal of 3D Printing  in Medicine (Future Medicine) and  Scientific Reports  ( Nature Research ). She is a fellow/ board member of the German National Academy of Science and Engineering, [ 28 ]  German Central Ethics Committee for Stem Cell Research, [ 29 ]  International and German Societies of Matrix Biology and the European Alliance for Medical and Biological Engineering and Science."}
{"_id": "WikiPedia_Cardio$$$corpus_182", "text": "Filip Swirski  is a Polish-Canadian-American scientist and educator serving as the Arthur and Janet C. Ross Professor of Medicine, Cardiology and Professor of  Radiology  at the  Icahn School of Medicine at Mount Sinai  and is the Director of the  Cardiovascular  Research Institute. He is also a member of the Biomedical Engineering and Imaging Institute (BMEII), the Marc and Jennifer Lipschultz Precision Immunology Institute (PrIISM), and The Friedman Brain Institutes (FBI) at Mount Sinai. His research partly focuses on innate and  inflammatory  mechanisms in cardiovascular disease. He is known for his work in cardioimmunology and notably for linking  atherosclerosis  with blood  monocytosis . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_183", "text": "Swirski earned his  Bachelor of Arts and Science  specializing in  biochemistry  and a Ph.D. in  immunology  at  McMaster University ,  Hamilton , Canada. He received an honorary  MS  from  Harvard Medical School  in 2020 for accomplishing a full professorship. He was professor at the Center for  Systems Biology  at  Massachusetts General Hospital  and at Harvard Medical School. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_184", "text": "Swirski focuses on understanding how  leukocytes  shape and are shaped by inflammation. His research uses  in vivo  models of acute and chronic inflammation relevant to cardiovascular,  neurodegenerative , infectious, and metabolic diseases. [ 5 ]  His writings reflect  translational  and fundamental cardiovascular and  neurodegenerative  science research, including  cell development , mind-marrow communication, and function. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_185", "text": "Partial list:"}
{"_id": "WikiPedia_Cardio$$$corpus_186", "text": "As of 2024, Swirski is credited with 38,923 citations and has an h-index of 95. [ 36 ]   His most cited contributions to date are on myocardial infarction, ventricular remodeling, inflammation,  stem cell  niche, hematopoiesis and hematopoietic stem cells. [ 37 ]  Between 2018 and 2019, articles reportedly focused mostly on inflammation (43.72%), bone marrow (17.21%) and immune system (17.21%). [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_187", "text": "Five most-cited peer-reviewed publications as of 2024 include: [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_188", "text": "Jennifer Eileen Van Eyk  is the Erika Glazer Chair in Women's Heart Health, the Director of Advanced Clinical Biosystems Institute in the Department of Biomedical Sciences, the Director of Basic Science Research in the Women's Heart Center, a Professor in Medicine and in Biomedical Sciences at Cedars-Sinai. [ 1 ]  She is a renowned scientist in the field of clinical proteomics."}
{"_id": "WikiPedia_Cardio$$$corpus_189", "text": "Jennifer E. Van Eyk was born in  Northern Ontario , Canada. [ 2 ]  She obtained a bachelor of science in biology and chemistry from the  University of Waterloo  in 1982. [ 3 ]  She received a PhD in biochemistry under the direction of  Robert S. Hodges  from  University of Alberta  in 1991. [ 4 ]  She conducted post-doctoral research at  University of Heidelberg , University of Alberta, and  University of Illinois at Chicago  with R. John Solaro. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_190", "text": "Van Eyk began her academic career in 1996 as an assistant professor in the Department of Physiology at  Queen's University , Kingston, Canada, and she was promoted to associate professor and received tenure in 2001. [ 3 ] [ 5 ]  She then left Canada to join  Johns Hopkins University  as the Director of the Proteomics Innovation Center in Heart Failure in 2003, and later Cedars-Sinai in 2014. [ 1 ] [ 5 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_191", "text": "Van Eyk is a member-at-large and a council member of  Human Proteome Organization , [ 6 ]  and the president of US Human Proteome Organization. [ 7 ]  She was a technical briefs editor at  Proteomics . [ 8 ]  She served on the editorial board of Proteomics: clinical application and Journal of Physiology and Circulation Research. [ 9 ]  She currently serves on the editorial board of  Clinical Proteomics . [ 10 ]  She is a Fellow of the  International Society for Heart Research . [ 11 ]  and is a Fellow of the  American Heart Association."}
{"_id": "WikiPedia_Cardio$$$corpus_192", "text": "She is an international leading scientist in clinical proteomics. [ 12 ]  She is the founding director of Cedars-Sinai Advanced Clinical Biosystems Research Institute, [ 13 ]  whose motto is \u201cfrom discovery to patient care\u201d. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_193", "text": "She is co-editor of  Clinical Proteomics: From Diagnosis to Therapy, [ 15 ]  an essential, important and impressive book in clinical proteomics and translational medicine. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_194", "text": "Her list of publications:  https://www.ncbi.nlm.nih.gov/sites/myncbi/1VsYqQYH8535l/bibliography/48183272/public/ ."}
{"_id": "WikiPedia_Cardio$$$corpus_195", "text": "Kenneth Walsh  is an American medical researcher specializing in the study of  cardiovascular medicine . He is a professor of medicine at the  University of Virginia School of Medicine . He was formerly a professor at  Tufts University . [ 1 ] \nAlong with  Mark T. Nelson , he succeeded  David Julius  in 2021 as the co- editor  of the peer-reviewed journal the  Annual Review of Physiology . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_196", "text": "Walsh has received an Established Investigator Award from the  American Heart Association  and the Irwin F. Page Investigator Award from the  Council on Arteriosclerosis . [ 3 ]  In 2011, he was one of five researchers named as Distinguished Scientists that year by the American Heart Association. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_197", "text": "This biographical article related to medicine in the United States is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_198", "text": "Earl Howard Wood  (January 1, 1912 \u2013 March 18, 2009) was an American cardiopulmonary physiologist who helped invent the  G-suit , brought heart catheterization into a clinical reality and introduced dynamic volumetric computed tomography for the study of the heart and lungs. [ 2 ] [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_199", "text": "Shortly after receiving an  M.D.  and  PhD  in physiology from the  University of Minnesota  medical school under the mentorship of Professor  Maurice B. Visscher , MD, [ 6 ]  Wood became a key member of a team, working in a laboratory at the  Mayo Clinic , tasked with helping military pilots and flight crew survive and function in high  G-force  environments. Based upon extensive physiologic testing via use of the human centrifuge installed at the Mayo Clinic, it was determined that blackout and then unconsciousness was caused by reduction of blood flow to the eyes first and then the brain. [ 7 ]  The solutions the team arrived at were the M-1 breath hold maneuver [ 8 ] [ 9 ]  and the  G-suit . [ 10 ] [ 11 ]  The M-1 maneuver consisted of a strained exhalation effort against a closed glottis designed to increase left ventricular pressure. (Although the references given are dated 1946-7, the work was performed much before then.  In, [ 7 ]  see the acknowledgments section [ 7 ] :\u200a342\u200a  explaining the closed nature of the research with restrictions placed on publication during the war.   During the war effort the Mayo Clinic laboratory  was operating with government  Confidential  secrecy.)  The G suit was a garment, produced by the  David Clark Company , which has air bladders situated at the calves, thighs, and abdomen of the wearer. The bladders inflate as the G-force acting on the aircraft increase, constricting the wearer's arteries, hence increasing blood pressure and blood flow to the brain."}
{"_id": "WikiPedia_Cardio$$$corpus_200", "text": "The G-suit was a superior solution to another alternative (a water-filled suit) being tested at the time, which was considered impractically heavy and cumbersome. The water-filled, pulsatile pressure suits were developed to effect venous return.  However, Wood and colleagues' detailed physiologic measurements demonstrated that what was required was augmentation of arterial pressure."}
{"_id": "WikiPedia_Cardio$$$corpus_201", "text": "Wood himself regularly tested the flight suits, taking many turns in a human centrifuge and plane dubbed the \"G-wiz\". He calculated that during more than a thousand rides, he had lost consciousness for an aggregate of at least fifteen minutes (without any observed lasting damage). Wood was awarded a Presidential Certificate of Merit by Harry Truman in 1947."}
{"_id": "WikiPedia_Cardio$$$corpus_202", "text": "The G-suit was adopted in the 1940s. The current models are based on the pattern Wood and his colleagues designed. Following World War II, Wood was recruited to participate in what was known as \" Operation Paperclip \" [ 12 ]  The goal was to keep the top German scientists away from Russia and working for the United States."}
{"_id": "WikiPedia_Cardio$$$corpus_203", "text": "In 1962, Wood was the tenth scientist to be named \"Career Investigator,\" of the American Heart Association. [ 13 ]  These funds allowed Wood considerable flexibility in regards to the directions of his research."}
{"_id": "WikiPedia_Cardio$$$corpus_204", "text": "After his work on the G-Suit, Wood worked on techniques for measuring cardiac blood flow. He was granted a  patent  for the ear oximeter, an optical instrument that measures blood oxygen levels without taking blood by examining the variation of light absorption as a function of oxygen saturation of hemoglobin. Integral to the work leading to the development of the G suit was the perfection of vascular catheterization methods needed to understand the distribution of blood pressure and flow.  Shortly after the end of World War II, open-heart surgery emerged with the Mayo contribution [ 14 ]  to the development of the heart-lung bypass machine initially developed by Gibbons [ 15 ]  and perfected by Wood and colleagues. [ 14 ] [ 16 ]  Wood's work at the Mayo Clinic lead to the development of many technologies [ 5 ]  allowing for the assessment of the heart and lungs including dye dilution methods serving to characterize cardiac output, [ 17 ]  methods for the assessment of central blood volume, [ 18 ]  the calculation of  pulmonary vascular resistance  (known as the \"Wood Unit\" and calculated by subtracting pulmonary capillary wedge pressure from the mean pulmonary arterial pressure and dividing by the cardiac output), [ 19 ] [ 20 ] [ 21 ]  analog subtraction angiography, and eventually the Dynamic Spatial Reconstructor (DSR), a predecessor to modern high speed volumetric  computed tomography  (CT) allowing for the evaluation of the beating heart and breathing lungs.  The DSR comprised 14 X-ray tubes and a hemicylindrical fluorescent screen imaged by 14 associated television cameras. [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_205", "text": "In all, Wood is noted for his contributions (together with members of the Biodynamics Research Unit (BRU), under his direction, within the physiology and biophysics department at the  Mayo Clinic ) in the following areas:"}
{"_id": "WikiPedia_Cardio$$$corpus_206", "text": "Wood's publication list, with more than 700 entries, is a testament to the number of fellows who trained under him and who became prominent researchers in their own right."}
{"_id": "WikiPedia_Cardio$$$corpus_207", "text": "Earl Wood was born to Inez Goff and William Clark Wood in Mankato, Minnesota on January 1, 1912 and started life on a subsistence farm. [ 4 ]   William Wood, in addition to farming, was a real estate businessman. Earl Wood earned a B.A. in Mathematics and Chemistry from Macalester College in 1934, and his MD degree and a PhD degree in physiology from the University of Minnesota. Earl was one of 5 brothers (Earl, Chester, Delbert, Harland and Abe) and a sister, Louise."}
{"_id": "WikiPedia_Cardio$$$corpus_208", "text": "All of Earl Wood's siblings grew up to be highly accomplished. [ 13 ]  Louise A. Wood was awarded the  Medal of Freedom  by President Truman for her services as overseas director of the American Red Cross during World War II. and became the executive director of the  Girl Scouts of the USA  from 1961 to 1972.  Harland G. Wood  was the first director of the department of biochemistry at the school of medicine and dean of sciences, Case Western Reserve University. As a biochemist, he was notable for proving in 1935 that animals, humans and bacteria utilized carbon dioxide [ 54 ]  and received the National Medal of Science. Chester was a teacher and a university administrator; Delbert was, in succession, a lawyer, a Federal Bureau of Investigation agent, and a railway executive; Abe was an internist and founder of a Colorado-based medical clinic. Not surprisingly, in 1950, Earl Wood's mother, Inez, was awarded the title of \"Minnesota Mother of the Year.\" [ 13 ]   Earl and his wife, Ada, had a daughter, Phoebe and three sons, Mark, Guy and E. Andrew."}
{"_id": "WikiPedia_Cardio$$$corpus_209", "text": "Rapid Interpretation of EKG's  is a best-selling textbook for over 30 years [ 1 ]  that teaches the basics of interpreting  electrocardiograms . It adopts a simplistic fill-in-the-blank style [ 2 ]  and is suited for medical students and junior residents. [ 1 ]  The book was written by  Dale Dubin ,  M.D. , a  plastic surgeon  and convicted felon, [ 3 ]  who has written several books on  cardiology  including  Ion Adventure in the Heartland: Exploring the Heart's Ionic-Molecular Microcosm [ 4 ]  and  Understanding Cardio-pulmonary Resuscitation . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_210", "text": "The large yellow book was originally published in 1972; the sixth and most recent edition was published in 2000. In the fiftieth printing, the author hid within the  copyright notice  an offer to give his prized 1965  Ford Thunderbird  (which was featured in several photographs in the book) to anyone who actually read the message and responded. Out of 60,000 copies in that printing, only 5 readers noticed and responded, and Dubin's own daughter delivered the car to the winner, a  Yale  medical student, as selected by a random drawing. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_211", "text": "Cardiology  (from  Ancient Greek     \u03ba\u03b1\u03c1\u03b4\u03af\u1fb1  (kardi\u0101) \u00a0'heart' and   - \u03bb\u03bf\u03b3\u03af\u03b1  ( -logia ) \u00a0'study') is the study of the heart. Cardiology is a branch of  medicine  that deals with disorders of the  heart  and the  cardiovascular system . The field includes  medical diagnosis  and treatment of  congenital heart defects ,  coronary artery disease ,  heart failure ,  valvular heart disease , and  electrophysiology .  Physicians  who specialize in this field of medicine are called  cardiologists , a sub-specialty of  internal medicine . Pediatric cardiologists are  pediatricians  who specialize in cardiology. Physicians who specialize in cardiac surgery are called  cardiothoracic surgeons  or  cardiac surgeons , a specialty of  general surgery . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_212", "text": "All cardiologists in the branch of medicine study the disorders of the heart, but the study of adult and child heart disorders each require different training pathways. Therefore, an adult cardiologist (often simply called \"cardiologist\") is inadequately trained to take care of children, and pediatric cardiologists are not trained to treat adult heart disease. Surgical aspects outside of cardiac rhythm device implant are not included in cardiology and are in the domain of  cardiothoracic surgery . For example,  coronary artery bypass surgery  (CABG),  cardiopulmonary bypass  and  valve replacement  are surgical procedures performed by surgeons, not cardiologists. Typically a cardiologist would first identify who is in need of cardiac surgery and refer them to a cardiac surgeon for the procedure. However, some invasive procedures such as  cardiac catheterization  and  pacemaker implantation  are performed by cardiologists."}
{"_id": "WikiPedia_Cardio$$$corpus_213", "text": "Cardiology is a specialty of  internal medicine ."}
{"_id": "WikiPedia_Cardio$$$corpus_214", "text": "To become a cardiologist in the  United States , a three-year residency in internal medicine is followed by a three-year fellowship in cardiology. It is possible to specialize further in a sub-specialty. Recognized sub-specialties in the U.S. by the  Accreditation Council for Graduate Medical Education  are  clinical cardiac electrophysiology ,  interventional cardiology , adult congenital heart disease, and advanced heart failure and transplant cardiology. Cardiologists may further become certified in echocardiography by the National Board of Echocardiography, [ 2 ]  in nuclear cardiology by the Certification Board of Nuclear Cardiology, in cardiovascular computed tomography by the Certification Board of Cardiovascular Computed Tomography in cardiovascular MRI by the Certification Board of Cardiovascular Magnetic Resonance. [ 3 ]  Recognized subspecialties in the U.S. by the  American Osteopathic Association Bureau of Osteopathic Specialists  include  clinical cardiac electrophysiology  and  interventional cardiology . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_215", "text": "In India, a three-year residency in General Medicine or Pediatrics after  M.B.B.S.  and then three years of residency in cardiology are needed to be a D.M. (holder of a Doctorate of Medicine [D.M.])/ Diplomate of National Board  (DNB) in Cardiology. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_216", "text": "Per  Doximity , adult cardiologists earn an average of $436,849 per year in the U.S. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_217", "text": "Cardiac electrophysiology is the science of elucidating, diagnosing, and treating the electrical activities of the heart. The term is usually used to describe studies of such phenomena by invasive (intracardiac)  catheter  recording of spontaneous activity as well as of cardiac responses to  programmed electrical stimulation  (PES). These studies are performed to assess complex  arrhythmias , elucidate symptoms, evaluate abnormal  electrocardiograms , assess risk of developing arrhythmias in the future, and design treatment.  These procedures increasingly include therapeutic methods (typically  radiofrequency ablation , or  cryoablation ) in addition to diagnostic and prognostic procedures."}
{"_id": "WikiPedia_Cardio$$$corpus_218", "text": "Other therapeutic modalities employed in this field include  antiarrhythmic drug  therapy and implantation of  pacemakers  and automatic  implantable cardioverter-defibrillators  (AICD). [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_219", "text": "The cardiac  electrophysiology study  typically measures the response of the injured or cardiomyopathic myocardium to PES on specific pharmacological regimens in order to assess the likelihood that the regimen will successfully prevent potentially fatal sustained  ventricular tachycardia  (VT) or  ventricular fibrillation  (VF) in the future. Sometimes a  series  of electrophysiology-study drug trials must be conducted to enable the cardiologist to select the one regimen for long-term treatment that best prevents or slows the development of VT or VF following PES. Such studies may also be conducted in the presence of a newly implanted or newly replaced cardiac pacemaker or AICD. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_220", "text": "Clinical cardiac electrophysiology is a branch of the medical specialty of cardiology and is concerned with the study and treatment of rhythm disorders of the heart. Cardiologists with expertise in this area are usually referred to as electrophysiologists. Electrophysiologists are trained in the mechanism, function, and performance of the electrical activities of the heart. Electrophysiologists work closely with other cardiologists and cardiac surgeons to assist or guide therapy for heart rhythm disturbances (arrhythmias). They are trained to perform interventional and surgical procedures to treat cardiac arrhythmia. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_221", "text": "The training required to become an electrophysiologist is long and requires eight years after medical school (within the U.S.). Three years of internal medicine residency, three years of cardiology fellowship, and two years of clinical cardiac electrophysiology. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_222", "text": "Cardiogeriatrics, or geriatric cardiology, is the branch of cardiology and geriatric medicine that deals with the cardiovascular disorders in elderly people."}
{"_id": "WikiPedia_Cardio$$$corpus_223", "text": "Cardiac disorders such as  coronary heart disease , including  myocardial infarction ,  heart failure ,  cardiomyopathy , and arrhythmias such as  atrial fibrillation , are common and are a major cause of mortality in elderly people. [ 10 ] [ 11 ]  Vascular disorders such as  atherosclerosis  and  peripheral arterial disease  cause significant morbidity and mortality in aged people. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_224", "text": "Cardiac imaging includes echocardiography (echo), cardiac magnetic resonance imaging (CMR), and computed tomography of the heart.\nThose who specialize in cardiac imaging may undergo more training in all imaging modes or focus on a single imaging modality."}
{"_id": "WikiPedia_Cardio$$$corpus_225", "text": "Echocardiography (or \"echo\") uses standard two-dimensional, three-dimensional, and  Doppler ultrasound  to create images of the heart. It is used to evaluate and quantify cardiac size and function, valvular function, and can assist with diagnosis and treatment of conditions including heart failure, heart attack, valvular heart disease, congenital heart defects, pericardial disease, and aortic disease. \nThose who specialize in echo may spend a significant amount of their clinical time reading echos and performing transesophageal echo, in particular using the latter during procedures such as insertion of a left atrial appendage occlusion device. Transesophageal echo provides higher spatial resolution than trans thoracic echocardiography and because the probe is located in the esophagus, it is not limited by attenuation due to anterior chest structures such as the ribs, chest wall, breasts, lungs that can hinder the quality of trans thoracic echocardiography. It is generally indicated for a variety of indications including: when the standard transthoracic echocardiogram is non diagnostic, for detailed evaluation of abnormalities that are typically in the far field, such as the aorta, left atrial appendage, evaluation of native or prosthetic heart valves, evaluation of cardiac masses, evaluation of endocarditis, valvular abscesses, or for the evaluation of cardiac source of embolus. It is frequently used in the setting of atrial fibrillation or atrial flutter to facilitate the clinical decision with regard to anticoagulation, cardioversion and/or radio frequency ablation. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_226", "text": "Cardiac MRI utilizes special protocols to image heart structure and function with specific sequences for certain diseases such as  hemochromatosis  and  amyloidosis ."}
{"_id": "WikiPedia_Cardio$$$corpus_227", "text": "Cardiac CT utilizes special protocols to image heart structure and function with particular emphasis on coronary arteries."}
{"_id": "WikiPedia_Cardio$$$corpus_228", "text": "Interventional cardiology is a branch of cardiology that deals specifically with the  catheter  based treatment of structural heart diseases. [ 15 ]  A large number of procedures can be performed on the heart by catheterization, including angiogram, angioplasty, atherectomy, and stent implantation. These procedures all involve insertion of a sheath into the  femoral artery  or radial artery (but, in practice, any large peripheral artery or vein) and  cannulating  the heart under  X-ray  visualization (most commonly  fluoroscopy ). This cannulation allows indirect access to the heart, bypassing the trauma caused by surgical opening of the chest."}
{"_id": "WikiPedia_Cardio$$$corpus_229", "text": "The main advantages of using the interventional cardiology or radiology approach are the avoidance of the scars and pain, and long post-operative recovery. Additionally, interventional cardiology procedure of primary  angioplasty  is now the gold standard of care for an acute myocardial infarction. This procedure can also be done proactively, when areas of the vascular system become occluded from  atherosclerosis . The Cardiologist will thread this sheath through the vascular system to access the heart. This sheath has a balloon and a tiny wire mesh tube wrapped around it, and if the cardiologist finds a blockage or  stenosis , they can inflate the balloon at the occlusion site in the vascular system to flatten or compress the plaque against the vascular wall. Once that is complete a  stent  is placed as a type of scaffold to hold the vasculature open permanently."}
{"_id": "WikiPedia_Cardio$$$corpus_230", "text": "A relatively newer specialization of cardiology is in the field of heart failure and heart transplant. Cardiomyopathy is a disease of the heart muscle that make it larger or stiffer, sometimes making the heart worse at pumping blood. [ 16 ]  Specialization of general cardiology to just that of the  cardiomyopathies  leads to also specializing in  heart transplant  and  pulmonary hypertension ."}
{"_id": "WikiPedia_Cardio$$$corpus_231", "text": "A recent specialization of cardiology is that of cardiooncology.\nThis area specializes in the cardiac management in those with cancer and in particular those with plans for  chemotherapy  or those who have experienced cardiac complications of chemotherapy."}
{"_id": "WikiPedia_Cardio$$$corpus_232", "text": "In recent times, the focus is gradually shifting to preventive cardiology due to increased  cardiovascular disease  burden at an early age. According to the WHO, 37% of all premature deaths are due to cardiovascular diseases and out of this, 82% are in low and middle income countries. [ 17 ]  Clinical cardiology is the sub specialty of cardiology which looks after preventive cardiology and cardiac rehabilitation. Preventive cardiology also deals with routine preventive checkup though noninvasive tests, specifically electrocardiography,  fasegraphy , stress tests,  lipid profile  and general physical examination to detect any cardiovascular diseases at an early age, while cardiac rehabilitation is the upcoming branch of cardiology which helps a person regain their overall strength and live a normal life after a cardiovascular event. A subspecialty of preventive cardiology is  sports cardiology . Because heart disease is the leading cause of death in the world including United States (cdc.gov), national health campaigns and randomized control research has developed to improve heart health."}
{"_id": "WikiPedia_Cardio$$$corpus_233", "text": "Helen B. Taussig  is known as the founder of pediatric cardiology. She became famous through her work with  Tetralogy  congenital heart defect in which  oxygenated and deoxygenated blood  enters the circulatory system resulting from a  ventricular septal defect  (VSD) right beneath the aorta. This condition causes newborns to have a bluish-tint,  cyanosis , and have a deficiency of oxygen to their tissues,  hypoxemia . She worked with  Alfred Blalock  and  Vivien Thomas  at the  Johns Hopkins Hospital  where they experimented with dogs to look at how they would attempt to surgically cure these \"blue babies\". They eventually figured out how to do just that by the  anastomosis  of the systemic artery to the pulmonary artery and called this the  Blalock-Taussig Shunt . [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_234", "text": "Tetralogy of Fallot ,  pulmonary atresia ,  double outlet right ventricle ,  transposition of the great arteries ,  persistent truncus arteriosus , and  Ebstein's anomaly  are various congenital cyanotic heart diseases, in which the  blood  of the newborn is not oxygenated efficiently, due to the heart defect."}
{"_id": "WikiPedia_Cardio$$$corpus_235", "text": "As more children with congenital heart disease are surviving into adulthood, a hybrid of adult and pediatric cardiology has emerged called adult congenital heart disease (ACHD).\nThis field can be entered as either adult or pediatric cardiology.\nACHD specializes in congenital diseases in the setting of adult diseases (e.g., coronary artery disease, COPD, diabetes) that is, otherwise, atypical for adult or pediatric cardiology."}
{"_id": "WikiPedia_Cardio$$$corpus_236", "text": "As the center focus of cardiology, the heart has numerous anatomical features (e.g.,  atria ,  ventricles ,  heart valves ) and numerous physiological features (e.g.,  systole ,  heart sounds ,  afterload ) that have been encyclopedically documented for many centuries. The heart is located in the middle of the abdomen with its tip slightly towards the left side of the abdomen."}
{"_id": "WikiPedia_Cardio$$$corpus_237", "text": "Disorders of the heart lead to  heart disease  and cardiovascular disease and can lead to a significant number of deaths: cardiovascular disease is the leading  cause of death  in the U.S. and caused 24.95% of total deaths in 2008. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_238", "text": "The primary responsibility of the heart is to pump blood throughout the body.\nIt pumps blood from the body \u2014 called the  systemic circulation  \u2014 through the  lungs  \u2014 called the  pulmonary circulation  \u2014 and then back out to the body. This means that the heart is connected to and affects the entirety of the body. Simplified, the heart is a circuit of the  circulation . [ citation needed ]  While plenty is known about the healthy heart, the bulk of study in cardiology is in disorders of the heart and restoration, and where possible, of function."}
{"_id": "WikiPedia_Cardio$$$corpus_239", "text": "The heart is a muscle that squeezes blood and functions like a pump. The heart's systems can be classified as either electrical or mechanical, and both of these systems are susceptible to failure or dysfunction."}
{"_id": "WikiPedia_Cardio$$$corpus_240", "text": "The electrical system of the heart is centered on the periodic contraction (squeezing) of the  muscle cells  that is caused by the  cardiac pacemaker  located in the  sinoatrial node .\nThe study of the electrical aspects is a sub-field of  electrophysiology  called  cardiac electrophysiology  and is epitomized with the electrocardiogram (ECG/EKG).\nThe  action potentials  generated in the pacemaker propagate throughout the heart in a specific pattern. The system that carries this potential is called the  electrical conduction system .\nDysfunction of the electrical system manifests in many ways and may include  Wolff\u2013Parkinson\u2013White syndrome ,  ventricular fibrillation , and  heart block . [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_241", "text": "The mechanical system of the heart is centered on the  fluidic movement  of blood and the functionality of the heart as a  pump .\nThe mechanical part is ultimately the purpose of the heart and many of the disorders of the heart disrupt the ability to move blood.\n Heart failure  is one condition in which the mechanical properties of the heart have failed or are failing, which means insufficient blood is being circulated. Failure to move a sufficient amount of blood through the body can cause damage or failure of other organs and may result in death if severe. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_242", "text": "Coronary circulation is the circulation of blood in the  blood vessels  of the  heart muscle  (the myocardium). The vessels that deliver oxygen-rich blood to the myocardium are known as coronary arteries. The vessels that remove the deoxygenated blood from the heart muscle are known as cardiac veins. These include the  great cardiac vein , the  middle cardiac vein , the  small cardiac vein  and the  anterior cardiac veins ."}
{"_id": "WikiPedia_Cardio$$$corpus_243", "text": "As the left and right coronary arteries run on the surface of the heart, they can be called epicardial coronary arteries. These arteries, when healthy, are capable of autoregulation to maintain coronary blood flow at levels appropriate to the needs of the heart muscle. These relatively narrow vessels are commonly affected by  atherosclerosis  and can become blocked, causing  angina  or myocardial infarction (a.k.a., a heart attack). The coronary arteries that run deep within the myocardium are referred to as subendocardial."}
{"_id": "WikiPedia_Cardio$$$corpus_244", "text": "The coronary arteries are classified as \"end circulation\", since they represent the only source of blood supply to the myocardium; there is very little redundant blood supply, which is why blockage of these vessels can be so critical."}
{"_id": "WikiPedia_Cardio$$$corpus_245", "text": "The cardiac examination (also called the \"precordial exam\"), is performed as part of a  physical examination , or when a patient presents with  chest pain  suggestive of a cardiovascular  pathology . It would typically be modified depending on the  indication  and integrated with other examinations especially the  respiratory examination . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_246", "text": "Like all medical examinations, the cardiac examination follows the standard structure of inspection, palpation and auscultation. [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_247", "text": "Cardiology is concerned with the normal functionality of the heart and the deviation from a healthy heart. Many disorders involve the heart itself, but some are outside of the heart and in the vascular system. Collectively, the two are jointly termed the cardiovascular system, and diseases of one part tend to affect the other."}
{"_id": "WikiPedia_Cardio$$$corpus_248", "text": "Coronary artery disease, also known as \"ischemic heart disease\", [ 24 ]  is a group of diseases that includes:  stable angina ,  unstable angina , myocardial infarction, and is one of the causes of  sudden cardiac death . [ 25 ]  It is within the group of cardiovascular diseases of which it is the most common type. [ 26 ]  A common symptom is  chest pain  or discomfort which may travel into the shoulder, arm, back, neck, or jaw. [ 27 ]  Occasionally it may feel like  heartburn . Usually symptoms occur with exercise or emotional  stress , last less than a few minutes, and get better with rest. [ 27 ]   Shortness of breath  may also occur and sometimes no symptoms are present. [ 27 ]  The first sign is occasionally a heart attack. [ 28 ]  Other complications include  heart failure  or an  irregular heartbeat . [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_249", "text": "Risk factors include:  high blood pressure ,  smoking ,  diabetes , lack of exercise,  obesity ,  high blood cholesterol , poor diet, and excessive  alcohol , among others. [ 29 ] [ 30 ]  Other risks include  depression . [ 31 ]  The underlying mechanism involves  atherosclerosis  of the  arteries of the heart . A number of tests may help with diagnoses including: electrocardiogram,  cardiac stress testing ,  coronary computed tomographic angiography , and  coronary angiogram , among others. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_250", "text": "Prevention is by eating a healthy diet, regular exercise, maintaining a healthy weight and not smoking. [ 33 ]  Sometimes medication for diabetes, high cholesterol, or high blood pressure are also used. [ 33 ]  There is limited evidence for screening people who are at low risk and do not have symptoms. [ 34 ]  Treatment involves the same measures as prevention. [ 35 ] [ 36 ]  Additional medications such as  antiplatelets  including  aspirin ,  beta blockers , or  nitroglycerin  may be recommended. [ 36 ]  Procedures such as  percutaneous coronary intervention  (PCI) or  coronary artery bypass surgery  (CABG) may be used in severe disease. [ 36 ] [ 37 ]  In those with stable CAD it is unclear if PCI or CABG in addition to the other treatments improve  life expectancy  or decreases heart attack risk. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_251", "text": "In 2013 CAD was the  most common cause of death  globally, resulting in 8.14 million deaths (16.8%) up from 5.74 million deaths (12%) in 1990. [ 26 ]  The risk of death from CAD for a given age has decreased between 1980 and 2010 especially in  developed countries . [ 39 ]  The number of cases of CAD for a given age has also decreased between 1990 and 2010. [ 40 ]  In the U.S. in 2010 about 20% of those over 65 had CAD, while it was present in 7% of those 45 to 64, and 1.3% of those 18 to 45. [ 41 ]  Rates are higher among men than women of a given age. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_252", "text": "Heart failure, or formally cardiomyopathy, is the impaired function of the heart, and there are numerous causes and forms of heart failure."}
{"_id": "WikiPedia_Cardio$$$corpus_253", "text": "The causes of cardiomyopathy can be  genetic , viral, or lifestyle-related. Key symptoms of cardiomyopathy include shortness of breath, fatigue, and irregular heartbeats. Understanding the specific function of cardiac muscle is crucial, as the heart muscle's main role is to pump blood throughout the body efficiently. [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_254", "text": "Cardiac arrhythmia, also known as \"cardiac dysrhythmia\" or \"irregular heartbeat\", is a group of conditions in which the  heartbeat  is too fast, too slow, or irregular in its rhythm. A  heart rate  that is too fast \u2013 above 100 beats per minute in adults \u2013 is called  tachycardia . A heart rate that is too slow \u2013 below 60 beats per minute \u2013 is called  bradycardia . [ 43 ]  Many types of arrhythmia present no symptoms. When symptoms are present, they may include  palpitations , or feeling a pause between heartbeats. More serious symptoms may include  lightheadedness ,  passing out ,  shortness of breath , or  chest pain . [ 44 ]  While most types of arrhythmia are not serious, some predispose a person to complications such as  stroke  or  heart failure . [ 43 ] [ 45 ]  Others may result in  cardiac arrest . [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_255", "text": "There are four main types of arrhythmia:  extra beats ,  supraventricular tachycardias ,  ventricular arrhythmias , and  bradyarrhythmias . Extra beats include  premature atrial contractions ,  premature ventricular contractions , and  premature junctional contractions . Supraventricular tachycardias include  atrial fibrillation ,  atrial flutter , and  paroxysmal supraventricular tachycardia . Ventricular arrhythmias include  ventricular fibrillation  and  ventricular tachycardia . [ 45 ] [ 46 ]  Arrhythmias are due to problems with the  electrical conduction system of the heart . [ 43 ]  Arrhythmias may occur in children; however, the normal range for the heart rate is different and depends on age. [ 45 ]  A number of tests can help diagnose arrhythmia, including an electrocardiogram and  Holter monitor . [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_256", "text": "Most arrhythmias can be effectively treated. [ 43 ]  Treatments may include medications, medical procedures such as a  pacemaker , and surgery. Medications for a fast heart rate may include  beta blockers  or  agents that attempt to restore a normal heart rhythm  such as  procainamide . This later group may have more significant side effects especially if taken for a long period of time. Pacemakers are often used for slow heart rates. Those with an irregular heartbeat are often treated with  blood thinners  to reduce the risk of complications. Those who have severe symptoms from an arrhythmia may receive urgent treatment with a jolt of electricity in the form of  cardioversion  or  defibrillation . [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_257", "text": "Arrhythmia affects millions of people. [ 49 ]  In Europe and North America, as of 2014, atrial fibrillation affects about 2% to 3% of the population. [ 50 ]  Atrial fibrillation and atrial flutter resulted in 112,000 deaths in 2013, up from 29,000 in 1990. [ 26 ]   Sudden cardiac death  is the cause of about half of deaths due to cardiovascular disease or about 15% of all deaths globally. [ 51 ]  About 80% of sudden cardiac death is the result of ventricular arrhythmias. [ 51 ]  Arrhythmias may occur at any age but are more common among older people. [ 49 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_258", "text": "Cardiac arrest is a sudden stop in effective  blood flow  due to the failure of the heart to contract effectively. [ 52 ]  Symptoms include  loss of consciousness  and  abnormal or absent breathing . [ 53 ] [ 54 ]  Some people may have  chest pain ,  shortness of breath , or  nausea  before this occurs. [ 54 ]  If not treated within minutes,  death  usually occurs. [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_259", "text": "The most common cause of cardiac arrest is  coronary artery disease . Less common causes include  major blood loss , lack of oxygen,  very low potassium ,  heart failure , and intense physical exercise. A number of inherited disorders may also increase the risk including  long QT syndrome . The initial heart rhythm is most often  ventricular fibrillation . [ 55 ]  The diagnosis is confirmed by finding no pulse. [ 53 ]  While a cardiac arrest may be caused by heart attack or heart failure these are not the same. [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_260", "text": "Prevention includes not smoking, physical activity, and maintaining a healthy weight. [ 56 ]  Treatment for cardiac arrest is immediate  cardiopulmonary resuscitation  (CPR) and, if a  shockable rhythm  is present,  defibrillation . [ 57 ]  Among those who survive  targeted temperature management  may improve outcomes. [ 58 ]  An  implantable cardiac defibrillator  may be placed to reduce the chance of death from recurrence. [ 56 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_261", "text": "In the  United States , cardiac arrest outside of  hospital  occurs in about 13 per 10,000 people per year (326,000 cases). In hospital cardiac arrest occurs in an additional 209,000 [ 59 ]  Cardiac arrest becomes more common with age. It affects males more often than females. [ 60 ]  The percentage of people who survive with treatment is about 8%. Many who survive have significant  disability . Many U.S. television shows, however, have portrayed unrealistically high survival rates of 67%. [ 61 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_262", "text": "Hypertension , also known as \"high blood pressure\", is a  long term   medical condition  in which the  blood pressure  in the  arteries  is persistently elevated. [ 62 ]  High blood pressure usually does not cause symptoms. [ 63 ]  Long term high blood pressure, however, is a major risk factor for  coronary artery disease ,  stroke ,  heart failure ,  peripheral vascular disease ,  vision loss , and  chronic kidney disease . [ 64 ] [ 65 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_263", "text": "Lifestyle factors can increase the risk of hypertension. These include  excess salt  in the diet,  excess body weight ,  smoking , and alcohol consumption. [ 63 ] [ 66 ]  Hypertension can also be caused by other diseases, or occur as a side-effect of drugs. [ 67 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_264", "text": "Blood pressure is expressed by two measurements, the  systolic  and  diastolic  pressures, which are the maximum and minimum pressures, respectively. [ 63 ]  Normal blood pressure when at rest is within the range of 100\u2013140  millimeters mercury  (mmHg) systolic and 60\u201390 mmHg diastolic. [ 68 ]  High blood pressure is present if the resting blood pressure is persistently at or above 140/90 mmHg for most adults. [ 66 ]  Different numbers apply to children. [ 69 ]  When diagnosing high blood pressure,  ambulatory blood pressure monitoring  over a 24-hour period appears to be more accurate than \"in-office\"  blood pressure measurement  at a physician's office or other blood pressure screening location. [ 62 ] [ 66 ] [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_265", "text": "Lifestyle changes and medications can lower blood pressure and decrease the risk of health complications. [ 71 ]  Lifestyle changes include weight loss, decreased salt intake, physical exercise, and a healthy diet. [ 66 ]  If changes in lifestyle are insufficient,  blood pressure medications  may be used. [ 71 ]  A regimen of up to three medications effectively controls blood pressure in 90% of people. [ 66 ]  The treatment of moderate to severe high arterial blood pressure (defined as >160/100 mmHg) with medication is associated with an improved  life expectancy  and reduced  morbidity . [ 72 ]  The effect of treatment for blood pressure between 140/90\u00a0mmHg and 160/100\u00a0mmHg is less clear, with some studies finding benefits [ 73 ] [ 74 ]  while others do not. [ 75 ]  High blood pressure affects between 16% and 37% of the population globally. [ 66 ]  In 2010, hypertension was believed to have been a factor in 18% (9.4 million) deaths. [ 76 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_266", "text": "Essential hypertension is the form of  hypertension  that by definition has no identifiable cause. It is the most common type of hypertension, affecting 95% of hypertensive patients, [ 77 ] [ 78 ] [ 79 ] [ 80 ]  it tends to be familial and is likely to be the consequence of an interaction between  environmental  and  genetic  factors.  Prevalence  of essential hypertension increases with  age , and individuals with relatively high blood pressure at younger ages are at increased risk for the subsequent development of hypertension.\nHypertension can increase the risk of  cerebral ,  cardiac , and  renal  events. [ 81 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_267", "text": "Secondary hypertension  is a type of  hypertension  which is caused by an identifiable underlying secondary cause. It is much less common than essential hypertension, affecting only 5% of hypertensive patients. It has many different causes including  endocrine diseases ,  kidney diseases , and  tumors . It also can be a  side effect  of many  medications . [ 82 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_268", "text": "Complications of hypertension  are clinical outcomes that result from  persistent elevation  of blood pressure. [ 83 ]  Hypertension is a risk factor for all clinical manifestations of  atherosclerosis  since it is a risk factor for atherosclerosis itself. [ 84 ] [ 85 ] [ 86 ] [ 87 ] [ 88 ]  It is an independent predisposing factor for  heart failure , [ 89 ] [ 90 ]   coronary artery disease , [ 91 ] [ 92 ]   stroke , [ 83 ]   renal disease , [ 93 ] [ 94 ] [ 95 ]  and  peripheral arterial disease . [ 96 ] [ 97 ]  It is the most important  risk factor  for  cardiovascular   morbidity  and  mortality , in  industrialized countries . [ 98 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_269", "text": "A congenital heart defect, also known as a \"congenital heart anomaly\" or \"congenital heart disease\", is a problem in the structure of the heart that is present at  birth . [ 99 ]  Signs and symptoms depend on the specific type of problem. [ 100 ]  Symptoms can vary from none to life-threatening. [ 99 ]  When present they may include rapid breathing,  bluish skin , poor weight gain, and feeling tired. [ 101 ]  It does not cause chest pain. [ 101 ]  Most congenital heart problems do not occur with other diseases. [ 100 ]  Complications that can result from heart defects include  heart failure . [ 101 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_270", "text": "The cause of a congenital heart defect is often unknown. [ 102 ]  Certain cases may be due to infections during  pregnancy  such as  rubella , use of certain medications or drugs such as  alcohol  or  tobacco , parents being closely related, or poor nutritional status or  obesity  in the mother. [ 100 ] [ 103 ]  Having a parent with a congenital heart defect is also a risk factor. [ 104 ]  A number of genetic conditions are associated with heart defects including  Down syndrome ,  Turner syndrome , and  Marfan syndrome . [ 100 ]  Congenital heart defects are divided into two main groups:  cyanotic heart defects  and  non-cyanotic heart defects , depending on whether the child has the potential to turn bluish in color. [ 100 ]  The problems may involve the interior walls of the heart, the  heart valves , or the large blood vessels that lead to and from the heart. [ 99 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_271", "text": "Congenital heart defects are partly preventable through  rubella vaccination , the adding of  iodine  to salt, and the adding of  folic acid  to certain food products. [ 100 ]  Some defects do not need treatment. [ 99 ]  Other may be effectively treated with  catheter based procedures  or  heart surgery . [ 105 ]  Occasionally a number of operations may be needed. [ 105 ]  Occasionally  heart transplantation  is required. [ 105 ]  With appropriate treatment outcomes, even with complex problems, are generally good. [ 99 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_272", "text": "Heart defects are the most common  birth defect . [ 100 ] [ 106 ]  In 2013 they were present in 34.3 million people globally. [ 106 ]  They affect between 4 and 75 per 1,000 live births depending upon how they are diagnosed. [ 100 ] [ 104 ]  About 6 to 19 per 1,000 cause a moderate to severe degree of problems. [ 104 ]  Congenital heart defects are the leading cause of birth defect-related deaths. [ 100 ]  In 2013 they resulted in 323,000 deaths down from 366,000 deaths in 1990. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_273", "text": "Tetralogy of Fallot  is the most common congenital heart disease arising in 1\u20133 cases per 1,000 births. The cause of this defect is a  ventricular septal defect  (VSD) and an  overriding aorta . These two defects combined causes deoxygenated blood to bypass the lungs and going right back into the circulatory system. The  modified Blalock-Taussig shunt  is usually used to fix the circulation. This procedure is done by placing a graft between the subclavian artery and the ipsilateral pulmonary artery to restore the correct blood flow."}
{"_id": "WikiPedia_Cardio$$$corpus_274", "text": "Pulmonary atresia  happens in 7\u20138 per 100,000 births and is characterized by the aorta branching out of the right ventricle. This causes the deoxygenated blood to bypass the lungs and enter the circulatory system. Surgeries can fix this by redirecting the aorta and fixing the right ventricle and pulmonary artery connection."}
{"_id": "WikiPedia_Cardio$$$corpus_275", "text": "There are two types of pulmonary atresia, classified by whether or not the baby also has a  ventricular septal defect . [ 107 ] [ 108 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_276", "text": "Double outlet right ventricle  (DORV) is when both great arteries, the pulmonary artery and the aorta, are connected to the right ventricle. There is usually a VSD in different particular places depending on the variations of DORV, typically 50% are subaortic and 30%. The surgeries that can be done to fix this defect can vary due to the different physiology and blood flow in the defected heart. One way it can be cured is by a VSD closure and placing conduits to restart the blood flow between the left ventricle and the aorta and between the right ventricle and the pulmonary artery. Another way is systemic-to-pulmonary artery shunt in cases associated with  pulmonary stenosis . Also, a  balloon atrial septostomy  can be done to relieve hypoxemia caused by DORV with the Taussig-Bing anomaly while surgical correction is awaited. [ 109 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_277", "text": "There are two different types of  transposition of the great arteries ,  Dextro-transposition of the great arteries  and  Levo-transposition of the great arteries , depending on where the chambers and vessels connect. Dextro-transposition happens in about 1 in 4,000 newborns and is when the right ventricle pumps blood into the aorta and deoxygenated blood enters the bloodstream. The temporary procedure is to create an  atrial septal defect . A permanent fix is more complicated and involves redirecting the pulmonary return to the right atrium and the systemic return to the left atrium, which is known as the  Senning procedure . The  Rastelli procedure  can also be done by rerouting the left ventricular outflow, dividing the pulmonary trunk, and placing a conduit in between the right ventricle and pulmonary trunk. Levo-transposition happens in about 1 in 13,000 newborns and is characterized by the left ventricle pumping blood into the lungs and the right ventricle pumping the blood into the aorta. This may not produce problems at the beginning, but will eventually due to the different pressures each ventricle uses to pump blood. Switching the left ventricle to be the systemic ventricle and the right ventricle to pump blood into the pulmonary artery can repair levo-transposition. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_278", "text": "Persistent truncus arteriosus  is when the  truncus arteriosus  fails to split into the aorta and pulmonary trunk. This occurs in about 1 in 11,000 live births and allows both oxygenated and deoxygenated blood into the body. The repair consists of a VSD closure and the Rastelli procedure. [ 110 ] [ 111 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_279", "text": "Ebstein's anomaly  is characterized by a right atrium that is significantly enlarged and a heart that is shaped like a box. This is very rare and happens in less than 1% of congenital heart disease cases. The surgical repair varies depending on the severity of the disease. [ 112 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_280", "text": "Pediatric cardiology is a sub-specialty of  pediatrics . To become a pediatric cardiologist in the U.S., one must complete a three-year residency in pediatrics, followed by a three-year fellowship in pediatric cardiology. Per  doximity , pediatric cardiologists make an average of $303,917 in the U.S. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_281", "text": "Diagnostic tests in cardiology  are the methods of identifying heart conditions associated with healthy vs. unhealthy,  pathologic  heart function. The starting point is obtaining a  medical history , followed by  Auscultation . Then  blood tests ,  electrophysiological procedures , and  cardiac imaging  can be ordered for further analysis. Electrophysiological procedures include electrocardiogram,  cardiac monitoring ,  cardiac stress testing , and the  electrophysiology study . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_282", "text": "Cardiology is known for  randomized controlled trials  that guide clinical treatment of cardiac diseases. While dozens are published every year, there are landmark trials that shift treatment significantly. Trials often have an acronym of the trial name, and this acronym is used to reference the trial and its results. Some of these landmark trials include:"}
{"_id": "WikiPedia_Cardio$$$corpus_283", "text": "Cardiophysics  is an  interdisciplinary   science  that stands at the junction of  cardiology  and  medical physics , with researchers using the methods of, and theories from,  physics  to study  cardiovascular system  at different levels of its organisation, from the molecular scale to whole organisms. Being formed historically as part of  systems biology ,  cardiophysics  designed to reveal connections between the physical mechanisms, underlying the organization of the cardiovascular system, and biological features of its functioning."}
{"_id": "WikiPedia_Cardio$$$corpus_284", "text": "Zbigniew R. Struzik seems to be a first author who used the term in a scientific publication in 2004."}
{"_id": "WikiPedia_Cardio$$$corpus_285", "text": "One can use interchangeably also the terms  cardiovascular physics ."}
{"_id": "WikiPedia_Cardio$$$corpus_286", "text": "The following  outline  is provided as an overview of and topical guide to  cardiology , the branch of medicine dealing with disorders of the human heart. [ 1 ]  The field includes medical diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular heart disease and electrophysiology. Physicians who specialize in cardiology are called cardiologists."}
{"_id": "WikiPedia_Cardio$$$corpus_287", "text": "Cardiology can be described as all of the following:"}
{"_id": "WikiPedia_Cardio$$$corpus_288", "text": "Heart  \u2013"}
{"_id": "WikiPedia_Cardio$$$corpus_289", "text": "The cardiac  physical exam  focuses on portions of the physical exam that elucidate information about diseases and disorders outlined below.\nClinical judgment, of course, should guide the physical exam but the following are pertinent things related to a general / broad cardiac exam."}
{"_id": "WikiPedia_Cardio$$$corpus_290", "text": "Coronary artery disease  is not currently reversible and eventually requires surgical management if it progresses."}
{"_id": "WikiPedia_Cardio$$$corpus_291", "text": "Various  cardiology diagnostic tests and procedures ."}
{"_id": "WikiPedia_Cardio$$$corpus_292", "text": "There are several classes of  pharmaceutical drugs  used in cardiology to manage various diseases and many of them have cardiovascular side effects."}
{"_id": "WikiPedia_Cardio$$$corpus_293", "text": "Drugs that manipulate the cardiovascular system do so through several ways.\nThe first is  ion channels , which are often manipulated to manage  arrhythmias .\nThe second is  receptors  of various types.\nThe third is manipulation of  enzymes ."}
{"_id": "WikiPedia_Cardio$$$corpus_294", "text": "Ion channels are responsible for  cell membrane  voltage, depolarization, and repolarization.\nThese actions lead to conduction of signals down nerves and contraction of cardiomyocytes.\nPerhaps the most prominent manipulation of ion channels is through  antiarrhythmic agents .\nThese agents are commonly classified by the type of ion they manipulate and named the  Vaughan Williams classification :"}
{"_id": "WikiPedia_Cardio$$$corpus_295", "text": "Specifically, types I, III, & IV manipulate ion channels while the others are not."}
{"_id": "WikiPedia_Cardio$$$corpus_296", "text": "The  adrenergic receptor  is a set of receptors that are commonly manipulated.\nFour properties of the heart \u2014  chronotropy ,  dromotropy ,  inotropy , &  lusitropy  \u2014 are manipulated by adrenergic receptors.\nFor example, the  \u03b21 receptor  increases all four of these properties: chronotropy at the  SA node , dromotropy through the  AV node , inotropy of the cardiomyocytes through increased calcium, and lusitropy through phosphorylation of  phospholamban .  Catecholamines  are a set of drugs and hormones that manipulate the adrenergic receptors. The natural catecholamines are  norepinephrine ,  epinephrine , and  dopamine . There are numerous other drugs (e.g.,  dobutamine ,  ephedrine ,  isoproterenol ) that manipulate the adrenergic receptors and have variable specificity for the receptors and are, thus, used for various reasons."}
{"_id": "WikiPedia_Cardio$$$corpus_297", "text": "Angiotensin II receptor antagonists  (ARBs) block the  angiotensin II receptors  that are linked to hypertension and heart failure, mainly through vasodilation & heart remodeling inhibition."}
{"_id": "WikiPedia_Cardio$$$corpus_298", "text": "ACE inhibitors  works upstream from angiotensin II receptor antagonists and have similar effects on management of hypertension and heart failure."}
{"_id": "WikiPedia_Cardio$$$corpus_299", "text": "Sodium nitroprusside  and  nitroglycerin  function by causing vasodilation through  nitric oxide , which manipulates  cGMP  levels through  guanylate cyclase ."}
{"_id": "WikiPedia_Cardio$$$corpus_300", "text": "COX inhibitors  (namely  aspirin ),  warfarin ,  direct Xa inhibitors ,  direct thrombin inhibitors ,  heparin ,  low-molecular weight heparins , antibodies (e.g.,  abciximab ), and a few others are used for  anticoagulation therapy .\nThis is important in those predisposed to blood clots (e.g.,  Factor V Leiden ) but also for thrombus formation when an  atherosclerotic  plaque rupture that would, otherwise, lead to  myocardial infarction ."}
{"_id": "WikiPedia_Cardio$$$corpus_301", "text": "Numerous drug classes have well-known cardiovascular side effects."}
{"_id": "WikiPedia_Cardio$$$corpus_302", "text": "This is a  list of  cardiology   mnemonics , categorized and alphabetized. For mnemonics in other medical specialities, see this  list of medical mnemonics ."}
{"_id": "WikiPedia_Cardio$$$corpus_303", "text": "CREAM :"}
{"_id": "WikiPedia_Cardio$$$corpus_304", "text": "C ongenital"}
{"_id": "WikiPedia_Cardio$$$corpus_305", "text": "R heumatic damage"}
{"_id": "WikiPedia_Cardio$$$corpus_306", "text": "E ndocarditis"}
{"_id": "WikiPedia_Cardio$$$corpus_307", "text": "A ortic dissection/  A ortic root dilatation"}
{"_id": "WikiPedia_Cardio$$$corpus_308", "text": "M arfan\u2019s"}
{"_id": "WikiPedia_Cardio$$$corpus_309", "text": "SAD : [ 1 ] p.\u00a029"}
{"_id": "WikiPedia_Cardio$$$corpus_310", "text": "S yncope"}
{"_id": "WikiPedia_Cardio$$$corpus_311", "text": "A ngina"}
{"_id": "WikiPedia_Cardio$$$corpus_312", "text": "D yspnoea"}
{"_id": "WikiPedia_Cardio$$$corpus_313", "text": "ABC'S [ 1 ] p.\u00a01"}
{"_id": "WikiPedia_Cardio$$$corpus_314", "text": "A ortic arch gives rise to:"}
{"_id": "WikiPedia_Cardio$$$corpus_315", "text": "B rachiocephalic trunk"}
{"_id": "WikiPedia_Cardio$$$corpus_316", "text": "Left  C ommon  C arotid"}
{"_id": "WikiPedia_Cardio$$$corpus_317", "text": "Left  S ubclavian"}
{"_id": "WikiPedia_Cardio$$$corpus_318", "text": "T oilet  P aper  M y  A ss, or  T hey  P ay  M e  A lcohol, or \"T\"hugs \"P\"ush \"Me\" \"A\"round.  [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_319", "text": "T ricuspid valve"}
{"_id": "WikiPedia_Cardio$$$corpus_320", "text": "P ulmonary semilunar valve"}
{"_id": "WikiPedia_Cardio$$$corpus_321", "text": "M itral (bicuspid) valve"}
{"_id": "WikiPedia_Cardio$$$corpus_322", "text": "A ortic semilunar valve"}
{"_id": "WikiPedia_Cardio$$$corpus_323", "text": "HILT : [ 1 ] p.\u00a029"}
{"_id": "WikiPedia_Cardio$$$corpus_324", "text": "H eaving"}
{"_id": "WikiPedia_Cardio$$$corpus_325", "text": "I mpalpable"}
{"_id": "WikiPedia_Cardio$$$corpus_326", "text": "L aterally displaced"}
{"_id": "WikiPedia_Cardio$$$corpus_327", "text": "T hrusting/  T apping"}
{"_id": "WikiPedia_Cardio$$$corpus_328", "text": "If it's impalpable, causes are  COPD : [ 1 ] p.\u00a029"}
{"_id": "WikiPedia_Cardio$$$corpus_329", "text": "C OPD"}
{"_id": "WikiPedia_Cardio$$$corpus_330", "text": "O besity"}
{"_id": "WikiPedia_Cardio$$$corpus_331", "text": "P leural,  P ericardial effusion"}
{"_id": "WikiPedia_Cardio$$$corpus_332", "text": "D extrocardia"}
{"_id": "WikiPedia_Cardio$$$corpus_333", "text": "A nticoagulants: To prevent embolization."}
{"_id": "WikiPedia_Cardio$$$corpus_334", "text": "B eta blockers: To block the effects of certain hormones on the heart to slow the heart rate."}
{"_id": "WikiPedia_Cardio$$$corpus_335", "text": "C alcium Channel Blockers: Help slow the heart rate by blocking the number of electrical impulses that pass through the AV node into the lower heart chambers (ventricles)."}
{"_id": "WikiPedia_Cardio$$$corpus_336", "text": "D igoxin: Helps slow the heart rate by blocking the number of electrical impulses that pass through the AV node into the lower heart chambers (ventricles)."}
{"_id": "WikiPedia_Cardio$$$corpus_337", "text": "E lectrocardioversion: A procedure in which electric currents are used to reset the heart's rhythm back to regular pattern. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_338", "text": "Pirates : [ 1 ] p.\u00a03"}
{"_id": "WikiPedia_Cardio$$$corpus_339", "text": "P ulmonary: PE, COPD"}
{"_id": "WikiPedia_Cardio$$$corpus_340", "text": "I atrogenic"}
{"_id": "WikiPedia_Cardio$$$corpus_341", "text": "R heumatic heart: mitral regurgitation"}
{"_id": "WikiPedia_Cardio$$$corpus_342", "text": "A therosclerotic: MI, CAD"}
{"_id": "WikiPedia_Cardio$$$corpus_343", "text": "T hyroid: hyperthyroid"}
{"_id": "WikiPedia_Cardio$$$corpus_344", "text": "S ick sinus syndrome"}
{"_id": "WikiPedia_Cardio$$$corpus_345", "text": "ABCD : [ 1 ] p.\u00a030"}
{"_id": "WikiPedia_Cardio$$$corpus_346", "text": "A nti-coagulate"}
{"_id": "WikiPedia_Cardio$$$corpus_347", "text": "B eta-block to control rate"}
{"_id": "WikiPedia_Cardio$$$corpus_348", "text": "C ardiovert"}
{"_id": "WikiPedia_Cardio$$$corpus_349", "text": "D igoxin"}
{"_id": "WikiPedia_Cardio$$$corpus_350", "text": "3 D's: [ 1 ] p.\u00a030"}
{"_id": "WikiPedia_Cardio$$$corpus_351", "text": "D iminished heart sounds"}
{"_id": "WikiPedia_Cardio$$$corpus_352", "text": "D istended jugular veins"}
{"_id": "WikiPedia_Cardio$$$corpus_353", "text": "D ecreased arterial pressure"}
{"_id": "WikiPedia_Cardio$$$corpus_354", "text": "B etablockers  A cting  E xclusively  A t  M yocardium: [ 1 ] p.\u00a030"}
{"_id": "WikiPedia_Cardio$$$corpus_355", "text": "B etaxolol"}
{"_id": "WikiPedia_Cardio$$$corpus_356", "text": "A cebutelol"}
{"_id": "WikiPedia_Cardio$$$corpus_357", "text": "E smolol"}
{"_id": "WikiPedia_Cardio$$$corpus_358", "text": "A tenolol"}
{"_id": "WikiPedia_Cardio$$$corpus_359", "text": "M etoprolol"}
{"_id": "WikiPedia_Cardio$$$corpus_360", "text": "LMNOP"}
{"_id": "WikiPedia_Cardio$$$corpus_361", "text": "L asix"}
{"_id": "WikiPedia_Cardio$$$corpus_362", "text": "M orphine"}
{"_id": "WikiPedia_Cardio$$$corpus_363", "text": "N itrites"}
{"_id": "WikiPedia_Cardio$$$corpus_364", "text": "O xygen"}
{"_id": "WikiPedia_Cardio$$$corpus_365", "text": "Vasso P ressors [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_366", "text": "FAILURE [ 1 ] p.\u00a030"}
{"_id": "WikiPedia_Cardio$$$corpus_367", "text": "F orgot medication"}
{"_id": "WikiPedia_Cardio$$$corpus_368", "text": "A rrhythmia/  A naemia"}
{"_id": "WikiPedia_Cardio$$$corpus_369", "text": "I schemia/ Infarction/ Infection"}
{"_id": "WikiPedia_Cardio$$$corpus_370", "text": "L ifestyle: taken too much salt"}
{"_id": "WikiPedia_Cardio$$$corpus_371", "text": "U pregulation of CO: pregnancy, hyperthyroidism"}
{"_id": "WikiPedia_Cardio$$$corpus_372", "text": "R enal failure"}
{"_id": "WikiPedia_Cardio$$$corpus_373", "text": "E mbolism: pulmonary"}
{"_id": "WikiPedia_Cardio$$$corpus_374", "text": "Darth Vader"}
{"_id": "WikiPedia_Cardio$$$corpus_375", "text": "D eath"}
{"_id": "WikiPedia_Cardio$$$corpus_376", "text": "A rrhythmia"}
{"_id": "WikiPedia_Cardio$$$corpus_377", "text": "R upture(free ventricular wall/ ventricular septum/ papillary muscles)"}
{"_id": "WikiPedia_Cardio$$$corpus_378", "text": "T amponade"}
{"_id": "WikiPedia_Cardio$$$corpus_379", "text": "H eart failure (acute or chronic)"}
{"_id": "WikiPedia_Cardio$$$corpus_380", "text": "V alve disease"}
{"_id": "WikiPedia_Cardio$$$corpus_381", "text": "A neurysm of Ventricles"}
{"_id": "WikiPedia_Cardio$$$corpus_382", "text": "D ressler's Syndrome"}
{"_id": "WikiPedia_Cardio$$$corpus_383", "text": "thrombo E mbolism (mural thrombus)"}
{"_id": "WikiPedia_Cardio$$$corpus_384", "text": "R ecurrence/ mitral  R egurgitation [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_385", "text": "DUST : [ 1 ] p.\u00a031"}
{"_id": "WikiPedia_Cardio$$$corpus_386", "text": "D epressed ventricular function"}
{"_id": "WikiPedia_Cardio$$$corpus_387", "text": "U nstable angina"}
{"_id": "WikiPedia_Cardio$$$corpus_388", "text": "S tenosis of the left main stem"}
{"_id": "WikiPedia_Cardio$$$corpus_389", "text": "T riple vessel disease"}
{"_id": "WikiPedia_Cardio$$$corpus_390", "text": "W i LL ia M   M a RR o W : [ 1 ] p.\u00a031"}
{"_id": "WikiPedia_Cardio$$$corpus_391", "text": "W  pattern in V1-V2 and  M  pattern in V3-V6 is  L eft bundle block."}
{"_id": "WikiPedia_Cardio$$$corpus_392", "text": "M  pattern in V1-V2 and  W  in V3-V6 is  R ight bundle block."}
{"_id": "WikiPedia_Cardio$$$corpus_393", "text": "RAMP : [ 1 ] p.\u00a031"}
{"_id": "WikiPedia_Cardio$$$corpus_394", "text": "R ecent MI"}
{"_id": "WikiPedia_Cardio$$$corpus_395", "text": "A ortic stenosis"}
{"_id": "WikiPedia_Cardio$$$corpus_396", "text": "M I in the last 7 days"}
{"_id": "WikiPedia_Cardio$$$corpus_397", "text": "P ulmonary hypertension"}
{"_id": "WikiPedia_Cardio$$$corpus_398", "text": "FROM JANE :"}
{"_id": "WikiPedia_Cardio$$$corpus_399", "text": "F ever"}
{"_id": "WikiPedia_Cardio$$$corpus_400", "text": "R oth's spots"}
{"_id": "WikiPedia_Cardio$$$corpus_401", "text": "O sler's nodes"}
{"_id": "WikiPedia_Cardio$$$corpus_402", "text": "M urmur of heart"}
{"_id": "WikiPedia_Cardio$$$corpus_403", "text": "J aneway lesions"}
{"_id": "WikiPedia_Cardio$$$corpus_404", "text": "A nemia"}
{"_id": "WikiPedia_Cardio$$$corpus_405", "text": "E mboli"}
{"_id": "WikiPedia_Cardio$$$corpus_406", "text": "Try   Pul ing  My   Aorta : [ 1 ] p.\u00a03"}
{"_id": "WikiPedia_Cardio$$$corpus_407", "text": "Tri cuspid"}
{"_id": "WikiPedia_Cardio$$$corpus_408", "text": "Pul monary"}
{"_id": "WikiPedia_Cardio$$$corpus_409", "text": "Mi tral (bicuspid)"}
{"_id": "WikiPedia_Cardio$$$corpus_410", "text": "Aorta"}
{"_id": "WikiPedia_Cardio$$$corpus_411", "text": "If the  R  is far from  P ,\nthen you have a  First Degree ."}
{"_id": "WikiPedia_Cardio$$$corpus_412", "text": "Longer, longer, longer, drop!\nThen you have a  Wenkebach ."}
{"_id": "WikiPedia_Cardio$$$corpus_413", "text": "if some  P' s don't get through,\nthen you have  Mobitz II ."}
{"_id": "WikiPedia_Cardio$$$corpus_414", "text": "If  P' s and  Q' s don't agree, then you have a  Third Degree . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_415", "text": "INFARCTIONS [ 1 ] p.\u00a034"}
{"_id": "WikiPedia_Cardio$$$corpus_416", "text": "I V access"}
{"_id": "WikiPedia_Cardio$$$corpus_417", "text": "N arcotic analgesics (e.g. morphine, pethidine)"}
{"_id": "WikiPedia_Cardio$$$corpus_418", "text": "F acilities for defibrillation (DF)"}
{"_id": "WikiPedia_Cardio$$$corpus_419", "text": "A spirin/ Anticoagulant (heparin)"}
{"_id": "WikiPedia_Cardio$$$corpus_420", "text": "R est"}
{"_id": "WikiPedia_Cardio$$$corpus_421", "text": "C onverting enzyme inhibitor"}
{"_id": "WikiPedia_Cardio$$$corpus_422", "text": "T hrombolysis"}
{"_id": "WikiPedia_Cardio$$$corpus_423", "text": "I V beta blocker"}
{"_id": "WikiPedia_Cardio$$$corpus_424", "text": "O xygen 60%"}
{"_id": "WikiPedia_Cardio$$$corpus_425", "text": "N itrates"}
{"_id": "WikiPedia_Cardio$$$corpus_426", "text": "S tool Softeners"}
{"_id": "WikiPedia_Cardio$$$corpus_427", "text": "ASK ME [ 1 ] p.\u00a032"}
{"_id": "WikiPedia_Cardio$$$corpus_428", "text": "A trial contraction"}
{"_id": "WikiPedia_Cardio$$$corpus_429", "text": "S ystole (ventricular contraction)"}
{"_id": "WikiPedia_Cardio$$$corpus_430", "text": "K losure (closure) of tricuspid valve, so atrial filling"}
{"_id": "WikiPedia_Cardio$$$corpus_431", "text": "M aximal atrial filling"}
{"_id": "WikiPedia_Cardio$$$corpus_432", "text": "E mptying of atrium"}
{"_id": "WikiPedia_Cardio$$$corpus_433", "text": "BOOMAR : [ 1 ] p.\u00a032"}
{"_id": "WikiPedia_Cardio$$$corpus_434", "text": "B ed rest"}
{"_id": "WikiPedia_Cardio$$$corpus_435", "text": "O piate"}
{"_id": "WikiPedia_Cardio$$$corpus_436", "text": "M onitor"}
{"_id": "WikiPedia_Cardio$$$corpus_437", "text": "A nticoagulate"}
{"_id": "WikiPedia_Cardio$$$corpus_438", "text": "R educe clot size"}
{"_id": "WikiPedia_Cardio$$$corpus_439", "text": "PULSE : [ 1 ] p.\u00a032"}
{"_id": "WikiPedia_Cardio$$$corpus_440", "text": "P ersistent chest pains"}
{"_id": "WikiPedia_Cardio$$$corpus_441", "text": "U pset stomach"}
{"_id": "WikiPedia_Cardio$$$corpus_442", "text": "L ightheadedness"}
{"_id": "WikiPedia_Cardio$$$corpus_443", "text": "S hortness of breath"}
{"_id": "WikiPedia_Cardio$$$corpus_444", "text": "E xcessive sweating"}
{"_id": "WikiPedia_Cardio$$$corpus_445", "text": "O BATMAN! [ 1 ] p.\u00a032"}
{"_id": "WikiPedia_Cardio$$$corpus_446", "text": "B eta blocker"}
{"_id": "WikiPedia_Cardio$$$corpus_447", "text": "A SA"}
{"_id": "WikiPedia_Cardio$$$corpus_448", "text": "T hrombolytics (e.g. heparin)"}
{"_id": "WikiPedia_Cardio$$$corpus_449", "text": "A ce prn"}
{"_id": "WikiPedia_Cardio$$$corpus_450", "text": "N itroglycerin"}
{"_id": "WikiPedia_Cardio$$$corpus_451", "text": "COAG : [ 1 ] p.\u00a032"}
{"_id": "WikiPedia_Cardio$$$corpus_452", "text": "C yclomorph"}
{"_id": "WikiPedia_Cardio$$$corpus_453", "text": "A spirin"}
{"_id": "WikiPedia_Cardio$$$corpus_454", "text": "G lycerol trinitrate"}
{"_id": "WikiPedia_Cardio$$$corpus_455", "text": "\"IL PQRST\"  (person has ill PQRST heart waves): [ 1 ] p.\u00a032"}
{"_id": "WikiPedia_Cardio$$$corpus_456", "text": "I ntensity"}
{"_id": "WikiPedia_Cardio$$$corpus_457", "text": "L occasion"}
{"_id": "WikiPedia_Cardio$$$corpus_458", "text": "P itch"}
{"_id": "WikiPedia_Cardio$$$corpus_459", "text": "Q uality"}
{"_id": "WikiPedia_Cardio$$$corpus_460", "text": "R adiation"}
{"_id": "WikiPedia_Cardio$$$corpus_461", "text": "S hape"}
{"_id": "WikiPedia_Cardio$$$corpus_462", "text": "T iming"}
{"_id": "WikiPedia_Cardio$$$corpus_463", "text": "8 S's : [ 1 ] p.\u00a032"}
{"_id": "WikiPedia_Cardio$$$corpus_464", "text": "S oft"}
{"_id": "WikiPedia_Cardio$$$corpus_465", "text": "S ystolic"}
{"_id": "WikiPedia_Cardio$$$corpus_466", "text": "S hort"}
{"_id": "WikiPedia_Cardio$$$corpus_467", "text": "S ounds (S1 & S2) normal"}
{"_id": "WikiPedia_Cardio$$$corpus_468", "text": "S ymptomless"}
{"_id": "WikiPedia_Cardio$$$corpus_469", "text": "S pecial tests normal (X-ray, EKG)"}
{"_id": "WikiPedia_Cardio$$$corpus_470", "text": "S tanding/  S itting (vary with position)"}
{"_id": "WikiPedia_Cardio$$$corpus_471", "text": "S ternal depression"}
{"_id": "WikiPedia_Cardio$$$corpus_472", "text": "L E ft sided murmurs louder with  E xpiration"}
{"_id": "WikiPedia_Cardio$$$corpus_473", "text": "R I ght sided murmurs louder with  I nspiration. [ 1 ] p.\u00a032"}
{"_id": "WikiPedia_Cardio$$$corpus_474", "text": "SCRIPT : [ 1 ] p.\u00a032"}
{"_id": "WikiPedia_Cardio$$$corpus_475", "text": "S ite"}
{"_id": "WikiPedia_Cardio$$$corpus_476", "text": "C haracter (e.g. harsh, soft, blowing)"}
{"_id": "WikiPedia_Cardio$$$corpus_477", "text": "PASS : P ulmonic &  A ortic"}
{"_id": "WikiPedia_Cardio$$$corpus_478", "text": "S tenosis= S ystolic."}
{"_id": "WikiPedia_Cardio$$$corpus_479", "text": "PAID :  P ulmonic &  A ortic"}
{"_id": "WikiPedia_Cardio$$$corpus_480", "text": "I nsufficiency= D iastolic. [ 1 ] p.\u00a032"}
{"_id": "WikiPedia_Cardio$$$corpus_481", "text": "CARDIAC RIND : [ 1 ] p.\u00a034"}
{"_id": "WikiPedia_Cardio$$$corpus_482", "text": "C ollagen vascular disease"}
{"_id": "WikiPedia_Cardio$$$corpus_483", "text": "A ortic aneurysm"}
{"_id": "WikiPedia_Cardio$$$corpus_484", "text": "D rugs (such as hydralazine)"}
{"_id": "WikiPedia_Cardio$$$corpus_485", "text": "I nfections"}
{"_id": "WikiPedia_Cardio$$$corpus_486", "text": "A cute renal failure"}
{"_id": "WikiPedia_Cardio$$$corpus_487", "text": "C ardiac infarction"}
{"_id": "WikiPedia_Cardio$$$corpus_488", "text": "R heumatic fever"}
{"_id": "WikiPedia_Cardio$$$corpus_489", "text": "I njury"}
{"_id": "WikiPedia_Cardio$$$corpus_490", "text": "N eoplasms"}
{"_id": "WikiPedia_Cardio$$$corpus_491", "text": "D ressler's syndrome"}
{"_id": "WikiPedia_Cardio$$$corpus_492", "text": "P ericarditi S : [ 1 ] p.\u00a034"}
{"_id": "WikiPedia_Cardio$$$corpus_493", "text": "P R depression in  p recordial leads."}
{"_id": "WikiPedia_Cardio$$$corpus_494", "text": "S T elevation."}
{"_id": "WikiPedia_Cardio$$$corpus_495", "text": "SICVD : [ 1 ] p.\u00a034"}
{"_id": "WikiPedia_Cardio$$$corpus_496", "text": "S ymmetry of leg musculature"}
{"_id": "WikiPedia_Cardio$$$corpus_497", "text": "I ntegrity of skin"}
{"_id": "WikiPedia_Cardio$$$corpus_498", "text": "C olor of toenails"}
{"_id": "WikiPedia_Cardio$$$corpus_499", "text": "V aricose veins"}
{"_id": "WikiPedia_Cardio$$$corpus_500", "text": "D istribution of hair"}
{"_id": "WikiPedia_Cardio$$$corpus_501", "text": "PATCH MED : [ 1 ] p.\u00a034"}
{"_id": "WikiPedia_Cardio$$$corpus_502", "text": "P ulmonary embolus"}
{"_id": "WikiPedia_Cardio$$$corpus_503", "text": "A cidosis"}
{"_id": "WikiPedia_Cardio$$$corpus_504", "text": "T ension pneumothorax"}
{"_id": "WikiPedia_Cardio$$$corpus_505", "text": "C ardiac tamponade"}
{"_id": "WikiPedia_Cardio$$$corpus_506", "text": "H ypokalemia/  H yperkalemia/  H ypoxia/  H ypothermia/  H ypovolemia"}
{"_id": "WikiPedia_Cardio$$$corpus_507", "text": "M yocardial infarction"}
{"_id": "WikiPedia_Cardio$$$corpus_508", "text": "E lectrolyte derangements"}
{"_id": "WikiPedia_Cardio$$$corpus_509", "text": "D rugs"}
{"_id": "WikiPedia_Cardio$$$corpus_510", "text": "ELEVATION: [ 1 ] p.\u00a034"}
{"_id": "WikiPedia_Cardio$$$corpus_511", "text": "E lectrolytes"}
{"_id": "WikiPedia_Cardio$$$corpus_512", "text": "L BBB"}
{"_id": "WikiPedia_Cardio$$$corpus_513", "text": "E arly repolarization"}
{"_id": "WikiPedia_Cardio$$$corpus_514", "text": "V entricular hypertrophy"}
{"_id": "WikiPedia_Cardio$$$corpus_515", "text": "A neurysm"}
{"_id": "WikiPedia_Cardio$$$corpus_516", "text": "T reatment (e.g. pericardiocentesis)"}
{"_id": "WikiPedia_Cardio$$$corpus_517", "text": "I njury (AMI, contusion)"}
{"_id": "WikiPedia_Cardio$$$corpus_518", "text": "O sborne waves (hypothermia)"}
{"_id": "WikiPedia_Cardio$$$corpus_519", "text": "N on-occlusive vasospasm"}
{"_id": "WikiPedia_Cardio$$$corpus_520", "text": "ABCDE: [ 1 ] p.\u00a035"}
{"_id": "WikiPedia_Cardio$$$corpus_521", "text": "A denosine"}
{"_id": "WikiPedia_Cardio$$$corpus_522", "text": "B eta-blocker"}
{"_id": "WikiPedia_Cardio$$$corpus_523", "text": "C alcium channel antagonist"}
{"_id": "WikiPedia_Cardio$$$corpus_524", "text": "E xcitation (vagal stimulation)"}
{"_id": "WikiPedia_Cardio$$$corpus_525", "text": "LAMB: [ 1 ] p.\u00a035"}
{"_id": "WikiPedia_Cardio$$$corpus_526", "text": "L idocaine"}
{"_id": "WikiPedia_Cardio$$$corpus_527", "text": "A miodarone"}
{"_id": "WikiPedia_Cardio$$$corpus_528", "text": "M exiltene/ Magnesium"}
{"_id": "WikiPedia_Cardio$$$corpus_529", "text": "N ever  l et  m onkeys  e at  b ananas:"}
{"_id": "WikiPedia_Cardio$$$corpus_530", "text": "N eutrophils"}
{"_id": "WikiPedia_Cardio$$$corpus_531", "text": "l ymphocytes"}
{"_id": "WikiPedia_Cardio$$$corpus_532", "text": "m onocytes"}
{"_id": "WikiPedia_Cardio$$$corpus_533", "text": "e osinophils"}
{"_id": "WikiPedia_Cardio$$$corpus_534", "text": "b asophils [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_535", "text": "The  abdominojugular test , also known as  abdominojugular reflux  ( AJR ), is a physical examination test useful in diagnosing  right ventricle  dysfunction, particularly  right ventricular failure . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_536", "text": "AJR is a test for measuring  jugular venous pressure  (JVP) through the  distention  of the  internal jugular vein . A positive AJR test correlates with the  pulmonary artery pressure  and thus is a marker for right heart dysfunction, [ 2 ]  specifically  right ventricular failure . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_537", "text": "Reflux  in this context means backup of the circulatory system and is not to be confused with  reflex . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_538", "text": "The clinician presses firmly over either the  right upper quadrant  of the abdomen (i.e., over the  liver ) or over the center of the abdomen  [ 2 ]  for 10 seconds with a pressure of 20 to 35\u00a0mm Hg while observing the swelling of the  internal jugular vein  in the  neck  and also observing to be sure the patient does not perform a  Valsalva maneuver . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_539", "text": "On an otherwise healthy individual, the jugular venous pressure remains constant or temporarily rises for a  heartbeat  or two, before returning to normal. This  negative result  would be indicated by a lack of swelling of the jugular vein. Negative abdominojugular reflux is seen in  Budd-Chiari syndrome ."}
{"_id": "WikiPedia_Cardio$$$corpus_540", "text": "A  positive result  is variously defined as either a sustained rise in the JVP of at least 3\u00a0cm or more  [ 4 ]  or a fall of 4\u00a0cm or more  [ 2 ]  after the examiner releases pressure. The AJR has a reported  sensitivity  of 24%  [ 5 ]  to 72%  [ 2 ]  and a  specificity  of 93% to 96%. The large discrepancy in sensitivity may be explained by the higher value being reported during performance in optimal conditions of a cardiac lab while the lower value was from a study in an emergency department."}
{"_id": "WikiPedia_Cardio$$$corpus_541", "text": "AbioCor   was a total  artificial heart  (TAH) developed by the  Massachusetts -based company  AbioMed . It was fully implantable within a patient, due to a combination of advances in miniaturization, biosensors,  plastics  and energy transfer. The AbioCor ran on a  rechargeable source of power . The internal battery was charged by a  transcutaneous energy transmission  (TET) system, meaning that no wires or tubes penetrated the skin, reducing the risk of infection. However, because of its size, this heart was only compatible with men who had a large frame. It had a product life expectancy of 18 months. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_542", "text": "AbioCor was surgically introduced into 15 total patients, 14 of them during a clinical trial and one after FDA approval. However, due to insufficient evidence of its efficacy, AbioMed abandoned further development of the product. [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_543", "text": "AbioMed was founded by Param Singh and  David Lederman . The company began development of the AbioCor device in the 1990s, beginning animal studies in 1998 in preparation to demonstrate readiness for formal clinical trials in humans. [ 5 ]  On January 30, 2001, the FDA granted AbioMed an investigational device exemption (IDE) for implantation into humans via a clinical trial. [ 9 ]  This opened the door for the first implantation of the AbioCor into  Robert Tools  on July 2, 2001. He lived for 151 days before having a fatal  cerebrovascular accident . [ 3 ] [ 10 ] [ 11 ]   Time  magazine awarded the AbioCor its Invention of the Year award in late 2001. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_544", "text": "The second patient, Tom Christerson, who was given less than a 20 percent chance of surviving 30 days at the time of his surgery, lived for 512 days after receiving the AbioCor, dying on February 7, 2003, due to the wearing out of an internal membrane of the AbioCor. [ 12 ]  An additional 12 patients had the device implanted into 2004, resulting in an average life span of less than five months among all 14 patients. In some cases the device extended survival by several months, allowing the patients to spend valuable time with family and friends. In two cases, the device extended survival by 10 and 17 months respectively, and one patient was discharged from the hospital to go home. For a patient to be eligible for implantation with the AbioCor, the person must have had severe  heart failure  (with failure of both  ventricles ) and had to be likely to die within two weeks without  transplantation . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_545", "text": "Though the device was initially rejected by FDA Circulatory System Devices Panel in 2005 for  Humanitarian Device Exemption  (HDE) status, [ 1 ]  it was eventually approved by the  Food and Drug Administration  on September 5, 2006, for HDE status. [ 13 ]  However, only one patient received the AbioCor after approval, a \"76-year-old man with congestive heart failure, who did not qualify for a heart transplant.\" [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_546", "text": "In August 2012, key AbioCor researcher and developer David Lederman died from pancreatic cancer. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_547", "text": "The company also had plans to improve the AbioCor with a second version based upon the AbioCor ventricles and the  Penn State  energy converter. It was expected to last for five years, more than triple the life expectancy of AbioCor. The company stated it would be 30 percent smaller than the original model, and it could be implanted in smaller men and women. Additional modifications were planned to reduce the patient's risk of stroke, which was a concern of the FDA. [ 10 ] [ 16 ]  As of March 2016 [update] , AbioCor II has not come to fruition, however. Additionally, the AbioCor product has been removed from the AbioMed website, with several news agencies reporting in 2015 that the company had quietly abandoned further development of the device. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_548", "text": "In 2019, Abiomed was marketing the  Impella  Ventricular Support Systems, left-side heart pump models \"intended to help pump blood in patients who need short-term support (up to 6 days)\". [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_549", "text": "The AbioCor heart is featured in the 2009 film  Crank: High Voltage , when it is transplanted into the main character  Chev Chelios 's ( Jason Statham ) chest after he had been abducted by Chinese mobsters in the very beginning of the movie. However, the heart depicted in the film has a much lower battery life but gives Chev  superhuman  athleticism when fully charged (for dramatic purposes). [ 18 ]  The model of the heart in the movie is called AviCor."}
{"_id": "WikiPedia_Cardio$$$corpus_550", "text": "Accelerated idioventricular rhythm  is a ventricular rhythm with a rate of between 40 and 120 beats per minute. Idioventricular means \u201crelating to or affecting the cardiac ventricle alone\u201d and refers to any ectopic ventricular arrhythmia. [ 1 ]   Accelerated idioventricular arrhythmias are distinguished from ventricular rhythms with rates less than 40 ( ventricular escape ) and those faster than 120 ( ventricular tachycardia ). [ 2 ]  Though some other references limit to between 60 and 100 beats per minute. [ 3 ]   It is also referred to as AIVR and \"slow ventricular tachycardia.\""}
{"_id": "WikiPedia_Cardio$$$corpus_551", "text": "It can be present at birth, [ 4 ]  however, it is more commonly associated with  reperfusion after myocardial injury . [ 2 ]  AIVR is generally considered to be a benign abnormal heart rhythm. It is typically temporary and does not require treatment."}
{"_id": "WikiPedia_Cardio$$$corpus_552", "text": "The  accelerated idioventricular rhythm  occurs when depolarization rate of a normally suppressed focus increases to above that of the \"higher order\" focuses (the sinoatrial node and the  atrioventricular node ). This most commonly occurs in the setting of a  sinus bradycardia . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_553", "text": "Accelerated idioventricular rhythm is the most common reperfusion arrhythmia in humans. However, ventricular tachycardia and ventricular fibrillation remain the most important causes of sudden death following spontaneous restoration of antegrade flow. [ 6 ]  Prior to the modern practice of  percutaneous coronary intervention  for  acute coronary syndrome , pharmacologic  thrombolysis  was more common and accelerated idioventricular rhythms were used as a sign of successful reperfusion. [ 7 ]  It is considered a benign arrhythmia especially in the setting of STEMI(where it is conventionally thought to be an indicator of reperfusion) that does not require intervention, though atrioventricular dyssynchrony can cause hemodynamic instability, which can be treated through overdrive pacing or  atropine . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_554", "text": "AIVR appears similar to  ventricular tachycardia  with wide QRS complexes (QRS >0.12s) and a regular rhythm. It can most easily be distinguished from VT in that the rate is less than 120 and usually less than 100 bpm. There may or may not be AV dissociation depending on whether it is due to ventricular escape or AV block. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_555", "text": "There is an established practice of using the  electrical conductance  of blood ( PV loops ) in heart  ventricles  to determine the instantaneous volume of the ventricle. This technique involves inserting a tetra-polar catheter into the ventricle and measuring conductance. This measured conductance is a combination of blood and muscle and various techniques are used to identify the blood conductance from the total measured conductance. Blood conductance can then be converted to volume using a linear (Baan) or a non-linear (Wei) relationship that relates conductance to volume."}
{"_id": "WikiPedia_Cardio$$$corpus_556", "text": "This approach is based on the idea that the total conductance, G, of a fluid between two electrodes is a function of the fluid's conductivity (reciprocal of resistivity) and volume. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_557", "text": "In  cardiology , a tetra-polar  catheter  is inserted into the ventricle and a constant current (I) is applied across the two outer  electrodes . This generates an electrical field within the ventricle and the two inner electrodes measure a  voltage  generated due to the electric field. This measured voltage (V) is used to determine conductance through a modified version of  Ohm's Law . Conductance (G) is the reciprocal of resistance (R) which changes the standard Ohm's equation from V=IR to V=I/G. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_558", "text": "Conductance is then related to blood volume though Baan's equation. [ 1 ]  When used in cardiology, the electric field generated is not limited to the blood (the fluid of interest) but also penetrates the heart wall, giving rise to additional conductance often called \"parallel conductance\" or \"muscle conductance\", G m  which must be removed. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_559", "text": "Various techniques have been attempted to remove the G m  contribution with varying degrees of success. The most common method is the  hypertonic saline  technique which involves injecting a bolus of hypertonic saline into the ventricle to alter blood conductivity without affecting the surrounding muscle. Another less commonly used technique involves evacuating the ventricle of blood and measuring muscle conductance alone with a conductance catheter. Clearly both techniques are unreliable, somewhat invasive and fail to account for the continuous variation in G m  over the  cardiac cycle . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_560", "text": "The  Admittance  technique is an improvement over the  Conductance  technique for the real-time removal of muscle conductance G m . Blood and muscle respond to alternating (AC) electrical currents very differently. Blood is purely resistive while muscle has both resistive and capacitive properties. The fixed charges in muscle cells create a significant  reactance  that causes a phase shift (time delay) in the measured signal, relative to the excitation signal. Admittance technology uses this phase shift to determine the instantaneous muscle conductance and remove it from the total measured conductance. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_561", "text": "The total Admittance (Y), of the blood filled ventricle is given by Y = G b  + G m  + i\u03c9C m  where: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_562", "text": "The signals G m  and C m  are both properties of cardiac muscle and vary in a fixed ratio. Thus the ratio of G m  to C m  is equal to the ratio of muscle conductivity (\u03c3) to muscle  permittivity  (\u03b5). The ratio \u03c3/\u03b5 is the constant of proportionality. Although both \u03c3 and \u03b5 are functions of the health of the heart tissue, they are relatively constant for short periods of time. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_563", "text": "Using this proportionality, one can rewrite the equation for G m  as G m  = (\u03c3/\u03b5)C m"}
{"_id": "WikiPedia_Cardio$$$corpus_564", "text": "Note that the imaginary component of Y depends only on the amount of muscle in the field of the catheter. This makes it easy to isolate by measuring the phase shift, \u03c6, of the measured signal: [ citation needed ] \ncos(\u03c6) = (G b  + G m )/Y \nsin(\u03c6) = \u03c9C m /Y \nHence, C m  = Y.sin(\u03c6)/\u03c9 \nalso, G m  = (\u03c3/\u03b5)C m"}
{"_id": "WikiPedia_Cardio$$$corpus_565", "text": "Thus, blood conductance is determined as G b  = Y.cos(\u03c6) - G m"}
{"_id": "WikiPedia_Cardio$$$corpus_566", "text": "Wei's equations can be applied to this calculated blood conductance G b  to obtain blood volume. [ 3 ]  Unlike Baan's equation, Wei's equation takes into account the non-linear nature of the  electrical field  and the dynamic nature of the  cardiac cycle  to give a more accurate representation of the blood volume. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_567", "text": "Admittance technique involves the measurement of both phase angle and total conductance in the ventricle. Thus, it is possible to  observe how the parallel conductance (muscle conductance) varies throughout the cardiac cycle. A plot showing both the blood and muscle contribution are shown in the figure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_568", "text": "Advanced cardiac life support ,   advanced cardiovascular life support  ( ACLS ) refers to a set of clinical guidelines established by the American Heart Association (AHA) for the urgent and emergent treatment of life-threatening cardiovascular conditions that will cause or have caused  cardiac arrest , using advanced medical procedures, medications, and techniques. ACLS expands on  Basic Life Support  (BLS) by adding recommendations on additional medication and advanced procedure use to the CPR guidelines that are fundamental and efficacious in BLS. ACLS is practiced by advanced medical providers including physicians, some nurses and paramedics; [ 1 ]  these providers are usually required to hold certifications in ACLS care."}
{"_id": "WikiPedia_Cardio$$$corpus_569", "text": "While \"ACLS\" is almost always semantically interchangeable with the term \" Advanced Life Support \" (ALS), when used distinctly, ACLS tends to refer to the immediate cardiac care, while ALS tends to refer to more specialized resuscitation care such as  ECMO  and  PCI . In the EMS community, \"ALS\" may refer to the advanced care provided by  paramedics  while \"BLS\" may refer to the fundamental care provided by  EMTs  and  EMRs ; without these terms referring to cardiovascular-specific care."}
{"_id": "WikiPedia_Cardio$$$corpus_570", "text": "Advanced cardiac life support refers to a set of guidelines used by medical providers to treat life-threatening cardiovascular conditions. These life-threatening conditions range from dangerous arrhythmias to cardiac arrest. ACLS algorithms frequently address at least five different aspects of peri-cardiac arrest care: Airway management, ventilation, CPR compressions (continued from BLS), defibrillation, and medications. Due to the seriousness of the diseases treated, the paucity of data known about most ACLS patients, and the need for multiple, rapid, simultaneous treatments, ACLS is executed as a standardized, algorithmic set of treatments. Successful ACLS treatment starts with diagnosis of the correct  EKG  rhythm causing the arrest. Common cardiac arrest rhythms covered by ACLS guidelines include:  ventricular tachycardia ,  ventricular fibrillation ,  Pulseless Electrical Activity , and  asystole . Dangerous, non-arrest rhythms typically covered includes:  narrow - and wide-complex  tachycardias ,  torsades de pointe ,  atrial fibrillation / flutter  with rapid ventricular response, and  bradycardia . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_571", "text": "Successful ACLS treatment generally requires a team of trained individuals. Common team roles include: Leader, back-up leader, 2 CPR performers, an airway/respiratory specialist, an IV access and medication administration specialist, a monitor/ defibrillator attendant, a pharmacist, a lab member to send samples, and a recorder to document the treatment. [ 3 ]  For in-hospital events, these members are frequently physicians, mid-level providers, nurses and allied health providers; while for out-of-hospital events, these teams are usually composed of a small number of EMTs and paramedics."}
{"_id": "WikiPedia_Cardio$$$corpus_572", "text": "ACLS algorithms include multiple, simultaneous treatment recommendations.  Some ACLS providers may be required to strictly adhere to these guidelines, however physicians may generally deviate to pursue different evidence-based treatment, especially if they are addressing an underlying cause of the arrest and/or unique aspects of a patient's care. ACLS algorithms are complex but the table, below, demonstrates common aspects of ACLS care. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_573", "text": "Due to the rapidity and complexity of ACLS care, as well as the recommendation that it be performed in a standardized fashion, providers must usually hold certifications in ACLS care. Certifications may be provided by a few different, generally national, organizations but their legitimacy is ultimately determined by hospital hiring and privileging boards; that is, ACLS certification is frequently a requirement for employment as a health care provider at most hospitals. [ 4 ]   ACLS certifications usually provide education on the aforementioned aspects of ACLS care  except  for specialized resuscitation techniques. Specialized resuscitation techniques are not covered by ACLS certifications and their use is restricted to further specialized providers. ACLS education is based on ILCOR recommendations which are then adapted to local practices by authoritative medical organizations such as the American Red Cross, the European Resuscitation Council, or the Resuscitation Council of Asia ."}
{"_id": "WikiPedia_Cardio$$$corpus_574", "text": "BLS proficiency is usually a prerequisite to ACLS training; however the initial portions of an ACLS class may cover CPR. [ 5 ]  Initial training usually takes around 15 hours and includes both classroom instruction and hands-on simulation experience; passing a test, with a practical component, at the end of the course is usually the final requirement to receive certification. [ 6 ]  After receiving initial certification, providers must usually recertify every two years in a class with similar content that lasts about seven hours.  Widely accepted providers of ACLS certification include, non-exclusively: American Heart Association, American Red cross,  European Resuscitation Council or the Australian Resuscitation Council."}
{"_id": "WikiPedia_Cardio$$$corpus_575", "text": "Holding ACLS certification simply attests a provider was tested on knowledge and application of ACLS guidelines. The certification does  not  supersede a provider's  scope of practice  as determined by state law or employer protocols; and does not, itself, provide any  license  to practice."}
{"_id": "WikiPedia_Cardio$$$corpus_576", "text": "Like a medical intervention, researchers have had to ask whether ACLS is effective. Data generally demonstrates that patients have better survival outcomes (increased ROSC, increased survival to hospital discharge and/or superior neurological outcomes) when they receive ACLS; [ 7 ]  however a large study of  ROC  patients showed that this effect may only be if ACLS is delivered in the first six minutes of arrest. [ 8 ]  This study also found that ACLS increases survival but does not produce superior neurological outcomes."}
{"_id": "WikiPedia_Cardio$$$corpus_577", "text": "Some studies have raised concerns that ACLS education can be inconstantly or inadequately taught which can result in poor retention, leading to poor ACLS performance. [ 9 ]  One study from 1998 looked at the ACLS use of epinephrine, atropine, bicarbonate, calcium, lidocaine, and bretylium in cardiac arrests and found that these medications were not associated with higher resuscitation rates. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_578", "text": "Research on ACLS can be challenging because ACLS is a bundle of care recommendations; with each individual treatment component being profoundly consequential. There is active debate within the resuscitation research community about the value of certain interventions. Active areas of research include determining the value of vasopressors in arrests, [ 11 ]  ideal airway use [ 12 ]  and different waveforms for defibrillation. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_579", "text": "Stemming from the need for standardized, evidence based ACLS guidelines, an international network of academic resuscitation organizations was created. The International Liaison Committee on Resuscitation (ILCOR) is the central, international institution that regional resuscitation committees strive to contribute to and disseminate information from. The centralization of resuscitation research around ILCOR reduces redundant work internationally, allows for collaboration between experts from many regional organizations, and produces higher quality, higher powered research."}
{"_id": "WikiPedia_Cardio$$$corpus_580", "text": "ILCOR  serves as a way for international resuscitation organizations to communicate and collaborate. [ 14 ]  ILCOR publishes  scientific evidence  reviews on resuscitation known as \"Continuous Evidence Evaluation (CEE) and Consensus on Science with Treatment Recommendations (CoSTRs)\". [ 15 ]  ILCOR uses 6 international task forces to review over 180 topics through a structured  systematic-review  process. ILCOR traditionally published updates and recommendations every five years but now conducts continuous review work. [ 16 ]  ILCOR produces international recommendations which are then adopted by regional resuscitation committees which publish guidelines. [ 17 ]  Regional guidelines can have more  medicolegal bearing  than ILCOR recommendations. [ 18 ]  ILCOR is composed of the following regional organizations:"}
{"_id": "WikiPedia_Cardio$$$corpus_581", "text": "The International Liaison Committee on Resuscitation (ILCOR) was established 1992 to serve as a way for international resuscitation organizations to communicate and collaborate. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_582", "text": "The ACLS guidelines were first published in 1974 by the  American Heart Association  and were updated in 1980, 1986, 1992, 2000, 2005, 2010, 2015. [ 22 ]  In the 2020 update the guidelines were restructured to align with ILCOR recommendations. These changes include the transition since 2015 away from the previous 5-year update cycle to an online format that can be updated as indicated by continuous evidence review. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_583", "text": "The first version of the  European Resuscitation Council  (ERC) guidelines were developed in 1992. The 2000 ERC guidelines were developed in collaboration with ILCOR. 5-year updates were published from 2000 to 2015 and annual updates have been published since 2017. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_584", "text": "An  Af-nest  or  Atrial Fibrillation Nest  (AFN) is a locus or cluster in the  atrial wall  with distinct electrical features and properties originated by  fibrillar myocardium . It plays as an \"electrical multiplier\" re-feeding the  atrial fibrillation ."}
{"_id": "WikiPedia_Cardio$$$corpus_585", "text": "One of the currently existing techniques to treat  atrial fibrillation  (AF) is based on thermo-coagulation of AFN. They are typically numerous at the  pulmonary veins  antrum. Several evidences have shown that the AFNs represent the true  substrate  of the AF. Many  congenital  and acquired conditions may cause this type of  myocardium . The higher the number of AFNs the easier the initiation and the longer the AF maintenance. Despite being fundamental in the AF  physiopathology  the long-lasting AF depends on additional factors. The most important is the \"Background  Tachycardia \" (BKT) which is a focal reentrant tachycardia caused by \"Fractal Micro-Reentry\". This special tachycardia exists even during AF, keeping the AFNs in a high frequency activation. This  tachycardia  has a unique mechanism of \"protection\" that prevents it from being reverted by the large amount of surrounding  stimuli  generated by the AF itself."}
{"_id": "WikiPedia_Cardio$$$corpus_586", "text": "Recent studies have shown that the BKT occurs within a more developed AFN or when there is a  confluence  of two or more of these elements. By using  spectral analysis , it is possible to observe that the \"Fractal Micro-Reentry\" phenomenon tends to occur depending on a critical amount of  fibrillar   myocardium . This is a small point in the atrial wall with numerous micro-reentries (in a three-dimensional model) inside the AFN, caused by \"cellular electrical disconnection\" with progressive  dichotomy  (biological fractal phenomenon), even without the presence of fibrosis and without the need of major  histological  changes. By this way, it may be present even in normal hearts that explain the \"Lone Atrial Fibrillation\". This intense micro-electrical activity stimulates the surrounding atrial  myocardium  that accepts the activation according to its refractory period. This produces a slightly irregular focal tachycardia, known as \"Background  Tachycardia \" responsible for AF maintenance with or without the contribution of many others AFNs or even of other BKT. The greater the number of these elements is, the longer the AF may last, even becoming permanent."}
{"_id": "WikiPedia_Cardio$$$corpus_587", "text": "Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes  (also known as  AIM-HIGH ) was a  randomized control trial  designed to assess the efficacy of  niacin  (extended-release) added to  statin  therapy in reducing cardiovascular events in patients with established  atherosclerotic cardiovascular disease  (ASCVD). These patients had well-controlled  low-density lipoprotein  (LDL) cholesterol but persistently low  high-density lipoprotein  (HDL) cholesterol and elevated  triglycerides . 3,414 patients with established ASCVD were enrolled. The mean follow-up period was three years. The trial was stopped early due to a lack of efficacy and a trend towards an increase in the incidence of ischemic stroke. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_588", "text": "Low HDL cholesterol and high triglycerides are recognized risk factors for cardiovascular disease, even in individuals with well-controlled LDL cholesterol. Niacin has been shown to increase HDL cholesterol and lower triglycerides, prompting an investigation into whether adding niacin to statin therapy could further reduce cardiovascular risk in this patient population. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_589", "text": "AIM-HIGH was a multicenter, randomized, double-blind, placebo-controlled trial sponsored by the  National Heart, Lung, and Blood Institute  (NHLBI). Additional funding and support was provided by  Abbott Laboratories  and  Merck . The study enrolled 3,414 patients with established ASCVD and dyslipidemia, characterized by low HDL cholesterol (<40\u00a0mg/dL for men and <50\u00a0mg/dL for women) and elevated triglycerides (150\u2013400\u00a0mg/dL). All participants were already on statin therapy to maintain LDL cholesterol levels between 40 and 80\u00a0mg/dL. Participants were randomly assigned to receive either extended-release niacin (1500\u20132000\u00a0mg daily) or a matching placebo. The primary endpoint was the time to first major cardiovascular event, including nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or death from coronary heart disease. Secondary endpoints were death from coronary heart disease (CHD), nonfatal myocardial infarction, ischemic stroke, or hospitalization for acute coronary syndrome (ACS). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_590", "text": "The results of the AIM-HIGH trial, published in 2011, showed that adding niacin to statin therapy did not significantly reduce the risk of cardiovascular events compared to statin therapy alone: [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_591", "text": "The findings of the AIM-HIGH trial had significant implications for the treatment of dyslipidemia in patients with established ASCVD: [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_592", "text": "AIM-HIGH contributed to a shift in clinical practice guidelines, emphasizing the limited additional benefit of niacin in patients with low HDL cholesterol and high triglycerides already receiving effective statin therapy. Subsequent guidelines have focused on intensifying statin therapy or considering other agents for specific lipid abnormalities rather than adding niacin. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_593", "text": "The  Anrep effect  describes the rapid increase in  myocardial   contractility  in response to the sudden rise in  afterload , the pressure the heart must work against to eject blood. [ 1 ] [ 2 ]  This adaptive mechanism allows the  heart  to sustain  stroke volume  and  cardiac output  despite increased resistance. It operates through  homeometric autoregulation , meaning that contractility adjustments occur independently of  preload  (the initial stretch of the heart muscle) or  heart rate . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_594", "text": "The Anrep effect is characterized by a two-step elevation in myocardial contractility, in response to elevated afterload, involving two distinct mechanistic phases: a primary, rapid rise in contractility driven by  sarcomeric  strain sensing, and a secondary, sustained phase of contraction mediated by  post-translational modifications  of  contractile proteins . [ 3 ] [ 4 ]  First described by  Gleb von Anrep  in 1912 [ 5 ]  and further elaborated in the 1960s by  Sarnoff  et al., [ 1 ] [ 2 ]  the Anrep effect represents a distinct cardiac regulation mechanism, differing fundamentally from the  Frank-Starling mechanism , [ 6 ]  the slow force response, [ 7 ] [ 8 ]  and the Gregg effect. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_595", "text": "While traditionally considered a short-term adaptation, recent studies suggest that the Anrep effect may also occur in chronic conditions involving persistent afterload elevation, such as  hypertrophic obstructive cardiomyopathy . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_596", "text": "The heart adjusts its pumping efficiency through changes in muscle length and load. When the cardiac muscle is stretched, it triggers a biphasic rise in force generation. The initial phase, governed by the Frank-Starling law (heterometric autoregulation), results in an immediate increase in contractile strength due to increased  end-diastolic volume . This adjustment helps balance cardiac output with changes in filling pressure. The second phase, termed the slow force response, unfolds over several minutes, reflecting a sustained increase in contractility when preload remains constant following the initial stretch. In contrast, the Anrep effect (homeometric autoregulation) enhances ventricular contractility in response to acute afterload elevation, independent of preload or heart rate variations. The Anrep effect is often confused with other regulatory processes (e.g., the slow force response, the Gregg phenomenon) but has unique, very distinct, characteristics:"}
{"_id": "WikiPedia_Cardio$$$corpus_597", "text": "The Frank-Starling mechanism describes how increased preload (ventricular filling) stretches cardiac muscle fibers, enhancing stroke work through length-dependent activation of the  myofilaments . This process aligns actin and myosin filaments for efficient cross-bridge formation while also recruiting myosin heads from dormant states into contraction-ready configurations. [ 6 ] [ 10 ]  Additionally, stretching the sarcomeres sensitizes the thin (actin) filaments to calcium, promoting stronger and more sustained contractions. [ 6 ]  By contrast, the Anrep effect occurs at constant preload, triggered solely by afterload. [ 1 ] [ 2 ] [ 3 ]  It is characterized by increased contractility (steeper end-systolic pressure-volume relationship) and higher stroke work, without changes in stroke volume or end-diastolic volume. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_598", "text": "This stretch-related (preload) response involves a gradual rise in contractility over several minutes (from 2 to 15 minutes, depending on species and experimental conditions) [ 7 ] [ 8 ] [ 11 ]  due to  stretch-activated ion channels  and  G-protein-coupled receptors . [ 7 ] [ 12 ]  It is mediated by  angiotensin II  and  endothelin-1 , which increase intracellular sodium and calcium concentrations through  sodium-calcium exchangers . In contrast, the afterload-dependent response of the Anrep effect is initiated in milliseconds and concludes within 10 seconds, bypassing extracellular calcium regulation through the slow force response. [ 3 ]  Additionally,  streptomycin , an inhibitor of stretch-activated ion channels, blocks the slow force response but does not affect the Anrep effect, reinforcing that the two mechanisms operate through distinct pathways. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_599", "text": "This effect describes increased contractility due to improved  coronary perfusion . [ 9 ]  It originates from changes in microvascular volume that trigger stretch-activated ion channels, resulting in increased intracellular calcium transient. [ 13 ]  The Gregg phenomenon generally begins to affect contractility approximately 5 seconds after onset, reaching peak force development within 40 seconds of sustained perfusion. [ 3 ]  However, the Anrep effect persists even in denervated, isolated hearts with constant coronary flow, eliminating perfusion-based explanations. [ 3 ]  Like the slow force response, the Gregg effect is sensitive to streptomycin, while the Anrep effect remains unaffected. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_600", "text": "The activation of the Anrep effect involves recruiting a significant portion of dormant  myosin motors  within  cardiomyocytes , as most myosin heads in each heart cell remain in a resting state. [ 4 ]  This recruitment transitions myosin from its inactive configuration to a contraction-ready state through a biphasic activation process that increases contractility in response to the afterload, and consequently elevates energy consumption:"}
{"_id": "WikiPedia_Cardio$$$corpus_601", "text": "The Anrep effect can be understood in terms of its  hemodynamic  impact on the heart during afterload increases: [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_602", "text": "These responses ensure the heart maintains stroke volume and cardiac output, despite increased afterload, at the cost of higher energy consumption. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_603", "text": "The Anrep effect was first described by Gleb von Anrep in 1912 [ 5 ]  during experiments involving splanchnic nerve stimulation in dogs. He observed that stimulating the splanchnic nerve caused peripheral vasoconstriction, which increased blood pressure and afterload. In response, cardiac contractility increased, a phenomenon Anrep attributed to the release of adrenaline from the suprarenal glands, independent of preload changes. Later,  Ernest Starling  suggested that enhanced coronary flow, improving myocardial nourishment (a concept later termed the Gregg effect [ 9 ] ), might explain the increase in contractility observed by von Anrep. [ 15 ]  However, both historical and recent research has demonstrated that the Anrep effect arises from an intrinsic property of the myocardium, independent of adrenaline release or coronary flow. [ 1 ] [ 2 ] [ 3 ]  In the mid-20th century, Sarnoff et al. [ 1 ] [ 2 ]  introduced the term homeometric autoregulation to describe the heart\u2019s ability to augment contractility in response to elevated afterload, independent of preload or hormonal stimulation. This concept distinguished the Anrep effect from the Frank-Starling law, which involves heterometric autoregulation, where increased preload enhances contractility by stretching myocardial fibers. Despite Sarnoff\u2019s clarification, some of his experiments reported a brief, transient increase in preload following afterload elevation. He dismissed this effect as non-essential for triggering the Anrep effect, yet this observation led to persistent confusion. To this day, some studies mistakenly associate the Anrep effect with the slow force response, despite clear differences in their underlying physiology."}
{"_id": "WikiPedia_Cardio$$$corpus_604", "text": "Although originally considered an acute and transient response, recent research suggests that the Anrep effect may persist in chronic conditions involving sustained afterload increases. One example is hypertrophic obstructive cardiomyopathy, where  left ventricular outflow tract obstruction  results in persistent afterload elevation, potentially activating the Anrep effect chronically. [ 4 ]  Understanding this mechanism has important implications for cardiac physiology, heart failure management, and therapeutic interventions targeting afterload reduction."}
{"_id": "WikiPedia_Cardio$$$corpus_605", "text": "The  Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial , also known as  ALLHAT , was a   randomized, double-blind , active-controlled study comparing at the same time, four different classes of  antihypertensive drugs  with the rate of  coronary heart disease  (CHD) events in \u2018high-risk\u2019 people with  hypertension . [ 1 ]  Participants were initially randomised to  chlorthalidone  ( diuretic ) versus  doxazosin  ( alpha-adrenergic blocker ),  lisinopril  ( ACE-inhibitor ), and  amlodipine  ( calcium channel blocker ). [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_606", "text": "The doxazosin arm was discontinued early on in the trial because of a higher rate of combined  cardiovascular events  and admissions for  heart failure  compared with chlorthalidone. The study concluded that major CHD events did not differ between initial use of chlorthalidone versus lisinopril or amlodipine. As a result, the  Joint National Committee  (7) guidelines of 2003, recommended the cheaper but equally effective diuretics as a first line treatment for hypertension. The study also confirmed the previously held views that ACE inhibitors were less effective in blood pressure control and stroke prevention in men of African and Caribbean descent. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_607", "text": "By the mid-1990s, there was increasing awareness of the relative reduction of risks for stroke and CHD with lowering blood pressure, and the main drugs in use were initially  diuretics  and  beta-blockers . [ 5 ]  Shortly after, other newer classes of blood pressure lowering drugs were developed and the ALLHAT study aimed to clarify their relative values with the aim to also answer which one to use first. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_608", "text": "The trial was supported mainly by the  National Heart, Lung and Blood Institute , part of the  National Institutes of Health  (NIH), and received some support from  Pfizer . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_609", "text": "Since 1971, the  Coordinating Center for Clinical Trials  ( [1] ) at The  University of Texas School of Public Health  has played a leading role in cardiovascular disease and vision research by serving as a coordinating center for 25 nationwide multicenter  clinical trials . The CCCT's primary function is to provide and coordinate all operations, procedures, and activities of a large-scale randomized controlled clinical trial. The CCCT serves as the Clinical Trials Center (Data and Clinical Coordinating Centers) for the ALLHAT. The CTC was led by C. Morton Hawkins (1993-2000) and  Barry R. Davis  (2000-2016)."}
{"_id": "WikiPedia_Cardio$$$corpus_610", "text": "In February 1994, initially 42,418 people, age over 55 years, with  stage I or II hypertension  or who were taking  medication for high blood pressure  were recruited across 623 centres in Canada, Puerto Rico, the US, and the US Virgin Islands. All had at least one other  CHD risk factor  including previous heart attack or  stroke ,  electrocardiogram  or  echocardiogram  verified  left ventricular hypertrophy  (LVH), a history of  type II diabetes mellitus , current  cigarette smoking , and low  high-density lipoprotein  cholesterol levels. [ 7 ]  35% were African American. [ 5 ]  The doxazosin arm was discontinued in January 2000 because of a higher rate of combined  cardiovascular events  and admissions for  heart failure  compared with chlorthalidone. Follow-up of the remaining 33,357 participants was completed in 2002. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_611", "text": "ALLHAT showed that major CHD events did not differ between initial use of chlorthalidone versus lisinopril or amlodipine. As diuretics proved equally effective and were cheaper, the Joint National Committee 7 guidelines of 2003, recommended diuretics as a first line treatment for hypertension. The study confirmed the previously held views that ACE inhibitors were less effective in blood pressure control and stroke prevention in men of African and Caribbean descent. The study also revealed that calcium channel blockers did not cause higher rates of gastrointestinal bleeding or cancers and they were not less effective than other antihypertensives. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_612", "text": "Aortic valve replacement  is a  cardiac surgery  procedure whereby a failing  aortic valve  is  replaced  with an  artificial heart valve . The aortic valve may need to be replaced because of  aortic regurgitation  (back flow), or if the valve is narrowed by  stenosis ."}
{"_id": "WikiPedia_Cardio$$$corpus_613", "text": "Current methods for aortic valve replacement include  open-heart surgery ,  minimally invasive cardiac surgery (MICS) ,  surgical aortic valve replacement  (SAVR) and  percutaneous or transcatheter aortic valve replacement  (TAVR; also PAVR, PAVI, TAVI)."}
{"_id": "WikiPedia_Cardio$$$corpus_614", "text": "A cardiologist can evaluate whether a  heart valve repair  or  valve replacement  would be of benefit. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_615", "text": "During the late 1940s and early 1950s, the first surgical approaches towards treating aortic valve stenosis had limited success. The first attempts were valvotomies, (i.e. cutting the valve while the heart is pumping). A ball valve prosthesis placed on the  descending thoracic aorta  (heterotopically) was developed by Hufnagel, Harvey and others to address aortic stenosis, but had disastrous complications. Later, with the innovation of cardiopulmonary bypass, the ball valve prosthesis was placed orthotopically (i.e. in same place as the original aortic valve). This first generation of prosthetic valves was durable, but needed intense anti-coagulation, and cardiac hemodynamics were compromised. During the mid-1950s, a single-leaflet prosthesis was developed by Bahnson  et al . In early 1960, Ross and  Barratt-Boyes  used allografts. Tissue prosthetic valves were introduced in 1965 by Binet in Paris, but they degenerated quickly because the tissue was insufficiently preserved. Carpentier solved this problem by introducing glutaraldehyde-preserved stent-mounted porcine valves. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_616", "text": "The aortic valve is one of the two  semilunar valves  of the heart with three cusps. It separates the heart from the  aorta . Each cusp is attached to the aortic wall creating a sinus called an  aortic sinus . The origins of the two  coronary arteries  are sited in two aortic sinuses. Cusps also known as leaflets are separated by  commissures . The posterior leaflet is in continuation with the anterior leaflet of the mitral valve (the tissue is called the aorto-mitral curtain). [ 4 ]  The aortic valve is opened during systole, the driving force for it to open is the difference in pressure between the contracting left ventricle of the heart and the aorta. During cardiac diastole (when the heart chamber gets bigger) the aortic valve closes. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_617", "text": "Aortic stenosis most commonly is the result of calcification of the cusps. Other reasons for stenosis are the  bicuspid valve  (some patients have only two cusps at the aortic valve instead of the usual three) and rheumatic aortic stenosis (now rare in the West). Obstruction at the level of the aortic valve causes increased pressure within the heart's left ventricle. This can lead to hypertrophy and ultimately dysfunction of the heart. While x-ray and ECG might indicate aortic stenosis, echocardiography is the diagnostic procedure of choice. US findings also help in grading the severity of the disease. In cases of symptomatic severe aortic stenosis, AVR is warranted. In cases of asymptomatic but severe aortic stenosis, more factors should be taken into consideration. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_618", "text": "Aortic regurgitation, on the other hand, has many causes: degeneration of the cusps, endocarditis, bicuspid aortic valve, aortic root dilatation, trauma, connective tissue disorders such as Marfan syndrome or Ehlers-Danlos lead to imperfect closure of the valve during diastole, hence the blood is returning from the aorta towards the left ventricle of the heart. Acute aortic regurgitation (caused by endocarditis, aortic dissection or trauma) ends up in pulmonary edema, because of the acute increase in left ventricle (LVEDP) that does not have time to adjust to the regurgitation. Chronic regurgitation, by contrast, gives the heart time to change shape, resulting in  eccentric hypertrophy , which has disastrous effects on the myocardium. Ultrasound is here also the best diagnostic mobility, either it is transthoracic or transesophageal.  [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_619", "text": "As long-term data on the survival and quality of life of people following valve replacement have become available, evidence-based guidelines for aortic valve replacement have been developed. These help healthcare professionals decide when aortic valve replacement is the best option for a patient. Two widely accepted sets of guidelines used by surgeons and cardiologists are the American Heart Association and American College of Cardiology Guidelines for the Management of Patients with Valvular Heart Disease, [ 8 ]  and the European Society of Cardiology and the European Association for Cardio\u2011Thoracic Surgery Guidelines for the management of valvular heart disease. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_620", "text": "Aortic stenosis  is treated with aortic valve replacement in order to avoid  angina ,  syncope , or  congestive heart failure . Individuals with severe aortic stenosis are candidates for aortic valve replacement once they develop symptoms or when their heart function is impacted. Some people with asymptomatic aortic stenosis may also be candidates for aortic valve replacement, especially if symptoms appear during  exercise testing . [ 9 ]  Patients with moderate aortic valve stenosis who need another type of cardiac surgery (i.e.  coronary artery bypass surgery ) should also have their valve addressed by the surgical team if  echocardiography  unveils significant heart problems. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_621", "text": "Low gradient aortic stenosis with concomitant left ventricular dysfunction poses a significant question to the anesthesiologist and the patient. Stress echocardiography (i.e. with dobutamine infusion) can help determine if the ventricle is dysfunctional because of aortic stenosis, or because the myocardium lost its ability to contract. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_622", "text": "Many people with  aortic insufficiency  often do not develop symptoms until they have had the condition for many years. [ 12 ]  Aortic valve replacement is indicated for symptoms such as  shortness of breath , and in cases where the heart has begun to enlarge (dilate) from pumping the increased volume of blood that leaks back through the valve. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_623", "text": "There are two basic types of replacement heart valve: tissue (bioprosthetic) valves and mechanical valves. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_624", "text": "Tissue heart valves are usually made from animal tissue (heterografts) mounted on a metal or polymer support. [ 14 ]  Bovine (cow) tissue is most commonly used, but some are made from porcine (pig) tissue. [ 15 ]  The tissue is treated to prevent rejection and calcification (where calcium builds up on the replacement valve and stops it working properly). [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_625", "text": "Occasionally, alternatives to animal tissue valves are used: aortic  homografts  and pulmonary  autografts . An aortic homograft is an aortic valve from a human donor, retrieved either after their death or from their heart if they are undergoing a heart transplant. [ 17 ]  A pulmonary autograft, also known as the  Ross procedure  is where the aortic valve is removed and replaced with the patient's own  pulmonary valve  (the valve between the right ventricle and the pulmonary artery). A pulmonary homograft (a pulmonary valve taken from a cadaver) is then used to replace the patient's own pulmonary valve. This procedure was first performed in 1967 and is used primarily in children, as it allows the patient's own pulmonary valve (now in the aortic position) to grow with the child. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_626", "text": "Tissue valves can last 10\u201320 years. [ 18 ]  However, they tend to deteriorate more quickly in younger patients. [ 19 ]  New ways of preserving the tissue for longer are being investigated. One such preservation treatment is now being used in a commercially available tissue heart valve. In sheep and rabbit studies, the tissue (called RESILIA tissue) had less  calcification  than control tissue. Mid-term data on the safety and haemodynamic performance of the Inspiris RESILIA aortic bioprosthesis are encouraging. [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_627", "text": "Stented and stentless tissue valves are available. Stented valves come in sizes from 19\u00a0mm to 29\u00a0mm. [ 22 ]  Stentless valves are directly sutured at the aortic root. The major advantage of stentless valves is that they limit  patient\u2013prosthesis mismatch  (when the area of the prosthetic valve is too small in relation to the size of the patient, increasing the pressure inside the valve [ 23 ] ) and can be helpful when dealing with small aortic root. However, stentless valves take more time than stented valves to implant. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_628", "text": "Mechanical valves are made from synthetic materials, such as titanium or  pyrolytic carbon . [ 25 ]  Their durability is long life, while tissue valves can last for up to 15\u201320 years. [ 26 ] [ 27 ] [ 13 ]  Since the risk of blood clots forming is higher with mechanical valves than with tissue valves, patients with mechanical heart valves are required to take anticoagulant (blood-thinning) drugs, such as  warfarin , long-life, making them more prone to bleeding (1% per year). [ 13 ]  The sound of the valve can be heard very rarely, often as clicks, and might be disturbing. [ 28 ]  The choice of prosthetic valve should be individualized, carefully considering each patient's unique circumstances. In that context, the new generation aortic mechanical valve (On-X) offers a potential lifetime solution without need for a repeat operation, while minimizing the risks of long-term anticoagulation due to reduced anticoagulation target INR of 1.5 to 2.0. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_629", "text": "Valve choice is a balance between the lower durability of tissue valves and the increased risk of blood clots and bleeding with mechanical valves. Guidelines suggest that patient age, lifestyle and medical history should all be considered when choosing a valve. Tissue valves deteriorate more rapidly in young patients and during pregnancy, but they are preferable for women who wish to have children because pregnancy increases the risk of blood clots. Typically, a mechanical valve is considered for patients under 60 years old, while a tissue valve is considered for patients over the age of 65 years. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_630", "text": "Surgical aortic valve replacement is conventionally done through a  median sternotomy , meaning the incision is made by cutting through the breastbone ( sternum ). Once the protective membrane around the heart ( pericardium ) has been opened, the patient is cannulated (aortic cannulation by a cannula placed on the  aorta  and a venous canulation by a single atrial venous cannula inserted through the right atrium). The patient is put on a  cardiopulmonary bypass  machine, also known as the heart\u2013lung machine. This machine breathes for the patient and pumps their blood around their body while the surgeon replaces the heart valve. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_631", "text": "Once on cardiopulmonary bypass, the patient's heart is stopped ( cardioplegia ). This can be done with a Y-type cardioplegic infusion catheter placed on the aorta, de-aired and connected to the cardiopulmonary bypass machine. Alternatively, a retrograde cardioplegic cannula can be inserted at the coronary sinus. Some surgeons also opt to place a vent in the left ventricle through the right superior pulmonary vein, because this helps to prevent left ventricular distention before and after cardiac arrest. When the set-up is ready, the aorta is clamped shut with a cross-clamp to stop blood pumping through the heart and cardioplegia is infused. The surgeon incises the aorta a few milometers above the sinotubular junction (just above the coronary ostia, where the coronary arteries join the aorta) \u2013 a process known as aortotomy. After this, cardioplegia is delivered directly through the ostia. [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_632", "text": "The heart is now still and the surgeon removes the patient's diseased aortic valve. The cusps of the aortic valve are excised, and calcium is removed (debrided) from the aortic annulus. The surgeon measures the size of the aortic annulus and fits a mechanical or tissue valve of the appropriate size. Usually the valve is fixed in place with sutures, although some sutureless valves are available. If the patient's aortic root is very small, the sutures are placed outside of the aortic root instead of at the annulus, to gain some extra space. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_633", "text": "Once the valve is in place and the aorta has been closed, patient is placed in a  Trendelenburg position  and the heart is de-aired and restarted. The patient is taken off the cardiopulmonary bypass machine.  Transesophageal echocardiogram  (an ultrasound of the heart done through the esophagus) can be used to verify that the new valve is functioning properly. Pacing wires are usually put in place, so that the heart can be manually controlled should any complications arise after surgery. Drainage tubes are also inserted, to drain fluids from the chest. These are usually removed within 36 hours, while the pacing wires are generally left in place until right before the patient is discharged from the hospital. [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_634", "text": "After surgical aortic valve replacement, the patient will usually stay in an  intensive care unit  for 12\u201336 hours. Unless complications arise, the patient is then able to go home after approximately four to seven days. [ 32 ]  Common complications include disturbances to the heart's rhythm ( heart block ), which typically require the permanent insertion of a  cardiac pacemaker . [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_635", "text": "Recovery from aortic valve replacement takes about three months if the patient is in good health. Patients are advised not to lift anything heavier than 10\u00a0lbs for several weeks, and not to do any heavy lifting for 4\u20136 months after surgery to avoid damaging their breastbone. Often patients will be referred to participate in  cardiopulmonary rehabilitation , which optimizes recovery and physical function in patients with recent cardiac surgeries. This can be done in an outpatient setting. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_636", "text": "Surgery usually relieves the aortic disease symptoms that led the patient to the operating room. The survival curve of patients who undergo aortic valve replacements is slightly inferior to the curve of their corresponding healthy same-aged same sex population. [ 35 ]  Pre-operative severe left ventricular hypertrophy is a contributing factor to morbidity. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_637", "text": "The risk of dying as a result of aortic valve replacement is estimated at 1\u20133%. [ 36 ] [ 37 ] [ 38 ]  Combining aortic valve replacement with coronary artery bypass grafting increases the risk of mortality. [ 36 ]  Older patients, as well as those who are frail and/or have other health problems ( comorbidities ), have a higher risk of experiencing complications. [ 37 ]  Possible problems include  cardiac infarction  or failure,  arrhythmia  or  heart block  typically requiring the permanent insertion of a  cardiac pacemaker , mediastinal bleeding,  stroke  and infection. Late complications include  endocarditis , thromboembolic events ( blood clots ), prosthetic valve dysfunction and paravalvular leak (blood flowing between the edge of the prosthetic valve and the cardiac tissue). [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_638", "text": "When dealing with a small aortic annulus, the surgeon might have to insert a prosthetic aortic valve of small size, with an orifice too small in relation to the size of the patient (patient\u2013prosthesis mismatch). This increases the pressure of the blood flowing through the valve, and can lead to worse outcomes. [ 23 ]  Various techniques, including stentless valves, have been utilized to avoid this problem. [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_639", "text": "Since the late 1990s, some cardiac surgeons have been performing aortic valve replacement using an approach referred to as minimally invasive cardiac surgery (MICS). [ 40 ]  Using this approach, the surgeon replaces the valve through a smaller chest incision (6\u201310\u00a0cm) than that for a median sternotomy. MICS typically requires shorter recovery times, and produces less visible scarring. [ 41 ]  Alternatively, aortic valve replacement can be performed with right minithoracotomy approach via the 2nd or 3rd intercostal space. There is growing evidence that this approach can reduce postoperative morbidity allowing less blood loss, less pain,\nfaster recovery, and a shorter hospital stay with no difference in mortality. [ 42 ]  This approach can be particularly valuable in higher risk and elderly patients. [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_640", "text": "Another alternative for many high-risk or elderly patients is transcatheter aortic valve replacement (TAVR, also known as TAVI, transcatheter aortic valve implantation). Rather than removing the existing valve, the new valve is pushed through it in a collapsed state. It is delivered to the site of the existing valve through a tube called a catheter, which may be inserted through the femoral artery in the thigh (transfemoral approach), or using a small incision in the chest and then through a large artery or the tip of the left ventricle (transapical approach). [ 44 ]  Fluoroscopy and  transthoracic echocardiogram  (TTE) are visual aids used to guide the process. [ 44 ]  Once the collapsed replacement valve is in place it is expanded, pushing the old valve's  leaflets  out of the way. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_641", "text": "Guidelines suggest TAVR for most patients aged 75 years and older, and surgical aortic valve replacement for most younger patients. [ 46 ]  Ultimately, the choice of treatment is  based on many factors. [ 47 ] [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_642", "text": "Systematic reviews  have addressed this comparison: [ 48 ] [ 49 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_643", "text": "The  apex beat  (lat.  ictus cordis ), also called the  apical impulse , [ 1 ]  is the  pulse  felt at the  point of maximum impulse  ( PMI ), which is the point on the  precordium  farthest outwards (laterally) and downwards (inferiorly) from the  sternum  at which the  cardiac  impulse can be felt. The cardiac impulse is the vibration resulting from the  heart  rotating, moving forward, and striking against the chest wall during  systole . The PMI is not the  apex of the heart  but is on the precordium not far from it. Another theory for the occurrence of the PMI is the early systolic contraction of the longitudinal fibers of the left ventricle located on the endocardial surface of this chamber. This period of the cardiac cycle is called isovolumic contraction. Because the contraction starts near the base of the left ventricle and spreads toward the apex most of the longitudinal fibers of the left ventricle have shortened before the apex. The rapidly increasing pressure developed by the shortening of these fibers causes the aortic valve to open and the apex to move outward causing the PMI. Anatomical dissection of the musculature of the apex reveals that muscle fibers are no longer longitudinal oriented but form a spiral mass of muscular tissues which may also have an effect on the ability of the apex to contract longitudinally. After the longitudinal fibers contract, the ejection of blood out of the left ventricle is accomplished by the torsional (as one would wring out a face cloth) action of the circumferential muscle fibers of the left ventricle that are in the mid-portion of the ventricle and contract after the longitudinal fibers. During the longitudinal fiber contraction, the volume of the left ventricle has not changed keeping the apex in intimate contact with the chest wall allowing the ability to feel the apex move outward before the heart empties greater than 55% of its volume and the apex falling away from the chest wall.  [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_644", "text": "The normal apex beat can be  palpated  in the  precordium  left 5th intercostal space, half-inch medial to the left midclavicular line and 3\u20134 inches left of left border of sternum."}
{"_id": "WikiPedia_Cardio$$$corpus_645", "text": "In children the apex beat occurs in the fourth rib interspace medial to the nipple. The apex beat may also be found at abnormal locations; in many cases of  dextrocardia , the apex beat may be felt on the right side."}
{"_id": "WikiPedia_Cardio$$$corpus_646", "text": "Lateral and/or inferior displacement of the apex beat usually indicates enlargement of the heart, called  cardiomegaly . The apex beat may also be displaced by other conditions:"}
{"_id": "WikiPedia_Cardio$$$corpus_647", "text": "Sometimes, the apex beat may not be palpable, either due to a thick chest wall, or conditions where the  stroke volume  is reduced; such as during  ventricular tachycardia  or  shock ."}
{"_id": "WikiPedia_Cardio$$$corpus_648", "text": "The character of the apex beat may provide vital  diagnostic  clues:"}
{"_id": "WikiPedia_Cardio$$$corpus_649", "text": "Sustained apex beat, namely prolonged upward cardiac force during  systole  in a  physical exam , can be seen in some  chronic  conditions such as  hypertension  and  aortic stenosis , especially in elderly and females. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_650", "text": "An algorithm for the classification of some common apex beat characteristics is shown in the image"}
{"_id": "WikiPedia_Cardio$$$corpus_651", "text": "The  arteriovenous oxygen difference , or  a-vO 2  diff , is the difference in the  oxygen  content of the  blood  between the  arterial blood  and the  venous blood . It is an indication of how much oxygen is removed from the blood in  capillaries  as the blood  circulates  in the body. The a-vO 2  diff and  cardiac output  are the main factors that allow variation in the body's total oxygen consumption, and are important in measuring  VO 2 . The a-vO 2  diff is usually measured in  millilitres  of oxygen per 100 millilitres of blood (mL/100 mL). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_652", "text": "The arteriovenous oxygen difference is usually taken by comparing the difference in the oxygen concentration of  oxygenated blood  in the  femoral ,  brachial , or  radial artery  and the oxygen concentration in the  deoxygenated blood  from the mixed supply found in the  pulmonary artery  (as an indicator of the typical mixed venous supply). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_653", "text": "Put in simple terms:"}
{"_id": "WikiPedia_Cardio$$$corpus_654", "text": "The usual unit for a-vO 2  diff is millilitres of oxygen per 100 millilitres of blood (mL/100 mL), [ 1 ]  however, particularly in medical uses, other units may be used, such as  micro   moles  per millilitre (\u03bcmol/mL). [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_655", "text": "In practice, a-vO 2  diff may be determined using the  Fick Principle  rather than by taking direct blood samples. In order to do so oxygen consumption (VO 2 ) may be measured using a  spirometer  to detect gaseous concentrations in exhaled air compared to inhaled air, while  cardiac output  can be determined using a  Doppler ultrasound . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_656", "text": "Arterial blood will generally contain an oxygen concentration of around 20 mL/100 mL. [ 1 ]  Venous blood with an oxygen concentration of 15 mL/100 mL would therefore lead to typical values of the a-vO 2  diff at rest of around 5 mL/100 mL. During intense exercise, however, the a-vO 2  diff can increase to as much as 16 mL/100 mL due to the working  muscles  extracting far more oxygen from the blood than they do at rest. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_657", "text": "Alternatively, in order to find the efficiency of the  lungs  in replenishing blood oxygen levels, the a-vO 2  diff may instead be taken by comparing blood from the pulmonary artery and the  pulmonary vein ; in this case a negative value for a-vO 2  diff would be obtained as the oxygen content of the blood would have increased. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_658", "text": "Physical exercise  leads to an increase in the arteriovenous oxygen difference in all individuals. As exercise intensities increase, the muscles increase the amount of oxygen they extract from the blood, and this therefore results in further increases in a-vO 2  diff. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_659", "text": "The maximum a-vO 2  diff is also usually greater in  trained   athletes  than in untrained individuals. [ citation needed ]  This is a result of  aerobic exercise  leading to  hypertrophy  of the  slow twitch muscle fibres  mainly due to increased capillarisation. The increase in capillary beds in the muscle means that blood supply to that muscle can be greater and  diffusion  of oxygen,  carbon dioxide , and other  metabolites  increases. [ 5 ]  With training the muscles also improve in their ability to extract oxygen from the blood and process the oxygen, [ 5 ]  possibly due to adaptations of the  mitochondria  and an increase in the muscle's  myoglobin  content. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_660", "text": "Research has shown that following the commencement of exercise there is a delay in the increase of the a-vO 2  diff, and that a-vO 2  diff only has a marginal impact in the total change in VO 2  in the early stages of exercise. The bulk of the early increase in oxygen consumption after a sudden change in exercise levels results from increased cardiac output. [ 3 ]  However it has also been found that the increase in the maximal a-vO 2  diff resulting from adaptations to a physical training program can account for most of the difference in  VO 2  max  in subjects participating in sub-maximal exercise. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_661", "text": "Arteriovenous oxygen difference is also used in other areas of study such as  medicine  and  medical research . For example, the a-vO 2  diff has been used to measure  cerebral blood flow  in  comatose  patients, assisting with their  diagnosis  and  treatment . [ 2 ]  The a-vO 2  diff has also been used to determine the effects of physical training in  coronary patients . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_662", "text": "An  artificial heart  is an  artificial organ  device that replaces the  heart . Artificial hearts are typically used to bridge the time to complete  heart transplantation  surgery, but research is ongoing to develop a device that could permanently replace the heart in the case that a heart transplant (from a deceased human or, experimentally, from a deceased genetically engineered pig) is unavailable or not viable. As of December\u00a02023 [update] , there are two commercially available full artificial heart devices; in both cases, they are for temporary use, of less than a year, for total heart failure patients awaiting a human heart to be transplanted into their bodies."}
{"_id": "WikiPedia_Cardio$$$corpus_663", "text": "Although other similar inventions preceded it from the late 1940s, the first artificial heart to be successfully implanted in a human was the Jarvik-7 in 1982, designed by a team including  Willem Johan Kolff ,  William DeVries   and  Robert Jarvik . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_664", "text": "An artificial heart is distinct from a  ventricular assist device  (VAD; for either one or both of the ventricles, the heart's lower chambers), which can be a permanent solution also, or the  intra-aortic balloon pump  \u2013 both devices are designed to support a failing heart. It is also distinct from a  cardiopulmonary bypass  machine, which is an external device used to provide the functions of both the heart and  lungs , used only for a few hours at a time, most commonly during  cardiac surgery . It is also distinct from a ventilator, used to support failing lungs, or the  extracorporeal membrane oxygenation  (ECMO), which is used to support those with both inadequate heart and lung function for up to days or weeks, unlike the bypass machine."}
{"_id": "WikiPedia_Cardio$$$corpus_665", "text": "A synthetic replacement for a heart remains a long-sought \"holy grail\" of modern medicine. The obvious benefit of a functional artificial heart would be to lower the need for  heart transplants  because the demand for organs always greatly exceeds supply."}
{"_id": "WikiPedia_Cardio$$$corpus_666", "text": "Although the heart is conceptually a pump, it embodies subtleties that defy straightforward emulation with synthetic materials and power supplies. [ citation needed ]  Artificial hearts have historically had issues from both a biomedical standpoint, regarding clotting and foreign object rejection, as well as longevity and practicality, regarding the lifespan of the device as well as the equipment required to run it."}
{"_id": "WikiPedia_Cardio$$$corpus_667", "text": "Since the inception of the device, artificial hearts have been continually improved as medical technology has. More recent devices, such as the Carmat heart, have sought to improve upon their predecessors by reducing complications resultant from device implant, such as  foreign-body rejection  and  thrombus . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_668", "text": "The first artificial heart was made by the Soviet scientist  Vladimir Demikhov  in 1938. It was implanted in a dog."}
{"_id": "WikiPedia_Cardio$$$corpus_669", "text": "On July 2, 1952, 41-year-old  Henry Opitek , suffering from shortness of breath, made medical history at  Harper University Hospital [ 3 ]  at  Wayne State University  in Michigan. The  Dodrill-GMR  heart machine, considered to be the first operational mechanical heart, was successfully used while performing heart surgery. [ 4 ] [ 5 ] \nOngoing research was done on calves at  Hershey Medical Center , Animal Research Facility, in Hershey, Pennsylvania, during the 1970s."}
{"_id": "WikiPedia_Cardio$$$corpus_670", "text": "Forest Dewey Dodrill , working closely with Matthew Dudley, used the machine in 1952 to bypass Henry Opitek's left ventricle for 50 minutes while he opened the patient's left atrium and worked to repair the mitral valve. In Dodrill's post-operative report, he notes, \"To our knowledge, this is the first instance of survival of a patient when a mechanical heart mechanism was used to take over the complete body function of maintaining the blood supply of the body while the heart was open and operated on.\" [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_671", "text": "A  heart\u2013lung machine  was first used in 1953 during a successful open heart surgery.  John Heysham Gibbon , the inventor of the machine, performed the operation and developed the heart\u2013lung substitute himself."}
{"_id": "WikiPedia_Cardio$$$corpus_672", "text": "Following these advances, scientific interest for the development of a solution for heart disease developed in numerous research groups worldwide."}
{"_id": "WikiPedia_Cardio$$$corpus_673", "text": "In 1949, a precursor to the modern artificial heart pump was built by doctors William Sewell and  William Glenn  of the  Yale School of Medicine  using an  Erector Set , assorted odds and ends, and dime-store toys. The external pump successfully bypassed the heart of a dog for more than an hour. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_674", "text": "On December 12, 1957,  Willem Johan Kolff , the world's most prolific inventor of artificial organs, implanted an artificial heart into a dog at Cleveland Clinic. The dog lived for 90 minutes."}
{"_id": "WikiPedia_Cardio$$$corpus_675", "text": "In 1958,  Domingo Liotta  initiated the studies of TAH (Total Artificial Heart) replacement at Lyon, France, and in 1959\u201360 at the  National University of C\u00f3rdoba , Argentina. He presented his work at the meeting of the American Society for Artificial Internal Organs held in Atlantic City in March 1961. At that meeting, Liotta described the implantation of three types of orthotopic (inside the pericardial sac) TAHs in dogs, each of which used a different source of external energy: an implantable electric motor, an implantable rotating pump with an external electric motor, and a pneumatic pump. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_676", "text": "Paul Winchell  designed a model of artificial heart with the assistance of  Henry Heimlich  (the inventor of the  Heimlich maneuver ) and submitted a patent for a mechanically driven artificial heart implementing a cam driven roller mechanism to compress flexible bags containing blood, on February 6, 1961. [ 10 ]  This is contrary to the popular claim that Winchell submitted the patent in the summer of 1956, as well as contrary to the claim that Winchell \"invented\" the artificial heart. [ 11 ]  In fact, two patents existed prior to Winchell's submission. These patents were filed April 10, 1956, [ 12 ]  and April 17, 1959, [ 13 ]  respectively. Winchell also claims that the design within his patent was used in later models of the Jarvik hearts, a claim in which Robert Jarvik, the principle designer of those hearts, denies on the basis that his pneumatically driven hearts share little in common with Winchell's mechanically actuated patent. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_677", "text": "In 1964, the  National Institutes of Health  started the Artificial Heart Program, with the goal of putting an artificial heart into a human by the end of the decade. [ 15 ]   The purpose of the program was to develop an implantable artificial heart, including the power source, to replace a failing heart. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_678", "text": "In February 1966,  Adrian Kantrowitz  rose to international prominence when he performed the world's first permanent implantation of a partial mechanical heart (left ventricular assist device) at  Maimonides Medical Center . [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_679", "text": "In 1967, Kolff left Cleveland Clinic to start the Division of Artificial Organs at the  University of Utah  and pursue his work on the artificial heart."}
{"_id": "WikiPedia_Cardio$$$corpus_680", "text": "Over the years, more than 200 physicians, engineers, students and faculty developed, tested and improved Kolff's artificial heart. To help manage his many endeavors, Kolff assigned project managers. Each project was named after its manager. Graduate student Robert Jarvik was the project manager for the artificial heart projects, for which the Jarvik line of artificial hearts get their name from. There, physician-engineer  Clifford Kwan-Gett  invented two components of an integrated pneumatic artificial heart system: a ventricle with hemispherical diaphragms that did not crush red blood cells (a problem with previous artificial hearts) and an external heart driver that inherently regulated blood flow without needing complex control systems. [ 18 ]  Jarvik also combined several modifications: an ovoid shape to fit inside the human chest, a more blood-compatible  polyurethane  developed by biomedical engineer Donald Lyman, and a fabrication method by Kwan-Gett that made the inside of the ventricles smooth and seamless to reduce dangerous stroke-causing blood clots. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_681", "text": "On April 4, 1969,  Domingo Liotta  and  Denton A. Cooley  replaced a dying man's heart with a mechanical heart inside the chest at  The Texas Heart Institute  in  Houston  as a bridge for a transplant. The man woke up and began to recover. After 64 hours, the pneumatic-powered artificial heart was removed and replaced by a donor heart. However thirty-two hours after transplantation, the man died of what was later proved to be an acute pulmonary infection, extended to both lungs, caused by fungi, most likely caused by an  immunosuppressive drug  complication. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_682", "text": "The original prototype of Liotta-Cooley artificial heart used in this historic operation is prominently displayed in the  Smithsonian Institution 's  National Museum of American History  \"Treasures of American History\" exhibit in Washington, D.C. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_683", "text": "The first clinical use of an artificial heart designed for permanent implantation rather than a bridge to transplant occurred in 1982 at the  University of Utah ."}
{"_id": "WikiPedia_Cardio$$$corpus_684", "text": "In 1981,  William DeVries  submitted a request to the FDA for permission to implant the Jarvik-7 into a human being. On December 1, 1982, William DeVries implanted the Jarvik-7 artificial heart into Barney Clark, a retired dentist from Seattle who had severe  congestive heart failure . Clark's case was highly publicized and received much media attention, garnering attention from television networks, newspapers and periodicals. Clark lived for 112 days tethered to the UtahDrive pneumatic drive console, a device weighing some 400 pounds (180\u00a0kg). During that time Clark required several re-operations, suffered seizures, experienced prolonged periods of confusion and a number of instances of bleeding and asked several times to be allowed to die. Clark, however, still believed his being part of the initial experiment was an important contribution to medicine, and maintained an overall positive outlook on his condition. [ 22 ] [ 23 ]  Barney Clark died on March 23, 1983, of multiorgan system failure. Despite the complications, DeVries considered Clark's case a success. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_685", "text": "DeVries subsequently moved his practice to Humana Hospital Audubon in Louisville, Kentucky to continue studies using the Jarvik-7. DeVries' first artificial heart patient in Louisville was  Bill Schroeder . DeVries replaced Schroeder's failing heart with a Jarvik-7 on November 25, 1984. Like Clark, Schroeder suffered from bleeding that required re-operation to resolve. In the first weeks the outlook was good and Schroeder was allowed to have a can of Coors beer and he was given a phone call by President  Reagan , in which he famously asked the president for an update on a late Social Security check. [ 25 ]  However, 19 days after the operation, Schroeder suffered the first of four  strokes . Despite this, his recovery continued and was allowed to live in a specially outfitted apartment near the hospital for a period of time, as well as use a newly developed battery-powered portable drive unit for the heart which allowed him to venture out of the hospital for short periods. Schroeder's health continued to decline as three more strokes plagued his time with the artificial heart. He died on August 6, 1986, from complications from a stroke, respiratory failure and sepsis, after 620 days with the artificial heart. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_686", "text": "Three more patients received the Jarvik-7 as a permanent heart. Murray Haydon, DeVries' third patient, received a Jarvik-7 on February 17, 1985. Haydon suffered pulmonary issues and was required to be on a mechanical ventilator for the duration of his time with the artificial heart. Haydon died of infection and kidney failure on June 19, 1986, after 488 days with his artificial heart. On April 7, 1985, Dr. Bjarne Semb of Karolinska Hospital in Stockholm Sweden implanted a Jarvik-7 in Swedish businessman Leif Stenberg. Stenberg lived 229 largely-uneventful days with the heart but suffered from a stroke and subsequently died on November 21, 1985. Jack Burcham was DeVries' fourth and final patient to receive a Jarvik-7 as a destination therapy. Burcham received his heart on April 14, 1985, but due to complications from the size of the device, bleeding and kidney failure, Burcham died just 10 days later on April 25, 1985. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_687", "text": "In the mid-1980s, artificial hearts were powered by large pneumatic drive consoles. Moreover, two sizable catheters had to cross the body wall to carry the pneumatic pulses to the implanted heart, greatly increasing the risk of infection. To speed development of a new generation of technologies, the  National Heart, Lung, and Blood Institute  opened a competition for implantable electrically powered artificial hearts. Three groups received funding:  Cleveland Clinic  in Cleveland, Ohio; the College of Medicine of  Pennsylvania State University  ( Penn State Milton S. Hershey Medical Center ) in Hershey, Pennsylvania; and AbioMed, Inc. of Danvers, Massachusetts. Despite considerable progress, the Cleveland program was discontinued after the first five years."}
{"_id": "WikiPedia_Cardio$$$corpus_688", "text": "On July 19, 1963, E. Stanley Crawford and  Domingo Liotta  implanted the first clinical  Left Ventricular Assist Device  (LVAD) at  The Methodist Hospital  in Houston, Texas, in a patient who had a cardiac arrest after surgery. The patient survived for four days under mechanical support but did not recover from the complications of the cardiac arrest; finally, the pump was discontinued, and the patient died."}
{"_id": "WikiPedia_Cardio$$$corpus_689", "text": "On 21 April 1966,  Michael DeBakey  and Liotta implanted the first clinical LVAD in a paracorporeal position (where the external pump rests at the side of the patient) at The Methodist Hospital in Houston, in a patient experiencing cardiogenic shock after heart surgery. The patient developed neurological and pulmonary complications and died after few days of LVAD mechanical support. In October 1966, DeBakey and Liotta implanted the paracorporeal Liotta-DeBakey LVAD in a new patient who recovered well and was discharged from the hospital after 10 days of mechanical support, thus constituting the first successful use of an LVAD for  postcardiotomy  shock."}
{"_id": "WikiPedia_Cardio$$$corpus_690", "text": "In 1990, Brian Williams was discharged from the  University of Pittsburgh Medical Center  (UPMC), becoming the first VAD patient to be discharged with Food and Drug Administration (FDA) approval. [ 29 ]  The patient was supported in part by bioengineers from the University of Pittsburgh's McGowan Institute. [ 29 ] [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_691", "text": "SynCardia Systems  is a company based in Tucson, Arizona, which currently has two separate models of their artificial heart available. It is available in a 70cc and 50cc size. The 70cc model is used for biventricular heart failure in adult men, while the 50cc is for children and women. [ 31 ]  As of 2014, more than 1,250 patients have received SynCardia artificial hearts. [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_692", "text": "The device has two drive systems available for patients to use; the Companion 2 in-hospital driver, approved by the FDA in 2012, or the Freedom Driver System, approved in 2014. The Companion 2 replaced the Circulatory Support System Console, which was the original drive system for the heart. The Freedom Driver System is a compact portable driver for greater mobility and can allow some patients to return home. [ 34 ] [ 35 ]  To power the heart, the drivers send pulsed air through the drivelines into the heart. The drivers also monitor blood flow for each ventricle. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_693", "text": "In 1991 the rights to the Jarvik-7 were transferred to CardioWest, who resumed testing of the heart. Following good results with the TAH as a bridge to  heart transplant , a trial of the CardioWest TAH was initiated in 1993 and completed in 2002. [ 37 ]  After the completion of this trial, CardioWest became SynCardia. The SynCardia total artificial heart was first approved for use in 2004 by the  US Food and Drug Administration . [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_694", "text": "Though the SynCardia shares its design with the Jarvik-7, improvements have been made throughout its lifespan, reducing the occurrence of stroke and bleeding. [ 33 ]  Lifespan while being supported by the device has also drastically improved, with one patient being supported by the device for over 1,700 days. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_695", "text": "In 2016, SynCardia filed for bankruptcy protection and was later acquired by the private equity firm Versa Capital Management. [ 39 ]  In 2021, SynCardia was acquired by Hunniwell Lake Ventures under its portfolio company, Picard Medical. [ 40 ]  In April 2023, SynCardia filed to become a publicly traded company via  SPAC . [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_696", "text": "On October 27, 2008, French professor and leading  heart transplant  specialist  Alain F. Carpentier  announced a timeline that a fully implantable artificial heart would be ready for clinical trial by 2011 and for alternative transplant in 2013. It was developed and would be manufactured by his biomedical firm  CARMAT SA , [ 42 ]  and venture capital firm Truffle Capital. The prototype used embedded electronic sensors and was made from chemically treated animal tissues, called \"biomaterials\", or a \"pseudo-skin\" of  biosynthetic ,  microporous materials . [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_697", "text": "According to a press-release by Carmat dated December 20, 2013, the first implantation of its artificial heart in a 75-year-old patient was performed on December 18, 2013, by the Georges Pompidou European Hospital team in Paris (France). [ 44 ]  The patient died 75 days after the operation. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_698", "text": "In Carmat's design, called the Aeson, two chambers are each divided by a membrane that holds hydraulic fluid on one side. A motorized pump moves hydraulic fluid in and out of the chambers. The pumped fluid causes the membrane to move, causing blood to pump through the heart. The blood-facing side of the membrane is made of tissue obtained from a sac that surrounds a cow's heart, to make the device more biocompatible. The Carmat device also uses valves made from cow heart tissue and has sensors to detect increased pressure within the device. Cardiac information is sent to an internal control system that can adjust the flow rate in response to increased demand, such as when a patient is exercising. [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_699", "text": "The Carmat Aeson is aimed to be used in cases of terminal heart failure, instead of being used as a bridge device while the patient awaits a transplant. [ 47 ]  At 900 grams it weighs nearly three times the typical heart and is targeted primarily towards obese men. It also requires the patient to carry around an additional  Li-Ion  battery. The projected lifetime of the artificial heart is around 5 years (230 million beats). [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_700", "text": "In 2016, trials for the Carmat \"fully artificial heart\" were banned by the National Agency for Security and Medicine in Europe after short survival rates were confirmed. The ban was lifted in May 2017. At that time, a European report stated that Celyad's C-Cure cell therapy for ischemic heart failure [ 49 ]  \"Could only help a subpopulation of Phase III study participants, and Carmat will hope that its artificial heart will be able to treat a higher proportion of heart failure patients\". [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_701", "text": "The Carmat artificial heart was approved for sale in the European Union, receiving a  CE marking  on December 22, 2020. [ 51 ]  As of December\u00a02023 [update] , the Carmat is only available in Europe as a bridge-to-transplant, for up to 180 days while awaiting a human heart transplant. In the United States it is only available in clinical trials. [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_702", "text": "The  U.S. Army  artificial heart pump was a compact, air-powered unit developed by Kenneth Woodward at  Harry Diamond Laboratories  in the early to mid-1960s. [ 53 ] [ 54 ]  The Army's heart pump was partially made of  plexiglass , and consisted of two valves, a chamber, and a suction flapper. [ 53 ]  The pump operated without any moving parts under the principle of fluid amplification \u2013 providing a pulsating air pressure source resembling a heartbeat. [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_703", "text": "The Jarvik line of hearts was developed by the now-defunct medical device company Symbion, by medical device researchers Willem Kolff and Robert Jarvik in conjunction with the University of Utah. These hearts were developed through animal trials and culminated in the Jarvik-7 100, the original model that was used in the first clinical trials of the heart. Jarvik-7 hearts were made primarily of a biocompatible plastics and polymers. These hearts used four Medtronic-Hall valves and consisted of two \u201cventricles\u201d which contained multi-layer low-stress diaphragms. [ 55 ]  The Jarvik-7 was powered pneumatically by two transcutaneous drivelines attached to a large compressed-air drive console, originally called the Utahdrive. The drive console contained two independent drive systems for redundancy, data recording devices and backup compressed air cylinders. [ 56 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_704", "text": "The Jarvik-7 was later developed in a smaller 70cc variant so that it would fit better in the chest cavities of more patients. Another development that came to the Jarvik-7 was the introduction of a battery-powered portable drive system the size of a briefcase that later patients took advantage of."}
{"_id": "WikiPedia_Cardio$$$corpus_705", "text": "Contrary to popular belief and erroneous articles in several periodicals, the Jarvik-7 heart was not permanently banned for use. After a hostile takeover, Symbion's facilities had lost FDA compliance in 1990 and required that the devices be destroyed. After the rights to the device had been transferred to then CardioWest Technologies, an investigational study was approved in 1993. CardioWest Technologies became SynCardia in 2003 who currently produces the modern version of the Jarvik-7, known as the  SynCardia  temporary Total Artificial Heart. [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_706", "text": "Since 1991, the Foundation for Cardiac Surgery Development (FRK) in  Zabrze , Poland, has been working on developing an artificial heart. Nowadays, [ when? ]  the Polish system for heart support POLCAS consists of the artificial ventricle POLVAD-MEV and the three controllers POLPDU-401, POLPDU-402 and POLPDU-501. Presented devices are designed to handle only one patient. The control units of the 401 and 402 series may be used only in hospital due to its big size, method of control and type of power supply. The control [ 57 ]  unit of 501 series is the latest product of FRK. Due to its much smaller size and weight, it is significantly more mobile solution. For this reason, it can be also used during supervised treatment conducted outside the hospital. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_707", "text": "In June 1996, a 46-year-old man received a total artificial heart implantation done by Jeng Wei at Cheng-Hsin General Hospital [ 58 ]  in  Taiwan . This technologically advanced pneumatic Phoenix-7 Total Artificial Heart was manufactured by Taiwanese dentist  Kelvin K. Cheng , Chinese physician T. M. Kao, and colleagues at the Taiwan TAH Research Center in  Tainan ,  Taiwan . With this experimental artificial heart, the patient's BP was maintained at 90\u2013100/40\u201350 mmHg and cardiac output at 4.2\u20135.8 L/min. [ 59 ]  The patient then received the world's first successful combined heart and kidney transplantation after bridging with a total artificial heart. [ 60 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_708", "text": "The first  AbioCor  to be surgically implanted in a patient was on July 3, 2001. [ 61 ]  The AbioCor is made of titanium and plastic with a weight of 0.9\u00a0kg (two pounds), and its internal battery can be recharged with a transduction device that sends power through the skin. [ 61 ]  The internal battery lasts for half an hour, and a wearable external battery pack lasts for four hours. [ 62 ]  The FDA announced on September 5, 2006, that the AbioCor could be implanted for humanitarian uses after the device had been tested on 15 patients. [ 63 ]  It is intended for critically ill patients who cannot receive a heart transplant. [ 63 ]  Some limitations of the current AbioCor are that its size makes it suitable for less than 50% of the female population and only about 50% of the male population, and its useful life is only 1\u20132 years. [ 64 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_709", "text": "By combining its valved ventricles with the control technology and roller screw developed at Penn State, AbioMed designed a smaller, more stable heart, the AbioCor II. This pump, which should be implantable in most men and 50% of women with a life span of up to five years, [ 64 ]  had animal trials in 2005, and the company hoped to get FDA approval for human use in 2008. [ 65 ]  After a great deal of experimentation,  AbioMed  has abandoned development of total artificial hearts as of 2015. [ 66 ]  Abiomed as of 2019 only markets heart pumps, [ 67 ]  \"intended to help pump blood in patients who need short-term support (up to 6 days)\", [ 68 ]  which are not total artificial hearts."}
{"_id": "WikiPedia_Cardio$$$corpus_710", "text": "On March 12, 2011, an experimental artificial heart was implanted in 55-year-old Craig Lewis at The Texas Heart Institute in Houston by  O. H. Frazier  and  William Cohn . The device was a combination of two modified  HeartMate II  pumps which had undergone  bovine trials . [ 69 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_711", "text": "So far, only one person has benefited from Frazier and Cohn's artificial heart. Craig Lewis had  amyloidosis  in 2011 and sought treatment. After obtaining permission from his family, Frazier and Cohn replaced his heart with their device. Lewis survived for another 5 weeks after the operation; he eventually died from liver and kidney failure due to his amyloidosis, after which his family asked that his artificial heart be unplugged. [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_712", "text": "On July 10, 2017, Nicholas Cohrs and colleagues presented a new concept of a soft total artificial heart in the Journal of Artificial Organs. [ 71 ]  The heart was developed in the Functionals Materials Laboratory at  ETH Zurich . [ 72 ]  (Cohrs was listed as a doctoral student in a group led by Professor Wendelin Stark at ETH Zurich.) [ 73 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_713", "text": "The soft artificial heart (SAH) is a silicone monoblock fabricated with the help of  3D bioprinting  technology. It weighs 390g, has a volume of 679\u00a0cm 3,  and is operated through pressurized air. \"Our goal is to develop an artificial heart that is roughly the same size as the patient's own one and which imitates the human heart as closely as possible in form and function\", Cohrs said in an interview. [ 74 ]  The SAH fundamentally moves and works like a natural heart, but the prototype only performed for 3000 beats (about 30 to 50 minutes at an average heart rate) [ 75 ]  in a hybrid mock circulation machine [ citation needed ]  before the silicone membrane (2.3\u00a0mm thick) between the Left Ventricle and the Air Expansion Chamber ruptured. [ 76 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_714", "text": "The working life of a more recent Cohrs prototype (using various polymers instead of silicone) [ citation needed ]  was still limited, according to reports in early 2018, with that model providing a useful life of 1 million heartbeats, roughly ten days in a human body. [ 77 ]  At the time, Cohrs and his team were experimenting with CAD software and 3D printing, striving to develop a model that would last up to 15 years. \"We cannot really predict when we could have a final working heart which fulfills all requirements and is ready for implantation. This usually takes years\", said Cohrs. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_715", "text": "Founded in 2008, the BiVACOR company has been developing a total artificial heart based on a rotary centrifugal pump. Artificial heart researchers and cardiologists O. H. Frazier and William Cohn are on the board of the BiVACOR company. The BiVACOR heart seeks to improve the artificial heart by using a magnetically levitated impeller which reduces clotting and only has a single moving part. This also reduces size and complexity, as well as only requiring a battery pack to run. The BiVACOR heart is not pulsatile like previous hearts and contains no valves, but is capable of generating \u201cbeats\u201d by rapidly changing the speed of the impeller. [ 78 ] [ 79 ]  BiVACOR has been tested as a replacement for a heart in a sheep. [ 80 ] [ 81 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_716", "text": "On November 10, 2023, the BiVACOR heart received FDA authorization under the investigational device exemption for use in human trials. [ 82 ]  In July 2024, a successful implantation of the BiVACOR artificial heart in a 57-year-old man with end-stage heart failure was conducted as part of its first-in-human clinical study at  Baylor St. Luke's Medical Center , with four more patients expected to be enrolled in the study. [ 83 ] [ 84 ]  A few weeks later, the second person, a 34-year-old man, had a BiVACOR artificial heart implanted at  Duke University Hospital  as a successful bridge to a heart transplant 10 days later. [ 85 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_717", "text": "A  centrifugal pump [ 86 ] [ 87 ]  or an  axial-flow pump [ 88 ] [ 89 ]  can be used as an artificial heart, resulting in the patient being alive without a  pulse ."}
{"_id": "WikiPedia_Cardio$$$corpus_718", "text": "A centrifugal artificial heart which alternately pumps the  pulmonary circulation  and the  systemic circulation , causing a pulse, has been described. [ 90 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_719", "text": "Researchers have constructed a heart out of foam. The heart is made out of flexible silicone and works with an external pump to push air and fluids through the heart. It currently cannot be implanted into humans, but offers a new concept in artificial hearts. [ 91 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_720", "text": "Patients who have some remaining heart function but who can no longer live normally may be candidates for ventricular assist devices (VAD), which do not replace the human heart but complement it by taking up much of the function. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_721", "text": "The first Left Ventricular Assist Device (LVAD) system was created by  Domingo Liotta  at  Baylor College of Medicine  in  Houston  in 1962. [ 92 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_722", "text": "Another VAD, the Kantrowitz CardioVad, designed by  Adrian Kantrowitz , boosts the native heart by taking up over 50% of its function. [ 93 ]  Additionally, the VAD can help patients on the wait list for a heart transplant. In a young person, this device could delay the need for a transplant by 10\u201315 years, or even allow the heart to recover, in which case the VAD can be removed. [ 93 ]  The artificial heart is powered by a battery that needs to be changed several times while still working. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_723", "text": "The first heart assist device was approved by the FDA in 1994, and two more received approval in 1998. [ 94 ]  While the original assist devices emulated the pulsating heart, newer versions, such as the Heartmate II, [ 95 ]  developed by The Texas Heart Institute of Houston, provides continuous flow. These pumps (which may be  centrifugal  or  axial flow ) are smaller and potentially more durable and last longer than the current generation of total heart replacement pumps. Another major advantage of a VAD is that the patient keeps the natural heart, which may still function for temporary back-up support if the mechanical pump were to stop. This may provide enough support to keep the patient alive until a solution to the problem is implemented. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_724", "text": "In August 2006, an artificial heart was implanted into a 15-year-old girl at the  Stollery Children's Hospital  in  Edmonton ,  Alberta . It was intended to act as a temporary fixture until a donor heart could be found. Instead, the artificial heart (called a  Berlin Heart ) allowed for natural processes to occur and her heart healed on its own. After 146 days, the Berlin Heart was removed, and the girl's heart functioned properly on its own. [ 96 ]  On 16 December 2011 the Berlin Heart gained U.S.  FDA  approval. The device has since been successfully implanted in several children including a 4-year-old Honduran girl at  Children's Hospital Boston . [ 97 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_725", "text": "Several continuous-flow ventricular assist devices have been approved for use in the European Union, and, as of August 2007, were undergoing clinical trials for FDA approval."}
{"_id": "WikiPedia_Cardio$$$corpus_726", "text": "In 2012, Craig Lewis, a 55-year-old Texan, presented at the  Texas Heart Institute  with a severe case of  cardiac amyloidosis . He was given an experimental continuous-flow artificial heart transplant which saved his life. Lewis died 5 weeks later of liver failure after slipping into a coma due to the  amyloidosis . [ 98 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_727", "text": "In 2012, a study published in the New England Journal of Medicine compared the Berlin Heart to extracorporeal membrane oxygenation (ECMO) and concluded that \"a ventricular assist device available in several sizes for use in children as a bridge to heart transplantation [such as the Berlin Heart] was associated with a significantly higher rate of survival as compared with ECMO.\" [ 99 ]  The study's primary author, Charles D. Fraser Jr., surgeon in chief at Texas Children's Hospital, explained: \"With the Berlin Heart, we have a more effective therapy to offer patients earlier in the management of their heart failure. When we sit with parents, we have real data to offer so they can make an informed decision. This is a giant step forward.\" [ 100 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_728", "text": "Suffering from end-stage heart failure, former Vice President  Dick Cheney  underwent a procedure at INOVA Fairfax Hospital, in Fairfax Virginia in July 2010, to have a Heartmate II VAD implanted. [ 1 ]  In 2012, he received a heart transplant at age 71 after 20 months on a waiting list."}
{"_id": "WikiPedia_Cardio$$$corpus_729", "text": "An  artificial heart valve  is a  one-way valve   implanted  into a person's  heart  to replace a  heart valve  that is not functioning properly ( valvular heart disease ). Artificial heart valves can be separated into three broad classes: mechanical heart valves, bioprosthetic tissue valves and engineered tissue valves."}
{"_id": "WikiPedia_Cardio$$$corpus_730", "text": "The human heart contains four valves:  tricuspid valve ,  pulmonary valve ,  mitral valve  and  aortic valve . Their main purpose is to keep blood flowing in the proper direction through the heart, and from the heart into the major blood vessels connected to it (the  pulmonary artery  and the  aorta ). Heart valves can malfunction for a variety of reasons, which can impede the flow of blood through the valve ( stenosis ) and/or let blood flow backwards through the valve ( regurgitation ). Both processes put strain on the heart and may lead to serious problems, including  heart failure . While some dysfunctional valves can be treated with drugs or repaired, others need to be replaced with an artificial valve. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_731", "text": "A heart contains four valves (tricuspid, pulmonary, mitral and aortic valves) which open and close as blood passes through the heart. [ 3 ]  Blood enters the heart in the right atrium and passes through the  tricuspid valve  to the right ventricle. From there, blood is pumped through the  pulmonary valve  to enter the lungs. After being oxygenated, blood passes to the left atrium, where is it pumped through the  mitral valve  to the left ventricle. The left ventricle pumps blood to the aorta through the  aortic valve ."}
{"_id": "WikiPedia_Cardio$$$corpus_732", "text": "There are many potential causes of heart valve damage, such as birth defects, age related changes, and effects from other disorders, such as rheumatic fever and infections causing  endocarditis .  High blood pressure  and heart failure which can enlarge the heart and arteries, and scar tissue can form after a  heart attack  or injury. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_733", "text": "The three main types of artificial heart valves are mechanical, biological (bioprosthetic/tissue), and tissue-engineered valves. In the US, UK and the European Union, the most common type of artificial heart valve is the bioprosthetic valve. Mechanical valves are more commonly used in Asia and Latin America. [ citation needed ]  Companies that manufacture heart valves include Edwards Lifesciences, [ 5 ]  Medtronic, [ 6 ]  Abbott (St.\u00a0Jude Medical), [ 7 ]  CryoLife, [ 8 ]  and LifeNet Health. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_734", "text": "Mechanical valves come in three main types \u2013 caged ball, tilting-disc and bileaflet \u2013 with various modifications on these designs. [ 10 ]  Caged ball valves are no longer implanted. [ 11 ]  Bileaflet valves are the most common type of mechanical valve implanted in patients today. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_735", "text": "The first artificial heart valve was the caged ball valve, a type of  ball check valve , in which a ball is housed inside a cage. When the heart contracts and the blood pressure in the chamber of the heart exceeds the pressure on the outside of the chamber, the ball is pushed against the cage and allows blood to flow. When the heart finishes contracting, the pressure inside the chamber drops and the ball moves back against the base of the valve forming a seal."}
{"_id": "WikiPedia_Cardio$$$corpus_736", "text": "In 1952,  Charles A. Hufnagel  implanted caged ball heart valves into ten patients (six of whom survived the operation), marking the first success in prosthetic heart valves. [ citation needed ]  A similar valve was invented by Miles 'Lowell' Edwards and  Albert Starr  in 1960, commonly referred to as the Starr-Edwards silastic ball valve. [ 13 ]  This consisted of a silicone ball enclosed in a  methyl metacrylate  cage welded to a ring. The Starr-Edwards valve was first implanted in a human on August 25, 1960, and was discontinued by Edwards Lifesciences in 2007. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_737", "text": "Caged ball valves are strongly associated with blood clot formation, so people who have one required a high degree of  anticoagulation , usually with a target  INR  of 3.0\u20134.5. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_738", "text": "Introduced in 1969, the first clinically available tilting-disc valve was the  Bjork-Shiley valve . [ 15 ]  Tilting\u2011disc valves, a type of  swing check valve , are made of a metal ring covered by an  ePTFE  fabric. The metal ring holds, by means of two metal supports, a disc that opens when the heart beats to let blood flow through, then closes again to prevent blood flowing backwards. The disc is usually made of an extremely hard carbon material ( pyrolytic carbon ), enabling the valve to function for years without wearing out. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_739", "text": "Introduced in 1979, bileaflet valves are made of two semicircular leaflets that revolve around struts attached to the valve housing. With a larger opening than caged ball or tilting-disc valves, they carry a lower risk of blood clots. They are, however, vulnerable to blood backflow. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_740", "text": "The major advantage of mechanical valves over bioprosthetic valves is their greater durability. [ 16 ]  Made from metal and/or  pyrolytic carbon , [ 10 ]  they can last 20\u201330 years. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_741", "text": "One of the major drawbacks of mechanical heart valves is that they are associated with an increased risk of  blood clots . Clots formed by red blood cell and platelet damage can block blood vessels leading to  stroke . People with mechanical valves need to take anticoagulants (blood thinners), such as  warfarin , for the rest of their life. [ 16 ]  Mechanical heart valves can also cause  mechanical hemolytic anemia , a condition where the  red blood cells  are damaged as they pass through the valve. [ citation needed ]   Cavitation , the rapid formation of microbubbles in a fluid such as blood due to a localized drop of pressure, can lead to mechanical heart valve failure, [ 17 ]  so cavitation testing is an essential part of the valve design verification process."}
{"_id": "WikiPedia_Cardio$$$corpus_742", "text": "Many of the complications associated with mechanical heart valves can be explained through  fluid mechanics . For example, blood clot formation is a side effect of high  shear stresses  created by the design of the valves. From an engineering perspective, an ideal heart valve would produce minimal pressure drops, have small regurgitation volumes, minimize turbulence, reduce prevalence of high stresses, and not create flow separations in the vicinity of the valve. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_743", "text": "Implanted mechanical valves can cause foreign body rejection. The blood may coagulate and eventually result in a hemostasis. The usage of anticoagulation drugs will be interminable to prevent thrombosis. [ 18 ] [ non-primary source needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_744", "text": "Bioprosthetic valves are usually made from animal tissue (heterograft/ xenograft ) attached to a metal or polymer support. [ 11 ]  Bovine (cow) tissue is most commonly used, but some are made from porcine (pig) tissue. [ 19 ] [ non-primary source needed ]  The tissue is treated to prevent rejection and  calcification . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_745", "text": "Alternatives to animal tissue valves are sometimes used, where valves are used from human donors, as in aortic  homografts  and pulmonary  autografts . An aortic homograft is an aortic valve from a human donor, retrieved either after their death or from a heart that is removed to be replaced during a heart transplant. [ 12 ]  A pulmonary autograft, also known as the  Ross procedure , is where the aortic valve is removed and replaced with the patient's own  pulmonary valve  (the valve between the right ventricle and the pulmonary artery). A pulmonary homograft (a pulmonary valve taken from a cadaver) is then used to replace the patient's own pulmonary valve. This procedure was first performed in 1967 and is used primarily in children, as it allows the patient's own pulmonary valve (now in the aortic position) to grow with the child. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_746", "text": "Bioprosthetic valves are less likely than mechanical valves to cause blood clots, so do not require lifelong anticoagulation. As a result, people with bioprosthetic valves have a lower risk of bleeding than those with mechanical valves. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_747", "text": "Tissue valves are less durable than mechanical valves, typically lasting 10\u201320 years. [ 20 ]   This means that people with bioprosthetic valves have a higher incidence of requiring another aortic valve replacement in their lifetime. [ 16 ]  Bioprosthetic valves tend to deteriorate more quickly in younger patients. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_748", "text": "In recent years, scientists have developed a new tissue preservation technology, with the aim of improving the durability of bioprosthetic valves. In sheep and rabbit studies, tissue preserved using this new technology had less  calcification  than control tissue. [ 22 ]  A valve containing this tissue is now marketed, but long-term durability data in patients are not yet available. [ 23 ] [ non-primary source needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_749", "text": "Current bioprosthetic valves lack longevity, and will calcify over time. [ 24 ]  When a valve calcifies, the valve cusps become stiff and thick and cannot close completely. [ 24 ]  Moreover, bioprosthetic valves can't grow with or adapt to the patient: if a child has bioprosthetic valves they will need to get the valves replaced several times to fit their physical growth. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_750", "text": "For over 30 years researchers have been trying to grow heart valves  in vitro . [ 25 ]  These tissue\u2011engineered valves involve seeding human cells on to a scaffold. [ 25 ]  The two main types of scaffold are natural scaffolds, such as decellularized tissue, or scaffolds made from degradable polymers. [ 26 ]  The scaffold acts as an  extracellular matrix , guiding tissue growth into the correct 3D structure of the heart valve. [ 26 ] [ 25 ]  Some tissue-engineered heart valves have been tested in clinical trials, [ 26 ]  but none are commercially available."}
{"_id": "WikiPedia_Cardio$$$corpus_751", "text": "Tissue engineered heart valves can be person-specific and 3D modeled to fit an individual recipient [ 27 ]  3D printing is used because of its high accuracy and precision of dealing with different biomaterials. [ 27 ]  Cells that are used for tissue engineered heart valves are expected to secrete the extracellular matrix (ECM). [ 24 ]  Extracellular matrix provides support to maintain the shape of the valves and determines the cell activities. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_752", "text": "Scientists can follow the structure of heart valves to produce something that looks similar to them, but since tissue engineered valves lack the natural cellular basis, they either fail to perform their functions like natural heart valves, or function when they are implanted but gradually degrade over time. [ citation needed ]  An ideal tissue engineered heart valve would be non-thrombogenic, biocompatible, durable, resistant to calcification, grow with the surrounding heart, and exhibit a physiological hemodynamic profile. [ 29 ]  To achieve these goals, the scaffold should be carefully chosen\u2014there are three main candidates: decellularized ECM (xenografts or homografts), natural polymers, and synthetic polymers. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_753", "text": "Mechanical and tissue valves are made of different materials. Mechanical valves are generally made of titanium and carbon. [ 30 ]  Tissue valves are made up of human or animal tissue. The valves composed of human tissue, known as allografts or homografts, are from donors' human hearts. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_754", "text": "Mechanical valves can be a better choice for younger people and people at risk of valve deterioration due to its durability. It is also preferable for people who are already taking blood thinners and people who would be unlikely to tolerate another valve replacement operation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_755", "text": "Tissue valves are better for older age groups as another valve replacement operation may not be needed in their lifetime. Due to the risk of forming blood clots for mechanical valves and severe bleeding as a major side effect of taking blood-thinning medications, people who have a risk of blood bleeding and are not willing to take warfarin may also consider tissue valves. Other patients who may be more suitable for tissue valves are people who have other planned surgeries and unable to take blood-thinning medications. People who plan to become pregnant may also consider tissue valves as warfarin causes risks in pregnancy. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_756", "text": "An artificial heart valve should ideally function like a natural heart valve. [ 11 ]  The functioning of natural heart valves is characterized by many advantages:"}
{"_id": "WikiPedia_Cardio$$$corpus_757", "text": "The performance of an artificial heart valve can be tested  in vitro  before clinical use by means of a  pulse duplicator . [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_758", "text": "Artificial heart valves are expected to last from 10 to 30 years. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_759", "text": "The most common problems with artificial heart valves are various forms of degeneration, including gross billowing of leaflets, ischemic mitral valve pathology, and minor chordal lengthening. [ 24 ]  The repairing process of the artificial heart valve regurgitation and stenosis usually requires an open-heart surgery, and a repair or partial replacement of regurgitant valves is usually preferred. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_760", "text": "Researchers are investigating catheter-based surgery that allows repair of an artificial heart valve without large incisions. [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_761", "text": "Researchers are investigating Interchangeable Prosthetic Heart Valve that allows redo and fast-track repair of an artificial heart valve.  [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_762", "text": "Atrial flutter  ( AFL ) is a common  abnormal heart rhythm  that starts in the  atrial chambers  of the  heart . [ 1 ]   When it first occurs, it is usually associated with a  fast heart rate  and is classified as a type of  supraventricular tachycardia . [ 2 ]  Atrial flutter is characterized by a sudden-onset (usually) regular abnormal heart rhythm on an  electrocardiogram  (ECG) in which the heart rate is fast. Symptoms may include  a feeling of the heart beating too fast, too hard, or skipping beats , chest discomfort,  difficulty breathing , a feeling as if one's stomach has dropped, a feeling of being light-headed, or  loss of consciousness ."}
{"_id": "WikiPedia_Cardio$$$corpus_763", "text": "Although this abnormal heart rhythm typically occurs in individuals with cardiovascular disease (e.g.,  high blood pressure ,  coronary artery disease , and  cardiomyopathy ) and  diabetes mellitus , it may occur spontaneously in people with otherwise normal hearts. It is typically not a stable rhythm and often degenerates into  atrial fibrillation  (AF). [ 3 ]   But rarely does it persist for months or years. Similar to the abnormal heart rhythm atrial fibrillation, atrial flutter also leads to poor contraction of the atrial chambers of the heart. This leads to the pooling of the blood in the heart and can lead to the formation of  blood clots  in the heart, which poses a significant risk of  breaking off and traveling through the bloodstream , resulting in  strokes ."}
{"_id": "WikiPedia_Cardio$$$corpus_764", "text": "A supraventricular tachycardia with a ventricular heart rate of 150 beats per minute is suggestive (though not necessarily diagnostic) of atrial flutter. Administration of  adenosine  in the vein (intravenously) can help medical personnel differentiate between atrial flutter and other forms of supraventricular tachycardia. [ 2 ]  Immediate treatment of atrial flutter centers on slowing the heart rate with medications such as  beta blockers  (e.g.,  metoprolol ) or  calcium channel blockers  (e.g.,  diltiazem ) if the affected person is not having chest pain, has not lost consciousness, and if their blood pressure is normal (known as stable atrial flutter). If the affected person is having chest pain, has lost consciousness, or has  low blood pressure  (unstable atrial flutter), then an urgent  electrical shock to the heart  to restore a normal heart rhythm is necessary. Long-term  use of blood thinners  (e.g.,  warfarin  or  apixaban ) is an important component of treatment to reduce the risk of blood clot formation in the heart and resultant strokes. [ 3 ] [ 4 ]   Medications used to restore a normal heart rhythm (antiarrhythmics)  such as  ibutilide  effectively control atrial flutter about 80% of the time when they are started but atrial flutter recurs at a high rate (70\u201390% of the time) despite continued use. [ 1 ]  Atrial flutter can be treated more definitively with a technique known as  catheter ablation . This involves the insertion of a catheter through a vein in the groin which is followed up to the heart and is used to identify and interrupt the electrical circuit causing the atrial flutter (by creating a small burn and scar)."}
{"_id": "WikiPedia_Cardio$$$corpus_765", "text": "Atrial flutter was first identified as an independent medical condition in 1920 by the British physician  Sir Thomas Lewis  (1881\u20131945) and colleagues. [ 5 ]  AFL is the second most common pathologic supraventricular tachycardia but occurs at a rate less than one-tenth of the most common supraventricular tachycardia (atrial fibrillation). [ 2 ] [ 3 ]  The overall incidence of AFL has been estimated at 88 cases per 100,000  person-years . The incidence of AFL is significantly lower (~5 cases/100,000 person-years) in those younger than age 50 and is far more common (587 cases/100,000 person-years) in those over 80 years of age. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_766", "text": "While atrial flutter can sometimes go unnoticed, its onset is often marked by characteristic sensations of the heart feeling like it is  beating too fast or hard .  Such sensations usually last until the episode resolves, or until the heart rate is controlled. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_767", "text": "Atrial flutter is usually well-tolerated initially (a high heart rate is, for most people just a normal response to exercise); however, people with other underlying heart diseases (such as  coronary artery disease ) or poor exercise tolerance may rapidly develop symptoms, such as  shortness of breath , chest pain, lightheadedness or dizziness,  nausea  and, in some patients, nervousness and feelings of impending doom. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_768", "text": "Prolonged atrial flutter with fast heart rates may lead to decompensation with loss of normal heart function ( heart failure ). This may manifest as exercise intolerance (exertional breathlessness), difficulty breathing at night, or swelling of the legs and/or abdomen. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_769", "text": "Although often regarded as a relatively benign heart rhythm problem, atrial flutter shares the same complications as the related condition  atrial fibrillation .  There is a paucity of published data directly comparing the two, but overall mortality in these conditions appears to be very similar. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_770", "text": "Rapid heart rates may produce significant symptoms in patients with pre-existing heart disease and can lead to  inadequate blood flow to the heart muscle  and even  a heart attack . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_771", "text": "In rare situations, atrial flutter associated with a fast heart rate persists for an extended period of time without being corrected to a normal heart rhythm and leads to a  tachycardia-induced cardiomyopathy . [ 1 ]  Even in individuals with a normal heart, if the heart beats too quickly for a prolonged period of time, this can lead to ventricular decompensation and heart failure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_772", "text": "Because there is little, if any, effective contraction of the  atria , there is stasis (pooling) of blood in the atria.  Stasis of blood in susceptible individuals can lead to the formation of a  thrombus  (blood clot) within the heart. A thrombus is most likely to form in the  atrial appendages . A blood clot in the left atrial appendage is particularly important as the left side of the heart supplies blood to the entire body through the arteries. Thus, any thrombus material that dislodges from this side of the heart can  embolize (break off and travel)  to the brain's arteries, with the potentially devastating consequence of a  stroke . Thrombus material can embolize to any other portion of the body, though usually with a less severe outcome. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_773", "text": "Sudden death is not directly associated with atrial flutter.  However, in individuals with a pre-existing accessory conduction pathway, such as the  bundle of Kent  in  Wolff-Parkinson-White syndrome , the accessory pathway  may  conduct activity from the atria to the ventricles at a rate that the AV node would usually block.  Bypassing the AV node, the atrial rate of 300 beats/minute leads to a ventricular rate of 300 beats/minute (1:1 conduction).  Even if the ventricles are able to sustain a cardiac output at such a high rate, 1:1 flutter with time may degenerate into  ventricular fibrillation , causing hemodynamic collapse and  death . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_774", "text": "Atrial flutter is caused by a  re-entrant rhythm . This usually occurs along the cavo-tricuspid isthmus of the right atrium though atrial flutter can originate in the left atrium as well. Typically initiated by a  premature electrical impulse arising in the atria , atrial flutter is propagated due to differences in  refractory periods  of atrial tissue. This creates electrical activity that moves in a localized self-perpetuating loop, which usually lasts about 200 milliseconds for the complete circuit. For each cycle around the loop,  an electric impulse results and propagates through the atria. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_775", "text": "The impact and symptoms of atrial flutter depend on the heart rate of the affected person. Heart rate is a measure of ventricular rather than atrial activity. Impulses from the atria are conducted to the ventricles through the  atrio-ventricular node (AV node) . In a person with atrial flutter, a 12-lead  electrocardiogram (ECG)  will demonstrate the atrial chambers of the heart contracting at a rate of 280\u2013300 beats per minute whereas the ventricular chambers of the heart typically beat at a rate of 140\u2013150 beats per minute. [ 2 ]  Due primarily to its longer refractory period, the AV node exerts a protective effect on heart rate by blocking atrial impulses in excess of about 180 beats/minute, for the example of a resting heart rate. (This block is dependent on the age of the patient and can be calculated roughly by subtracting patient age from 220).  If the flutter rate is 300 beats per minute, only half of these impulses will be conducted, giving a ventricular rate of 150 beats per minute, or a 2:1  heart block .  The addition of rate-controlling drugs or conduction system disease can increase this block substantially [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_776", "text": "Typical atrial flutter is recognized on an electrocardiogram by the presence of characteristic \"flutter waves\" at a regular rate of 250 to 350 beats per minute. Flutter waves may not be evident on an ECG in atypical forms of atrial flutter. Individual flutter waves may be symmetrical, resembling p-waves, or maybe asymmetrical with a \"sawtooth\" shape, rising gradually and falling abruptly or vice versa. If atrial flutter is suspected clinically but is not clearly evident on ECG, acquiring a  Lewis lead  ECG may be helpful in revealing flutter waves. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_777", "text": "There are two types of atrial flutter, the common  type I  and rarer  type II . [ 11 ]   Most individuals with atrial flutter will manifest only one of these.  Rarely someone may manifest both types; however, they can manifest only one type at a time. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_778", "text": "Type I atrial flutter, also known as common atrial flutter or typical atrial flutter, has an atrial rate of 240 to 340 beats/minute.  However, this rate may be slowed by  antiarrhythmic agents . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_779", "text": "The reentrant loop circles the right atrium, passing through the  cavo-tricuspid isthmus  \u2013 a body of fibrous tissue in the lower atrium between the  inferior vena cava , and the  tricuspid valve . [ 1 ]   Type I flutter is further divided into two subtypes, known as counterclockwise atrial flutter and clockwise atrial flutter depending on the direction of current passing through the loop. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_780", "text": "Type II (atypical) atrial flutter follows a significantly different re-entry pathway to type I flutter, and is typically faster, usually 340\u2013350 beats/minute. [ 12 ]  Atypical atrial flutter rarely occurs in people who have not undergone previous heart surgery or previous catheter ablation procedures. Left atrial flutter is considered atypical and is common after incomplete left atrial ablation procedures. [ 13 ]  Atypical atrial flutter originating from the right atrium and heart's septum have also been described. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_781", "text": "In general, atrial flutter should be  managed in the same way as atrial fibrillation .  Because both rhythms can lead to the formation of a  blood clot  in the atrium, individuals with atrial flutter usually require some form of  anticoagulation  or  antiplatelet  agent.  Both rhythms can be associated with dangerously fast heart rates and thus require medication to control the heart rate (such as  beta blockers  or  calcium channel blockers ) and/or rhythm control with  class III antiarrhythmics  (such as  ibutilide  or  dofetilide ). However, atrial flutter is more resistant to correction with such medications than atrial fibrillation. [ 1 ]  For example, although the class III antiarrhythmic agent ibutilide is an effective treatment for atrial flutter, rates of recurrence after treatment are quite high (70\u201390%). [ 1 ]   Additionally, there are some specific considerations particular to treatment of atrial flutter. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_782", "text": "Atrial flutter is considerably more sensitive to electrical  direct current cardioversion  than atrial fibrillation, with a shock of only 20 to 50 Joules commonly being enough to cause a return to a normal heart rhythm (sinus rhythm). Exact placement of the pads does not appear important. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_783", "text": "Due to the reentrant nature of atrial flutter, it is often possible to ablate the circuit that causes atrial flutter with  radiofrequency catheter ablation  or  pulsed field ablation . Catheter ablation wasconsidered to be a first-line treatment method for many people with typical atrial flutter due to its high rate of success (>90%) and low incidence of complications, [ 1 ]  although pulsed field ablation now offers a non-thermal option. This is done in the cardiac electrophysiology lab by causing a ridge of scar tissue in the cavotricuspid isthmus that crosses the path of the circuit that causes atrial flutter. Eliminating conduction through the isthmus prevents reentry, and if successful, prevents the recurrence of the atrial flutter. Atrial fibrillation often occurs (30% within 5 years) after catheter ablation for atrial flutter. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_784", "text": "Auenbrugger's sign  is a bulging of the  epigastrium  seen in cases of severe  pericardial effusion . It is often not spotted because pericardial effusion can be caught on  echocardiography  before it progresses this far. [ 1 ]  It is named after  Joseph Leopold Auenbrugger . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_785", "text": "Auenbrugger's sign  at  Who Named It?"}
{"_id": "WikiPedia_Cardio$$$corpus_786", "text": "This  medical sign  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_787", "text": "The  Baskerville effect , or the  Hound of the Baskervilles effect , is the alleged  self-fulfilling prophecy  that there is an increase in rate of mortality through  heart attacks  on days considered unlucky because of the psychological stress this causes on superstitious people.  The term derives from the  Sherlock Holmes   novel   The Hound of the Baskervilles  in which a hellish-looking dog chases Sir Charles Baskerville, sufferer of a chronic heart disease. According to legend, the dog cursed his family, Baskerville runs in great fear and dies of a heart attack \"with an expression of horror in his face\"."}
{"_id": "WikiPedia_Cardio$$$corpus_788", "text": "The Baskerville effect was named by David Phillips and his colleagues at the  University of California, San Diego , on a paper where they reported that the daily number of deaths of  Chinese  and  Japanese Americans  from heart attacks between 1973 and 1998 was 7 percent higher on the fourth of the month compared to the average for the other days in that month, while this was not observed in the general American population. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_789", "text": "Four (\u56db, formal writing: \u8086,  pinyin  si4) is considered an  unlucky number  in  Chinese , and hence in the  Japanese  and  Korean , because it sounds like \"death\" (\u6b7b  pinyin  si3).  Some Chinese and Japanese  hotels  and hospitals do not use it as a room number (the way that American architects don't use 13 as a floor number in office or hotel buildings). The authors, seeing how telephone line subscribers could choose the last four digits in their telephone numbers, found evidence that  the number 4 is avoided  among Chinese and Japanese Americans by searching the California Yellow Pages for telephone numbers of Chinese and Japanese restaurants, and finding that these had significantly fewer numbers 4 in this last section (366 out of 4748, or 7.71 percent) than it would be expected by chance (10 percent), a pattern not observed on restaurants listed as American. [ 1 ]  An analysis of the 20,000 computerized death certificates of Asian-Americans in San Diego, Phillips discovered that there was a 13 percent uptick in death rates on the fourth of the month. [ 2 ] [ 3 ]  The hypothesis was that the peak was caused by stress induced by the  superstition  surrounding this number. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_790", "text": "In 2002,  Gary Smith  commented that Phillips and colleagues had omitted data from several heart disease categories, picking only those that happened to have a higher rate on the fourth day, calling them \"chronic heart diseases\".  Smith also pointed out that they had not done this on their previous studies of Jewish deaths near  Passover  and Chinese deaths near the  Harvest Moon , where they had used all heart disease categories. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_791", "text": "Smith also found no statistically relevant peaks on day 4 in data from 1969\u20131988 and 1999\u20132001 for total coronary deaths, inpatients, or the subset of heart diseases used by Phillips and colleagues, adding that there were more deaths on day 5 in the 1969\u20131988 data, and more deaths on day 3 in the 1999\u20132001 data. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_792", "text": "In 2003, Nirmal Panesar and colleagues looked for this effect on the Chinese population of  Hong Kong .  They looked at mortality data from 1995 to 2000, comparing the days of the month with \"deathly connotations\" (4, 14 and 24) with the other days of the month on both the  Lunar  and  Gregorian  calendars, and found no statistically significant difference. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_793", "text": "In early 2018,  Jonathan Jarry  analysed this phenomenon, citing both Smith's and Panesar et al's papers, pointing out that, if the effect was real, a bigger effect would be seen in Asia, while the opposite occurs. [ 6 ]  Jarry states that the peak observed on the original study appears because of what the researchers decided to compare it to, and quotes cardiologist  Christopher Labos  as concluding that \"while the number of deaths on day 4 may be higher than average, it is not actually statistically higher than any individual day.\""}
{"_id": "WikiPedia_Cardio$$$corpus_794", "text": "Bendopnea  is a newly described symptom, normally of  heart failure , meaning  shortness of breath  felt when leaning forward. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  It was introduced by Thibodeau et al. in 2014. [ 1 ] [ 2 ]  Patients with heart failure often experience this when bending over to tie a shoe, putting socks on, or other activities requiring bending downwards. [ 1 ] [ 2 ]  It has been defined as occurring within 30 seconds of bending over, but could occur in as few as 8 seconds in severe cases. [ 3 ]  When a patient is in heart failure, it often means the  ventricular filling pressures  are high at baseline. [ 1 ] [ 2 ]  When said person bends forward, it causes a further increase in ventricular filling pressures that causes dyspnea, especially in patients with lower  cardiac indices . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_795", "text": "The term \"bendopnea\" (meaning \"bent\" and \"breath\") was coined to be easily identifiable among patients and physicians. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_796", "text": "Bendopnea should be distinguished from  orthopnea  (shortness of breath while lying down),  trepopnea  (shortness of breath while lying on one side), and  platypnea  (shortness of breath relieved by lying down and worsened when upright) with or without  orthodeoxia  (oxygen desaturation)."}
{"_id": "WikiPedia_Cardio$$$corpus_797", "text": "This medical  symptom  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_798", "text": "A  bioartificial heart  is an engineered  heart  that contains the  extracellular structure  of a  decellularized  heart and cellular components from a different source. Such hearts are of particular interest for therapy as well as research into  heart disease . The first bioartificial hearts were created in 2008 using cadaveric rat hearts. [ 1 ] [ 2 ] [ 3 ]  In 2014, human-sized bioartificial pig hearts were constructed. [ 4 ]  Bioartificial hearts have not been developed yet for clinical use, although the recellularization of porcine hearts with human cells opens the door to  xenotransplantation . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_799", "text": "Heart failure is one of the leading causes of death. In 2013, an estimate of 17.3 million deaths per year out of the 54 million total deaths was caused by cardiovascular diseases, meaning that 31.5% of the world's total death was caused by this. [ 6 ]  Often, the only viable treatment for end-stage heart failure is organ transplantation. [ 5 ]  Currently organ supply is insufficient to meet the demand, which presents a large limitation in an end-stage treatment plan. [ 2 ] [ 5 ]  A theoretical alternative to traditional transplantation processes is the engineering of personalized bioartificial hearts. Researchers have had many successful advances in the engineering of cardiovascular tissue and have looked towards using decellularized and recellularized cadaveric hearts in order to create a functional organ. [ 5 ]  Decellularization-recellularization involves using a cadaveric heart, removing the cellular contents while maintaining the protein matrix ( decellularization ), and subsequently facilitating growth of appropriate cardiovascular tissue inside the remaining matrix (recellularization). [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_800", "text": "Over the past years, researchers have identified populations of cardiac stem cells that reside in the adult human heart. This discovery sparked the idea of regenerating the heart cells by taking the stem cells inside the heart and reprogramming them into cardiac tissues. [ 7 ]  The importance of these stem cells are self-renewal, the ability to differentiate into  cardiomyocytes , endothelial cells and smooth vascular muscle cells, and clonogenicity. These stem cells are capable of becoming  myocytes , which are for stabilizing the topography of the intercellular components, as well as to help control the size and shape of the heart, as well as vascular cells, which serve as a cell reservoir for the turnover and the maintenance of the mesenchymal tissues. [ 7 ]  However,  in vivo  studies have demonstrated that the regenerative ability of implanted cardiac stem cells lies in the associated macrophage-mediated immune response and concomitant fibroblast-mediated wound healing and not in their functionality, since these effects were observed for both live and dead stem cells. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_801", "text": "The preferred method to remove all cellular components from a heart is perfusion decellularization. This technique involves perfusing the heart with detergents such as  SDS  and  Triton X-100  dissolved in  distilled water . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_802", "text": "The remaining ECM is composed of structural elements such as collagen, laminin, elastin and fibronectin. The ECM scaffold promotes proper cellular proliferation and differentiation, vascular development, as well as providing mechanical support for cellular growth. [ 5 ]  Because minimal DNA material remains after the decellularization process, the engineered organ is biocompatible with the transplant recipient, regardless of species.  Unlike traditional transplant options, recellularized hearts are less immunogenic and have a decreased risk of rejection. [ 2 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_803", "text": "Once the decellularized heart has been sterilized to remove any pathogens, the recellularization process can occur. [ 2 ]  Multipotent cardiovascular progenitors are then added to the decellularized heart and with additional exogenous growth factors, are stimulated to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_804", "text": "The most promising results come from recellularized rat hearts. After only 8 days of maturation, the heart models were stimulated with an electrical signal to provide pacing. The heart models showed a unified contraction with a force equivalent to ~2% of a normal rat heart or ~25% of that of a 16-week-old human heart. [ 1 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_805", "text": "Although far from use in a clinical setting, there have been great advances in the field of bioartificial heart generation. [ 2 ] [ 5 ] [ 10 ]   The use of decellularization and recellularization processes, has led to the production of a three dimensional matrix that promotes cellular growth; the repopulation of the matrix containing appropriate cell composition; and the bioengineering of organs demonstrating functionality (limited) and responsiveness to stimuli. [ 2 ] [ 5 ]  This area shows immense promise and with future research may redefine treatment of end stage heart failure."}
{"_id": "WikiPedia_Cardio$$$corpus_806", "text": "The  Biomedical Research Center  (BRC) is a research center at  Qatar University  focusing on biomedical research. BRC was founded in 2014, and partners with the  Ministry of Public Health (Qatar) , and  Hamad Medical Corporation (HMC) . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_807", "text": "The incidence of genetic disorders in  Qatar  is high, [ 4 ]  with the top three causes of death in the country being cancer, heart diseases, and diabetes. [ 5 ] [ 6 ]  The government saw the creation of BRC as a strategy for proactively preventing diseases to help foster public health. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_808", "text": "BRC labs received the  ISO/IEC - 17025  accreditation from the American Association for Laboratory Accreditation (A2LA). [ 9 ]  This research center focus on  infectious diseases  ( virology  and  microbiology ),  metabolic disorders , and biomedical  omics . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_809", "text": "Since its establishment in 2014, the BRC has published over 530 research papers. [ 11 ] [ 12 ]  The centre's research projects encompass a range of areas, including:"}
{"_id": "WikiPedia_Cardio$$$corpus_810", "text": "BRC Introduced the use of  zebrafish  as an animal model in biomedical research [ 36 ] [ 37 ] [ 32 ] [ 38 ] [ 39 ] [ 40 ]  and established a facility for it in 2015. [ 41 ] [ 42 ] [ 43 ]  The facility is used as a research unit to study many genetic diseases. [ 32 ]  The Ministry of Public Health articulated an institutional research policy (IRP) on the use of zebrafish in research, [ 44 ]  which Qatar University backed."}
{"_id": "WikiPedia_Cardio$$$corpus_811", "text": "The BRC facilities include: [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_812", "text": "A  bioresorbable stent  is a tube-like device ( stent ) that is used to open and widen clogged heart arteries and then dissolves or is absorbed by the body. It is made from a material that can release a drug to prevent scar tissue growth. It can also restore normal vessel function and avoid long-term complications of metal stents. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_813", "text": "In medicine, a  stent  is any device which is inserted into a  blood vessel  or other anatomical internal duct to expand it to prevent or alleviate a blockage.  Traditionally, such devices are fabricated from metal mesh and remain in the body permanently or until removed through further surgical intervention.  A bioresorbable stent (also called bioresorbable scaffold, biodegradable stent or naturally-dissolving stent) serves the same purpose, but is manufactured from a material that may dissolve or be absorbed in the body. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_814", "text": "The use of metal  drug-eluting stents  presents some potential drawbacks. These include a predisposition to late stent  thrombosis , prevention of late vessel adaptive or expansive remodeling, hindrance of surgical revascularization, and impairment of imaging with multislice  CT . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_815", "text": "To overcome some of these potential drawbacks, several companies are pursuing the development of bioresorbable scaffolds or bioabsorbable stents. Like metal stents, placement of a bioresorbable stent will restore blood flow and support the vessel through the healing process. However, in the case of a bioresorbable stent, the stent will gradually resorb and be benignly cleared from the body, enabling a natural reconstruction of the arterial wall and restoration of vascular function. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_816", "text": "Studies have shown that the most critical period of vessel healing is largely complete by approximately three to nine months. [ 6 ] [ 7 ] [ 8 ]   Therefore, the goal of a bioresorbable or \"temporary\" stent is to fully support the vessel during this critical period, and then resorb from the body when it is no longer needed."}
{"_id": "WikiPedia_Cardio$$$corpus_817", "text": "Bioabsorbable scaffolds, or naturally dissolving stents, that have been investigated include base materials that are either metals or polymers. While polymer-based scaffolds had a strong presence at first, they have meanwhile lost some appeal due to safety concerns and focus is now moved towards metallic magnesium-based scaffolds. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_818", "text": "Metal stent candidates are  magnesium ,  iron ,  zinc  and their alloys. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_819", "text": "Magnesium -based scaffolds have been approved for use in several countries around the world. The only commercially available magnesium-based scaffold consists of a magnesium alloy, approximately 95% of which resorbs within one year of implantation. [ 11 ] [ 12 ] [ 13 ]  Thousands of commercially available magnesium-based scaffolds have been implanted. Clinical results suggest that magnesium-based scaffolds may be a viable option in avoiding the drawbacks of permanent stents. [ 14 ] [ 15 ] [ 16 ] [ 17 ]  While degrading harmlessly, it has been shown to possess a functional degradation time of about 30 days  in vivo .  This is much short of the three-to-six month window desired for bioabsorbable stents.  Thus, much attention has been given to drastically reducing the rate of magnesium corrosion by alloying, coating, etc. [ 18 ]  Many novel methods have surfaced to minimize the penetration rate and hydrogen evolution rate (or, in layman's terms, the  corrosion  rate).  One of the most successful has involved the creation of  bioabsorbable metallic glasses  via rapid solidification.  Other, alternative solutions have included the development of magnesium\u2013 rare-earth  (Mg-RE) alloys, which benefit from the low  cytotoxicity  of RE elements.  Coatings  and sophisticated materials processing routes are currently being developed to further decrease the corrosion rate. However, a number of issues remain limiting the further development of Mg biomaterials in general. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_820", "text": "Iron  stents were shown using an  in vivo  evaluation method based on the murine abdominal aorta to generate an iron oxide-filled cavity in the vascular wall [ 20 ]  that is unlikely to be metabolized safely. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_821", "text": "Zinc  shows desirable physiological corrosion behavior, meeting a benchmark penetration rate of 20 micrometers per year. [ 22 ]  However, Zn has poor mechanical behavior, with a tensile strength of around 100\u2013150 MPa and an elongation of 0.3\u20132%, which is far from reaching the strength required as an orthopedic implant or stent material. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_822", "text": "Polymer-based stents have been approved for use in some countries around the world. These are based on poly(L-lactide) ( PLLA ), chosen because it is able to maintain a radially strong scaffold that breaks down over time into lactic acid, a naturally occurring molecule that the body can use for metabolism. Other polymers in development include tyrosine poly carbonate and salicylic acid. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_823", "text": "An example of a naturally dissolving stent is the 'Absorb' stent  'produced by  Abbott [ 25 ]  that has several design components and features:  base scaffold : a poly(L-lactide) polymer similar to that in dissolvable stitches is shaped into a tube made up of zigzag hoops linked together by bridges; drug-eluting layer': a mixture of poly-D, L-lactide (PDLLA) and everolimus; 'markers': a pair of radio-opaque platinum markers at the ends that allow the device to be visualized during angiography; 'delivery system': a balloon delivery system. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_824", "text": "Recently however, Polymer-based scaffolds, in particular Poly-L-Lactide Acid (PLLA) scaffolds, have raised serious concerns on the scaffold performance particularly in terms of safety which led to the commercial discontinuation of the main representative Absorb. [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_825", "text": "Clinical research has shown that resorbable scaffolds, or naturally dissolving stents, offer comparable efficacy and safety profile to drug-eluting stents. Specifically, the Magmaris resorbable magnesium scaffold [ 28 ]  has reported a favorable safety profile with low target lesion failure and scaffold thrombosis rates. These clinical results are comparable to thin-strutted drug-eluting stents in similar patient populations. [ 29 ] [ 30 ] [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_826", "text": "The Absorb naturally dissolving stent has also been investigated in single-arm trials and in randomized trials comparing it to a  drug-eluting stent . Early and late major adverse cardiac events, revascularizations, and scaffold thromboses have been uncommon and similar to the Xience DES, a market leader in the drug eluting stent category. [ 33 ] [ 34 ] [ 35 ] [ 36 ] [ 37 ]  Studies in real-world patients are ongoing. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_827", "text": "Imaging studies show that the Absorb naturally dissolving stent begins to dissolve from six to 12 months and is fully dissolved between two and three years after it is placed in the artery. [ 35 ]  Two small platinum markers remain to mark the location of the original PCI. The artery is able to dilate and contract, called vasomotion, similar to a healthy blood vessel at two years. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_828", "text": "In the US, the first fully absorbable stent was approved by FDA in 2016. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_829", "text": "3N56 ,  1YK1"}
{"_id": "WikiPedia_Cardio$$$corpus_830", "text": "4879"}
{"_id": "WikiPedia_Cardio$$$corpus_831", "text": "18158"}
{"_id": "WikiPedia_Cardio$$$corpus_832", "text": "ENSG00000120937"}
{"_id": "WikiPedia_Cardio$$$corpus_833", "text": "ENSMUSG00000029019"}
{"_id": "WikiPedia_Cardio$$$corpus_834", "text": "P16860"}
{"_id": "WikiPedia_Cardio$$$corpus_835", "text": "P40753"}
{"_id": "WikiPedia_Cardio$$$corpus_836", "text": "NM_002521"}
{"_id": "WikiPedia_Cardio$$$corpus_837", "text": "NM_001287348 NM_008726"}
{"_id": "WikiPedia_Cardio$$$corpus_838", "text": "NP_002512 NP_002512"}
{"_id": "WikiPedia_Cardio$$$corpus_839", "text": "NP_001274277 NP_032752"}
{"_id": "WikiPedia_Cardio$$$corpus_840", "text": "Brain natriuretic peptide  ( BNP ), also known as  B-type natriuretic peptide , is a  hormone  secreted by  cardiomyocytes  in the  heart ventricles  in response to stretching caused by increased ventricular blood volume. [ 5 ]  BNP is one of the three natriuretic peptides, in addition to atrial natriuretic peptide ( ANP ) and C-type natriuretic peptide (  CNP ). [ 6 ]  BNP was first discovered in porcine brain tissue in 1988, which led to its initial naming as \"brain natriuretic peptide\", although subsequent research revealed that BNP is primarily produced and secreted by the ventricular myocardium (heart muscle) in response to increased ventricular blood volume and stretching. To reflect its true source, BNP is now often referred to as \"B-type natriuretic peptide\" while retaining the same acronym.  [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_841", "text": "The 32-amino acid polypeptide BNP-32 is secreted attached to a 76\u2013amino acid  N-terminal  fragment in the  prohormone  called  NT-proBNP  (BNPT), which is biologically inactive. Once released, BNP binds to and activates the  atrial natriuretic factor receptor NPRA , and to a lesser extent  NPRB , in a fashion similar to  atrial natriuretic peptide  (ANP) but with 10-fold lower affinity. The  biological half-life  of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing."}
{"_id": "WikiPedia_Cardio$$$corpus_842", "text": "The physiologic actions of BNP are similar to those of ANP and include decrease in  systemic   vascular resistance  and  central venous pressure  as well as an increase in  natriuresis . The net effect of these peptides is a decrease in blood pressure due to the decrease in systemic vascular resistance and, thus, afterload. Additionally, the actions of both BNP and ANP result in a decrease in cardiac output due to an overall decrease in central venous pressure and preload as a result of the reduction in blood volume that follows natriuresis and diuresis. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_843", "text": "BNP is synthesized as a 134-amino acid preprohormone (preproBNP), encoded by the human gene NPPB. Removal of the 26-residue N-terminal signal peptide generates the prohormone, proBNP, which is stored intracellularly as an O-linked  glycoprotein ; proBNP is subsequently cleaved between arginine-102 and serine-103 by a specific convertase (probably  furin  or  corin ) into NT-proBNP and the biologically active 32-amino acid polypeptide BNP-32, which are secreted into the blood in equimolar amounts. [ 9 ] [ 10 ]  Cleavage at other sites produces shorter BNP peptides with unknown biological activity. [ 11 ]  Processing of proBNP may be regulated by O-glycosylation of residues near the cleavage sites. [ 12 ]  The synthesis of BNP in cardiomyocytes is stimulated by pro-inflammatory cell factors, such as interleukin-1\u03b2, interleukin-6 and tumor necrosis factor-\u03b1. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_844", "text": "Relaxes vascular smooth muscle in arterioles and venules by:"}
{"_id": "WikiPedia_Cardio$$$corpus_845", "text": "Promotes uterine spiral artery remodeling, which is important for preventing pregnancy-induced hypertension. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_846", "text": "BNP and NT-proBNP are measured by  immunoassay . [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_847", "text": "A preoperative BNP can be predictive of a risk of an acute cardiac event during vascular surgery.  A  cutoff  of 100 pg/ml has a  sensitivity  of approximately 100%, a  negative predictive value  of approximately 100%, a  specificity  of 90%, and a  positive predictive value  of 78% according to data from the  United Kingdom . [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_848", "text": "BNP is cleared by binding to natriuretic peptide receptors (NPRs) and neutral endopeptidase (NEP). Less than 5% of BNP is cleared renally. NT-proBNP is the inactive molecule resulting from cleavage of the prohormone Pro-BNP and is reliant solely on the kidney for excretion. The  achilles heel  of the NT-proBNP molecule is the overlap in kidney disease in the heart failure patient population. [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_849", "text": "Some laboratories report in units ng per Litre (ng/L), which is equivalent to pg/mL"}
{"_id": "WikiPedia_Cardio$$$corpus_850", "text": "There is a diagnostic 'gray area', often defined as between 100 and 500 pg/mL, for which the test is considered inconclusive, but, in general, levels above 500 pg/ml are considered to be an indicator of heart failure. This so-called gray zone has been addressed in several studies, and using clinical history or other available simple tools can help make the diagnosis. [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_851", "text": "BNP has been suggested as a predictor for a variety of  medical states , including cardiovascular mortality in diabetics [ 28 ]  and cardiac impairment in cancer patients. [ 29 ] [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_852", "text": "BNP was found to have an important role in prognostication of heart surgery patients [ 31 ]  and in the emergency department. [ 32 ]  It has been shown that combining BNP with other tools like  impedance cardiography  (ICG) can improve early diagnosis of heart failure and advance prevention strategies. [ 33 ] [ 34 ]  Utility of BNP has also been explored in various settings like  preeclampsia ,  intensive care , shock and  end-stage renal disease  (ESRD). [ 35 ] [ 36 ] [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_853", "text": "The effect or race and gender on value of BNP and its utility in that context has been studied extensively. [ 38 ] [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_854", "text": "The BNP test is used as an aid in the diagnosis and assessment of severity of heart failure. A recent meta-analysis concerning effects of BNP testing on clinical outcomes of patients presenting to the emergency department with acute dyspnea revealed that BNP testing led to a decrease in admission rates and decrease in mean length of stay, although neither was statistically significant. Effects on all cause hospital mortality was inconclusive. [ 41 ]  The BNP test is also used for the risk stratification of patients with acute coronary syndromes. [ 42 ] [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_855", "text": "When interpreting an elevated BNP level, values may be elevated due to factors other than heart failure. Lower levels are often seen in obese patients. [ 44 ]  Higher levels are seen in those with renal disease, in the absence of heart failure."}
{"_id": "WikiPedia_Cardio$$$corpus_856", "text": "Recombinant BNP,  nesiritide , has been suggested as a treatment for decompensated heart failure.  However, a clinical trial failed to show a benefit of nesiritide in patients with  acute decompensated heart failure . [ 45 ]  Blockade of  neprilysin , a protease known to degrade members of the natriuretic peptide family, has also been suggested as a possible treatment for heart failure. Dual administration of neprilysin inhibitors and  angiotensin receptor blockers  has been shown to be advantageous to  ACE inhibitors , the current first-line therapy, in multiple settings. [ 46 ] [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_857", "text": "attribution : copied from  Brain natriuretic peptide  version as of 13:57, 4 December 2019"}
{"_id": "WikiPedia_Cardio$$$corpus_858", "text": "Branchial hearts  are accessory pumps that supplement the action of the  systemic heart  in a  cephalopod 's body. They are  myogenic  in nature. [ 1 ]  Branchial hearts are always in pairs located at the base of the  gills . Each branchial heart consists of a single chamber. [ 1 ] [ 2 ]  They pump blood through the gills via the afferent branchial veins. Since they only circulate  venous blood , branchial hearts function under predominantly  anaerobic  conditions. [ 1 ]  Branchial hearts also appear to be involved in  hemocyanin  synthesis. [ 3 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_859", "text": "Each branchial heart is directly connected to a branchial heart appendage or pericardial gland. [ 4 ]  The action of the branchial hearts is necessary for the production of primary  urine  in these appendages via pressure filtration. [ 5 ]  Branchial hearts may have evolved from the pericardial glands of  nautiloids , such as those still found in modern  nautiluses . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_860", "text": "This  cephalopod -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_861", "text": "The  European Society of CardioVascular Surgery  (ESCVS) is a medical society founded in 1951 in Turin, Italy. Its first president was  Ren\u00e9 Leriche , first Congress held in Strasbourg in 1952 and its initial members were made up of 40 physicians representing 11 countries in Europe. It is a chapter of the International Society of Angiology, which later became the International Society for Cardiovascular Surgery. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_862", "text": "This article about a scientific organization is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_863", "text": "The  Broadbent inverted sign  is a  clinical sign  in which pulsation is seen on the postero-lateral wall of the left side of the chest in time with  cardiac systole . This was originally thought to be due to an  aneurysm  of the  left atrium , but is now known to be more commonly associated with  left ventricular hypertrophy . [ 1 ]  The sign is named after  Sir William Broadbent . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_864", "text": "Broadbent sign  is a  clinical sign  in which the 11th and 12th  ribs  are indrawn during systolic phase of a heartbeat, with narrowing of the  intercostal space  posteriorly, which is seen in case  adhesive pericarditis  due to  pericardial  adhesions to the  diaphragm . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_865", "text": "During diseased status of adhesive pericarditis, the pericardium of the heart may adhere not only to the  central tendon of diaphragm , but also to a large area of muscular portion of  diaphragm  as well as anterior chest wall. Thus when the heart contracts, the adhesion portion may be dragged inward and downward (if the main contraction force is toward central tendon of diaphragm). [ 2 ]  Besides, absent palpable apical impulse can also be detected in the case of adhesive pericarditis."}
{"_id": "WikiPedia_Cardio$$$corpus_866", "text": "The sign is named after  Walter Broadbent , and was published in his first paper in 1895, although it may have been inspired by his father,  Sir William Broadbent . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_867", "text": "Cannon A waves , or cannon  atrial   waves , are waves seen occasionally in the  jugular vein  of humans with certain  cardiac arrhythmias . When the  atria  and  ventricles  happen to  contract  simultaneously, the  right atrium  contracts against a closed  tricuspid valve , resulting in back pressure into the venous system that can be seen in the  jugular venous pulse  as a high-amplitude \"cannon wave\". [ 1 ] [ 2 ]  It is associated with heart block, in particular  third-degree (complete) heart block . [ 3 ]  It is also seen in  pulmonary hypertension . [ 3 ]  Cannon A waves may also be seen in  ventricular tachycardia  due to the inherent  AV dissociation  of the arrhythmia. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_868", "text": "This wave will cause  pulsation  in the neck and abdomen,  headache ,  cough , and  jaw  pain. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_869", "text": "This  cardiovascular system  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_870", "text": "The  Cardiac Arrest Registry to Enhance Survival  or  CARES  was initiated in 2004 as an agreement between the  Centers for Disease Control and Prevention  and the Department of Emergency Medicine at  Emory University . It is a simple but powerful database that allows cities to collect a small set of performance measures from  9-1-1 ,  first responders ,  fire departments , and  Emergency Medical Services , and link it with outcome data from  hospitals . [ 1 ]  This data enables cities to perform internal benchmarking and improve their response to  cardiac arrest  by strengthening the  chain of  survival  in their community. [ 2 ] [ 3 ]  Because most EMS systems don't measure their response effectively, they are unable to implement change in an effective manner. [ 4 ]  Since the program's inception, survival from cardiac arrest in the city of Atlanta has increased from 3% to 15%. [ 5 ]  For the last half of 2007, survival in Atlanta increased to 31.2%. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_871", "text": "According to the  CDC , the specific objectives of the project are: [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_872", "text": "New Castle County, Delaware"}
{"_id": "WikiPedia_Cardio$$$corpus_873", "text": "The  Cardiac Electrophysiology Society  ( CES ) is an international society of basic and clinical scientists and physicians interested in  cardiac electrophysiology  and  arrhythmias . [ 1 ]  The Cardiac Electrophysiology Society's founder was George Burch in 1949 and its current president is Jonathan C. Makielski, M.D."}
{"_id": "WikiPedia_Cardio$$$corpus_874", "text": "This article about a medical organization or association is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_875", "text": "The  cardiac nerves  are autonomic nerves which supply the  heart . [ 1 ]  They include:"}
{"_id": "WikiPedia_Cardio$$$corpus_876", "text": "The nerves go down to the root of the neck with these following association:"}
{"_id": "WikiPedia_Cardio$$$corpus_877", "text": "Posterior: \"prevertebral fascia overlying anterolateral surface of vertebral bodies\""}
{"_id": "WikiPedia_Cardio$$$corpus_878", "text": "Superior: \"common carotid artery\""}
{"_id": "WikiPedia_Cardio$$$corpus_879", "text": "Inferior: \"subclavian artery\""}
{"_id": "WikiPedia_Cardio$$$corpus_880", "text": "Laterally: \"sympathetic trunk\" [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_881", "text": "This  neuroanatomy  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_882", "text": "Cardiac psychology  is a specialization of  health psychology  that focuses on the primary and secondary prevention of  heart disease  by incorporating strategies to address the  emotional  and  behavioral  barriers to  lifestyle  changes (e.g.  smoking cessation ), and that seeks to enhance recovery in cardiac patients by means of providing patients tools (e.g. stress management and psychotherapy) to cope with life and physical changes associated with their disease. Cardiac psychologists can help cardiac patients across the lifespan: prevention, pre-surgery, post-surgery, and  rehabilitation  of cardiac disease with a particular emphasis on achieving optimal  quality of life  outcomes.\nCardiac psychology  includes both  research  and  clinical practice  aspects."}
{"_id": "WikiPedia_Cardio$$$corpus_883", "text": "The earliest published mention of cardiac psychology in  Western medicine  literature was in 1628 when  William Harvey  wrote that \"a mental disturbance provoking pain, excessive joy, hope or anxiety extends to the heart, where it affects temper.\" [ 1 ] \nResearch labs have been founded at  Tilburg University ,  Tilburg  Netherlands [ 2 ]  led by  Susanne Pedersen , [ 3 ]  and at  East Carolina University ,  Greenville, North Carolina [ 4 ]  led by  Samuel Sears , [ 5 ]  that focus on psychological aspects of cardiac disease. Cardiac psychology as a term was first used by Robert Allan, PhD, and Stephen Schiedt, MD, as a title of their 1996 book,  Heart and Mind: The Practice of Cardiac Psychology  and launched increased attention to the clinical practice of cardiac psychology. More recently, additional texts, such as  Psychotherapy with Cardiac Patients , (2008) by Ellen Dornelas, [ 6 ]  have attempted to update the literature related to clinical techniques used in the care of cardiac patients. Significant research reviews have also been published spanning psychological factors in cardiac care, [ 7 ] [ 8 ]  implantable electronic medical devices ( pacemaker ,  implantable cardioverter-defibrillator , etc.) [ 9 ] [ 10 ]  and  congestive heart failure . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_884", "text": "Cardiogeriatrics , or  geriatric cardiology , is the branch of  cardiology  and  geriatric medicine  that deals with the cardiovascular disorders in  elderly people ."}
{"_id": "WikiPedia_Cardio$$$corpus_885", "text": "Cardiac disorders such as  coronary heart disease , including  myocardial infarction ,  heart failure ,  cardiomyopathy , and  arrhythmias  such as  atrial fibrillation , are common and are a major cause of mortality in elderly people. [ 1 ] [ 2 ] [ 3 ]  Vascular disorders such as  atherosclerosis  and  peripheral arterial disease  cause significant morbidity and mortality in aged people. [ 1 ] [ 2 ] [ 3 ]  Guidelines of the Cardiogeriatrics Department of the Brazilian Cardiology Society were published in English. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_886", "text": "The  American Journal of Geriatric Cardiology [ 4 ]  is the official journal of the  Society of Geriatric Cardiology . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_887", "text": "Cardiomyoplasty  is a surgical procedure in which healthy  muscle  from another part of the body is wrapped around the  heart  to provide support for the failing heart. [ 1 ]  Most often the  latissimus dorsi muscle  is used for this purpose. A special pacemaker is implanted to make the skeletal muscle contract. If cardiomyoplasty is successful and increased cardiac output is achieved, it usually acts as a bridging therapy, giving time for damaged  myocardium  to be treated in other ways, such as remodeling by cellular therapies. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_888", "text": "Cellular cardiomyoplasty  is a method which augments myocardial function and cardiac output by directly growing new muscle cells in the damaged myocardium (heart muscle). Tissue engineering, which is now being categorized as a form of regenerative medicine, can be defined as biomedical engineering to reconstruct, repair, and improve biological tissues. Research efforts in tissue engineering have been ongoing and it is emerging as one of the key areas of medical research. Furthermore, there are vast developments in tissue engineering, which involve leveraging of technologies from biomaterials, molecular medicine, biochemistry, nanotechnology, genetic and biomedical engineering for regeneration and cell expansion targets to restructure and/or repair human organs. Injection of cardiomyogenic and/or angiogenic stem cells have been proposed as alternatives to existing treatments. For cardiovascular application, skeletal myoblasts are of great interest as they can be easily isolated and are associated with high proliferation rate. These cells have also been demonstrated to be  hypoxia -resistant."}
{"_id": "WikiPedia_Cardio$$$corpus_889", "text": "Bone marrow contains different cell populations, which exhibit excellent plasticity toward cardiogenic and endothelial cells. These cell populations are endothelial progenitor cells, hematopoietic stem cells and mesenchymal stem cells.  Adipose tissue host progenitor cells with reported interesting cardiomyogenic and vasculogenic potential in the sense that they improve heart functions and reduce infarction size in rodent animal models.  Subcutaneous adipose tissue is also a source of mesenchymal stem cells and have demonstrated positive outcomes in terms of cardiovascular tissue remodeling. Mammal hearts also host naturally occurring cardiac stem cells which may be capable of differentiating themselves into cardiomyocytes, endothelial cells and cardiac fibroblasts. [ 4 ]  This self-regeneration capacity gives rise to alternatives to classical cellular therapies whereby administration of growth factors such as Thymosin \u03b24 for cell activation and migration are solely necessary. Largely democratized in terms of population information, embryonic stem cells are known for their strong capacity for expansion and differentiation into cardiomyocytes, endothelial cells and cardiac fibroblasts."}
{"_id": "WikiPedia_Cardio$$$corpus_890", "text": "However, if non autologous, immunosuppression therapy is associated with such treatment. Hence, research has been focused on induced pluripotent stem cells (iPSCs) from somatic human tissue. Further to cell and necessary relevant growth factor selection, cell delivery is an important issue.  Indeed, the intracoronary route is the most straightforward cell delivery route as associated with intramyocardial cellular retention; retention rates are however low, i.e. exceed 10%. Washed off cells reach other organs or die, which can be an issue at the time of prepare ICH module 8. Other alternative injection routes have been studied, namely injection  via sternotomy, endomyocardial  and intracoronary routes. Nevertheless, all methods aforementioned have been associated with limited cardiac function improvements and limited cell survival once implanted in the fibrous myocardium."}
{"_id": "WikiPedia_Cardio$$$corpus_891", "text": "To resume, stem cells and delivery routes aforementioned are suitable for cardiomyoplasty as demonstrated safe with some degree of benefit for the patient. However, cardiac remodelling remains limited due to limited cell residency, impact of mechanical forces onto cell survival and tissue hypoxia. Furthermore, lack of cellular electrochemical coupling can lead to arrhythmias. Another point of consideration concerns the use of embryonic stem cells, whereby indifferentiation yields uncontrolled proliferation and possible consequent formation of teratomas. Also iPSCs have been associated with viral infection and eventual oncogenicity. Cardiac tissue engineering is a new technology based on the use of combinations of cells with regenerative capacity, biological and/or synthetic materials, cell signaling agents to induce the regeneration of an organ or damaged tissue. In an ideal scenario, regenerated tissue would reproduce sophisticated asymmetric helicodoidal architecture of the myocardium with the production of specialized extracellular matrix to stimulate vascularization in the implanted tissue. From a cellular perspective, [ 5 ]  available techniques are monolayer cell construct onto temperature-sensitive polymer, where their detachment is driven by behavior of the mechanical properties of the synthetic support without the need of any enzymatic digestion such as trypsin. Cardiomyocites sheets have also been successfully implanted with an observed contractile function as a result of inter-cellular communication between the host and graft. However, from a practical point of view, such approach lacks of translational character as all studies share the lack of reproducibility, i.e. a construct of similar characteristics of the native tissue does not guarantee the same results. Another approach resides in the use of hydrogels. Natural hydrogels such as Matrigel, [ 6 ]  collagen and fibrin have been used as entrapment matrices, wherein the cells to be injected are embedded. However the associated high pressure of injection is associated with a high mortality rate for the cells thereby negatively impacting the benefit ratio of this approach. Furthermore, from a technical point of view, due to the polydispersity of these natural hydrogels, purification is a requisite but very difficult step. Synthetic hydrogels, such as  polyethylene glycol , polylactic acid, polylactic acid-co-glycolic acid, polycaprolactone, polyacrylamide and polyurethane have been proposed.  Metalloproteinase-sensitive polyethylene is of particular interest. Indeed, this polymer modulates its mechanical and biophysical properties accordingly to enzymatic activities associated with cardiomyogenic differentiation of implanted cells. To date, no hydrogel matrix is FDA-approved for stem cell therapy use despite a large number of biomaterials currently commercially available."}
{"_id": "WikiPedia_Cardio$$$corpus_892", "text": "A general comment on hydrogel based technologies:"}
{"_id": "WikiPedia_Cardio$$$corpus_893", "text": "Natural hydrogel are well tolerated by the host and cells due to their mimicking the natural ECM in terms of backbone and microstructure. However they suffer from batch to batch variation (a drawback for current Good Manufacturing Practices (cGMPs) required for clinical application), high degradation rates, and poor tenability. Synthetic hydrogels are reproducible, tunable and amenable regulatory and manufacturing protocols. [ 7 ] [ 8 ] [ 9 ]  Their chemical modification permits the integration of cellular attachment sites and a certain control over degradation rates. Semi-synthetic hydrogels share characteristics of both classes. Indeed, they permit either the modification of the purified natural biopolymers or by coupling the synthetic component with integrin and/or growth factor binding sites."}
{"_id": "WikiPedia_Cardio$$$corpus_894", "text": "A frequent type of syncope, termed  vasovagal syncope  is originated by intense cardioinhibition, mediated by a sudden  vagal  reflex, that causes transitory  cardiac arrest  by  asystole  and/or transient total  atrioventricular block . [ 1 ] [ 2 ]  It is known as \u201cVaso-vagal Syncope\u201d, \u201cNeurocardiogenic Syncope\u201d or \u201cNeurally-mediated Reflex Syncope\u201d. [ 3 ]  Although many different therapies have been tried in this condition, severe and refractory cases have been treated with  pacemaker  implantation despite great controversies about its benefit. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_895", "text": "The \u201c Cardioneuroablation \u201d is a technique created in the nineties and patented in  USA , aiming to eliminate the cardiac branch of vagal reflex in order to treat the neurocardiogenic syncope without pacemaker implantation. [ 6 ] [ 7 ]  It is performed without  surgery , by using  radiofrequency   catheter ablation  with one-day hospital. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_896", "text": "The results up to 100 months follow-up are showing better outcome than clinical measures or pacemaker implantation with changing the tilt-test on to normal and by absence of syncope in more than 90% of patients without medications. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_897", "text": "Cardiooncology ,  cardio-oncology  or  cardiovascular oncology  is an interdisciplinary field of  medicine  which study the molecular and clinical alterations in  cardiovascular system  during the different methods of  treatment of cancer , especially  chemotherapy  and  targeted therapy . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_898", "text": "Since 2018 the  European Society of Cardiology  has had a council of cardio-oncology. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_899", "text": "Cardiovascular physiology  is the study of the  cardiovascular system , specifically addressing the  physiology  of the  heart  (\"cardio\") and  blood vessels  (\"vascular\")."}
{"_id": "WikiPedia_Cardio$$$corpus_900", "text": "These subjects are sometimes addressed separately, under the names  cardiac physiology  and  circulatory physiology . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_901", "text": "Although the different aspects of cardiovascular physiology are closely interrelated, the subject is still usually divided into several subtopics. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_902", "text": "Under most circumstances, the body attempts to maintain a steady  mean arterial pressure . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_903", "text": "When there is a major and immediate decrease (such as that due to  hemorrhage  or  standing up ), the body can increase the following:"}
{"_id": "WikiPedia_Cardio$$$corpus_904", "text": "In turn, this can have a significant impact upon several other variables:"}
{"_id": "WikiPedia_Cardio$$$corpus_905", "text": "A  cardiovascular technician , also known as a  vascular technician , is health professional that deal with the  circulatory system ."}
{"_id": "WikiPedia_Cardio$$$corpus_906", "text": "Technicians who use  ultrasound  to examine the  heart chambers ,  valves , and  vessels  are referred to as cardiac sonographers. [ 1 ]  They use ultrasound instrumentation to create images called echocardiograms. An  echocardiogram  may be performed while the patient is either resting or physically active. Technicians may administer medication to physically active patients to assess their heart function. Cardiac sonographers also may assist  transesophageal echocardiography , which involves placing a tube in the patient's  esophagus  to obtain ultrasound images. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_907", "text": "Those who assist in the diagnosis of disorders affecting the circulation are known as vascular technologist, vascular specialists or vascular sonographers. They obtain a medical history, evaluate pulses and assess blood flow in arteries and veins by listening to the vascular flow sounds for abnormalities. Then they perform a  noninvasive  procedure using ultrasound instrumentation to record vascular information such as vascular blood flow,  blood pressure , changes in limb volume,  oxygen saturation ,  cerebral circulation , peripheral circulation, and abdominal circulation. Many of these tests are performed during or immediately after surgery."}
{"_id": "WikiPedia_Cardio$$$corpus_908", "text": "Cardiovascular  technicians who obtain EKGs are known as electrocardiograph (or EKG) technicians. To take a basic  EKG , which traces electrical impulses transmitted by the heart, technicians attach  electrodes  to the patient's chest, arms, and legs, and then manipulate switches on an EKG machine to obtain a reading. An EKG is printed out for interpretation by the physician. This test is done before most kinds of surgery or as part of a routine physical examination, especially on persons who have reached middle age or who have a history of cardiovascular problems."}
{"_id": "WikiPedia_Cardio$$$corpus_909", "text": "EKG technicians with advanced training setup Holter monitor and stress testing. For Holter monitoring, technicians place electrodes on the patient's chest and attach a portable EKG monitor to the patient's belt. Following 24 or more hours of normal activity by the patient, the technician removes a tape from the monitor and places it in a scanner. After checking the quality of the recorded impulses on an electronic screen, the technician usually prints the information from the tape for analysis by a physician. Physicians use the output from the scanner to diagnose heart ailments, such as heart rhythm abnormalities or problems with  pacemakers ."}
{"_id": "WikiPedia_Cardio$$$corpus_910", "text": "For a treadmill stress test, EKG technicians document the patient's medical history, explain the procedure, connect the patient to an EKG monitor, and obtain a baseline reading and resting blood pressure. Next, they monitor the heart's performance while the patient is walking on a treadmill, gradually increasing the treadmill's speed to observe the effect of increased exertion."}
{"_id": "WikiPedia_Cardio$$$corpus_911", "text": "The position is generally unlicensed and skills are learned on the job; however, two- and four-year training programs to learn advanced ECG technical skills are available at junior colleges and community colleges. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_912", "text": "Carney complex  and its subsets  LAMB syndrome [ 1 ]  and  NAME syndrome [ 1 ]  are  autosomal dominant  conditions comprising  myxomas  of the heart and skin, hyperpigmentation of the skin ( lentiginosis ), and  endocrine  overactivity. [ 2 ] [ 3 ]  It is distinct from  Carney's triad . Approximately 7% of all cardiac myxomas are associated with Carney complex. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_913", "text": "The spotty skin pigmentation and lentigines occur most commonly on the face, especially on the lips, eyelids,  conjunctiva  and oral mucosa. [ 3 ]   Cardiac myxomas  may lead to  embolic strokes  and  heart failure [ 4 ]  and may present with fever, joint pain, shortness of breath, diastolic rumble and tumor plop. Myxomas may also occur outside the heart, usually in the skin and breast. Endocrine tumors may manifest as disorders such as  Cushing syndrome . The most common  endocrine gland  manifestation is an ACTH-independent Cushing's syndrome due to  primary pigmented nodular adrenocortical disease  (PPNAD). [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_914", "text": "The LAMB  acronym  refers to  lentigines ,  atrial   myxomas , and  blue nevi . [ 1 ]  NAME refers to  nevi , atrial myxoma, myxoid neurofibromas, and  ephelides . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_915", "text": "Testicular cancer, particularly  Sertoli cell  type, is associated with Carney syndrome. [ 7 ]  Thyroid and pancreas cancer may also occur. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_916", "text": "Although  J Aidan Carney  also described  Carney's triad  it is entirely different. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_917", "text": "Carney complex is most commonly caused by mutations in the  PRKAR1A  gene on  chromosome 17  (17q23-q24) [ 11 ] \nwhich may function as a  tumor-suppressor gene . The encoded protein is a type 1A regulatory subunit of protein kinase A. Inactivating  germline mutations  of this gene are found in 70% of people with Carney complex. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_918", "text": "Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at  chromosome 2  (2p16). [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_919", "text": "Both types of Carney complex are  autosomal dominant . Despite dissimilar genetics, there appears to be no  phenotypic  difference between PRKAR1A and chromosome 2p16 mutations. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_920", "text": "Cardiac myxomas can be difficult to manage surgically because of recurrence within the heart, often far away from the site of the initial tumor. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_921", "text": "In 1914 an American neurosurgeon,  Harvey Cushing , reported on a patient with a pituitary tumour on whom he had operated. The post mortem findings as reported were consistent with Carney complex, though at the time this condition had yet to be described. In 2017 archived tissue from the operation in Cushing's report was subjected to DNA sequencing, revealing an Arg74His ( arginine  to  histidine :  guanine  (G)->  adenosine  (A)  transition  in the second  codon  position of the 74th codon in the protein) mutation in the PRKAR1A gene, confirming a diagnosis of Carney complex. Therefore, Cushing's paper appears to be the first report of this complex. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_922", "text": "The  central  governor  is a proposed process in the brain that regulates exercise in regard to a neurally calculated safe  exertion by the body. In particular, physical activity is controlled so that its intensity cannot threaten the body\u2019s  homeostasis  by causing  anoxic  damage to the  heart muscle . The central governor limits exercise by reducing the neural recruitment of muscle fibers. This reduced recruitment causes the sensation of  fatigue . The existence of a central governor was suggested to explain fatigue after prolonged strenuous exercise in long-distance running and other endurance sports, but its ideas could also apply to other causes of exertion-induced fatigue."}
{"_id": "WikiPedia_Cardio$$$corpus_923", "text": "The existence of a central governor was proposed by  Tim Noakes  in 1997, but a similar idea was suggested in 1924 by  Archibald Hill . It was first published as a full theory by Tim Noakes, Alan St Clair Gibson and Vicki Lambert in five linked articles in the British Journal of Sports Medicine in 2004-2005 [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_924", "text": "In contrast to this idea is the one that fatigue is due to peripheral \"limitation\" or \"catastrophe.\" In this view, regulation by fatigue occurs as a consequence of a failure of homeostasis directly in muscles."}
{"_id": "WikiPedia_Cardio$$$corpus_925", "text": "The 1922  Nobel Prize in Physiology or Medicine  winner  Archibald Hill  proposed in 1924 that the heart was protected from anoxia in strenuous exercise by the existence of a governor."}
{"_id": "WikiPedia_Cardio$$$corpus_926", "text": "the heart is able to regulate its output, to some extent, in accordance with the degree of saturation of the arterial blood ... we suggest that, in the body (either in the heart muscle itself or in the nervous system), there is some mechanism which causes a slowing of the circulation as soon as a serious degree of unsaturation occurs, and  vice versa . This mechanism would tend, to some degree, to act as a \u2018governor\u2019, maintaining a reasonably high degree of saturation of the blood: the breathing of a gas mixture rich in oxygen would produce a greater degree of saturation of the blood and so allow the output to increase until the \u2018governor\u2019 stopped it again. We realise the danger of a hypothesis partly suggested by teleological reasoning: in this case, however, we can see no other explanation of our experimental results pp. 163 [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_927", "text": "This hypothesis was disregarded and further research upon exercise fatigue was modeled in terms of it being due to a mechanical failure of the exercising muscles (\"peripheral muscle fatigue\"). This failure was caused either by an inadequate oxygen supply to the exercising muscles, lactic acid buildup, or total energy depletion in the exhausted muscles. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_928", "text": "Tim Noakes , a professor of exercise and sports science at the  University of Cape Town , in 1997 [ 4 ]  has renewed Hill\u2019s argument on the basis of modern research. Along with collaborators Alan St Clair Gibson and Vicki Lambert, they suggested that the power output by muscles during exercise is continuously adjusted in regard to calculations made by the brain in regard to a safe level of exertion. These neural calculations factor in earlier experience with strenuous exercise, the planning duration of the exercise, and the present metabolic state of the body. These brain models [ 5 ]  ensure that body homeostasis is protected, and an emergency reserve margin is maintained. [ 6 ] [ 7 ] [ 8 ] [ 9 ]  This neural control adjusts the number of activated skeletal muscle motor units, a control which is subjectively experienced as  fatigue . This process, though occurring in the brain, is outside conscious control."}
{"_id": "WikiPedia_Cardio$$$corpus_929", "text": "the rising perception of discomfort produced by exhausting exercise progressively reduces the conscious desire to over-ride this control mechanism, which, if it were to be reduced, would lead to the recruitment of more motor units. Thus the presence of conscious over-ride would be undesirable because it would increase or maintain the exercise intensity, thereby threatening homoeostasis ... as exercise performance is centrally regulated by the CNS, then fatigue should no longer be considered a physical event but rather a sensation or emotion, separate from an overt physical manifestation\u2014for example, the reduction in force output by the active muscles. Rather we now suggest that the physical manifestation of any increasing perception of fatigue may simply be an alteration in the subconsciously regulated pace at which the exercise is performed. Hence the novel suggestion is that the conventional understanding of fatigue is flawed because it makes no distinction between the sensation itself and the physical expression of that sensation which, we suggest, is the alteration in the subconsciously regulated pacing strategy consequent on changing motor unit recruitment/derecruitment by the CNS. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_930", "text": "Noakes, St Clair Gibson and Lambert created the idea of the central governor in the context of prolonged endurance exercise. However, they have noted that the central processes involved might also underlie the existence of other kinds of fatigue:"}
{"_id": "WikiPedia_Cardio$$$corpus_931", "text": "This new interpretation is the first to allow a more reasonable description of a number of phenomena that defy rational explanation according to the traditional \u2018\u2018limitations\u2019\u2019 models of fatigue. These include, among many others, the chronic fatigue syndrome, in which affected individuals experience evident fatigue at rest, and the role of psychological and motivational factors,  centrally (brain) acting pharmaceutical agents,  hypnosis, shouting or sudden unexpected gunshots,  or other forms of distraction including music or premeditated deception on human exercise performance. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_932", "text": "In support of this, placebos (which must be mediated by a central process) have a powerful effect upon not only fatigue in prolonged exercise, [ 12 ] [ 13 ]  but also upon short term endurance exercise such as sprint speed, [ 14 ]  the maximum weight that could be lifted with leg extension, [ 15 ]  and the tolerance of  ischemic  pain and power when a tourniqueted hand squeezes a spring exerciser 12 times. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_933", "text": "The existence of a central governor over physiology has been questioned since \u2018physiological catastrophes\u2019 can and do occur in athletes (important examples in  marathons  have been  Dorando Pietri ,  Jim Peters  and  Gabriela Andersen-Schiess ). This suggests that humans can over-ride \u2018the central governor\u2019. [ 17 ]  Moreover, a variety of peripheral factors in addition to those such as lactic acid build up can impair muscle power and might act to protect against \"catastrophe\". [ 18 ]  Another objection is that models incorporating conscious control also provide an alternative explanation  [ 19 ]  (see Noakes\u2019 reply). [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_934", "text": "Exercise fatigue has also been attributed to the direct effects of exercise upon the brain such as increased cerebral levels of  serotonin , reduced level of  glutamate  secondary to uptake of ammonia in the brain, brain hyperthermia, and  glycogen  depletion in brain cells. [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_935", "text": "Cerebral circulation  is the movement of  blood  through a network of  cerebral arteries  and  veins  supplying the  brain . The rate of cerebral  blood flow  in an adult  human  is typically 750  milliliters  per  minute , or about 15% of  cardiac output .  Arteries  deliver  oxygenated  blood,  glucose  and other nutrients to the brain.  Veins  carry \"used or spent\" blood back to the  heart , to remove  carbon dioxide ,  lactic acid , and other  metabolic  products. The  neurovascular unit  regulates cerebral blood flow so that activated neurons can be supplied with energy in the right amount and at the right time. [ 1 ]  Because the  brain  would quickly suffer damage from any stoppage in blood supply, the cerebral circulatory system has safeguards including  autoregulation  of the  blood vessels . The failure of these safeguards may result in a  stroke . The  volume  of blood in circulation is called the  cerebral blood flow . Sudden intense accelerations change the  gravitational forces  perceived by bodies and can severely  impair cerebral circulation  and normal functions to the point of becoming serious life-threatening conditions."}
{"_id": "WikiPedia_Cardio$$$corpus_936", "text": "The following description is based on idealized human cerebral circulation. The pattern of circulation and its  nomenclature  vary between organisms."}
{"_id": "WikiPedia_Cardio$$$corpus_937", "text": "Blood supply to the brain is normally divided into anterior and posterior segments, relating to the different arteries that supply the brain. The two main pairs of arteries are the  internal carotid arteries  (supply the anterior brain) and  vertebral arteries  (supplying the  brainstem  and posterior brain). [ 2 ]  The anterior and posterior cerebral circulations are interconnected via bilateral  posterior communicating arteries . They are part of the  circle of Willis , which provides backup circulation to the brain. In case one of the supply arteries is occluded, the circle of Willis provides interconnections between the anterior and the posterior cerebral circulation along the floor of the cerebral vault, providing blood to tissues that would otherwise become  ischemic . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_938", "text": "The  anterior  cerebral circulation  is the blood supply to the anterior portion of the brain including  eyes . It is supplied by the following arteries:"}
{"_id": "WikiPedia_Cardio$$$corpus_939", "text": "The  posterior cerebral circulation  is the blood supply to the posterior portion of the brain, including the  occipital lobes ,  cerebellum  and  brainstem .\nIt is supplied by the following arteries:"}
{"_id": "WikiPedia_Cardio$$$corpus_940", "text": "The venous drainage of the cerebrum can be separated into two subdivisions:  superficial and deep."}
{"_id": "WikiPedia_Cardio$$$corpus_941", "text": "The superficial system is composed of  dural venous sinuses ,  sinuses  (channels) within the  dura mater . The dural sinuses are therefore located on the surface of the cerebrum.  The most prominent of these sinuses is the  superior sagittal sinus  which is located in the sagittal plane under the midline of the cerebral vault, posteriorly and inferiorly to the  confluence of sinuses , where the superficial drainage joins with the sinus that primarily drains the deep venous system.  From here, two  transverse sinuses  bifurcate and travel laterally and inferiorly in an S-shaped curve that forms the  sigmoid sinuses  which go on to form the two  jugular veins . In the neck, the  jugular veins  parallel the upward course of the  carotid arteries  and drain blood into the  superior vena cava . The veins puncture the relevant dural sinus, piercing the arachnoid and dura mater as  bridging veins  that drain their contents into the sinus. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_942", "text": "The deep venous system is primarily composed of traditional  veins  inside the deep structures of the brain, which join behind the midbrain to form the  great cerebral vein  (vein of Galen).  This vein merges with the  inferior sagittal sinus  to form the  straight sinus  which then joins the superficial venous system mentioned above at the  confluence of sinuses ."}
{"_id": "WikiPedia_Cardio$$$corpus_943", "text": "The maturation of blood vessels in the brain is a  critical process  that occurs postnatally. [ 6 ]  It involves the acquisition of key barrier and contractile properties essential for brain function. During the early postnatal phase,  endothelial cells  (ECs) and  vascular smooth muscle cells  (VSMCs) undergo significant molecular and functional changes."}
{"_id": "WikiPedia_Cardio$$$corpus_944", "text": "Endothelial cells begin to express  P-glycoprotein , a crucial  efflux transporter  that helps protect the brain by expelling harmful substances. [ 7 ]  This efflux capacity is progressively acquired and becomes fully functional by the postnatal period. Additionally, VSMCs, which initially populate the arterial network, start to express contractile proteins such as smooth muscle  actin  (SMA) and  myosin-11 , transforming VSMCs into contractile cells capable of regulating blood vessel tone and cerebral blood flow."}
{"_id": "WikiPedia_Cardio$$$corpus_945", "text": "The expression of Myh11 in VSMCs acts as a developmental switch, with significant upregulation occurring from birth to the age of 2 to 5 years. [ 6 ]  This is a critical period needed for the establishment of vessel contractility and the overall functionality of the cerebral circulation."}
{"_id": "WikiPedia_Cardio$$$corpus_946", "text": "Cerebral blood flow  (CBF) is the blood supply to the  brain  in a given period of time. [ 8 ]  In an adult, CBF is typically 750 millilitres per minute or 15.8\u2009\u00b1\u20095.7% of the  cardiac output . [ 9 ]  This equates to an average  perfusion  of 50 to 54 millilitres of blood per 100 grams of brain tissue per minute. [ 10 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_947", "text": "The radio index of cerebral blood flow/cardiac output (CCRI) decreases by 1.3% per decade, even though cardiac output remains unchanged. [ 9 ] \u00a0Across the adult lifespan, women have a higher CCRI than men. [ 9 ]  CBF is inversely associated with  body mass index . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_948", "text": "CBF is tightly regulated to meet the brain's  metabolic  demands. [ 10 ] [ 13 ]  Too much blood (a clinical condition of a normal homeostatic response of  hyperemia ) [ 1 ]  can raise  intracranial pressure  (ICP), which can compress and damage delicate brain tissue. Too little blood flow ( ischemia ) results if blood flow to the brain is below 18 to 20 ml per 100 g per minute, and tissue death occurs if flow dips below 8 to 10 ml per 100 g per minute. In brain tissue, a  biochemical cascade  known as the  ischemic cascade  is triggered when the tissue becomes ischemic, potentially resulting in damage to and the death of  brain cells . Medical professionals must take steps to maintain proper CBF in patients who have conditions like  shock ,  stroke ,  cerebral edema , and  traumatic brain injury ."}
{"_id": "WikiPedia_Cardio$$$corpus_949", "text": "Cerebral blood flow is determined by a number of factors, such as  viscosity  of blood, how dilated  blood vessels  are, and the net pressure of the flow of blood into the brain, known as  cerebral perfusion pressure , which is determined by the body's  blood pressure . Cerebral perfusion pressure (CPP) is defined as the mean arterial pressure (MAP) minus the intracranial pressure (ICP). In normal individuals, it should be above 50\u00a0mm Hg. Intracranial pressure should not be above 15\u00a0mm Hg (ICP of 20\u00a0mm Hg is considered as intracranial hypertension). [ 14 ]  Cerebral blood vessels are able to change the flow of blood through them by altering their diameters in a process called  cerebral autoregulation ; they constrict when systemic blood pressure is raised and dilate when it is lowered. [ 15 ]  Arterioles also constrict and dilate in response to different chemical concentrations. For example, they dilate in response to higher levels of  carbon dioxide  in the blood and constrict in response to lower levels of carbon dioxide. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_950", "text": "For example, assuming a person with an arterial partial pressure of carbon dioxide ( PaCO2 ) of 40 mmHg (normal range of 38\u201342 mmHg) [ 16 ]  and a CBF of 50 ml per 100g per min. If the PaCO2 dips to 30 mmHg, this represents a 10 mmHg decrease from the initial value of PaCO2. Consequently, the CBF decreases by 1ml per 100g per min for each 1mmHg decrease in PaCO2, resulting in a new CBF of 40ml per 100g of brain tissue per minute. In fact, for each 1 mmHg increase or decrease in PaCO2, between the range of 20\u201360 mmHg, there is a corresponding CBF change in the same direction of approximately 1\u20132 ml/100g/min, or 2\u20135% of the CBF value. [ 17 ]  This is why small alterations in respiration pattern can cause significant changes in global CBF, specially through PaCO2 variations. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_951", "text": "CBF is equal to the  cerebral perfusion pressure  (CPP) divided by the cerebrovascular resistance (CVR): [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_952", "text": "Control of CBF is considered in terms of the factors affecting CPP and the factors affecting CVR. CVR is controlled by four major mechanisms:"}
{"_id": "WikiPedia_Cardio$$$corpus_953", "text": "Increased  intracranial pressure  (ICP) causes decreased blood perfusion of  brain cells  by mainly two mechanisms:"}
{"_id": "WikiPedia_Cardio$$$corpus_954", "text": "Cerebral perfusion pressure is the net  pressure  gradient causing  cerebral blood flow  to the brain (brain  perfusion ).  It must be maintained within narrow limits; too little pressure could cause brain tissue to become  ischemic  (having inadequate blood flow), and too much could raise  intracranial pressure ."}
{"_id": "WikiPedia_Cardio$$$corpus_955", "text": "Arterial spin labeling  (ASL),  phase contrast magnetic resonance imaging  (PC-MRI), and  positron emission tomography  (PET) are  neuroimaging  techniques that can be used to measure CBF. ASL and PET can also be used to measure regional CBF (rCBF) within a specific brain region.\nrCBF at one location can be measured over time by  thermal diffusion [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_956", "text": "ocular group:   central retinal"}
{"_id": "WikiPedia_Cardio$$$corpus_957", "text": "The  chain of survival  refers to a series of actions that, properly executed, reduce the mortality associated with  sudden cardiac arrest . Like any chain, the chain of survival is only as strong as its weakest link. [ 1 ] [ 2 ]  The six interdependent links in the chain of survival are early recognition of sudden cardiac arrest and access to emergency medical care, [ 3 ]  early  CPR , early defibrillation, early  advanced cardiac life support , and physical and emotional recovery. The first three links in the chain can be performed by lay bystanders, while the second three links are designated to medical professionals. [ 4 ]  Currently, between 70 and 90% of cardiac arrest patients die before they reach the hospital. [ 4 ]  However, a cardiac arrest does not have to be lethal if bystanders can take the right steps immediately. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_958", "text": "According to the American Heart Association, out-of-hospital cardiac arrest can affect more than 300,000 people in the United States each year. [ 5 ]  Three minutes after the onset of cardiac arrest, a lack of blood flow starts to damage the brain, and 10 minutes after, the chances of survival are low. [ 6 ]  Therefore, bystanders have only a few minutes to act to optimize a person's chances of survival and recovery. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_959", "text": "To improve survival outcomes for people who have experienced out-of-hospital cardiac arrest, the American Heart Association\u2013International Liaison Committee on Resuscitation recommended the chain of survival concept in the early 2000s. [ 3 ]  Originally, the chain consisted of four steps: early access to emergency medical care was the first link, the second link was early CPR, early defibrillation was the third link, and the final link was early advanced cardiac life support. [ 3 ]  Over the years, the American Heart Association has added two new links to the chain: post-resuscitation care in 2010, [ 7 ] [ 3 ]  and physical and emotional recovery in 2020. [ 4 ]  Also in 2020, the American Heart Association issued a new pediatric chain of survival for infants, children, and adolescents. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_960", "text": "Mary M. Newman, co-founder and president/CEO of the Sudden Cardiac Arrest (SCA) Foundation and previous executive director of the National Center for Early Defibrillation at the University of Pittsburgh, [ 9 ]  developed the chain of survival metaphor and first described it  [ 6 ]  in an article she wrote for the  Journal of Emergency Medical Services  in 1989, [ 10 ]  and further promoted in an editorial she wrote for the first issue of  Currents in Emergency Cardiac Care  in 1990. [ 11 ]  The American Heart Association later adopted the concept and elaborated on it in its 1992 guidelines for  cardiopulmonary resuscitation  and emergency cardiac care, [ 12 ] [ 13 ]  The International Liaison Committee on Resuscitation (ILCOR) echoed the concept in 1997. [ 1 ]  The links of the Chain of survival are described below."}
{"_id": "WikiPedia_Cardio$$$corpus_961", "text": "Ideally, someone must recognize an impending cardiac arrest or otherwise witness the cardiac arrest and activate the  EMS system  as early as possible with an immediate call to the emergency services. Unfortunately, many persons experiencing symptoms (for example, angina) that may lead to a cardiac arrest ignore these warning symptoms or, recognizing these warning symptoms correctly, fail to activate the EMS system, preferring to contact relatives instead (e.g., the elderly often contact their adult offspring rather than contact emergency services). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_962", "text": "To be most effective, bystanders should provide CPR immediately after a patient collapses. In their  2015 guidelines , the American Heart Association re-emphasized the importance of more bystanders performing hands-only CPR until EMS personnel arrive because, at present, fewer than 40% of people who have an out-of-hospital cardiac arrest receive CPR from a bystander. [ 4 ]  The guidelines recommend lay rescuers start CPR on a person with presumed cardiac arrest because the overall risk of harm to patients from CPR is low, even if their heart hasn't stopped beating. [ 4 ]  Properly performed CPR can keep the heart in a shockable rhythm for 10\u201312 minutes longer. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_963", "text": "Most adults who can be saved from cardiac arrest are in  ventricular fibrillation  or pulseless  ventricular tachycardia , which means their heart has fallen out of rhythm. [ 14 ]  Early defibrillation is the link in the chain most likely to improve survival since defibrillation can help shock the heart back into a regular beat. [ 15 ]  Early, rapid defibrillation is considered the most important link in the chain of survival. [ 15 ]  Rapid defibrillation outside of the hospital improves the chances of survival by as much as 30%, and involves using an automated external defibrillator (AED) to shock the patient's heart. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_964", "text": "While CPR keeps blood flowing artificially, [ 17 ]  rapid defibrillation is the only way to restart the heart and reset it to a healthy rhythm. [ 18 ]  And while only 40% of adults experiencing cardiac arrest receive CPR, fewer than 12% receive shocks from an AED before EMS arrival. [ 8 ]  What is more, the chances of the patient's survival decrease by as much as 10% with every minute that they do not receive rapid defibrillation. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_965", "text": "AEDs are becoming more common in businesses, schools, and even the home as the public becomes more aware of the importance of rapid defibrillation. [ 20 ] [ 6 ]  AEDs come with pre-recorded instructions and are easy to use. [ 18 ]  If an AED is not available, bystanders will need to continue CPR until emergency responders arrive with a defibrillator, which is why it is important to recognize cardiac arrest and call for help quickly. [ 21 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_966", "text": "Public access defibrillation may be the key to improving survival rates in out-of-hospital cardiac arrest, [ 1 ]  but is of the greatest value when the other links in the chain do not fail."}
{"_id": "WikiPedia_Cardio$$$corpus_967", "text": "Early  advanced cardiac life support  by paramedics is another critical link in the chain of survival. In communities with survival rates > 20%, a minimum of two of the rescuers are trained to the advanced level. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_968", "text": "Some ACLS ambulance providers will administer medications to manage pain, arrhythmias, shock, and pulmonary congestion; monitor the heart rhythm to identify any potentially lethal cardiac arrhythmias; or initiate transcutaneous pacing. [ 15 ]  ACLS ambulance providers use the mnemonic \"MONA\" (morphine, oxygen, nitroglycerin, and aspirin) to reflect the out-of-hospital therapies they will use for cardiac arrest. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_969", "text": "Often, ACLS ambulance providers will attach an electrocardiogram to the patient and transmit its findings to the receiving hospital or care facility, which leads to earlier diagnosis of a heart attack, and significantly reduces time to treatment at the hospital. [ 15 ]  This prearrival ECG and notification has been shown to improve patient outcomes. [ 15 ]  In the event of a complication at the scene of the event or on the way to the hospital, ACLS ambulance providers can administer life saving therapies, including CPR, rapid defibrillation, airway management, and intravenous medications. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_970", "text": "In October 2020, the American Heart Association added the recovery phase as the sixth link in the chain of survival. [ 4 ]  Recovery consists of cardiac arrest survivors receiving treatment, surveillance, and rehabilitation at a hospital. [ 4 ]  It also includes an assessment for anxiety, depression, and post-traumatic stress, which can all lead to future repeated events.\u00a0Before being discharged from the hospital, the American Heart Association recommends that cardiac arrest survivors receive rehabilitation assessment and treatment for physical, neurologic, cardiopulmonary, and cognitive impairments. [ 4 ] [ 8 ]  They also recommend that cardiac arrest survivors and their caregivers receive comprehensive, multidisciplinary discharge planning to include medical and rehabilitative treatment recommendations and return to activity and work expectations. [ 4 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_971", "text": "A patient's recovery from cardiac arrest continues long after their initial hospitalization following the event, so the American Heart Association recommended in their 2020 guidelines that patients have formal assessment and support for their physical, cognitive, and psychosocial needs. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_972", "text": "Computer-aided auscultation  ( CAA ), or  computerized assisted auscultation , is a digital form of  auscultation . It includes the recording, visualization, storage, analysis and sharing of  digital recordings  of heart or lung sounds. The recordings are obtained using an electronic stethoscope or similarly suitable recording device.\nComputer-aided auscultation is designed to assist health care professionals who perform auscultation as part of their diagnostic process. Commercial CAA products are usually classified as  clinical decision support systems  that support medical professionals in making a diagnosis. As such they are medical devices and require certification or approval from a competent authority (e.g.  FDA  approval,  CE conformity  issued by notified body)."}
{"_id": "WikiPedia_Cardio$$$corpus_973", "text": "Compared to traditional auscultation, computer-aided auscultation (CAA) offers a range of improvements beneficial to multiple stakeholders:"}
{"_id": "WikiPedia_Cardio$$$corpus_974", "text": "In a CAA system, sounds are recorded through an electronic stethoscope. The audio data is transferred to an electronic device via  Bluetooth  or an audio cable connection. Special software on that device visualizes, stores and analyzes the data. With some of the more sophisticated CAA systems, the CAA analysis yields results that can be used to objectify diagnoses ( decision support system ). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_975", "text": "The components of a CAA system depend on its complexity. Whereas some of the simpler systems provide only visualization or storage options, other systems combine visualization, storage, analysis and the ability to electronically manage said data."}
{"_id": "WikiPedia_Cardio$$$corpus_976", "text": "Electronic stethoscopes  (also digital stethoscopes) convert acoustic sound waves into digital electrical signals. These signals are then amplified by means of transducers and currently reach levels up to 100 times higher than traditional acoustic stethoscopes. Additionally, electronic stethoscopes can be used to filter out background noise, a feature that can be safety-relevant and facilitate more accurate diagnoses. Whereas sound amplification and filtering are the main functions of an electronic stethoscope, the ability to access the sounds through external means via Bluetooth or audio cables makes them an ideal sound-capturing device for CAA systems. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_977", "text": "Devices that can be used to connect to an electronic stethoscope and record the audio signal (e.g. heart or lung sounds) include PC, laptop and mobile devices like smartphones or tablets. Generally, CAA systems include software that can visualize the incoming audio signal. More sophisticated CAA systems include live noise detection algorithms, designed to help the user achieve the best possible recording quality."}
{"_id": "WikiPedia_Cardio$$$corpus_978", "text": "A key feature of CAA systems is the automated analysis of the recorded audio signals by signal processing algorithms. Such algorithms can run directly on the device used for making the recording, or be hosted in a cloud connected to the device. The degree of autonomy of currently available analysis algorithms varies greatly. While some systems operate fully autonomously, [ 7 ]  early PC-based systems required significant user interaction and interpretation of results, [ 8 ]  and other analysis systems require some degree of assistance by the user like manual confirmation/correction of estimated heart rates. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_979", "text": "Recorded sounds and associated analytical and patient data can be electronically stored, managed or archived. Patient identifying information might be handled or stored in the process. If the stored data classifies as PHI (protected health information), a system hosting such data must be compliant with country-specific data protection laws like  HIPAA  for the US or the  Data Protection Directive  for the EU. Storage options for current CAA systems range from the basic ability to retrieve a downloadable PDF report to a comprehensive cloud-based interface for electronic management of all auscultation-based data. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_980", "text": "The user can review all their patient records (including replaying the audio files) via a user interface, e.g. via a web-portal in the browser or stand-alone software on the electronic device. Other functionalities include sharing records with other users, exporting patient records and integration into  EHR systems ."}
{"_id": "WikiPedia_Cardio$$$corpus_981", "text": "Computer-aided auscultation aimed at detecting and characterizing heart murmurs is called computer-aided heart auscultation (also known as automatic heart sound analysis)."}
{"_id": "WikiPedia_Cardio$$$corpus_982", "text": "Auscultation of the heart using a stethoscope is the standard examination method worldwide to screen for heart defects by identifying murmurs. It requires that an examining physician have acute hearing and extensive experience. An accurate diagnosis remains challenging for various reasons including noise, high heart rates, and the ability to distinguish innocent from pathological murmurs.\nProperly performed, the auscultatory examination of the heart is commonly regarded as an inexpensive, widely available tool in the detection and management of heart disease. [ 10 ]  The auscultation skills of physicians, however, have been reported to be declining. [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ] \nThis leads to missed disease diagnoses and/or excessive costs for unnecessary and expensive diagnostic testing. A study suggests that more than one third of previously undiagnosed congenital heart defects in newborns are missed by their 6-week examination. [ 18 ]  More than 60% of referrals to medical specialists for costly echocardiography are due to a misdiagnosis of an innocent murmur. [ 14 ]  CAA of the heart thus has the potential to become a cost-effective screening and diagnostic tool, provided that its underlying algorithms have been clinical tested in stringent, blinded fashions for their ability to detect the difference between normal and abnormal heart sounds."}
{"_id": "WikiPedia_Cardio$$$corpus_983", "text": "Heart murmurs  (or cardiac murmurs) are audible noises through a stethoscope, generated by a turbulent flow of blood. Heart murmurs need to be distinguished from  heart sounds  which are primarily generated by the beating heart and the heart valves snapping open and shut.\nGenerally, heart murmurs are classified as  innocent  (also called physiological or functional) or pathological (abnormal). Innocent murmurs are usually harmless, often caused by physiological conditions outside the heart, and the result of certain benign structural defects. Pathological murmurs are most often associated with heart valve problems but may also be caused by a wide array of structural heart defects.\nVarious characteristics constitute a qualitative description of heart murmurs, including timing ( systolic murmur  and  diastolic murmur ), shape, location, radiation,  intensity , pitch and quality.\nCAA systems typically categorize heart sounds and murmurs as Class I and Class III according to the American Heart Association: [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_984", "text": "More sophisticated CAA systems provide additional descriptive murmur information like murmur timing, grading, or the ability to identify the positions of the S1/S2 heart sounds."}
{"_id": "WikiPedia_Cardio$$$corpus_985", "text": "The detection of heart murmurs in CAA systems is based on the analysis of digitally recorded heart sounds.\nMost approaches use the following four stages:"}
{"_id": "WikiPedia_Cardio$$$corpus_986", "text": "The most common types of performance measures for CAA systems are based on two approaches: retrospective (non-blinded) studies using existing data and prospective blinded clinical studies on new patients.\nIn retrospective CAA studies, a classifier is trained with  machine learning  algorithms using existing data. The performance of the classifier is then assessed using the same data. Different approaches are used to do this (e.g.,  k-Fold cross-validation ,  leave-one-out cross-validation ).\nThe main shortcoming of judging the quality (sensitivity, specificity) of a CAA system based on retrospective performance data alone comes from the risk that the approaches used can overestimate the true performance of a given system. Using the same data for training and validation can itself lead to significant  overfitting  of the validation set, because most classifiers can be designed to analyse known data very well, but might not be general enough to correctly classify unknown data; i.e. the results look much better than they would if tested on new, unseen patients. \u201cThe true performance of a selected network (CAA system) should be confirmed by measuring its performance on a third independent set of data called a test set\u201d. [ 20 ]  In summary, the reliability of retrospective, non-blinded studies are usually considered to be much lower than that of prospective clinical studies because they are prone to selection bias and retrospective bias. Published examples include Pretorius et al. [ 21 ] \nProspective clinical studies, on the other hand, are better suited to assess the true performance of a CAA system (provided that the study is blinded and well controlled). In a prospective clinical study to evaluate the performance of a CAA system, the output of the CAA system is compared to the  gold standard  diagnoses. In the case of heart murmurs, a suitable gold standard diagnosis would be auscultation-based expert physician diagnosis, stratified by an  echocardiogram-based  diagnosis. Published examples include Lai et al. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_987", "text": "Computing in Cardiology  (formerly known as  Computers in Cardiology ) is a scientific conference held annually since 1974. It brings together scientists from medicine, bioengineering, and other related fields, focused on the application of computational methods in  cardiology . Papers presented at the conference are published by the  Institute of Electrical and Electronics Engineers . Since 2006, papers at the conference have been published under a  Creative Commons  license. The current president of the board of directors is Rob S. Macleod. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_988", "text": "Since 2000, the conference has hosted the annual Physionet/CinC data challenge. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_989", "text": "Computing in Cardiology is abstracted and indexed in:"}
{"_id": "WikiPedia_Cardio$$$corpus_990", "text": "Contrast-enhanced ultrasound  ( CEUS ) is the application of  ultrasound   contrast medium  to traditional  medical sonography . Ultrasound  contrast agents  rely on the different ways in which sound waves are reflected from interfaces between substances. This may be the surface of a small air bubble or a more complex structure. Commercially available contrast media are gas-filled  microbubbles  that are administered intravenously to the  systemic circulation . Microbubbles have a high degree of  echogenicity  (the ability of an object to reflect ultrasound waves). There is a great difference in echogenicity between the gas in the microbubbles and the soft  tissue  surroundings of the body. Thus,  ultrasonic imaging  using microbubble contrast agents enhances the ultrasound  backscatter , (reflection) of the ultrasound waves, to produce a  sonogram  with increased contrast due to the high echogenicity difference. Contrast-enhanced ultrasound can be used to image blood  perfusion  in organs, measure  blood flow  rate in the  heart  and other organs, and for other applications."}
{"_id": "WikiPedia_Cardio$$$corpus_991", "text": "Targeting  ligands  that bind to  receptors  characteristic of  intravascular  diseases can be conjugated to  microbubbles , enabling the microbubble complex to accumulate selectively in areas of interest, such as  diseased  or abnormal tissues. This form of molecular imaging, known as targeted contrast-enhanced ultrasound, will only generate a strong ultrasound signal if targeted microbubbles bind in the area of interest. Targeted contrast-enhanced ultrasound may have many applications in both  medical diagnostics  and medical therapeutics. However, the targeted technique has not yet been approved by the FDA for clinical use in the United States."}
{"_id": "WikiPedia_Cardio$$$corpus_992", "text": "Contrast-enhanced ultrasound is regarded as safe in adults, comparable to the safety of  MRI contrast agents , and better than  radiocontrast agents  used in  contrast CT scans . The more limited safety data in children suggests that such use is as safe as in the adult population. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_993", "text": "An  echocardiogram  is a study of the  heart  using ultrasound. A bubble echocardiogram is an extension of this that uses simple air bubbles as a contrast medium during this study and often has to be requested specifically."}
{"_id": "WikiPedia_Cardio$$$corpus_994", "text": "Although colour Doppler can be used to detect abnormal flows between the chambers of the heart (e.g.,  persistent (patent) foramen ovale ), it has a limited  sensitivity . When specifically looking for a defect such as this, small air bubbles can be used as a contrast medium and injected intravenously, where they travel to the right side of the heart. The test would be positive for an abnormal communication if the bubbles are seen passing into the left side of the heart. (Normally, they would exit the  heart  through the  pulmonary artery  and be stopped by the lungs.) This form of bubble contrast medium is generated on an  ad hoc  basis by the testing clinician by agitating  normal saline  (e.g., by rapidly and repeatedly transferring the saline between two connected syringes) immediately prior to injection. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_995", "text": "There are a variety of microbubble contrast agents. Microbubbles differ in their shell makeup, gas core makeup, and whether or not they are targeted. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_996", "text": "Regardless of the shell or gas core composition, microbubble size is fairly uniform. They lie within a range of 1\u20134 micrometres in diameter. That makes them smaller than  red blood cells , which allows them to flow easily through the circulation as well as the microcirculation."}
{"_id": "WikiPedia_Cardio$$$corpus_997", "text": "Targeted microbubbles are under preclinical development. They retain the same general features as untargeted microbubbles, but they are outfitted with ligands that bind specific receptors expressed by cell types of interest, such as inflamed cells or cancer cells. Current microbubbles in development are composed of a lipid monolayer shell with a perfluorocarbon gas core. The lipid shell is also covered with a  polyethylene glycol  (PEG) layer. PEG prevents microbubble aggregation and makes the microbubble more non-reactive. It temporarily \"hides\" the microbubble from the immune system uptake, increasing the amount of circulation time, and hence, imaging time. [ 11 ]  In addition to the PEG layer, the shell is modified with molecules that allow for the attachment of  ligands  that bind certain  receptors . These ligands are attached to the microbubbles using  carbodiimide ,  maleimide , or biotin-streptavidin coupling. [ 11 ]  Biotin-streptavidin is the most popular coupling strategy because  biotin's  affinity for  streptavidin  is very strong and it is easy to label the ligands with biotin. Currently, these ligands are  monoclonal antibodies  produced from animal cell cultures that bind specifically to receptors and molecules expressed by the target cell type. Since the antibodies are not humanized, they will elicit an immune response when used in human therapy. Humanizing antibodies is an expensive and time-intensive process, so it would be ideal to find an alternative source of ligands, such as synthetically manufactured targeting  peptides  that perform the same function, but without the immune issues. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_998", "text": "There are two forms of contrast-enhanced ultrasound, untargeted (used in the clinic today) and targeted (under preclinical development). The two methods slightly differ from each other."}
{"_id": "WikiPedia_Cardio$$$corpus_999", "text": "Untargeted microbubbles, such as the aforementioned SonoVue, Optison, or Levovist, are injected intravenously into the systemic circulation in a small bolus. The microbubbles will remain in the systemic circulation for a certain period of time. During that time, ultrasound waves are directed on the area of interest. When microbubbles in the blood flow past the imaging window, the microbubbles'  compressible  gas cores  oscillate  in response to the high frequency sonic energy field, as described in the  ultrasound  article. The microbubbles reflect a unique  echo  that stands in stark contrast to the surrounding tissue due to the orders of magnitude mismatch between microbubble and tissue echogenicity. The ultrasound system converts the strong echogenicity into a contrast-enhanced image of the area of interest. In this way, the bloodstream's echo is enhanced, thus allowing the clinician to distinguish  blood  from surrounding tissues. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1000", "text": "Targeted contrast-enhanced ultrasound works in a similar fashion, with a few alterations. Microbubbles targeted with ligands that bind certain molecular markers that are expressed by the area of imaging interest are still injected systemically in a small bolus. Microbubbles theoretically travel through the circulatory system, eventually finding their respective targets and binding specifically. Ultrasound waves can then be directed on the area of interest. If a sufficient number of microbubbles have bound in the area, their compressible gas cores oscillate in response to the high frequency sonic energy field, as described in the  ultrasound  article. The targeted microbubbles also reflect a unique echo that stands in stark contrast to the surrounding tissue due to the orders of magnitude mismatch between microbubble and tissue echogenicity. The ultrasound system converts the strong echogenicity into a contrast-enhanced image of the area of interest, revealing the location of the bound microbubbles. [ 12 ]  Detection of bound microbubbles may then show that the area of interest is expressing that particular molecular marker, which can be indicative of a certain disease state, or identify particular cells in the area of interest. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1001", "text": "Untargeted contrast-enhanced ultrasound is currently applied in  echocardiography  and  radiology . Targeted contrast-enhanced ultrasound is being developed for a variety of medical applications."}
{"_id": "WikiPedia_Cardio$$$corpus_1002", "text": "Untargeted microbubbles like Optison and Levovist are currently used in echocardiography. In addition, SonoVue [ 13 ]  ultrasound contrast agent is used in radiology for lesion characterization."}
{"_id": "WikiPedia_Cardio$$$corpus_1003", "text": "On top of the strengths mentioned in the  medical sonography  entry, contrast-enhanced ultrasound adds these additional advantages:"}
{"_id": "WikiPedia_Cardio$$$corpus_1004", "text": "In addition to the weaknesses mentioned in the  medical sonography  entry, contrast-enhanced ultrasound has the following disadvantages:"}
{"_id": "WikiPedia_Cardio$$$corpus_1005", "text": "Cor triatriatum  (or  triatrial heart ) [ 1 ]  is a  congenital heart defect  where the left  atrium  (cor triatriatum sinistrum) or right atrium (cor triatriatum dextrum) is subdivided by a thin  membrane , resulting in three atrial chambers (hence the name)."}
{"_id": "WikiPedia_Cardio$$$corpus_1006", "text": "Cor triatriatum represents 0.1% of all  congenital   cardiac malformations  and may be associated with other cardiac defects in as many as 50% of cases. The  membrane  may be complete or may contain one or more  fenestrations  of varying size."}
{"_id": "WikiPedia_Cardio$$$corpus_1007", "text": "Cor triatriatum sinistrum is more common. [ 2 ]  In this defect, there is typically a proximal chamber that receives the  pulmonic veins  and a distal (true) chamber located more  anteriorly  where it empties into the  mitral valve . The membrane that separates the  atrium  into two parts varies significantly in size and shape. It may appear similar to a diaphragm or be funnel-shaped, band-like, entirely intact (imperforate) or contain one or more openings (fenestrations) ranging from small, restrictive-type to large and widely open."}
{"_id": "WikiPedia_Cardio$$$corpus_1008", "text": "In the  pediatric  population, this anomaly may be associated with major  congenital  cardiac lesions such as  tetralogy of Fallot ,  double outlet right ventricle ,  coarctation of the aorta , partial  anomalous pulmonary venous connection , persistent left  superior vena cava  with unroofed  coronary sinus ,  ventricular septal defect ,  atrioventricular septal (endocardial cushion) defect , and common  atrioventricular canal . Rarely,  asplenia  or  polysplenia  has been reported in these patients. In the adult, cor triatriatum is frequently an isolated finding."}
{"_id": "WikiPedia_Cardio$$$corpus_1009", "text": "Cor triatriatum dextrum is extremely rare and results from the complete persistence of the right  sinus valve  of the  embryonic heart . The membrane divides the right atrium into a proximal (upper) and a distal (lower) chamber. The upper chamber receives the  venous blood  from both  vena cavae  and the lower chamber is in contact with the  tricuspid valve  and the right  atrial appendage ."}
{"_id": "WikiPedia_Cardio$$$corpus_1010", "text": "The natural history of this defect depends on the size of the communicating orifice between the upper and lower atrial chambers. If the communicating orifice is small, the patient is critically ill and may succumb at a young age (usually during infancy) to congestive  heart failure  and  pulmonary edema . [ 3 ]  If the connection is larger, patients may present in childhood or young adulthood with a clinical picture similar to that of  mitral stenosis . As the malformed membrane calcifies with age, thus further narrowing such opening, decreased  cardiac output  produces features of pulmonary venous  hypertension  and right heart failure\u2014including symptoms of  dyspnea  and  orthopnea , easy  fatigability ,  palpitations  and  shortness of breath , among others. [ 3 ]  Cor triatriatum may also be an incidental finding when it is nonobstructive."}
{"_id": "WikiPedia_Cardio$$$corpus_1011", "text": "Primarily diagnosed with imaging, such as  echocardiogram  (ultrasound of the heart),  CT , and/or  MRI . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1012", "text": "Treatment of Cor triatriatum varies among cases and is dependent upon presentation of symptoms\u2014incidental finding of the condition in  asymptomatic  patients does not typically require immediate medical management, but for those exhibiting  dyspnea  and  pulmonary congestion , surgical intervention is required. The disorder can be treated surgically by removing the membrane dividing the atrium. The  surgery , which usually occurs by first excising the diaphragm and then closing the  atrial septum , has a reported survival of 90% at five years, with almost all patients becoming  asymptomatic  post-surgery."}
{"_id": "WikiPedia_Cardio$$$corpus_1013", "text": "A  coronary care unit  ( CCU ) or  cardiac intensive care unit  ( CICU ) is a hospital ward specialized in the care of  patients  with  heart attacks ,  unstable angina ,  cardiac dysrhythmia  and (in practice) various other cardiac conditions that require continuous monitoring and treatment."}
{"_id": "WikiPedia_Cardio$$$corpus_1014", "text": "The main feature of coronary care is the availability of  telemetry  or the continuous monitoring of the cardiac rhythm by  electrocardiography . This allows early intervention with  medication ,  cardioversion  or  defibrillation , improving the prognosis. As  arrhythmias  are relatively common in this group, patients with myocardial infarction or unstable angina are routinely admitted to the coronary care unit. For other indications, such as  atrial fibrillation , a specific indication is generally necessary, while for others, such as  heart block , coronary care unit admission is standard. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1015", "text": "In the United States, cardiac conditions accounted for eight of the eighteen conditions and procedures with high ICU utilization (ICU utilization in more than 40% of stays) in 2011. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1016", "text": "In the United States, coronary care units are usually subsets of  intensive care units  (ICU) dedicated to the care of critically ill cardiac patients. These units are usually present in hospitals that routinely engage in cardiothoracic surgery. Invasive monitoring such as with  pulmonary artery catheters  is common, as are supportive modalities such as  mechanical ventilation  and  intra-aortic balloon pumps  (IABP)."}
{"_id": "WikiPedia_Cardio$$$corpus_1017", "text": "Certain hospitals, such as Johns Hopkins  [1] , maintain mixed units consisting of both acute care units for the critically ill, and intermediate care units for patients who are not critical."}
{"_id": "WikiPedia_Cardio$$$corpus_1018", "text": "Acute coronary care units (ACCUs), also called \"critical coronary care units\" (CCCUs), are equivalent to intensive care in the level of service provided. Patients with acute myocardial infarction,  cardiogenic shock , or post-operative \"open-heart\" patients commonly abide here."}
{"_id": "WikiPedia_Cardio$$$corpus_1019", "text": "Subacute coronary care units (SCCUs), also called progressive care units (PCUs), intermediate coronary care units (ICCUs), or stepdown units,  provide a level of care intermediate to that of the intensive care unit and that of the general medical floor. These units typically serve patients who require cardiac telemetry, such as those with  unstable angina ."}
{"_id": "WikiPedia_Cardio$$$corpus_1020", "text": "Coronary care units developed in the 1960s when it became clear that close monitoring by specially trained staff,  cardiopulmonary resuscitation  and medical measures could reduce the mortality from complications of cardiovascular disease. The first description of a CCU was given in 1961 to the  British Thoracic Society  by  Desmond Julian , who founded the first CCU at the  Royal Infirmary of Edinburgh  in 1964. [ 2 ]  Early CCUs were also located in  Sydney ,  Kansas City ,  Toronto  and  Philadelphia . The first coronary care unit in the US was opened at Bethany Medical Center in  Kansas City, Kansas  by Hughes Day, and he coined the term. [ 3 ] [ 4 ]  Bethany Medical Center is also where the first \"crash carts\" were developed. [ 5 ]  Studies published in 1967 revealed that those observed in a coronary care setting had consistently better outcomes. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1021", "text": "DF Beck performed the first successful resuscitation of a physician with myocardial infarction in 1953, and pioneered the use of open-chest defibrillation. Zoll introduced external defibrillation in Boston in 1956, and Kouwenhoven and colleagues at Johns Hopkins highlighted the effectiveness of a combo of mouth-to-mouth, sternal compression, and closed chest defibrillation in restoring cardiac function in ventricular fibrillation patients. The first diagnostic angiogram was discovered by Mason Sones in 1958, due to an accidental injection of dye directly into the coronary artery rather than into the entire circulation - something that was previously believed to be fatal. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1022", "text": "These developments led to an interest in intensive care for myocardial infarction. In 1967, Thomas Killip and John Kimball published a report of 250 patients with acute MI's, who had experienced significantly better survival rates in CCUs compared to other institutions. This, along with other reports, led to an increase in coronary care units. Now catheterization units are commonplace in large cities. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1023", "text": "Coronary circulation  is the  circulation of blood  in the  arteries  and  veins  that supply the  heart muscle  (myocardium).\n Coronary arteries  supply  oxygenated  blood to the heart muscle.  Cardiac veins  then drain away the blood after it has been deoxygenated.\nBecause the rest of the body, and most especially the  brain , needs a steady supply of oxygenated blood that is free of all but the slightest interruptions, the heart is required to function continuously. Therefore its circulation is of major importance not only to its own tissues but to the entire body and even the  level of consciousness  of the brain from moment to moment.\nInterruptions of coronary circulation quickly cause heart attacks ( myocardial infarctions ), in which the heart muscle is damaged by  oxygen starvation . Such interruptions are usually caused by  coronary ischemia  linked to  coronary artery disease , and sometimes to  embolism  from other causes like obstruction in blood flow through vessels."}
{"_id": "WikiPedia_Cardio$$$corpus_1024", "text": "Coronary arteries  supply blood to the myocardium and other components of the heart. Two coronary arteries originate from the left side of the heart at the beginning (root)  left ventricle . There are three  aortic sinuses  (dilations) in the wall of the aorta just superior to the aortic semilunar valve. Two of these, the  left posterior aortic sinus  and  anterior aortic sinus , give rise to the  left  and  right coronary arteries , respectively. The third sinus, the  right posterior aortic sinus , typically does not give rise to a vessel. Coronary vessel branches that remain on the surface of the heart and follow the sulci of the heart are called  epicardial  coronary arteries. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1025", "text": "The left coronary artery distributes blood to the left side of the heart, the left atrium and ventricle, and the interventricular septum. The  circumflex artery  arises from the left coronary artery and follows the  coronary sulcus  to the left. Eventually, it will fuse with the small branches of the right coronary artery. The larger  left anterior descending artery  (LAD), is the second major branch arising from the left coronary artery. It follows the anterior interventricular sulcus around the pulmonary trunk. Along the way it gives rise to numerous smaller branches that interconnect with the branches of the  posterior interventricular artery , forming  anastomoses . An anastomosis is an area where vessels unite to form interconnections that normally allow blood to circulate to a region even if there may be partial blockage in another branch. The anastomoses in the heart are very small. Therefore, this ability is somewhat restricted in the heart so a  coronary artery blockage  often results in  myocardial infarction  causing  death of the cells  supplied by the particular vessel. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1026", "text": "The right coronary artery proceeds along the coronary sulcus and distributes blood to the right atrium, portions of both ventricles, and the  heart conduction system . Normally, one or more  marginal arteries  arise from the right coronary artery inferior to the right atrium. The marginal arteries supply blood to the superficial portions of the right ventricle. On the posterior surface of the heart, the right coronary artery gives rise to the posterior interventricular artery, also known as the posterior descending artery. It runs along the posterior portion of the interventricular sulcus toward the apex of the heart, giving rise to branches that supply the interventricular septum and portions of both ventricles. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1027", "text": "The  vessels  that remove the deoxygenated  blood  from the  heart  muscle are the cardiac  veins . These include the  great cardiac vein , the  middle cardiac vein , the  small cardiac vein , the  smallest cardiac veins , and the  anterior cardiac veins . Cardiac veins carry blood with a poor level of  oxygen , from the  myocardium  to the  right atrium . Most of the blood of the coronary veins returns through the  coronary sinus . The  anatomy  of the veins of the heart is very variable, but generally it is formed by the following veins: heart veins that go into the coronary sinus: the  great cardiac vein , the  middle cardiac vein , the  small cardiac vein , the posterior vein of the  left ventricle , and the  oblique vein of Marshall . Heart veins that go directly to the right atrium: the anterior cardiac veins, the  smallest cardiac veins  (Thebesian veins). [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1028", "text": "There are some anastomoses between branches of the two coronary arteries.  However the coronary arteries are functionally end arteries and so these meetings are referred to as potential  anastomoses , which lack function, as opposed to true anastomoses like that in the palm of the hand. This is because blockage of one coronary artery generally results in death of the heart tissue due to lack of sufficient blood supply from the other branch. When two arteries or their branches join, the area of the myocardium receives dual blood supply. These junctions are called anastomoses. If one coronary artery is obstructed by an  atheroma , the second artery is still able to supply oxygenated blood to the myocardium. However, this can only occur if the atheroma progresses slowly, giving the anastomoses a chance to proliferate. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1029", "text": "Under the most common configuration of coronary arteries, there are three areas of anastomoses. Small branches of the LAD (left anterior descending/anterior interventricular) branch of the left coronary join with branches of the posterior interventricular branch of the right coronary in the interventricular sulcus (groove). More superiorly, there is an anastomosis between the circumflex artery (a branch of the left coronary artery) and the right coronary artery in the atrioventricular groove. There is also an anastomosis between the septal branches of the two coronary arteries in the interventricular septum. The photograph shows area of heart supplied by the right and the left coronary arteries. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1030", "text": "The left and right coronary arteries occasionally arise by a common trunk, or their number may be increased to three; the additional branch being the posterior coronary artery (which is smaller in size). In rare cases, a person will have the third coronary artery run around the root of the aorta. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1031", "text": "Occasionally, a coronary artery will exist as a double structure (i.e. there are two arteries, parallel to each other, where ordinarily there would be one). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1032", "text": "The artery that supplies the posterior third of the  interventricular septum  \u2013 the  posterior descending artery  (PDA) [ 3 ]  determines the coronary dominance. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1033", "text": "Approximately 70% of the general population are right-dominant, 20% are co-dominant, and 10% are left-dominant. [ 4 ] \nA precise anatomic definition of dominance would be the artery which gives off supply to the AV node i.e. the AV nodal artery. Most of the time this is the right coronary artery. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1034", "text": "The  papillary muscles  attach the  mitral valve  (the valve between the  left atrium  and the  left ventricle ) and the  tricuspid valve  (the valve between the  right atrium  and the  right ventricle ) to the wall of the heart.  If the papillary muscles are not functioning properly, the mitral valve may leak during contraction of the left ventricle.  This causes some of the blood to travel \"in reverse\", from the left ventricle to the left atrium, instead of forward to the aorta and the rest of the body.  This leaking of blood to the left atrium is known as  mitral regurgitation .  Similarly, the leaking of blood from the right ventricle through the tricuspid valve and into the right atrium can also occur, and this is described as  tricuspid insufficiency  or tricuspid regurgitation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1035", "text": "The anterolateral papillary muscle more frequently receives two blood supplies:  left anterior descending  (LAD) artery and the  left circumflex artery  (LCX). [ 5 ] \nIt is therefore more frequently resistant to  coronary ischemia  (insufficiency of oxygen-rich blood).  On the other hand, the posteromedial papillary muscle is usually supplied only by the PDA. [ 5 ]   This makes the posteromedial papillary muscle significantly more susceptible to  ischemia .  The clinical significance of this is that a  myocardial infarction  involving the PDA is more likely to cause mitral regurgitation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1036", "text": "During contraction of the  ventricular  myocardium ( systole ), the subendocardial coronary vessels (the vessels that enter the myocardium) are compressed due to the high ventricular pressures.\nThis compression results in momentary retrograde blood flow (i.e., blood flows backward toward the aorta) which further inhibits perfusion of myocardium during systole.\nHowever, the epicardial coronary vessels (the vessels that run along the outer surface of the heart) remain open.\nBecause of this, blood flow in the subendocardium stops during ventricular contraction.\nAs a result, most myocardial perfusion occurs during heart relaxation ( diastole ) when the subendocardial coronary vessels are open and under lower pressure.\nFlow never comes to zero in the right coronary artery, since the right ventricular pressure is less than the diastolic blood pressure. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1037", "text": "The heart regulates the amount of  vasodilation  or vasoconstriction of the coronary arteries based upon the oxygen requirements of the heart. This contributes to the filling difficulties of the coronary arteries.\nCompression remains the same. Failure of oxygen delivery caused by a decrease in blood flow in front of increased oxygen demand of the heart results in tissue  ischemia , a condition of oxygen deficiency. Brief ischemia is associated with intense chest pain, known as  angina . Severe ischemia can cause the heart muscle to die from hypoxia, such as during a  myocardial infarction .  Chronic moderate ischemia causes contraction of the heart to weaken, known as myocardial hibernation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1038", "text": "In addition to metabolism, the coronary circulation possesses unique pharmacologic characteristics. Prominent among these is its reactivity to adrenergic stimulation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1039", "text": "The following are the named branches of the coronary circulation in a right-dominant heart: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1040", "text": "The  vessels  that deliver  oxygen -rich  blood  to the  myocardium  are the  coronary arteries . When the  arteries  are healthy, they are capable of autoregulating themselves to maintain the coronary blood flow at levels appropriate to the needs of the  heart muscle ."}
{"_id": "WikiPedia_Cardio$$$corpus_1041", "text": "The relatively narrow coronary arteries are commonly affected by  atherosclerosis  and can become blocked, causing  angina  or a  heart attack . The coronary arteries are classified as \"terminal circulation\", since they represent the only source of blood supply to the myocardium; there is very little redundant blood supply, that is why blockage of these vessels can be so critical. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1042", "text": "This article incorporates text from the  CC BY  book:  OpenStax College,  Anatomy & Physiology. OpenStax CNX. 30 July 2014."}
{"_id": "WikiPedia_Cardio$$$corpus_1043", "text": "A  coronary CT calcium scan  is a  computed tomography (CT) scan  of the heart for the assessment of severity of  coronary artery disease . Specifically, it looks for calcium deposits in atherosclerotic plaques in the coronary arteries that can narrow arteries and increase the risk of heart attack. [ 1 ]  These plaques are the cause of most heart attacks, and become calcified as they develop."}
{"_id": "WikiPedia_Cardio$$$corpus_1044", "text": "These calcifications can be detected by CT imaging because of their opacity to x-rays. This severity can be presented as an Agatston score or coronary artery calcium (CAC) score. The CAC score is an independent marker of risk for cardiac events, cardiac mortality, and all-cause mortality. [ 2 ]  In addition, it provides additional prognostic information to other cardiovascular risk markers. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1045", "text": "Obstructions may be present even with an Agatston score of zero, especially in younger patients. [ 3 ]  A typical coronary CT calcium scan is done without the use of  radiocontrast  agent but it can also be performed using contrast-enhanced images as well, such as in  coronary CT angiography . [ 4 ]  The exam is best performed with cardiac gating to eliminate motion but can also be estimated in the presence of motion."}
{"_id": "WikiPedia_Cardio$$$corpus_1046", "text": "The well-established indications for the use of the CAC score include stratification of global cardiovascular risk for asymptomatic patients: intermediate risk based on the Framingham risk score (class I); low risk based on a family history of early coronary artery disease (CAD) (class IIa); and low-risk patients with diabetes (class IIa). [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1047", "text": "In symptomatic patients, the pre-test probability should always be given weight in the interpretation of the CAC score as a filter or tool to indicate the best method to facilitate the diagnosis. Therefore, the use of the CAC score alone is limited in symptomatic patients. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1048", "text": "In patients with diabetes, the CAC score helps identify the individuals most at risk, who could benefit from screening for silent ischemia and from more aggressive clinical treatment. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1049", "text": "However,  coronary CT angiography  (CTA) is superior to coronary CT calcium scanning in determining the risk of Major Adverse Cardiac Events (MACE). [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1050", "text": "There is potential to measure CAC on chest radiographs taken for other indications, possibly allowing some primary screening for  coronary artery disease  without adding to radiation exposure and with minimal marginal cost. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1051", "text": "The  Agatston score , named after its developer  Arthur Agatston , is a measure of calcium on a coronary CT calcium scan. [ 7 ]  The original work, published in 1990, [ 8 ]  was based on  electron beam computed tomography  (also known as ultrafast CT or EBCT). The score is calculated using a weighted value assigned to the highest density of calcification in a given coronary artery."}
{"_id": "WikiPedia_Cardio$$$corpus_1052", "text": "The density is measured in  Hounsfield units , and score of 1 for 130\u2013199 HU, 2 for 200\u2013299 HU, 3 for 300\u2013399 HU, and 4 for 400 HU and greater. This weighted score is then multiplied by the area (in square millimeters) of the coronary calcification. For example, a \"speck\" of coronary calcification in the left anterior descending artery measures 4 square millimeters and has a peak density of 270 HU. The score is therefore 8 (4 square millimeters \u00d7 weighted score of 2)."}
{"_id": "WikiPedia_Cardio$$$corpus_1053", "text": "The tomographic slices of the heart are 3 millimeters thick and average about 50\u201360 slices from the coronary artery ostia to the inferior wall of the heart. The calcium score of every calcification in each coronary artery for all of the tomographic slices is then summed up to give the total coronary artery calcium score (CAC score). [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1054", "text": "The Agatston score is frequently used today because of its long history of clinical validation. Several variations of the Agatston score have been described, including mass-based calcium scoring, volume-based calcium scoring, or lesion-specific calcium-scoring have been developed. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1055", "text": "A lesion-specific calcium score has been developed. [ 11 ]  Each individual calcified lesion is characterized and measured using parameters including the width, length, density, and distance from the entrance of the major coronary arteries. [ 12 ]  Research has shown that the lesion-specific calcium scoring method is superior to the traditional  Agatston score  for the prediction of significant blockages in the heart. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1056", "text": "On average, a single scan will expose a patient to about 2.3 millisieverts of radiation, equivalent to 23 chest x-rays (front and side views). [ 13 ] [ 14 ]  That average covers a wide range of doses depending on equipment type and scanning protocol. Using modern equipment and protocols, a 1 millisievert exposure is possible. [ 15 ]  Because the exact radiation exposure for a specific patient depends on the equipment type in use, the patients build and a variety of scanning options (such as retrospective vs prospective gating) it is difficult for a patient to know what their radiation exposure will be."}
{"_id": "WikiPedia_Cardio$$$corpus_1057", "text": "A 2009 study indicated that for every 100,000 people screened with CAC testing every 5 years between ages 45 to 75 years (men) or 55 to 75 years (women), there would be 42 (men) or 62 (women) additional radiation induced cancer cases. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1058", "text": "Coronary flow reserve  ( CFR ) is the maximum increase in blood flow through the  coronary arteries  above the normal resting volume. [ 1 ]  Its measurement is often used in medicine to assist in the treatment of conditions affecting the coronary arteries and to determine the efficacy of treatments used."}
{"_id": "WikiPedia_Cardio$$$corpus_1059", "text": "When demand for oxygen in the  myocardium  is increased, the  vascular resistance  of the coronary arteries has the ability to reduce, and this can increase the volume of blood passing through the blood vessels.  This reduction occurs because the arteries  dilate , which causes an increase in the diameter of the  lumen . [ 2 ] [ 3 ]  The greatest potential for this change is normally in the branches ( arterioles ) of the coronary artery that penetrate the myocardium, rather than those on the surface of the heart.\n [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1060", "text": "Coronary flow reserve can be measured through a variety of methods, including digital subtraction  cineangiography  with  coronary catheterization , [ 4 ]   doppler echocardiography , [ 5 ]  and  positron emission tomography  (PET). [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1061", "text": "Coronary flow reserve is used in diagnostics and treatment of patients with conditions such as  coronary artery disease  and  syndrome X . [ 7 ]  In the treatment of these conditions,  vasodilators  are used to allow sufficient blood to flow past a  stenosis , for example, and the measurement of CFR enables the efficacy of such interventions to be measured.\n [ 3 ]   In patients with  Anderson-Fabry disease , there is evidence to suggest that CFR can be reduced. [ 5 ] \nWhen coronary flow reserve is used in medicine, it is often expressed with a numerical value, which is formed by dividing the maximal coronary blood flow by resting blood flow.  This allows for an objective view, which can aid diagnosis and treatment. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1062", "text": "Coronary reflex  is the change of coronary diameter in response to chemical, neurological or mechanical stimulation of the  coronary arteries .\nThe coronary reflexes are stimulated differently from the rest of the  vascular system . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1063", "text": "Cocaine abuse  frequently can cause a coronary spasm, resulting in a spontaneous  myocardial infarction . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1064", "text": "Cough  CPR  is the subject of a hoax email that began circulating in 1999. [ citation needed ]  It is described as a \"resuscitation technique\" in which through prolonged  coughing  and deep breathing every 2 seconds, a person suffering a  cardiac dysrhythmia  immediately before  cardiac arrest  can keep conscious until help arrives (or until the person can get to the nearest hospital). Neither the  American Heart Association  nor the  American Red Cross  endorses cough CPR during a heart attack. [1]"}
{"_id": "WikiPedia_Cardio$$$corpus_1065", "text": "This confusion appears to revolve primarily over the public's failure to discriminate between a  heart attack ,  cardiac arrest , and cardiac dysrhythmias. A heart attack occurs when an occlusion (e.g. blood clot) of an artery in the heart slowly causes tissue to die. This can result in chest pain and discomfort, and requires immediate medical attention to resolve the occlusion by emergency surgery or  cardiac clot-busting drugs . A cardiac dysrhythmia is primarily an electrical problem within the heart, and is sometimes treated with electrolytes, vagal maneuver, or electrical cardioversion.  Many dysrhythmias may herald an impending heart attack. [ medical citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1066", "text": "Cough CPR has been the subject of a series of  chain email  campaigns. These emails are typically of the following format: [ citation needed ]   (See Snopes for this and other citation issues.)  [2]"}
{"_id": "WikiPedia_Cardio$$$corpus_1067", "text": "HOW TO SURVIVE A HEART ATTACK WHEN ALONE"}
{"_id": "WikiPedia_Cardio$$$corpus_1068", "text": "Since many people are alone when they suffer a heart attack, this article seemed in order. Without help the person whose heart stops beating properly and who begins to feel Faint, has only about 10 seconds left before losing consciousness. However, these victims can help themselves by coughing repeatedly and very vigorously. A deep breath should be taken before each cough, and the cough must be deep and prolonged, as when producing sputum from deep inside the chest. A breath and a cough must be repeated about every two seconds without let up until help arrives, or until the heart is felt to be beating normally again. Deep breaths get oxygen into the lungs and coughing movements squeeze the heart and keep the blood circulating."}
{"_id": "WikiPedia_Cardio$$$corpus_1069", "text": "Coxsackie B  is a group of six  serotypes  of  coxsackievirus  (CVB1-CVB6), a  pathogenic   enterovirus , that trigger illnesses ranging from a mild febrile rash to full-fledged  pericarditis  and  myocarditis  ( coxsackievirus-induced cardiomyopathy ). [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1070", "text": "The genome of Coxsackie B virus consists of approximately 7,400 base pairs. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1071", "text": "The various members of the Coxsackie B group were discovered almost entirely in the United States, appearing originally in  Connecticut ,  Ohio ,  New York , and  Kentucky , although a sixth member of the group has been found in the  Philippines . [ 1 ]   However, all six serotypes have a global distribution and are a relatively common cause of gastrointestinal upset. The name reflects  the first isolation from Coxsackie, New York . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1072", "text": "Infections are most commonly spread by the  Fecal-oral route , emphasizing the importance of good hygiene, especially hand-washing. [ 2 ]  Oral-oral and  respiratory droplets  can also be means of transmission. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1073", "text": "Coxsackie B infections have been reported to account for nearly a quarter of all  enterovirus  infections. [ 5 ]  Nearly half of all reported cases of Coxsackie B infections occur before the age of five. [ 5 ]  For the CBV1 serotype, two-thirds of  Centers for Disease Control and Prevention  reported infections in the United States were for children under one year of age. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1074", "text": "Symptoms of infection with viruses in the Coxsackie B grouping include  fever ,  headache ,  sore throat , gastrointestinal distress, extreme  fatigue  as well as  chest  and  muscle pain . It can also lead to  spasms  in arms and legs.  This presentation is known as pleurodynia or  Bornholm disease  in many areas.  Patients with chest pain should see a doctor immediately\u2014in some cases, viruses in the Coxsackie B family progress to myocarditis or pericarditis, which can result in permanent heart damage or death.  Coxsackie B virus infection may also induce  aseptic meningitis .  As a group, they are the most common cause of unexpected  sudden death , and may account for up to 50% of such cases. [ 6 ]   The incubation period for the Coxsackie B viruses ranges from 2 to 6 days, and illness may last for up to 6 months in extreme cases, but may resolve as quickly as two days.  Infection usually occurs between the months of May and June, but do not show symptoms until October in temperate Northern Hemisphere regions. People should ideally spend 1 month resting during the height of infection.  Another cause of this virus is from a dirty wound from an accident. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1075", "text": "Enterovirus infection is diagnosed mainly via  serological  tests such as  ELISA [ 7 ]  and from  cell culture . [ 1 ]   Because the same level and type of care is given regardless of type of Coxsackie B infection, it is mostly unnecessary for treatment purposes to diagnose which virus is causing the symptoms in question, though it may be epidemiologically useful. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1076", "text": "Coxsackie B infections usually do not cause serious disease, although for newborns in the first 1\u20132 weeks of life, Coxsackie B infections can easily be fatal. [ 2 ]  The pancreas is a frequent target, which can cause  pancreatitis . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1077", "text": "Coxsackie B3 (CB3) infections are the most common enterovirus cause of  myocarditis  and  sudden cardiac death . [ 8 ]  CB3 infection causes  ion channel  pathology in the heart, leading to  ventricular arrhythmia . [ 8 ]  Studies in mice suggest that CB3 enters cells by means of  toll-like receptor\u00a04 . [ 9 ]  Both CB3 and CB4 exploit cellular  autophagy  to promote  replication . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1078", "text": "The B4 Coxsackie viruses (CB4) serotype was suggested to be a possible cause of  diabetes mellitus type 1  (T1D). [ 10 ]  An  autoimmune  response to Coxsackie virus\u00a0B infection upon the  islets of Langerhans  may be a cause of T1D. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1079", "text": "Other research implicates strains B1, A4, A2 and A16 in the destruction of  beta cells , [ 11 ] [ 12 ]  with some suggestion that strains B3 and B6 may have protective effects via immunological cross-protection."}
{"_id": "WikiPedia_Cardio$$$corpus_1080", "text": "As of 2008 [update] , there is no well-accepted treatment for the Coxsackie B group of viruses. [ 1 ]   Palliative care  is available, however, and patients with chest pain or  stiffness of the neck  should be examined for signs of cardiac or  central nervous system  involvement, respectively.  Some measure of prevention can usually be achieved by basic sanitation on the part of food-service workers, though the viruses are highly contagious.  Care should be taken in washing ones hands and in cleaning the body after swimming.  In the event of Coxsackie-induced myocarditis or pericarditis,  anti-inflammatories  can be given to reduce damage to the heart muscle. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1081", "text": "Enteroviruses are usually only capable of acute infections that are rapidly cleared by the adaptive immune response. [ 13 ] [ 14 ]  However, mutations which enterovirus B serotypes such as coxsackievirus B and  echovirus  acquire in the host during the acute phase can transform these viruses into the non-cytolytic form (also known as non-cytopathic or defective enterovirus). [ 15 ]  This form is a mutated  quasispecies [ 13 ]  of enterovirus which is capable of causing persistent infection in human tissues, and such infections have been found in the pancreas in type 1 diabetes, [ 16 ] [ 17 ]  in chronic myocarditis and  dilated cardiomyopathy , [ 18 ] [ 13 ] [ 19 ]  in valvular heart disease, [ 20 ]  in  myalgic encephalomyelitis , [ 21 ] [ 22 ]  and in Sj\u00f6gren's syndrome. [ 23 ]   In these persistent infections, viral RNA is present at very low levels, and some researchers believe it is just a fading remnant of the acute infection [ 14 ]  although others scientists believe this persistent viral RNA may have pathological effects and cause disease. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1082", "text": "The  CPK-MB test  (creatine phosphokinase-MB), also known as  CK-MB test , is a  cardiac marker [ 3 ]  used to assist diagnoses of an  acute myocardial infarction ,  myocardial ischemia , or  myocarditis . It measures the blood level of CK-MB (creatine kinase myocardial band), the bound combination of two variants (isoenzymes  CKM  and  CKB ) of the enzyme  phosphocreatine kinase . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1083", "text": "In some locations, the test has been superseded by the  troponin test . However, recently, there have been improvements to the test that involve measuring the ratio of the CK-MB1 and CK-MB2 isoforms. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1084", "text": "The newer test detects different  isoforms  of the B subunit specific to the myocardium whereas the older test detected the presence of cardiac-related  isoenzyme  dimers. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1085", "text": "Many cases of CK-MB levels exceeding the blood level of total CK have been reported, especially in newborns with cardiac malformations, especially ventricular septal defects. This reversal of ratios is in favor of pulmonary emboli or vasculitis. An autoimmune reaction creating a complex molecule of CK and IgG should be taken into consideration. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1086", "text": "Das Reizleitungssystem des S\u00e4ugetierherzens  (English: \" The Conduction System of the Mammalian Heart \") is a scientific  monograph  published in 1906 by  Sunao Tawara . It has been recognized by cardiologists as a monumental discovery, [ 1 ]  and a milestone in  cardiac electrophysiology \". [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1087", "text": "The monograph revealed the existence of the  atrioventricular node  and the function of  Purkinje cells . It was used by  Arthur Keith  and  Martin Flack  as a detailed guide in their attempts to verify the existence of the  Bundle of His , which subsequently led to their discovery of the  sinoatrial node . Throughout the beginning of the 20th century, Tawara's monograph influenced the work of many cardiologists and it was later cited by  Willem Einthoven  in his anatomical interpretation of the  electrocardiogram . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1088", "text": "Prior to Tawara's discoveries, it was assumed that electrical conduction through the  Bundle of His  was slow, because of the long interval between  atrial  and  ventricular  contractions. The Swiss cardiologist  Wilhelm His, Jr.  assumed that the heart bundle was connected directly to the base of the ventricle, and physiologists incorrectly taught that the base of the ventricle contracted first, followed by the apex. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1089", "text": "However, Tawara postulated that ventricular contraction occurs in the opposite manner, with the apex contracting earlier than the base. He also believed that the heart's electrical conduction was not slow but rapid. Working under the guidance of his mentor,  Ludwig Aschoff , Tawara performed a histological examination of 150 hearts with  myocarditis  (which led to the discovery of  Aschoff bodies ), and he began examining the atrioventricular bundle before embarking on a comprehensive study of the anatomy and histology of the heart's conduction system. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1090", "text": "The implications of his work were immediately recognized by Aschoff, who arranged for it to be published in the form of a  monograph . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1091", "text": "Tawara's monograph, titled \" Das Reizleitungssystem des S\u00e4ugetierherzens \" (English: \" The Conduction System of the Mammalian Heart \") was published in 1906. The most important discoveries are listed below:"}
{"_id": "WikiPedia_Cardio$$$corpus_1092", "text": "Tawara commented that the system represents a transporting or conducting pathway, and \"because the pathway is not a ductal, but a continuously related protoplasmic cord, conduction of excitation impulses surely must take place there.\" [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1093", "text": "On 26 September 1905, shortly before the monograph was due to be published,  Ludwig Aschoff  wrote an article about Tawara's work. It was subsequently read by the Scottish cardiologist  James Mackenzie  and forwarded to anatomist  Arthur Keith , who was attempting to confirm the existence of the  Bundle of His . Despite putting in his best efforts, he failed to locate the structure. On 15 January 1906, Keith wrote a letter to Mackenzie and acknowledged his skepticism about its existence: \" I have given up the search for His' bundle\u2014having come to the conclusion that there is not and never was any such thing. \u201d [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1094", "text": "In response to Arthur Keith's skepticism, Mackenzie forwarded Aschoff's article about Tawara's findings, which stimulated Keith's renewal of his studies on the cardiac conduction system. [ 5 ]  Despite having written a letter to  The Lancet  about his failure to locate the  Bundle of His  and his increasing doubts about its existence, Keith (with his student  Martin Flack ) later reported that they had succeeded in locating the structure by following the detailed descriptions and figures in Tawara's monograph. [ 6 ]  In a paper published in  The Lancet  on 11 August 1906, they acknowledged the monograph's high degree of accuracy:"}
{"_id": "WikiPedia_Cardio$$$corpus_1095", "text": "Encouraged by their initial success and inspired by Tawara's discovery of the  atrioventricular node , Keith and Flack extended their studies and eventually discovered the  sinoatrial node  in 1907. [ 4 ]  They wrote that they were examining other regions of the heart for \"peculiar musculature\" similar to the one discovered by Tawara. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1096", "text": "In 1908, the Dutch physiologist  Willem Einthoven  referred to Tawara\u2019s monograph as the anatomical basis for interpreting the electrocardiogram. [ 3 ]  In his monograph, Tawara theorized about the velocity of the excitatory process in the conduction system and the mode of ventricular contraction. Together with his anatomic findings and physiological assumptions, it contributed to the rapid popularization of  electrocardiography . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1097", "text": "In 1909, the American pathologist  Lydia DeWitt  created the first 3D wax model of the conduction system, using Tawara\u2019s description as a guide. [ 10 ]  In 1911, the British cardiologist  Thomas Lewis  reviewed the auriculo-ventricular connection system and described Tawara's discoveries in  Das Reizleitungssystem des Saugetierherzens  as the \"main advance\" in knowledge about the system:"}
{"_id": "WikiPedia_Cardio$$$corpus_1098", "text": "In his autobiography published in 1950,  Arthur Keith  explained how he had systematically searched for Tawara's system to verify its components:"}
{"_id": "WikiPedia_Cardio$$$corpus_1099", "text": "Acknowledging the significance and implications of these discoveries, Keith commented: \"With the discovery of the conducting system of Tawara, heart research entered a new epoch.\" [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1100", "text": "Shortly before his death,  Wilhelm His, Jr.  published a personal account about the discovery of the  Bundle of His . He noted that it took ten years before anatomists began to pay attention to the bundle, starting with the studies of Retzer and Brauning in 1903, followed by the \"important work of Tawara\" in 1906, and the subsequent discovery of the sinus node which completed the system. He credited Tawara for connecting the bundle with the  Purkinje fibers  and for declaring it the heart's conduction system. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1101", "text": "In clinical  cardiology  the term  \"diastolic function\"  is most commonly referred as how the  heart  fills. [ 1 ]  Parallel to \"diastolic function\", the term \" systolic  function\" is usually referenced in terms of the left ventricular  ejection fraction  (LVEF), which is the ratio of  stroke volume  and  end-diastolic volume . [ 2 ]  Due to the epidemic of  heart failure , [ 3 ]  particularly the cases determined as  diastolic heart failure , it is increasingly urgent and crucial to understand the meaning of \u201cdiastolic function\u201d. Unlike \"systolic function\", which can be simply evaluated by LVEF, there are no established dimensionless parameters for \"diastolic function\" assessment. [ 4 ]  Hence to further study \"diastolic function\" the complicated and speculative physiology must be taken into consideration."}
{"_id": "WikiPedia_Cardio$$$corpus_1102", "text": "How the heart works during its filling period still has many misconceptions remaining. To better understand diastolic function, it is crucial to realize that the left  ventricle  is a mechanical  suction pump  at, and for a little while after, the  mitral valve  opening. [ 5 ]  In other words, when mitral valve opens, the  atrium  does not push  blood  into the ventricle, instead, it is the ventricle that mechanically \"sucks\" in blood from the  atrium . [ 6 ] [ 7 ]  The energy that drives the suction process is generated from phase of  systole . During systole, to overcome the peripheral arterial load at ejection, ventricle contracts, which also compresses elastic tissues internal to and external to the  myocardium . Then, when  cardiac muscle  relaxes, the energy captured by compressed elements releases, driving the recoil of ventricular wall until a new balanced equilibrium state is reached. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1103", "text": "During  diastole , the ventricle of heart must remain elastic or compliant enough and have capacity to hold incoming blood to guarantee effectiveness of the filling phase. Hence stiffness and relaxation are ventricle's intrinsic feature parameters that are practical in evaluating and quantifying diastolic function. [ 9 ]  In addition,  volumetric load [ 10 ]  serves as an extrinsic indicating parameter that modulates diastolic function."}
{"_id": "WikiPedia_Cardio$$$corpus_1104", "text": "The most established index to describe left ventricular diastolic function is Tau, left ventricular diastolic time constant. Measurement of Tau is traditionally delivered in a catheter lab by an invasive method. Recently, non-invasive measurement of Tau is available for mitral regurgitation or aortic regurgitation patients in an Echo lab. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1105", "text": "There have been many attempts intending for extracting both intrinsic and extrinsic properties. Early attempts concentrated on pulse-wave Doppler-echo measured trans-mitral flow velocity contours. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1106", "text": "In terms of filling, diastolic intervals consist of early rapid filling E-waves followed by  diastasis  and followed by atrial systole-generated A-waves. Empirically, E- and A- wave contours were simplified as triangles. Nowadays, triangle-based indexes, such as the peak velocities of the E- and A-waves and ratio of them, the deceleration time and time duration of the E-wave, and the velocity time integral of both E- and A- waves, are usually measured and evaluated. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1107", "text": "The triangular approach applies to E-wave shape conveniently, especially in the past when the images rendered by technology back in days are of poor resolution quality. Nevertheless, with rapidly improving temporal resolution and image processing capabilities, the curvature of E-wave contours can be clearly identified with detailed information revealed."}
{"_id": "WikiPedia_Cardio$$$corpus_1108", "text": "Due to advancement of modern medical imaging technology, the measurement of even smaller (i.e. tissue) velocities are possible to be made, which even leads to capability to measure the longitudinal displacements of the  mitral annulus . The shapes of mitral annular velocity contours used to be approximated to be triangles, whose peak height is label to be E\u2019. E\u2019 proved useful in selected patient populations for estimation of  end-diastolic pressure  (EDP). [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1109", "text": "Other innovative imaging modalities consist of techniques such as  speckle tracking . Speckle tracking enables strain and strain-rate measurements. It is a relatively recent instance of technological progress, due to the fact that it relies on the information content inherent in the seemingly random arrangement of bright speckles present in all echocardiographic images. [ 12 ]  Even though a variety of echo-based imaging technologies represent multiple levels of research innovation, much remains to be studied in relation to how to interpret the recorded data embedded in images."}
{"_id": "WikiPedia_Cardio$$$corpus_1110", "text": "Door-to-balloon  is a time measurement in emergency cardiac care (ECC), specifically in the treatment of  ST segment elevation myocardial infarction  (or STEMI). The interval starts with the patient's arrival in the  emergency department , and ends when a catheter guidewire crosses the culprit lesion in the  cardiac cath lab . Because of the adage that \"time is muscle\", meaning that delays in treating a myocardial infarction increase the likelihood and amount of  cardiac muscle  damage due to localised  hypoxia , [ 1 ] [ 2 ] [ 3 ] [ 4 ]   ACC / AHA  guidelines recommend a door-to-balloon interval of no more than 90 minutes. [ 5 ]  As of 2006 in the United States, fewer than half of STEMI patients received reperfusion with primary  percutaneous coronary intervention  (PCI) within the guideline-recommended timeframe. [ 6 ]  It has become a core quality measure for the  Joint Commission on Accreditation of Healthcare Organizations  (TJC). [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1111", "text": "The benefit of prompt, expertly performed primary percutaneous coronary intervention over thrombolytic therapy for acute ST elevation myocardial infarction is now well established. [ 10 ]  Few hospitals can provide PCI within the 90 minute interval, [ 11 ]  which prompted the American College of Cardiology (ACC) to launch a national Door to Balloon (D2B) Initiative in November 2006. The D2B Alliance seeks to \"take the extraordinary performance of a few hospitals and make it the ordinary performance of every hospital.\" [ 12 ]  Over 800 hospitals have joined the D2B Alliance as of March 16, 2007. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1112", "text": "The D2B Alliance advocates six key  evidence-based  strategies and one optional strategy to help reduce door-to-balloon times: [ 12 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1113", "text": "On May 30, 2007, the  American Heart Association  launched 'Mission: Lifeline', a \"community-based initiative aimed at quickly activating the appropriate chain of events critical to opening a blocked artery to the heart that is causing a heart attack.\" [ 15 ]  It is seen as complementary to the ACC's D2B Initiative. [ 16 ]  The program will concentrate on patient education to make the public more aware of the signs of a heart attack and the importance of calling  9-1-1  for  emergency medical services  (EMS) for transport to the hospital. [ 15 ]  In addition, the program will attempt to improve the diagnosis of STEMI patients by EMS personnel. [ 15 ]  According to Alice Jacobs, MD, who led the work group that addressed STEMI systems, [ 17 ]  when patients arrive at non-PCI hospitals they will stay on the EMS stretcher with paramedics in attendance while a determination is made as to whether or not the patient will be transferred. [ 17 ]  For walk-in STEMI patients at non-PCI hospitals, EMS calls to transfer the patient to a PCI hospital should be handled with the same urgency as a 9-1-1 call. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1114", "text": "Although incorporating a prehospital 12 lead ECG into critical pathways for STEMI patients is listed as an optional strategy by the D2B Alliance, the fastest median door-to-balloon times have been achieved by hospitals with paramedics who perform 12 lead ECGs in the field. [ 18 ]   EMS  can play a key role in reducing the first-medical-contact-to-balloon time, sometimes referred to as EMS-to-balloon (E2B) time, [ 19 ]  by performing a 12 lead  ECG  in the field and using this information to triage the patient to the most appropriate medical facility. [ 20 ] [ 21 ] [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1115", "text": "Depending on how the prehospital 12 lead ECG program is structured, the 12 lead ECG can be transmitted to the receiving hospital for physician interpretation, interpreted on-site by appropriately trained paramedics, or interpreted on-site by paramedics with the help of computerized interpretive algorithms. [ 24 ]  Some EMS systems utilize a combination of all three methods. [ 19 ]  Prior notification of an inbound STEMI patient enables time saving decisions to be made prior to the patient's arrival. This may include a \"cardiac alert\" or \"STEMI alert\" that calls in off duty personnel in areas where the  cardiac cath lab  is not staffed 24 hours a day. [ 19 ]  The 30-30-30 rule takes the goal of achieving a 90-minute door-to-balloon time and divides it into three equal time segments. Each STEMI care provider (EMS, the emergency department, and the cardiac cath lab) has 30 minutes to complete its assigned tasks and seamlessly \"hand off\" the STEMI patient to the next provider. [ 19 ]  In some locations, the emergency department may be bypassed altogether. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1116", "text": "Bradley et al. (Circulation 2006) performed a qualitative analysis of 11 hospitals in the National Registry of Myocardial Infarction that had median door-to-balloon times = or < 90 minutes. They identified 8 themes that were present in all 11 hospitals: [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1117", "text": "Granger et al. (Circulation 2007) identified the following criteria of an ideal primary PCI center. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1118", "text": "Granger et al. (Circulation 2007) identified the following barriers to timely access to primary PCI. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1119", "text": "The  Duke Activity Status Index  ( DASI ) is an assessment tool used to  evaluate the functional capacity  of patients with  cardiovascular disease  (CVD), such as  coronary artery disease ,  myocardial infarction , and  heart failure . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1120", "text": "In  clinical practice , DASI can be used to assess the effects of medical treatments and cardiac rehabilitation as well. [ 2 ]  Positive responses are summed up to get a total score, which ranges from 0 to 58.2. Higher scores would indicate a higher functional capacity. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1121", "text": "The instrument is copyrighted by one of its authors, Mark Hlatky. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1122", "text": "Duke Treadmill Score  is one of the tools for predicting the risk of  ischemia  or  infarction  in the  heart muscle . [ 1 ]  The calculation is done based on the information obtained from an  exercise test  by this formula: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1123", "text": "In which, the exercise duration is written in \"minutes\" and the ST changes in \"millimetres\". [ 1 ]  Angina index will be zero if no pain appears during the exercise, one if the pain is limited to the exercise period but the patient can continue the exercise ( typical angina ), and two if a limiting pain occurs which is a reason to stop the exercise test. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1124", "text": "Duke treadmill scores typically range from -25 (highest risk) to +15 (lowest risk).  One-year  mortality  and five-year survival rates respectively for the results of the Duke treadmill score have been reported as: [ 4 ] [ 5 ] \n [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1125", "text": "Echocardiography , also known as  cardiac ultrasound , is the use of  ultrasound  to examine the  heart . It is a type of  medical imaging , using standard ultrasound or  Doppler ultrasound . [ 1 ]  The visual image formed using this technique is called an  echocardiogram , a  cardiac echo , or simply an  echo ."}
{"_id": "WikiPedia_Cardio$$$corpus_1126", "text": "Echocardiography is routinely used in the diagnosis, management, and follow-up of patients with any suspected or known  heart diseases . It is one of the most widely used diagnostic imaging modalities in cardiology. It can provide a wealth of helpful information, including the size and shape of the heart (internal chamber size quantification), pumping capacity, location and extent of any tissue damage, and assessment of valves. An echocardiogram can also give physicians other estimates of heart function, such as a calculation of the  cardiac output ,  ejection fraction , and  diastolic  function (how well the heart relaxes)."}
{"_id": "WikiPedia_Cardio$$$corpus_1127", "text": "Echocardiography is an important tool in assessing wall motion abnormality in patients with suspected cardiac disease. It is a tool which helps in reaching an early diagnosis of  myocardial infarction , showing regional wall motion abnormality. Also, it is important in treatment and follow-up in patients with  heart failure , by assessing  ejection fraction . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1128", "text": "Echocardiography can help detect  cardiomyopathies , such as  hypertrophic cardiomyopathy , and dilated cardiomyopathy. The use of stress echocardiography may also help determine whether any chest pain or associated symptoms are related to heart disease."}
{"_id": "WikiPedia_Cardio$$$corpus_1129", "text": "The most important advantages of echocardiography are that it is not invasive (does not involve breaking the skin or entering body cavities) and has no known risks or side effects. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1130", "text": "Not only can an echocardiogram create ultrasound images of heart structures, but it can also produce accurate assessment of the blood flowing through the heart by Doppler echocardiography, using pulsed- or continuous-wave Doppler ultrasound. This allows assessment of both normal and abnormal blood flow through the heart. Color Doppler, as well as spectral Doppler, is used to visualize any abnormal communications between the left and right sides of the heart, as well as any leaking of blood through the valves (valvular regurgitation), and can also estimate how well the valves open (or do not open in the case of valvular stenosis). The Doppler technique can also be used for tissue motion and velocity measurement, by  tissue Doppler echocardiography ."}
{"_id": "WikiPedia_Cardio$$$corpus_1131", "text": "Echocardiography was also the first ultrasound subspecialty to use intravenous contrast. Echocardiography is performed by  cardiac sonographers , cardiac physiologists (UK), or physicians trained in echocardiography."}
{"_id": "WikiPedia_Cardio$$$corpus_1132", "text": "Recognized as the \"Father of Echocardiography\", the Swedish physician  Inge Edler  (1911\u20132001), a graduate of  Lund University , was the first of his profession to apply ultrasonic pulse echo imaging in diagnosing cardiac disease, which the acoustical physicist  Floyd Firestone  had developed to detect defects in metal castings. In fact, Edler in 1953 produced the first echocardiographs using an industrial Firestone-Sperry Ultrasonic Reflectoscope. In developing echocardiography, Edler worked with the physicist  Carl Hellmuth Hertz , the son of the  Nobel laureate   Gustav Hertz  and grandnephew of  Heinrich Rudolph Hertz . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1133", "text": "Health societies recommend the use of echocardiography for initial diagnosis when a change in the patient's clinical status occurs and when new data from an echocardiogram would result in the physician changing the patient's care. [ 7 ]  Diagnostic criteria for numerous cardiac diseases are based on echocardiography studies. For example, the differentiation of mild, moderate, and severe valvular disease is based upon measured criteria. Another example is the estimation of heart function by the left ventricular ejection fraction (LVEF) has vast uses including classification of heart failure and cut offs for implantation of  implantable cardioverter-defibrillators ."}
{"_id": "WikiPedia_Cardio$$$corpus_1134", "text": "Health societies do not recommend routine testing when the patient has no change in clinical status or when a physician is unlikely to change care for the patient based on the results of testing. [ 7 ]  A common example of overuse of echocardiography when not indicated is the use of routine testing in response to a patient diagnosis of mild  valvular heart disease . [ 8 ]  In this case, patients are often asymptomatic for years before the onset of deterioration and the results of the echocardiogram would not result in a change in care without other change in clinical status. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1135", "text": "Echocardiography has a vast role in  pediatrics , diagnosing patients with valvular heart disease and other congenital abnormalities. An emerging branch is  fetal echocardiography , which involves echocardiography of an unborn fetus. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1136", "text": "There are three primary types of echocardiography: transthoracic, transesophageal, and intracardic.\nStress testing utilizes tranthoracic echo in combination with an exercise modality (e.g., a treadmill).\nIntravascular ultrasound is included below, but is as the name indicates more \"ultrasound\" than \"echocardiography\" as it is imaging the walls of a vessel rather than the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_1137", "text": "A standard echocardiogram is also known as a transthoracic echocardiogram (TTE) or cardiac ultrasound, and it is used for rapid evaluation of a patient at their bedside. [ 9 ] [ 10 ]  In this case, the echocardiography transducer (or probe) is placed on the chest wall (or  thorax ) of the subject, and images are taken through the chest wall. This is a non-invasive, highly accurate, and quick assessment of the overall function of the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_1138", "text": "TTE utilizes several \"windows\" to image the heart from different perspectives. Each window has advantages and disadvantages for viewing specific structures within the heart and, typically, numerous windows are utilized within the same study to fully assess the heart. Parasternal long and parasternal short axis windows are taken next to the sternum, the apical two/three/four chamber windows are taken from the apex of the heart (lower left side), and the subcostal window is taken from underneath the edge of the last rib."}
{"_id": "WikiPedia_Cardio$$$corpus_1139", "text": "TTE utilizes one- (\"M mode\"), two-, and three-dimensional ultrasound (time is implicit and not included) from the different windows. These can be combined with pulse wave or continuous wave Doppler to visualize the velocity of blood flow and structure movements. Images can be enhanced with \"contrast\" that are typically some sort of micro bubble suspension that reflect the ultrasound waves."}
{"_id": "WikiPedia_Cardio$$$corpus_1140", "text": "A transesophageal echocardiogram is an alternative way to perform an echocardiogram. A specialized probe containing an ultrasound transducer at its tip is passed into the patient's  esophagus  via the mouth, allowing image and Doppler evaluation from a location directly behind the heart. It is most often used when transthoracic images are suboptimal and when a clearer and more precise image is needed for assessment. This test is performed in the presence of a cardiologist, anesthesiologist, registered nurse, and ultrasound technologist. Conscious sedation and/or localized numbing medication may be used to make the patient more comfortable during the procedure."}
{"_id": "WikiPedia_Cardio$$$corpus_1141", "text": "TEE, unlike TTE, does not have discrete \"windows\" to view the heart. The entire esophagus and stomach can be utilized, and the probe advanced or removed along this dimension to alter the perspective on the heart. Most probes include the ability to deflect the tip of the probe in one or two dimensions to further refine the perspective of the heart. Additionally, the ultrasound crystal is often a two-dimension crystal and the ultrasound plane being used can be rotated electronically to permit an additional dimension to optimize views of the heart structures. Often, movement in all of these dimensions is needed."}
{"_id": "WikiPedia_Cardio$$$corpus_1142", "text": "TEE can be used as stand-alone procedures, or incorporated into catheter- or surgical-based procedures. For example, during a  valve replacement  surgery the TEE can be used to assess the valve function immediately before repair/replacement and immediately after. This permits revising the valve mid-surgery, if needed, to improve outcomes of the surgery."}
{"_id": "WikiPedia_Cardio$$$corpus_1143", "text": "A stress echocardiogram, also known as a stress echo, uses ultrasound imaging of the heart to assess the wall motion in response to physical stress. First, images of the heart are taken \"at rest\" to acquire a baseline of the patient's wall motion at a resting heart rate. The patient then walks on a treadmill or uses another exercise modality to increase the heart rate to his or her target heart rate, or 85% of the age-predicted maximum heart rate (220 \u2212 patient's age). Finally, images of the heart are taken \"at stress\" to assess wall motion at the peak heart rate. A stress echo assesses wall motion of the heart; it does not, however, create an image of the coronary arteries directly. Ischemia of one or more coronary arteries could cause a wall motion abnormality, which could indicate coronary artery disease. The gold standard test to directly create an image of the coronary arteries and directly assess for stenosis or occlusion is a cardiac catheterization. A stress echo is not invasive and is performed in the presence of a licensed medical professional, such as a cardiologist, and a cardiac sonographer."}
{"_id": "WikiPedia_Cardio$$$corpus_1144", "text": "Intracardiac echocardiography (ICE) is specialized form of echocardiography that uses catheters to insert the ultrasound probe inside the heart to view structures from within the heart.\nICE is often used as a part of the cardiac procedure of crossing the  interatrial septum  with a transseptal puncture to permit catheter access from the right atrium to the left atrium; alternative access to the left heart would be retrograde through the  aorta  and across the  aortic valve  into the left ventricle."}
{"_id": "WikiPedia_Cardio$$$corpus_1145", "text": "ICE has the benefit over transthoracic echocardiography in that an operator who is performing a sterile procedure can also operate the ICE catheter and it is not limited to visibility problems that can arise with transthoracic or transesophageal echo. Though, there are image quality limitations due to size constraints of the probe being limited to a catheter."}
{"_id": "WikiPedia_Cardio$$$corpus_1146", "text": "ICE is often inserted through the femoral vein and into the right atrium.\nFrom the right atrium, visualization of the interatrial septum, all four cardiac chambers, all four valves, and the pericardial space (for an effusion) can be readily visualized.\nIt can also be advanced across the atrial septum into the left atrium to visualize the left atrial appendage during  left atrial appendage occlusion  device deployment."}
{"_id": "WikiPedia_Cardio$$$corpus_1147", "text": "Utilization of ICE imagery can be incorporated into the 3-D models built with  electroanatomic mapping  systems."}
{"_id": "WikiPedia_Cardio$$$corpus_1148", "text": "Intravascular ultrasound (IVUS) is a specialized form of echocardiography that uses a catheter to insert the ultrasound probe inside blood vessels. This is commonly used to measure the size of blood vessels and to measure the internal diameter of the blood vessel. For example, this can be used in a  coronary angiogram  to assess the narrowing of the coronary artery. If the catheter is retraced in a controlled manner, then an internal map can be generated to see the contour of the vessel and its branches."}
{"_id": "WikiPedia_Cardio$$$corpus_1149", "text": "The various modes describe how the ultrasound crystals are used to obtain information. These modes are common to all types of echocardiography."}
{"_id": "WikiPedia_Cardio$$$corpus_1150", "text": "A-scan or one dimensional ultrasound represents over half the standard ECHO exam.  For example, it is how aortic stenosis valve area (or any obstruction).  It is also how pressures are calculated in the heart such as right ventricle systolic pressure (RVSP).  It is usually used in the form of Doppler measurements.  There are two forms, pulse and continuous.  Pulsed allows velocities to be calculated in a specific place, but has a limited velocity range is can be used.  Continuous wave allows the velocity to be measured from zero to the fastest blood velocities a diseased heart can generate.  However, it can not tell you where in the A-scan the high velocity is coming from.  Continuous wave would be used to calculate aortic stenosis because you know the high velocity is coming from the stenosis region.  Pulsed would be used to find a ventricular septal defect where there should be no velocity across the septum and the pulsed tells you the location."}
{"_id": "WikiPedia_Cardio$$$corpus_1151", "text": "Brightness mode is often synonymous with \"2D\" and is very commonly used in echocardiography."}
{"_id": "WikiPedia_Cardio$$$corpus_1152", "text": "Motion mode is infrequently used in modern echocardiography. It has specific uses and has the benefit of very high temporal fidelity (e.g., measuring LV size at end diastole)."}
{"_id": "WikiPedia_Cardio$$$corpus_1153", "text": "Strain rate imaging is an ultrasound method for imaging regional differences in contraction (dyssynergy) in for instance  ischemic heart disease  or dyssynchrony due to  Bundle branch block . Strain rate imaging measures either regional systolic deformation (strain) or the rate of regional deformation (strain rate). The methods used are either  tissue Doppler  or  Speckle tracking echocardiography ."}
{"_id": "WikiPedia_Cardio$$$corpus_1154", "text": "Three-dimensional echocardiography (also known as  four-dimensional  echocardiography when the picture is moving) is possible using a matrix array ultrasound probe and an appropriate processing system. It enables detailed anatomical assessment of cardiac pathology, particularly valvular defects, [ 11 ]  and cardiomyopathies. [ 12 ]  The ability to slice the virtual heart in infinite planes in an anatomically appropriate manner and to reconstruct three-dimensional images of anatomic structures make it unique for the understanding of the congenitally malformed heart. [ 13 ]  Real-time three-dimensional echocardiography can be used to guide the location of  bioptomes  during right ventricular endomyocardial biopsies, placement of catheter-delivered valvular devices, and in many other intraoperative assessments. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1155", "text": "Three-dimensional echocardiography technology may feature anatomical intelligence, or the use of organ-modeling technology, to automatically identify anatomy based on generic models.  All generic models refer to a dataset of anatomical information that uniquely adapts to variability in patient anatomy to perform specific tasks. Built on feature recognition and segmentation algorithms, this technology can provide patient-specific three-dimensional modeling of the heart and other aspects of the anatomy, including the brain, lungs, liver, kidneys, rib cage, and vertebral column. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1156", "text": "Contrast echocardiography or contrast-enhanced ultrasound is the addition of an ultrasound contrast medium, or imaging agent, to traditional ultrasonography. The ultrasound contrast is made up of tiny microbubbles filled with a gas core and protein shell. This allows the microbubbles to circulate through the cardiovascular system and return the ultrasound waves, creating a highly reflective image. There are multiple applications in which contrast-enhanced ultrasound can be useful. The most commonly used application is in the enhancement of LV endocardial borders for assessment of global and regional systolic function. Contrast may also be used to enhance visualization of wall thickening during stress echocardiography, for the assessment of LV thrombus, or for the assessment of other masses in the heart. Contrast echocardiography has also been used to assess blood perfusion throughout myocardium in the case of coronary artery disease."}
{"_id": "WikiPedia_Cardio$$$corpus_1157", "text": "Echocardiography can at many times be subjective, meaning that the person reading the echo may have personal input that affects the interpretation of the findings, leading to so-called \"inter-observer variability\", where different echocardiographers might produce different reports when examining the same images. [ 16 ] [ 17 ]  It necessitated the development of accreditation programs around the world. The aim of such programs is to standardize the practice of echocardiography and to ensure that practitioners have the proper training prior to practicing echocardiography which will eventually limit inter-observer variability. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1158", "text": "At the European level  [ 19 ]  individual and laboratory accreditation is provided by the European Association of Echocardiography (EAE). There are three subspecialties for individual accreditation: Adult Transthoracic Echocardiography ( TTE ), Adult Transesophageal Echocardiography ( TEE ) and Congenital Heart Disease Echocardiography (CHD)."}
{"_id": "WikiPedia_Cardio$$$corpus_1159", "text": "In the UK, accreditation is regulated by the British Society of Echocardiography. Accredited radiographers, sonographers, or other professionals are required to pass a mandatory exam. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1160", "text": "The \"Intersocietal Accreditation Commission for Echocardiography\" (IAC) sets standards for echo labs across the US. Cardiologists and sonographers who wish to have their laboratory accredited by IAC must comply with these standards. The purpose of accreditation is to maintain quality and consistency across echocardiography labs in the United States. Accreditation is offered in adult and pediatric transthoracic and transesophageal echocardiography, as well as adult stress and fetal echo. Accreditation is a two-part process. Each facility will conduct a detailed self-evaluation, paying close attention to the IAC Standards and Guidelines. The facility will then complete the application and submit actual case studies to the board of directors for review. Once all requirements have been met, the lab will receive certification. IAC certification is a continual process and must be maintained by the facility: it may include audits or site visits by the IAC. There are several states in which Medicare and/or private insurance carriers require accreditation (credentials) of the laboratory and/or sonographer for reimbursement of echocardiograms."}
{"_id": "WikiPedia_Cardio$$$corpus_1161", "text": "There are two credentialing bodies in the United States for sonographers, the  Cardiovascular Credentialing International  (CCI), established in 1968, and the  American Registry for Diagnostic Medical Sonography  (ARDMS), established in 1975. Both CCI and ARDMS have earned the prestigious  ANSI-ISO 17024  accreditation for certifying bodies from the International Organization for Standardization ( ISO ). [ citation needed ]  Accreditation is granted through the American National Standards Institute (ANSI). Recognition of ARDMS programs in providing credentials has also earned the ARDMS accreditation with the National Commission for Certifying Agencies (NCCA). The NCCA is the accrediting arm of the National Organization for Competency Assurance (NOCA)."}
{"_id": "WikiPedia_Cardio$$$corpus_1162", "text": "Under both credentialing bodies, sonographers must first document completion of prerequisite requirements, which contain both didactic and hands-on experience in the field of ultrasound. Applicants must then take a comprehensive exam demonstrating knowledge in both the physics of ultrasound and the clinical competency related to their specialty. Credentialed sonographers are then required to maintain competency in their field by obtaining a certain number of Continuing Medical Education credits, or CME's."}
{"_id": "WikiPedia_Cardio$$$corpus_1163", "text": "In 2009, New Mexico and Oregon became the first two states to require licensure of sonographers. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1164", "text": "The  American Society of Echocardiography  (ASE) is a professional organization made up of physicians, sonographers, nurses, and scientists involved in the field of echocardiography. One of the most important roles that the ASE plays is providing their recommendations through the ASE Guidelines and Standards, providing resource and educational opportunities for sonographers and physicians in the field."}
{"_id": "WikiPedia_Cardio$$$corpus_1165", "text": "There have been various institutes who are working on use of  Artificial intelligence  in Echo but they are at a very early stage and still needs full development. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1166", "text": "The most commonly used terminology in echocardiography diagnostics are:"}
{"_id": "WikiPedia_Cardio$$$corpus_1167", "text": "Electrical cardiometry  is a method based on the model of  Electrical Velocimetry , and non-invasively measures  stroke volume  (SV),  cardiac output  (CO), and other  hemodynamic  parameters through the use of 4 surface ECG electrodes.  Electrical cardiometry is a method trademarked by Cardiotronic, Inc., and is U.S. FDA approved for use on adults, children, and neonates. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1168", "text": "The measured bioimpedance over  time  can be expressed as the superposition of three components: [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1169", "text": "where Z 0  is the quasi-static portion of the  electrical impedance  (base impedance), \u0394Z R  are the changes of impedance due to the  respiratory  cycle, and \u0394Z C  are the changes of impedance due to the  cardiac  cycle.  \u0394Z R  is considered an artifact akin to the estimation of stroke volume and is therefore suppressed. Exclusion of derived  volumetric  data may diminish the overall product."}
{"_id": "WikiPedia_Cardio$$$corpus_1170", "text": "The timely measurement of \u0394Z C  (dZ(t)) reveals a waveform with shape similar to an arterial pressure waveform.  The calculated first time derivative of dZ(t) is the  \n \n \n \n \n \n \n d \n Z \n ( \n t \n ) \n \n \n d \n t \n \n \n \n \n \n {\\displaystyle {\\frac {dZ(t)}{dt}}} \n \n  waveform, which contains landmarks that allow determination of left-ventricular ejection time (LVET) and peak aortic blood acceleration.  The peak aortic blood acceleration occurs at the steepest slope of the dZ(t) waveform, and at the peak of the  \n \n \n \n \n \n \n d \n Z \n ( \n t \n ) \n \n \n d \n t \n \n \n \n \n \n {\\displaystyle {\\frac {dZ(t)}{dt}}} \n \n  waveform. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1171", "text": "Electrical velocimetry  (EV) is the model upon which electrical cardiometry is based.  EV is based on the fact that the conductivity of the blood in the aorta changes during the cardiac cycle.  EV was developed by Dr. Bernstein and Dr. Osypka in 2001, as a new model for interpreting the bioimpedance signals of the thorax. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1172", "text": "Prior to opening of the aortic valve, the red blood cells (erythrocytes) assume a random orientation (there is no blood flow in the aorta).  When the electric current is applied from the outer electrodes, the current must circumference these red blood cells, therefore resulting in a higher voltage measurement, and thus, a lower conductivity.  Shortly after aortic valve opening, the pulsatile blood flow forces the red blood cells to align in parallel with the blood flow.  When the electric current is then applied, it is able to easily pass the red blood cells in the aorta resulting in a lower voltage, and thus, a higher conductivity.  The change from random orientation to alignment of red blood cells upon opening of aortic valve generates a characteristic steep increase of conductivity or dZ(t) (corresponding to a steep decrease of impedance) \u2013 beat to beat. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1173", "text": "The model considers the peak amplitude of  \n \n \n \n \n \n \n d \n Z \n ( \n t \n ) \n \n \n d \n t \n \n \n \n \n \n {\\displaystyle {\\frac {dZ(t)}{dt}}} \n \n  divided by the base impedance Z 0  as an index for peak aortic acceleration, and as an index of contractility of the heart, or ICON.  The general equation for estimating stroke volume by means of thoracic electrical bioimpedance calculates the product of a patient constant C P  (in ml), the mean blood velocity index  \n \n \n \n \n \n \n v \n \u00af \n \n \n \n \n \n {\\displaystyle {\\bar {v}}} \n \n FT  (measured in s \u22121  during flow time, and FT (flow time measured in s): [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1174", "text": "S \n \n V \n \n T \n E \n B \n \n \n = \n \n C \n \n P \n \n \n \u22c5 \n \n \n \n \n v \n \u00af \n \n \n \n \n F \n T \n \n \n \u22c5 \n F \n T \n \n \n {\\displaystyle SV_{TEB}=C_{P}\\cdot {\\bar {v}}_{FT}\\cdot FT}"}
{"_id": "WikiPedia_Cardio$$$corpus_1175", "text": "The model of electrical velocimetry derives the mean blood velocity index  \n \n \n \n \n \n \n v \n \u00af \n \n \n \n \n \n {\\displaystyle {\\bar {v}}} \n \n FT  from the measured index for peak aortic acceleration ICON. [ 4 ]   The higher the mean blood velocity during flow time, the more SV the left ventricle ejects.  The 'volume of electrically participating tissue' (V EPT ) is used as the patient constant.  The V EPT  is derived primarily from the body mass. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1176", "text": "Impedance cardiography  is a method of non-invasively monitoring hemodynamics, through the use of 4 dual sensors placed on the neck and chest.  Both Impedance cardiography and Electrical Cardiometry derive SV and CO from measurements of TEB, but the underlying model is what differs.  The Impedance Cardiography model contributes the rapid change of bioimpedance which occurs shortly after aortic valve opening to the expansion of the compliant ascending aorta, assuming that more blood volume temporarily stored in the ascending aorta contributes to a decrease in bioimpedance (or an increase in conductity of the thorax).  The underlying model never proved accurate in patients with small cardiac outputs, hence it was never U.S. FDA approved for use in children or neonates. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1177", "text": "The electrical and impedance signals are processed, and then utilized to measure and calculate hemodynamic parameters such as cardiac output, stroke volume, systemic vascular resistance, thoracic fluid index, ICON (index of contractility), and systolic time ratio."}
{"_id": "WikiPedia_Cardio$$$corpus_1178", "text": "Endomyocardial biopsy  (EMB) is an  invasive procedure  used routinely to obtain small  samples  of  heart muscle , primarily for detecting  rejection  of a donor  heart  following  heart transplantation . It is also used as a  diagnostic tool  in some  heart diseases . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1179", "text": "A  bioptome  is used to gain access to the heart via a sheath inserted into the  right internal jugular  or less commonly the  femoral vein . [ 1 ]  Monitoring during the procedure consists of performing  ECGs  and blood pressures. [ 1 ]  Guidance and confirmation of correct positioning of the bioptome is made by  echocardiography  or  fluoroscopy . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1180", "text": "The risk of complications is less than 1% when performed by an experienced physician in a specialist centre. [ 1 ]  Serious complications include perforation of the heart with  pericardial tamponade ,  haemopericardium ,  AV block ,  tricuspid regurgitation  and  pneumothorax . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1181", "text": "EMB, sampling  myocardium  was first pioneered in Japan by S. Sakakibra and S. Konno in 1962. [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1182", "text": "The main reason for performing an EMB is to assess  allograft  rejection following heart transplantation and sometimes to evaluate  cardiomyopathy , some  heart disease  research and  ventricular arrhythmias , [ 4 ]  or unexplained  ventricular dysfunction . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1183", "text": "Visualising the  microscopic appearance  of the heart muscle allows the detection of  cell-mediated  or  antibody-mediated  rejection and is recommended episodically during the first year after heart transplantation. Occasionally, monitoring continues beyond one year. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1184", "text": "The use of EMB in heart transplant rejection surveillance remains the  gold standard test , although the pre-test predictors of rejection  cardiac magnetic resonance imaging  (CMR) and  gene expression profiling , are increasingly used. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1185", "text": "EMB has a role in the diagnosis of viral  myocarditis  and inflammatory myocarditis. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1186", "text": "EMB of the right ventricle via the internal jugular vein is standard after heart transplant.  [ 4 ]  A  bioptome  is used to gain access to the heart via a sheath inserted into the  right internal jugular  or less commonly the  femoral vein . [ 1 ]  Monitoring during the procedure consists of performing ECGs and blood pressures. Guidance and confirmation of correct positioning of the bioptome is made by  echocardiography  or  fluoroscopy [ 1 ]  before the biopsy specimen is taken and in the case of transplants, usually three [ 4 ]  or four or more samples are taken. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1187", "text": "Endomyocardial fibrosis  can occur if biopsies are performed repeatedly. This risk is reduced if the operator is experienced. Unlike for rejection detection, for diagnosing heart disease, different biopsy sites within the heart are targeted. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1188", "text": "It is possible but less common to biopsy the left ventricle via the  femoral arteries . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1189", "text": "The accuracy of diagnosis by EMB depends on whether the correct site is biopsied. There is a risk that a diagnosis can be missed if the biopsy misses the diseased part of heart muscle, particularly with myocardial inflammation or fibrosis. [ 5 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1190", "text": "An experienced pathologist trained in biopsy analysis and interpretation also reflects EMB\u2019s reliability. Variability between pathologists has been observed.  [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1191", "text": "A frequent concern regarding EMB has been its safety. [ 1 ]  However, it has a low risk of less than 1% when performed by an experienced physician in a specialist centre. [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1192", "text": "Possible complications, which almost all occur at time of procedure, [ 4 ]  include rupture of the  right intraventricular septum , conduction block, arrhythmias,  pneumothorax ,  tricuspid regurgitation ,  atrioventricular fistula , [ 8 ]  and  pulmonary embolism . Death has been reported, but is rare. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1193", "text": "Early heart biopsies, sampling  pericardium , in the latter half of the 1950s were performed through a  cut  in the left  intercostal space  at the  costochondral junction . [ 6 ]  However this method risked lung and  coronary blood vessel  damage,  cardiac tamponade  and  arrhythmias . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1194", "text": "EMB, sampling  myocardium , has evolved since it was first pioneered in Japan by S. Sakakibra and S. Konno in 1962. [ 1 ]  The concept of introducing a biopsy needle through the right internal or external jugular vein to reach the right intraventricular septum for the purpose of sampling the heart muscle was initiated in 1965 by R. T. Bulloch. In 1972, the bioptome and procedure was modified by  Philip Caves . This was to allow access  percutaneously . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1195", "text": "The  ESC Congress  is the annual congress of the  European Society of Cardiology  (ESC), the largest medical congress in Europe. It gathers over 30,000 active participants (mainly cardiologists) and takes place every year in August/September  in a different European city. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1196", "text": "The first ESC Congress was held in 1950 and from then on every 4 years [ 1 ]  until 1988, when it became an annual event."}
{"_id": "WikiPedia_Cardio$$$corpus_1197", "text": "After the 2017 ESC Congress,  Barcelona    became the city with most congresses since 1988(6), followed by  Stockholm    (5) and then by  Amsterdam    and  Vienna    and  Munich    (4 times each as of 2018).\nSome congresses (1994 and 2006) were organised jointly with the World Heart Federation [ 2 ]  under the name of \"World Congress of Cardiology\"."}
{"_id": "WikiPedia_Cardio$$$corpus_1198", "text": "The  Fick principle  states that blood flow to an organ can be calculated using a marker substance if the following information is known:"}
{"_id": "WikiPedia_Cardio$$$corpus_1199", "text": "Developed by  Adolf Eugen Fick  (1829\u20131901), the Fick principle has been applied to the measurement of  cardiac output . Its underlying principles may also be applied in a variety of clinical situations."}
{"_id": "WikiPedia_Cardio$$$corpus_1200", "text": "In Fick's original method, the \"organ\" was the entire human body and the marker substance was oxygen. The first published mention was in conference proceedings from July 9, 1870 from a lecture he gave at that conference; [ 1 ]  it is this publishing that is most often used by articles to cite Fick's contribution.The principle may be applied in different ways. For example, if the blood flow to an organ is known, together with the arterial and venous concentrations of the marker substance, the uptake of marker substance by the organ may then be calculated. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1201", "text": "In Fick's original method, the following variables are measured: [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1202", "text": "From these values, we know that:"}
{"_id": "WikiPedia_Cardio$$$corpus_1203", "text": "where"}
{"_id": "WikiPedia_Cardio$$$corpus_1204", "text": "This allows us to say"}
{"_id": "WikiPedia_Cardio$$$corpus_1205", "text": "and hence calculate cardiac output."}
{"_id": "WikiPedia_Cardio$$$corpus_1206", "text": "Note that ( C a  \u2013  C v ) is also known as the  arteriovenous oxygen difference . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1207", "text": "In reality, this method is rarely used due to the difficulty of collecting and analysing the gas concentrations.  However, by using an assumed value for oxygen consumption, cardiac output can be closely approximated without the cumbersome and time-consuming oxygen consumption measurement.  This is sometimes called an assumed Fick determination. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1208", "text": "A commonly used value for O 2  consumption at rest is  125\u00a0 mL  O 2  per minute per square meter of  body surface area . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1209", "text": "The Fick principle relies on the observation that the total uptake of (or release of) a substance by the peripheral tissues is equal to the product of the blood flow to the peripheral tissues and the arterial-venous concentration difference (gradient) of the substance. In the determination of cardiac output, the substance most commonly measured is the  oxygen  content of  blood  thus giving the arteriovenous oxygen difference, and the flow calculated is the flow across the pulmonary system.  This gives a simple way to calculate the cardiac output: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1210", "text": "Assuming there is no intracardiac shunt, the pulmonary blood flow equals the systemic blood flow.  Measurement of the arterial and venous oxygen content of blood involves the sampling of blood from the pulmonary artery (low oxygen content) and from the pulmonary vein (high oxygen content).  In practice, sampling of peripheral arterial blood is a surrogate for pulmonary venous blood. Determination of the oxygen consumption of the peripheral tissues is more complex."}
{"_id": "WikiPedia_Cardio$$$corpus_1211", "text": "The calculation of the arterial and venous oxygen concentration of the blood is a straightforward process.  Almost all oxygen in the blood is bound to  hemoglobin   molecules  in the  red blood cells .  Measuring the content of hemoglobin in the blood and the percentage of saturation of hemoglobin (the oxygen saturation of the blood) is a simple process and is readily available to physicians.  Using the fact that each  gram  of hemoglobin can carry  1.34\u00a0 mL  of  O 2 , the oxygen content of the blood (either arterial or venous) can be estimated by the following formula:"}
{"_id": "WikiPedia_Cardio$$$corpus_1212", "text": "Assuming a hemoglobin concentration of  15\u00a0 g/dL  and an oxygen saturation of 99%, the oxygen concentration of arterial blood is approximately  200\u00a0 mL  of O 2  per L."}
{"_id": "WikiPedia_Cardio$$$corpus_1213", "text": "The saturation of mixed venous blood is approximately 75% in health. Using this value in the above equation, the oxygen concentration of mixed venous blood is approximately  150\u00a0 mL  of O 2  per L."}
{"_id": "WikiPedia_Cardio$$$corpus_1214", "text": "Therefore, using the assumed Fick determination, the approximated cardiac output for an average man (1.9 m3) is:"}
{"_id": "WikiPedia_Cardio$$$corpus_1215", "text": "Cardiac output may also be estimated with the Fick principle using production of  carbon dioxide  as a marker substance. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1216", "text": "The principle can also be used in  renal physiology  to calculate  renal blood flow . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1217", "text": "In this context, it is not oxygen which is measured, but a marker such as  para-aminohippurate . However, the principles are essentially the same."}
{"_id": "WikiPedia_Cardio$$$corpus_1218", "text": "In the fetal  heart , the  foramen ovale  ( / f \u0259 \u02c8 r e\u026a m \u0259n   o\u028a \u02c8 v \u00e6 l i ,   - m \u025b n -,   - \u02c8 v \u0251\u02d0 -,   - \u02c8 v e\u026a -/ [ 1 ] [ 2 ] [ 3 ] ), also  foramen Botalli  or the  ostium secundum of Born , allows blood to enter the left  atrium  from the right atrium. It is one of two fetal  cardiac shunts , the other being the  ductus arteriosus  (which allows blood that still escapes to the right ventricle to bypass the  pulmonary circulation ). Another similar adaptation in the fetus is the  ductus venosus . In most individuals, the foramen ovale closes at birth. It later forms the  fossa ovalis ."}
{"_id": "WikiPedia_Cardio$$$corpus_1219", "text": "The foramen ovale (from  Latin \u00a0'oval hole') forms in the late fourth week of  gestation , as a small passageway between the septum secundum and the ostium secundum. Initially the atria are separated from one another by the  septum primum  except for a small opening below the septum, the  ostium primum . As the septum primum grows, the ostium primum narrows and eventually closes. Before it does so, bloodflow from the  inferior vena cava  wears down a portion of the septum primum, forming the  ostium secundum . Some embryologists postulate that the ostium secundum may be formed through  programmed cell death . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1220", "text": "The ostium secundum provides communication between the atria after the ostium primum closes completely. Subsequently, a second wall of tissue, the  septum secundum , grows over the ostium secundum in the right atrium. Blood then passes from the right to left atrium only by way of a small passageway in the septum secundum and then through the ostium secundum. This passageway is called the foramen ovale . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1221", "text": "The foramen ovale often closes at birth. At birth, when the lungs become functional, the pulmonary vascular pressure decreases and the left atrial pressure exceeds that of the right. This forces the  septum primum  against the  septum secundum , functionally closing the foramen ovale. In time the septa eventually fuse, leaving a remnant of the foramen ovale, the  fossa ovalis ."}
{"_id": "WikiPedia_Cardio$$$corpus_1222", "text": "A  fetus  receives oxygen not from its lungs, but from the mother's oxygen-rich blood via the  placenta . Oxygenated blood from the placenta travels through the umbilical cord to the right atrium of the fetal heart. As the fetal lungs are non-functional at this time, the blood bypasses them through two cardiac shunts. The first is the foramen ovale (the valve present between them called eustachian valve)  which shunts blood from the right atrium to the left atrium. The second is the  ductus arteriosus  which shunts blood from the pulmonary artery (which, after birth, carries blood from the right side of the heart to the lungs) to the descending aorta. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1223", "text": "In about 25% of adults the foramen ovale does not close completely, but remains as a small  patent foramen ovale (\"PFO\") . [ 5 ]  In most of these individuals, the PFO causes no problems and remains undetected throughout life."}
{"_id": "WikiPedia_Cardio$$$corpus_1224", "text": "PFO has long been studied because of its role in  paradoxical embolism  (an  embolism  that travels from the venous side to the arterial side). This may lead to a  stroke  or  transient ischemic attack .  Transesophageal echocardiography  is considered the most accurate investigation to demonstrate a patent foramen ovale. A patent foramen ovale may also be an incidental finding."}
{"_id": "WikiPedia_Cardio$$$corpus_1225", "text": "The  fossa ovalis  is a depression in the  right atrium  of the  heart , at the level of the  interatrial septum , the wall between right and  left atrium . The  fossa ovalis  is the remnant of a thin fibrous sheet that covered the  foramen ovale  during  fetal  development."}
{"_id": "WikiPedia_Cardio$$$corpus_1226", "text": "During fetal development, the foramen ovale allows blood to pass from the right atrium to the  left atrium , bypassing the nonfunctional fetal lungs while the fetus obtains its oxygen from the  placenta . A flap of tissue called the  septum primum  acts as a valve over the foramen ovale during that time. After birth, the introduction of air into the lungs causes the pressure in the  pulmonary circulatory  system to drop. This change in pressure pushes the septum primum against the  atrial septum , closing the foramen. [ 1 ]  The septum primum and atrial septum eventually fuse together to form a complete seal, leaving a depression called the fossa ovalis. By age two, about 75% of people have a completely sealed fossa ovalis. An unfused fossa ovalis is called a  patent foramen ovale . Depending on the circumstances, a patent foramen ovale may be completely asymptomatic, or may require surgery. [ 1 ]  The  limbus of fossa ovalis  ( annulus ovalis ) is the prominent oval margin of the fossa ovalis in the right atrium. It is most distinct above and at the sides of the fossa ovalis; below, it is deficient. A small slit-like valvular opening is occasionally found, at the upper margin of the fossa, leading upward beneath the limbus, into the  left atrium ; it is the remains of the fetal aperture the foramen ovale between the two  atria ."}
{"_id": "WikiPedia_Cardio$$$corpus_1227", "text": "Almost immediately after the infant is born, the foramen ovale and  ductus arteriosus  close. The major changes that are made by the body occur at the first breath (in the case of heart and lung functions) and up to weeks after birth (such as the liver's  enzyme synthesis ). The foramen ovale becomes the fossa ovalis as the foramen closes while edge of the septum secundum in right atrium becomes the anulus ovalis, so the depression beneath it becomes the fossa ovalis. [ 2 ] [ unreliable medical source? ]  This enables respiration and circulation independent from the mother's placenta."}
{"_id": "WikiPedia_Cardio$$$corpus_1228", "text": "With the child's first breath, the lung sends  oxygenated blood  to the left atrium. As a result, pressure in the left atrium is higher than that of the right, and the increased pressure holds the interatrial flap (which covers the foramen ovale) shut, therefore closing the foramen ovale as well. [ 2 ]  In normal development, the closed foramen ovale fuses with the interatrial wall. During the first breath, vasoconstriction causes the ductus arteriosus to close, and during adult years, tissue occludes what once was the ductus arterious, creating the  ligamentum arteriosum . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1229", "text": "Aneurysms  can occur in adulthood if the foramen ovale is not closed correctly. An aneurysm happens when an artery becomes enlarged in a localized area due to weakening of the arterial wall. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1230", "text": "When this type of aneurysm occurs in the area of the fossa ovalis, an enlarged pouch is formed. This pouch can protrude into the right atrium or the left atrium. The cause of this aneurysm is the result of abnormal, increased pressure within the heart. Even if the foramen ovale does seal shut, an aneurysm may occur, usually on the side of the right atrium. If the aneurysm stretches too far, it can narrow the opening of the  inferior vena cava . [ 5 ]  This type of aneurysm can be a result of  plaque  build-up in the arteries from  coronary heart disease , as well as diseases of the  aortic valve  or  mitral valve . Surgery may be useful in helping to cope with the aneurysm."}
{"_id": "WikiPedia_Cardio$$$corpus_1231", "text": "If the atrial septum does not close properly, it leads to a patent foramen ovale (PFO). This type of defect generally works like a flap valve, opening during certain conditions of increased pressure in the chest, such as during strain while having a bowel movement, cough, or sneeze. With enough pressure, blood may travel from the right atrium to the left. If there is a  clot  in the right side of the heart, it can cross the PFO, enter the left atrium, and travel out of the heart and to the brain, causing a  stroke . If the clot travels into a  coronary artery  it can cause a  heart attack . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1232", "text": "The  fourth heart sound  or  S 4  is an extra  heart sound  that occurs during late diastole, immediately before the normal two \"lub-dub\" heart sounds (S 1  and S 2 ). It occurs just after atrial contraction and immediately before the  systolic  S 1  and is caused by the atria contracting forcefully in an effort to overcome an abnormally stiff or hypertrophic ventricle."}
{"_id": "WikiPedia_Cardio$$$corpus_1233", "text": "This produces a rhythm classically compared to the cadence of the word \" Tennessee .\" [ 1 ] [ full citation needed ] [ 2 ]  One can also use the phrase \" A -stiff-wall\" to help with the cadence (a S 4 , stiff S 1 , wall S 2 ), as well as the pathology of the S 4  sound. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1234", "text": "The normal heart sounds, S 1  and S 2 , are produced during the closing of the  atrioventricular valves  and  semilunar valves , respectively.  The closing of these valves produces a brief period of turbulent flow, which produces sound. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1235", "text": "The S 4  sound occurs, by definition, immediately before S 1 , while the atria of the heart are vigorously contracting. [ 5 ]   It is manifest as a vibration of 20 to 30\u00a0Hz within the ventricle. [ 5 ]   While the mechanism is not absolutely certain, it is generally accepted that S 4  is caused by stiffening of the walls of the ventricles (usually the left), which produces abnormally turbulent flow as the atria contract to force blood into the ventricle. [ 5 ] [ 4 ]  This for example occurs in conditions that decrease ventricular compliance like  left ventricular hypertrophy . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1236", "text": "S 4  is sometimes audible in the elderly due to a more rigid ventricle. When loud, it is a sign of a pathologic state, [ 6 ]  usually a failing left ventricle. If the problem lies with the left ventricle, the gallop rhythm will be heard best at the cardiac apex.  It will become more apparent with exercise, with the patient lying on the left-hand side, or with the patient holding  expiration .  If the problem is in the right ventricle, the abnormal sound will be most evident on the lower left hand side of the  sternum  and will get louder with exercise and quick, deep  inspiration . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1237", "text": "S 4  has also been termed an  atrial gallop  or a  presystolic gallop  because of its occurrence late in the heart cycle. It is a type of  gallop rhythm  by virtue of having an extra sound; the other gallop rhythm is called  S 3 . The two are quite different, but they may sometimes occur together forming a  quadruple gallop . If the  heart rate  is also very fast ( tachycardia ), it can become difficult to distinguish between S 3  and S 4  thus producing a single sound called a  summation gallop ."}
{"_id": "WikiPedia_Cardio$$$corpus_1238", "text": "The S4 heart sound itself does not require treatment; rather plans should be laid to stop the progression of whatever causes the underlying ventricular dysfunction. The S4 heart sound is a secondary manifestation of a primary disease process and treatment should be focused on treating the underlying, primary disease."}
{"_id": "WikiPedia_Cardio$$$corpus_1239", "text": "Fractional flow reserve  (FFR) is a diagnostic technique used in  coronary catheterization . FFR measures pressure differences across a  coronary artery   stenosis  (narrowing, usually due to  atherosclerosis ) to determine the likelihood that the stenosis impedes oxygen delivery to the heart muscle ( myocardial   ischemia ). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1240", "text": "Fractional flow reserve is defined as the pressure after (distal to) a stenosis relative to the pressure before the stenosis. [ 2 ]  The result is an absolute number; an FFR of 0.80 means that a given stenosis causes a 20% drop in  blood pressure . In other words, FFR expresses the maximal flow down a vessel in the presence of a stenosis compared to the maximal flow in the hypothetical absence of the stenosis."}
{"_id": "WikiPedia_Cardio$$$corpus_1241", "text": "During coronary catheterization, a  catheter  is inserted into the  femoral  (groin) or  radial arteries  (wrist) using a sheath and guidewire. FFR uses a small sensor on the tip of the wire (commonly a  transducer ) to measure pressure, temperature and flow to determine the exact severity of the  lesion . This is done during maximal blood flow ( hyperemia ), which can be induced by injecting products such as  adenosine  or  papaverine . A pullback of the pressure wire is performed, and pressures are recorded across the vessel. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1242", "text": "When interpreting FFR measurements, higher values indicate a non-significant stenosis, whereas lower values indicate a significant lesion. There is no absolute cut-off point at which an FFR measurement is considered abnormal. However, reviews of clinical trials show a cut-off range between 0.75 and 0.80 has been used when determining significance. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1243", "text": "Fractional flow reserve (FFR) is the ratio of maximum blood flow distal to a stenotic lesion to normal maximum flow in the same vessel. It is calculated using the pressure ratio"}
{"_id": "WikiPedia_Cardio$$$corpus_1244", "text": "F \n F \n R \n = \n \n \n \n p \n \n d \n \n \n \n p \n \n a \n \n \n \n \n \n \n {\\displaystyle FFR={\\frac {p_{d}}{p_{a}}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_1245", "text": "where  \n \n \n \n \n p \n \n d \n \n \n \n \n {\\displaystyle p_{d}} \n \n  is the pressure distal to the lesion, and  \n \n \n \n \n p \n \n a \n \n \n \n \n {\\displaystyle p_{a}} \n \n  is the pressure proximal to the lesion."}
{"_id": "WikiPedia_Cardio$$$corpus_1246", "text": "The decision to perform a  percutaneous coronary intervention  (PCI) is usually based on angiographic results alone.  Angiography  can be used for the visual evaluation of the inner diameter of a vessel. In ischemic heart disease, deciding which narrowing is the culprit lesion is not always clear-cut. Fractional flow reserve can provide a functional evaluation by measuring the pressure decline caused by a vessel narrowing. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1247", "text": "FFR has certain advantages over other techniques to evaluate narrowed coronary arteries, such as coronary angiography,  intravascular ultrasound  or  CT coronary angiography . For example, FFR takes into account collateral flow, which can render an anatomical blockage functionally unimportant. Also, standard angiography can underestimate or overestimate narrowing, because it only visualizes contrast inside a vessel. [ 5 ]  Finally, when compared to other indices of vessel narrowing, FFR seems to be less vulnerable to variability between patients. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1248", "text": "Other techniques can also provide information which FFR cannot. Intravascular ultrasound, for example, can provide information on  plaque vulnerability , whereas FFR measures are only determined by plaque thickness. There are newly developed technologies that can assess both plaque vulnerability and FFR from CT by measuring the vasodilitative capacity of the arterial wall.  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1249", "text": "FFR allows real-time estimation of the effects of a narrowed vessel, and allows for simultaneous treatment with balloon dilatation and stenting. On the other hand, FFR is an  invasive  procedure for which non-invasive (less drastic) alternatives exist, such as  cardiac stress testing . In this test, physical exercise or intravenous medication (adenosine/dobutamine) is used to increase the workload and oxygen demand of the heart muscle, and ischemia is detected using  ECG  changes or  nuclear imaging ."}
{"_id": "WikiPedia_Cardio$$$corpus_1250", "text": "In the DEFER study, fractional flow reserve was used to determine the need for stenting in patients with intermediate single vessel disease. In stenosis patients with an FFR of less than 0.75, outcomes were significantly worse. In patients with an FFR of 0.75 or more however, stenting did not influence outcomes. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1251", "text": "The  Fractional Flow Reserve versus Angiography for Multivessel Evaluation  (FAME) study evaluated the role of FFR in patients with multivessel coronary artery disease. [ 8 ]  In 20 centers in Europe and the United States, 1005 patients undergoing  percutaneous coronary intervention  with  drug eluting stent  implantation were randomized to intervention based on angiography or based on fractional flow reserve in addition to angiography. In the angiography arm of the study, all suspicious-looking lesions were stented. In the FFR arm, only angiographically suspicious lesions with an FFR of 0.80 or less were stented. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1252", "text": "In the patients whose care was guided by FFR, fewer stents were used (2.7\u00b11.2 and 1.9\u00b11.3, respectively). After one year, the primary endpoint of death, nonfatal  myocardial infarction , and repeat  revascularization  were lower in the FFR group (13.2% versus 18.3%), largely attributable to fewer stenting procedures and their associated complications. There also was a non-significant higher number of patients with residual  angina   (81% versus 78%). In the FFR group, hospital stay was slightly shorter (3.4 vs 3.7 days) and procedural costs were less ($5,332 vs $6,007). FFR did not prolong procedure (around 70 minutes in both groups)."}
{"_id": "WikiPedia_Cardio$$$corpus_1253", "text": "A  fusion beat  occurs when electrical impulses from different sources act upon the same region of the heart at the same time. [ 1 ]  If it acts upon the  ventricular  chambers it is called a  ventricular fusion beat , whereas colliding currents in the  atrial chambers  produce  atrial fusion beats ."}
{"_id": "WikiPedia_Cardio$$$corpus_1254", "text": "Ventricular fusion beats can occur when the heart's natural rhythm and the impulse from a  pacemaker  coincide to activate the same part of a ventricle at the same time, causing visible variation in configuration and height of the  QRS complex  of an  electrocardiogram  reading of the heart's activity. [ 2 ]  This contrasts with the pseudofusion beat wherein the pacemaker impulse does not affect the complex of the natural beat of the heart. Pseudofusion beats are normal. Rare or isolated fusion beats caused by pacemakers are normal as well, but if they occur too frequently may reduce cardiac output and so can require adjustment of the pacemaker. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1255", "text": "A  gallop rhythm  refers to a (usually abnormal) rhythm of the heart on  auscultation . [ 1 ]  It includes three or four sounds, thus resembling the sounds of a  gallop ."}
{"_id": "WikiPedia_Cardio$$$corpus_1256", "text": "The normal heart rhythm contains two audible  heart sounds  called S 1  and S 2  that give the well-known \"lub-dub\" rhythm; they are caused by the closing of  valves  in the heart. The  first heart sound  (S1) is closure of the valve at the end of ventricular filling (the tricuspid and mitral valves); the  second heart sound  (S2), is closure of the aortic and/or the pulmonary valves as the ventricles relax. Extra sounds, ( third  and/or  fourth heart sound , can be normal, especially in children, or with severe exercise, but are generally heard (on the left side) when ventricular function is impaired, e.g., in case of acute infarction or severe cardiac failure.  The sounds are thought to be caused by the atrium, facing back-pressure, forcing volume into an incompletely emptied ventricle. Then, given tachycardia, a \"gallop\" is produced. With right-sided back pressure after pulmonary embolism, and therefore an incompletely emptied right ventricle, a right-sided gallop can occur."}
{"_id": "WikiPedia_Cardio$$$corpus_1257", "text": "Gallop rhythms may be heard in young or athletic people, but may also be a sign of serious cardiac problems like  heart failure  as well as  pulmonary edema .\nGallop rhythms may be associated with the following: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1258", "text": "The  Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico  ( GISSI ) (Italian group for the study of the survival of myocardial infarction) is a  cardiology  research group founded as a collaboration between two Italian organisations \u2013 the  Mario Negri Institute for Pharmacological Research  and the Associazione Nazionale dei Medici Cardiologi Ospedalieri (ANMCO). [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1259", "text": "Four large-scale clinical trials (GISSI 1, [ 3 ]  GISSI 2, [ 3 ]  GISSI 3, [ 4 ]  GISSI Prevention [ 5 ] ) have involved over 60,000 people with  acute myocardial infarction  (AMI). [ 1 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1260", "text": "Glycogen phosphorylase isoenzyme BB  (abbreviation:  GPBB ) is an  isoenzyme  of  glycogen phosphorylase . This isoform of the enzyme exists in cardiac (heart) and brain tissue."}
{"_id": "WikiPedia_Cardio$$$corpus_1261", "text": "The enzyme is one of the \"new  cardiac markers \" which are discussed to improve early diagnosis in  acute coronary syndrome . A rapid rise in blood levels can be seen in  myocardial infarction  and  unstable angina ."}
{"_id": "WikiPedia_Cardio$$$corpus_1262", "text": "Other enzymes related to glycogen phosphorylase are abbreviated as  GPLL  (liver) and  GPMM  (muscle)."}
{"_id": "WikiPedia_Cardio$$$corpus_1263", "text": "This  medical  diagnostic article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1264", "text": "Wayne Robert Griffin  (born 1975) is the second person in Australia to be implanted with the SynCardia Total  artificial heart . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1265", "text": "The  artificial heart  surgery was performed on 20 August 2010, by Dr. Phillip Spratt, the head of the Heart and Lung Transplant Unit of  St Vincent's Hospital .\nHe was assisted by Dr. Paul Jantz and supervised by Dr. Jack Copeland. The surgery was filmed by  60 Minutes Australia  as \"The Ultimate Bypass\", which was aired in September 2010."}
{"_id": "WikiPedia_Cardio$$$corpus_1266", "text": "This biographical article related to medicine in Australia is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1267", "text": "Hajdu\u2013Cheney syndrome , also called  acroosteolysis with osteoporosis and changes in skull and mandible ,  arthrodentoosteodysplasia  and  Cheney syndrome , [ 1 ]  is an extremely rare  autosomal   dominant   congenital disorder [ 2 ] [ 3 ]  of the  connective tissue  characterized by severe and excessive  bone resorption  leading to  osteoporosis  and a wide range of other possible symptoms. Mutations in the  NOTCH2  gene, identified in 2011, cause HCS. HCS is so rare that only about 50 cases have been reported worldwide since the discovery of the syndrome in 1948 [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1268", "text": "Hajdu\u2013Cheney syndrome causes many issues with an individual's connective tissues. Some general characteristics of an individual with Hajdu\u2013Cheney syndrome include bone flexibility and deformities, short stature, delayed  acquisition of speech  and  motor skills ,  dolichocephalic  skull,  Wormian bone , small maxilla, hypoplastic frontal sinuses, basilar impression, joint laxity, bulbous finger tips and severe osteoporosis. Wormian bone occurs when extra bones appear between cranial sutures. Fetuses with Hajdu\u2013Cheney syndrome often will not be seen to unclench their hands on obstetrical ultrasound. They may also have low-set ears and their eyes may be farther apart than on a usual child, called  hypertelorism . Children's heads can have some deformities in their shape and size ( plagiocephaly ). Early tooth loss and bone deformities, such as serpentine tibiae and fibulae, are also common in those affected. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1269", "text": "Hajdu\u2013Cheney syndrome is a monogenic disorder. The disorder is inherited and controlled by a single pair of genes. A single copy of the mutant gene on an autosome causes HCS. HCS is an autosomal dominant disorder, only one parent with the defective gene is needed to pass the disorder to the offspring. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1270", "text": "Mutations within the last coding exon of  NOTCH2  that remove the  PEST  domain and escape the  nonsense-mediated mRNA decay  have been shown to be the main cause of Hajdu\u2013Cheney syndrome. [ 5 ] [ 6 ] [ 7 ]  The NOTCH2 gene plays a very important role in skeletogenesis. Mutations of NOTCH2 that seem to cause HCS occur in the last coding exon of the gene (exon 34). These mutations remove PEST domains, which mediate proteosomal destruction of the protein. These PEST domains are removed due to the premature stop codon in the amino acid sequence. All HCS alleles are observed to have premature protein destruction before the PEST sequence is fully translated. The result is a mature  NOTCH2  gene with a partially completed PEST sequence. In some cases, no PEST sequence at all is seen. This leads to the no proteosomal destruction of the protein. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1271", "text": "The  NOTCH2  gene is ubiquitously expressed in all embryonic tissue. When researching HCS in mice, the homozygous deletion of  NOTCH2  leads to death. This observation is important because it explains how the HCS phenotype is not isolated to only one system of the body.  NOTCH2  is also shown to regulate RANK-L osteoclastogenesis, which is the production of functional osteoclasts. Osteoclasts are the component that breaks bone down. This is why bone loss is observed in HCS patients, due to the overactivation of RANK-L. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1272", "text": "The mechanism thought to cause HCS is an abnormality in osteoblast and osteoid function. These are major components of bone development, and the low function of each leads to the weak bones that characterize HCS. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1273", "text": "One of the main methods of pinpointing a  NOTCH2  mutation that leads to HCS is through whole genome sequencing. This is then followed by exome capture by means of in-solution hybridization. The exome part of the genome consists of exons. Parallel sequencing follows the hybridization, which results in about 3.5 Gb of sequence data. These sequence data are then analyzed. Through sequence analysis and symptom presentation in HCS patients, this proves to be the most definitive method of diagnosis. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1274", "text": "Laboratory testing reveals multiple mutations of HCS. Two genetic variants result in sporadic HCS symptoms, which are HCS-02 and HCS-03. These mutations produce symptoms that come and go, but have been present  de novo . HCS-03 was identified as the variant that is passed through affected family members and presents symptoms throughout the lifetime of the individual. All variants of HCS lead to the same premature termination of PEST sequences which compromise normal function of  NOTCH2 .  NOTCH  has four different receptors, which have an affinity for similar ligands. They are classified as single-pass transmembrane receptors. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1275", "text": "Since about 2002, some patients with this disorder have been offered drug therapy with  bisphosphonates  (a class of osteoporosis drugs) to treat problems with bone resorption associated with the bone breakdown and skeletal malformations that characterize this disorder. Brand names include Actonel (risedronate/alendronate), made by Merck Pharmaceuticals. Other drugs include Pamidronate, made by Novartis and Strontium Ranelate, made by Eli Lilly. However, for more progressive cases, surgery and bone grafting are necessary. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1276", "text": "It is named after Nicholas Hajdu (1908\u20131987), a Hungarian-English radiologist working in the UK and William D. Cheney, MD (1899\u20131985), a US radiologist. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1277", "text": "The  Hancock Aortic Tissue Valve  is a  prosthetic heart valve  used in  cardiac surgery  to replace a damaged or diseased aortic valve. [ 1 ]  It is a bioprosthetic valve, meaning it is constructed using biological tissues, specifically  porcine  (pig) valve tissue. [ 2 ]  This valve is widely utilized in the field of cardiovascular surgery to restore proper blood flow through the heart. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1278", "text": "The Hancock Aortic Tissue Valve was invented by  Warren Hancock . [ 4 ]  In the late 1960s and early 1970s, Warren Hancock, an American engineer, collaborated with the medical community to develop a cutting-edge bioprosthetic heart valve. The valve was first introduced by the American company  Medtronic . [ 1 ]  The design of the Hancock valve is based on the concept of xenografts, utilizing pig tissue due to its structural similarities to human heart valves. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1279", "text": "The Hancock Aortic Tissue Valve is composed of  porcine  valve tissue mounted within a supporting stent frame. [ 6 ]  The valve is sewn into a fabric-covered sewing ring, facilitating secure attachment within the patient's aortic annulus during the implantation procedure. The design aims to closely mimic the natural function of the human aortic valve, allowing for efficient blood flow and minimizing the risk of complications. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1280", "text": "The Hancock Aortic Tissue Valve is commonly used in patients requiring aortic valve replacement due to conditions such as aortic stenosis or aortic regurgitation. [ 7 ]  The choice between a mechanical or bioprosthetic valve depends on various factors, including the patient's age, lifestyle, and medical history. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1281", "text": "Prosthetic heart valves, including the Hancock Aortic Tissue Valve, are not without drawbacks. Structural degradation is a risk, potentially necessitating reoperation. [ 13 ] [ 3 ]  Studies have indicated the need for ongoing research and improvement in bioprosthetic valve technology to address such concerns [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1282", "text": "The implantation of the Hancock Aortic Tissue Valve typically involves  open-heart surgery . [ 14 ]  During the procedure, the damaged or diseased native aortic valve is removed, and the prosthetic valve is sutured in its place. The secure attachment of the valve is crucial to ensure proper functionality and prevent complications such as leakage."}
{"_id": "WikiPedia_Cardio$$$corpus_1283", "text": "The  HDL-Atherosclerosis Treatment Study , also known as  HATS , was a three-year double-blind trial involving 160 people with coronary heart disease (CHD) who had a low HDL and near normal LDL. The study compared  a combination of  simvastatin  and  niacin  with antioxidant vitamin therapy. Using angiography, coronary artery stenosis progressed when using placebo or antioxidant alone, and regressed with the combination of simvastatin and niacin. The study demonstrated a 90% reduction in CHD death, nonfatal heart attacks,  stroke , or revascularization for worsening  angina . It was published in 2001. [ 1 ] [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1284", "text": "This  medical  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1285", "text": "The  Heart Failure Society of America  is an American organization of heart failure experts who have an interest in heart function and  heart failure .   Founded in 1995, [ 1 ]  it provides a forum for experts and patients with the aim of reducing the burden of heart failure. [ 2 ] \nIt has produced advice on categorizing heart failure [ 3 ]  and it produces guidelines including the 2010 comprehensive heart failure practice guidelines when  Douglas L. Mann  was served as the president [ 4 ]  and the 2013 Guideline for the Management of Heart Failure. [ 5 ]  In 2018, a forum was created with people of various stages of advanced heart failure and specialists in cardiology. [ 6 ] \nPast presidents have included  Mandeep R. Mehra , who took up the position in 2016. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1286", "text": "The  Heart Protection Study  was a  randomized controlled trial  run by the  Clinical Trial Service Unit , and funded by the  Medical Research Council  (MRC) and the  British Heart Foundation  (BHF) in the  United Kingdom . It studied the use of the  cholesterol lowering drug ,  simvastatin  40\u00a0mg and  vitamin  supplementation ( vitamin E ,  vitamin C  and  beta carotene ) in people who were at risk of  cardiovascular disease . It was led by  Jane Armitage , an epidemiologist at the  Clinical Trial Service Unit . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1287", "text": "An outline of the study protocol was published in 1999. [ 3 ]  Initial results [ 4 ]  were published in 2002, which indicated that vitamins made little difference in modifying cardiovascular risk, but that simvastatin could significantly reduce the risk of cardiovascular events. Further publications, from 2003 and 2004, were concerned with the efficacy of simvastatin in diabetes patients [ 5 ]  and preventing stroke. [ 6 ]  A 2005 paper analyses the cost-effectiveness of a prescribing strategy similar to the one employed in the study. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1288", "text": "The HPS is to date the largest study to investigate the use of  statins  in the prevention of  cardiovascular disease . While there have been concerns about side-effects associated with statins ( myopathy  and  rhabdomyolysis ), these were rare in this study. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1289", "text": "The  number needed to treat  in the study was 57 to postpone one death and 19 to prevent one cardiovascular \"event\" (in those taking the drug simvastatin for 5 years). There was no mortality benefit in women with a statistical \"p-value\" that did not reach significance (0.08) while the Kaplan-Meier mortality curves, for men and women separately, have not been published as of 2016.  Cancer  risk was not significantly lower in the treatment group; in fact, there was no difference except for non-melanoma skin cancers, wherein the placebo group had a barely-significant lower risk of diagnosis. No worsening of  lung disease  was found, an initial concern with statin drugs, and simvastatin did not decrease  osteoporosis . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1290", "text": "\u00a35.5M plus drug supply was received from Merck and \u00a35.5M plus drug supply from Roche.\n [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1291", "text": "Redirect to:"}
{"_id": "WikiPedia_Cardio$$$corpus_1292", "text": "Heart rate turbulence (HRT)  is a baroreflex-mediated adjustment of  heart rate  which acts as a counter-mechanism to  premature ventricular contraction  (PVC). [ 1 ]  It consists of a brief speed-up in heart rate, followed by a slow decrease back to the baseline rate. PVCs can occur naturally in most otherwise-healthy adults, so measuring the characteristics of a given person's HRT can offer a non-invasive way to evaluate certain aspects of their cardiac or autonomic function without applying artificial external stimuli. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1293", "text": "The measured values of HRT parameters have been shown to be a  statistically significant  prediction of the probability of dying from cardiac disease after a patient suffers a  myocardial infarction . [ 2 ]  HRT can also be used to predict death in patients with  congestive heart failure  from a lethal  arrhythmia . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1294", "text": "The concept of HRT was introduced to the medical community by Georg Schmidt and colleagues from the  Technical University of Munich  in 1999 in the British medical journal  the Lancet . [ 4 ]  While studying PVC characteristics, Schmidt and his colleagues noticed that heart rate seemed to speed up after a  PVC . To clarify, they listed the time from one heartbeat's  R-wave  to the next R-wave (called RR intervals) and synchronized these lists to the time of the PVC beat and averaged the values in the list. A plot of this averaged RR interval list (called a PVC tachogram) not only confirmed their observation that heart rate sped up for a few beats after a PVC, but highlighted another less obvious feature, that heart rate then slows down beyond what it was before the PVC, before returning to the original heart rate."}
{"_id": "WikiPedia_Cardio$$$corpus_1295", "text": "Schmidt reasoned that just as loss of variability in heart rate indicated patients more likely to be at high risk of dying after a heart attack, this phenomenon might also be an indicator of a healthy control of heart rate in such patients. They proceeded to test this hypothesis using 24-hour electrocardiogram ( Holter monitor ) recordings from one hundred survivors of  heart attacks  with frequent PVCs. Greater turbulence seemed correlated with better prognosis. They then used this data to determine the optimal discriminating threshold between normal and abnormal HRT values, and came up with the values TS=2.5, TO=0%. Now came the test. These thresholds were applied to Holter records from a total of 1191 patients who had experienced a heart attack. There were 162 deaths (13.6%) during the follow-up period of about two years. Patients with abnormal HRTs were approximately three-times more likely to die than those with normal HRTs, beating out some other commonly used predictors."}
{"_id": "WikiPedia_Cardio$$$corpus_1296", "text": "HRT is widely considered [ by whom? ]  to be a  baroreflex  phenomenon. A PVC interrupts the normal  cardiac cycle , so the  ventricles  of the  heart  do not have time to fill up to their normal level, before contracting and pumping their contents out. This results in a pulse ( blood pressure ) weaker than expected and triggers normal homeostatic mechanisms that try to compensate by constricting arteries and increasing heart rate (the turbulence onset part of HRT). This is accomplished by the brain reflexively withdrawing the  parasympathetic  nerve signals and increasing the  sympathetic  nerve signals it sends to the heart. The compensatory  constriction of the arteries  and increased heart rate can cause blood pressure to overshoot normal values, triggering the opposite baroreflex. This time, the brain increases parasympathetic signalling and decreases sympathetic signalling, causing a decrease in heart rate (the turbulence slope part of HRT)."}
{"_id": "WikiPedia_Cardio$$$corpus_1297", "text": "The exact quantitative contribution of the parasympathetic and sympathetic nervous flow to the heart to HRT is unknown. Some researchers [ like whom? ]  assert that HRT is solely dependent upon parasympathetic activity because  atropine , a parasympathetic activity blocker abolishes HRT while a  beta-blocker  (sympathetic blocker) has no effect on HRT. [ citation needed ]  The contribution of the  compensatory pause , the pause between the PVC and the next normal beat, to HRT is also unknown. Whether the single beat blood pressure increase after a compensatory pause occurs in both normal and compromised hearts as well is at present uncertain. To date, no physiological parameter has been linked in a quantitative manner to turbulence slope [ citation needed ] , whereas turbulence onset was shown by researchers in  Calgary , Canada, to be linearly dependent upon duration of subnormal blood pressure in a well designed experiment. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1298", "text": "The reason that the size of HRT after a PVC can be used as a predictor of cardiac death is suggested by its mechanism. Parasympathetic nervous activity to the heart is believed to be protective and sympathetic nervous activity, deleterious, to the heart. [ citation needed ]  Especially after a heart attack, sympathetic nervous activity tends to be increased. A healthy HRT indicates the presence of a healthy amount of  parasympathetic  activity, countering sympathetic activity. To take a wider view, however, it may be that a healthy HRT is also an indication of a healthy brain, and is the reason a small HRT also predicts a likelihood of death from non-cardiac causes as well as from cardiac causes. [ editorializing ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1299", "text": "Heart rate variability  ( HRV ) is the physiological phenomenon of variation in the time interval between heartbeats. It is measured by the variation in the beat-to-beat interval."}
{"_id": "WikiPedia_Cardio$$$corpus_1300", "text": "Other terms used include \"cycle length variability\", \"R\u2013R variability\" (where R is a point corresponding to the peak of the  QRS complex  of the  ECG  wave; and R\u2013R is the interval between successive Rs), and \"heart period variability\". [ 1 ]  Measurement of the RR interval is used to derive heart rate variability. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1301", "text": "Methods used to detect beats include ECG, blood pressure,\n ballistocardiograms , [ 2 ] [ 3 ] \nand the pulse wave signal derived from a  photoplethysmograph  (PPG). ECG is considered the gold standard for HRV measurement [ 4 ]   because it provides a direct reflection of cardiac electric activity. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1302", "text": "Reduced HRV has been shown to be a predictor of mortality after  myocardial infarction [ 6 ] [ 7 ]  although others have shown that the information in HRV relevant to acute myocardial infarction survival is fully contained in the mean  heart rate . [ 8 ] \nA range of other outcomes and conditions may also be associated with modified (usually lower) HRV, including  congestive heart failure ,  diabetic neuropathy , post\u2013 cardiac-transplant  depression, susceptibility to  SIDS  and poor survival in  premature babies , [ citation needed ]  as well as fatigue severity in  chronic fatigue syndrome . [ 9 ]  On the other hand, for patients having high blood pressure ( hypertension ), higher HRV is a risk factor for  atrial fibrillation . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1303", "text": "There is interest in HRV in the field of  psychophysiology . For example, HRV is related to emotional arousal. High-frequency (HF) activity has been found to decrease under conditions of acute time pressure and emotional strain [ 12 ]  and elevated anxiety state, [ 13 ]  presumably related to focused attention and motor inhibition. [ 13 ]  HRV has been shown to be reduced in individuals reporting to worry more. [ 14 ]  In individuals with  post-traumatic stress disorder  (PTSD), HRV and its HF component (see below) is reduced whilst the low-frequency (LF) component is elevated. Furthermore, PTSD patients demonstrated no LF or HF reactivity to recalling a traumatic event. [ 15 ]  Statistical quantitative differences have also been found among healthy, depressed, and psychotic people.  [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1304", "text": "The neurovisceral integration is a model of HRV that views the central autonomic network as the decision maker of cognitive, behavioral and physiological regulation as they pertain to a continuum of emotion. [ 17 ]  The neurovisceral integration model describes how the  prefrontal cortex  regulates activity in  limbic structures  which act to suppress parasympathetic nervous system (PSNS) activity and activate sympathetic nervous system (SNS) circuits. [ 18 ]  Variation in the output of these two branches of the autonomic system produces HRV [ 19 ]  and activity in the prefrontal cortex can hence modulate HRV. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1305", "text": "HRV is reported to be an index of the influence of both the parasympathetic and the sympathetic nervous system. [ 21 ]  For example, high HRV is shown to reflect proper emotion regulation, decision-making, and attention, and low HRV reflects the opposite. [ 21 ]  The parasympathetic nervous system works to decrease the heart rate, while the SNS works to increase the heart rate. [ 17 ]  For example, someone with high HRV may reflect increased parasympathetic activity, and someone with low HRV may reflect increased sympathetic activity. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1306", "text": "Emotions stem from the time and impact of a situation on a person. [ 23 ]  The ability to regulate emotions is essential for social environments and well-being. [ 17 ]  HRV has provided a window to the physiological components associated with emotional regulation. [ 21 ]  HRV has been shown to reflect emotional regulation at two different levels, while resting and while completing a task. Research suggests that a person with higher HRV while resting can provide more appropriate emotional responses compared to those that have low HRV at rest. [ 21 ]  Empirical research found that HRV can reflect better emotional regulation by those with higher resting HRV, particularly with  negative emotions . [ 24 ]  However, HRV is elevated by negative news in persons who react more strongly to negative news than to positive news. [ 25 ]  When completing a task, HRV is subject to change, especially when people need to regulate their emotions. Most importantly, individual differences are related to the ability to regulate emotions. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1307", "text": "Previous research has suggested that a large part of the attention regulation is due to the default inhibitory properties of the prefrontal cortex. [ 21 ]  Top-down processes from the prefrontal cortex provide parasympathetic influences, and if for some reason, those influences are active, attention can suffer. [ 21 ]  Researchers have suggested that HRV can index attention. It was found that groups with high anxiety and low HRV have poor attention. [ 27 ]  In line with this research, it has also been suggested that increased attention has been linked to high HRV and increased vagus nerve activity. [ 21 ]  The vagus nerve activity reflects the physiological modulation of the parasympathetic and sympathetic nervous system. [ 17 ]  The activity behind the prefrontal cortex and the parasympathetic and sympathetic nervous system can influence heart activity. However, people are not all affected the same. A systematic review of HRV and cognitive function suggested that resting HRV can predict individual differences in attentional performance. Furthermore, HRV has been able to index the role of attention and performance, supporting high HRV as a biomarker of increased attention and performance. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1308", "text": "Decision-making skills are found to be indexed by HRV in several studies. Previous research has suggested that both emotion and attention are linked to decision making; for example, poor decision making is linked to the inability to regulate or control emotions and attention and vice versa. [ 27 ]  Decision making is negatively affected by lower HRV and positively affected by higher levels of HRV. Most importantly, resting-state HRV was found to be a significant predictor of cognitive functions such as decision making. [ 29 ]  HRV, accompanied by a psychological state such as anxiety, has been found to lead to poor decisions. For example, a group of researchers found that low HRV was an index of higher uncertainty leading to poor decision-making skills, especially those with higher levels of anxiety. [ 27 ]  HRV was also used to assess decision-making skills in a high-risk game and was found to be an index higher sympathetic activation (lower HRV) when making decisions involving risk. [ 30 ]  HRV can index psychological concepts, such as the ones outlined above, to assess the demand for the situations that people experience."}
{"_id": "WikiPedia_Cardio$$$corpus_1309", "text": "The  polyvagal theory [ 31 ] [ 32 ]  is another way to describe the pathways in the  autonomic nervous system  that mediate HRV. The polyvagal theory highlights three main ordinal processes, inactive response to an environmental threat, the active response to an environmental threat, and the fluctuation between the connect and disconnect to an environmental threat. [ 17 ]  This theory, like others, [ 33 ]  decomposes heart rate variability based on frequency domain characteristics. However, it places more emphasis on respiratory sinus arrhythmia and its transmission by a hypothesized neural pathway distinct from other components of HRV. [ 34 ]   There is anatomic [ 35 ]   and physiological [ 36 ]  evidence for a polyvagal control of the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_1310", "text": "Variation in the beat-to-beat interval is a physiological phenomenon. The  SA node  receives several different inputs and the instantaneous heart rate or RR interval and its variation are the results of these inputs. [ 37 ]  Contribution of the respiratory rhythm to sinus arrhythmia in normal unanesthetized subjects during mechanical hyperventilation with positive pressure. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1311", "text": "The main inputs are the  sympathetic  and the  parasympathetic nervous system  (PSNS) and  humoral factors . Respiration gives rise to waves in heart rate mediated primarily via the PSNS, and it is thought that the lag in the  baroreceptor  feedback loop may give rise to 10 second waves in heart rate (associated with  Mayer waves  of blood pressure), but this remains controversial. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1312", "text": "Factors that affect the input are the  baroreflex ,  thermoregulation ,  hormones ,  sleep\u2013wake cycle , meals, physical activity, and  stress ."}
{"_id": "WikiPedia_Cardio$$$corpus_1313", "text": "Decreased PSNS activity or increased SNS activity will result in reduced HRV. High frequency (HF) activity (0.15 to 0.40\u00a0Hz), especially, has been linked to PSNS activity. Activity in this range is associated with the respiratory sinus arrhythmia (RSA), a vagally mediated modulation of heart rate such that it increases during inspiration and decreases during expiration. Less is known about the physiological inputs of the low frequency (LF) activity (0.04 to 0.15\u00a0Hz). Though previously thought to reflect SNS activity, it is now widely accepted that it reflects a mixture of both the SNS and PSNS. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1314", "text": "There are two primary fluctuations:"}
{"_id": "WikiPedia_Cardio$$$corpus_1315", "text": "The regulation of heart rate, encompassing both acceleration and deceleration of the heartbeat, is highly specific. Distinct patterns in heart rate can be observed during everyday movements, such as kneeling down or standing up. These patterns reflect highly sensitive physiological regulatory mechanisms that enable a healthy heart to adapt to various life influences. [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1316", "text": "Errors in the location of the instantaneous heart beat will result in errors in the calculation of the HRV. HRV is highly sensitive to artifact and errors in as low as even 2% of the data will result in unwanted biases in HRV calculations. To ensure accurate results therefore it is critical to manage artifact and RR errors appropriately prior to performing any HRV analyses. [ 43 ] [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1317", "text": "Robust management of artifacts, including RWave identification, interpolation and exclusion requires a high degree of care and precision. This can be very time-consuming in large studies with data recorded over long durations. Software packages are able to assist users with a variety of robust and tested artifact management tools.  These software programs also include some automated capability but it is important that a human review any automated artifact management and edit accordingly."}
{"_id": "WikiPedia_Cardio$$$corpus_1318", "text": "The most widely used methods can be grouped under time-domain and frequency-domain. A joint European and American task-force described standards in HRV measurements in 1996. [ 19 ]  Other methods have been proposed, such as non-linear methods."}
{"_id": "WikiPedia_Cardio$$$corpus_1319", "text": "These [ 45 ]  are based on the beat-to-beat or NN intervals, which are analysed to give variables such as: [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1320", "text": "The series of NN intervals also can be converted into a geometric pattern such as:\nGeometric Measures HRV triangular index: integral of density distribution / maximum of density distribution maximum\nHRV triangular index = Number of all NN intervals / maximum number. Dependent on the length of the bin -> quote the bin size+ relative insensitive to the analytic quality of the series of NN intervals \u2013 need of reasonable number of NN intervals to generate the geometric pattern (in practice 20 min to 24 h) \u2013 not appropriate to assess short-term changes in HRV"}
{"_id": "WikiPedia_Cardio$$$corpus_1321", "text": "Frequency domain methods [ 45 ]  assign bands of frequency and then count the number of NN intervals that match each band. The bands are typically high frequency (HF) from 0.15 to 0.4\u00a0Hz, low frequency (LF) from 0.04 to 0.15\u00a0Hz, and the very low frequency (VLF) from 0.0033 to 0.04\u00a0Hz. [ 50 ]  HF power reflects stimulation by the  parasympathetic nervous system  (PNS), whereas LF power reflects stimulation by both the  sympathetic nervous system  (SNS) and the PNS. [ 50 ]  VLF power is associated with  thermoregulation , the  renin\u2013angiotensin system . and peripheral  vasomotor  activity. [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1322", "text": "Several methods of analysis are available.  Power spectral density  (PSD), using parametric or nonparametric methods, provides basic information on the power distribution across frequencies. One of the most commonly used PSD methods is the  discrete Fourier transform .\nMethods for the calculation of PSD may be generally classified as nonparametric and parametric. In most instances, both methods provide comparable results. The advantages of the  nonparametric  methods are (1) the simplicity of the algorithm used ( fast Fourier transform  [FFT] in most of the cases) and (2) the high processing speed.  The advantages of  parametric  methods are (1) smoother spectral components that can be distinguished independent of preselected frequency bands, (2) easy postprocessing of the spectrum with an automatic calculation of low- and high-frequency power components with an easy identification of the central frequency of each component, and (3) an accurate estimation of PSD even on a small number of samples on which the signal is supposed to maintain stationarity. The basic disadvantage of parametric methods is the need of verification of the suitability of the chosen model and of its complexity (that is, the order of the model)."}
{"_id": "WikiPedia_Cardio$$$corpus_1323", "text": "In addition to classical FFT-based methods used for the calculation of frequency parameters, a more appropriate PSD estimation method is the  Lomb\u2013Scargle periodogram . [ 51 ]  Analysis has shown that the LS periodogram can produce a more accurate estimate of the PSD than FFT methods for typical RR data. Since the RR data is an unevenly sampled data, another advantage of the LS method is that in contrast to FFT-based methods it is able to be used without the need to resample and detrend the RR data."}
{"_id": "WikiPedia_Cardio$$$corpus_1324", "text": "Alternatively, to avoid artefacts that are created when calculating the power of a signal that includes a single high-intensity peak (for example caused by an arrhythmic heart beat), the concept of the 'instantaneous Amplitude' has been introduced, which is based on the Hilbert transform of the RR data. [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1325", "text": "A newly used HRV index, [ citation needed ]  which depends on the wavelet entropy measures, is an alternative choice. The wavelet entropy measures are calculated using a three-step procedure defined in the literature. First, the wavelet packet algorithm is implemented using the Daubechies 4 (DB4) function as the mother wavelet with a scale of 7. Once the wavelet coefficients are obtained, the energy for each coefficient are calculated as described in the literature. After calculating the normalized values of wavelet energies, which represent the relative wavelet energy (or the probability distribution), the wavelet entropies are obtained using the definition of entropy given by Shannon."}
{"_id": "WikiPedia_Cardio$$$corpus_1326", "text": "Given the complexity of the mechanisms regulating heart rate, it is reasonable to assume that applying HRV analysis based on methods of non-linear dynamics will yield valuable information. Although  chaotic behavior  has been assumed, more rigorous testing has shown that heart rate variability cannot be described as a low dimensional chaotic process. [ 53 ]  However, application of chaotic globals to HRV has been shown to predict diabetes status. [ 54 ]  The most commonly used non-linear method of analysing heart rate variability is the  Poincar\u00e9 plot . Each data point represents a pair of successive beats, the x-axis is the current RR interval, while the y-axis is the previous RR interval. HRV is quantified by fitting mathematically defined geometric shapes to the data. [ 55 ]  Other methods used are the  correlation dimension , symbolic dynamics, [ 56 ]  nonlinear predictability, [ 53 ]  pointwise correlation dimension, [ 57 ]   approximate entropy,  sample entropy , [ 58 ]  multiscale entropy analysis, [ 59 ]  sample asymmetry [ 60 ]  and memory length (based on inverse statistical analysis). [ 61 ] [ 62 ]  It is also possible to represent long range correlations geometrically. [ 63 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1327", "text": "Sequences of RR intervals have been found to have long-term correlations. [ 63 ]  However, one flaw with these analyses is their lack of goodness-of-fit statistics, i.e. values are derived that may or may not have adequate statistical rigor. Different types of correlations have been found during different sleep stages. [ 63 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1328", "text": "A basic problem is that all the parameters used to characterize HRV strongly depend on heart rate, [ 64 ]  but many articles have not adjusted properly or at all for HR differences when comparing HRV in multiple circumstances. [ 65 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1329", "text": "However, the exact HRV(HR) relationship is still a matter of debate. For time domain parameters (RMSSD, SDNN, etc.) the results imply that, if there exists a universal function, it should be either exponential or hyperbolic in nature. [ 66 ] [ 64 ] [ 65 ]  The evaluation procedures used to determine HRV(HR) function have not allowed to decide between these options, so far."}
{"_id": "WikiPedia_Cardio$$$corpus_1330", "text": "A new evaluation method has recently allowed to determine a HRV(HR) function with unprecedented precision: [ 67 ]  it can be described by two descending exponential components for healthy individuals, in general."}
{"_id": "WikiPedia_Cardio$$$corpus_1331", "text": "Time domain methods are preferred to frequency domain methods when short-term recordings are investigated. This is due to the fact that the recording should be at least 10 times the wavelength of the lowest frequency bound of interest. Thus, recording of approximately 1 minute is needed to assess the HF components of HRV (i.e., a lowest bound of 0.15\u00a0Hz is a cycle of 6.6 seconds and so 10 cycles require ~60 seconds), while more than 4 minutes are needed to address the LF component (with a lower bound of 0.04\u00a0Hz). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1332", "text": "Although time domain methods, especially the SDNN and RMSSD methods, can be used to investigate recordings of long durations, a substantial part of the long-term variability is day\u2013night differences. Thus, long-term recordings analyzed by time domain methods should contain at least 18 hours of analyzable ECG data that include the whole night. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1333", "text": "Although  cardiac automaticity  is intrinsic to various pacemaker tissues, heart rate and rhythm are largely under the control of the autonomic nervous system. The parasympathetic influence on heart rate is mediated via release of acetylcholine by the vagus nerve. Muscarinic acetylcholine receptors respond to this release mostly by an increase in cell membrane K+ conductance. Acetylcholine also inhibits the hyperpolarization-activated \"pacemaker\" current. The \"Ik decay\" hypothesis proposes that pacemaker depolarization results from slow deactivation of the delayed rectifier current, Ik, which, due to a time-independent background inward current, causes diastolic depolarization. Conversely, the \"If activation\" hypothesis suggests that after action potential termination, If provides a slowly activating inward current predominating over decaying Ik, thus initiating slow diastolic depolarization. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1334", "text": "The sympathetic influence on heart rate is mediated by release of epinephrine and norepinephrine. Activation of \u03b2-adrenergic receptors results in cAMP-mediated phosphorylation of membrane proteins and increases in ICaL and in If the result is an acceleration of the slow diastolic depolarization."}
{"_id": "WikiPedia_Cardio$$$corpus_1335", "text": "Under resting conditions, vagal tone prevails and variations in heart period are largely dependent on vagal modulation. The vagal and sympathetic activity constantly interact. Because the sinus node is rich in acetylcholinesterase, the effect of any vagal impulse is brief because the acetylcholine is rapidly hydrolyzed. Parasympathetic influences exceed sympathetic effects probably through two independent mechanisms: a cholinergically induced reduction of norepinephrine released in response to sympathetic activity, and a cholinergic attenuation of the response to an adrenergic stimulus."}
{"_id": "WikiPedia_Cardio$$$corpus_1336", "text": "The RR interval variations present during resting conditions represent beat-by-beat variations in cardiac autonomic inputs. However, efferent vagal (parasympathetic) activity is a major contributor to the HF component, as seen in clinical and experimental observations of autonomic maneuvers such as electrical vagal stimulation, muscarinic receptor blockade, and vagotomy. More problematic is the interpretation of the LF component, which was considered by some as a marker of sympathetic modulation (especially when expressed in normalized units) but is now known to include both sympathetic and vagal influences. For example, during sympathetic activation the resulting tachycardia is usually accompanied by a marked reduction in total power, whereas the reverse occurs during vagal activation. Thus the spectral components change in the same direction and do not indicate that LF faithfully reflects sympathetic effects."}
{"_id": "WikiPedia_Cardio$$$corpus_1337", "text": "HRV measures fluctuations in autonomic inputs to the heart rather than the mean level of autonomic inputs. Thus, both withdrawal and saturatingly high levels of autonomic input to the heart can lead to diminished HRV."}
{"_id": "WikiPedia_Cardio$$$corpus_1338", "text": "A reduction of HRV has been reported in several cardiovascular and noncardiovascular diseases."}
{"_id": "WikiPedia_Cardio$$$corpus_1339", "text": "Depressed HRV after MI may reflect a decrease in vagal activity directed to the heart. HRV in patients surviving an acute MI reveal a reduction in total and in the individual power of spectral components. The presence of an alteration in neural control is also reflected in a blunting of day-night variations of RR interval. In post-MI patients with a very depressed HRV, most of the residual energy is distributed in the VLF frequency range below 0.03\u00a0Hz, with only a small respiration-related variations."}
{"_id": "WikiPedia_Cardio$$$corpus_1340", "text": "In neuropathy associated with diabetes mellitus characterized by alteration in small nerve fibers, a reduction in time domain parameters of HRV seems not only to carry negative prognostic value but also to precede the clinical expression of autonomic neuropathy. In diabetic patients without evidence of autonomic neuropathy, reduction of the absolute power of LF and HF during controlled conditions was also reported. Similarly, diabetic patients can be differentiated from normal controls on the basis of reduction in HRV. [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1341", "text": "A very reduced HRV with no definite spectral components has been reported in patients with a recent heart transplant. The appearance of discrete spectral components in a few patients is considered to reflect cardiac reinnervation. This reinnervation may occur as early as 1 to 2 years after transplantation and is assumed to be of sympathetic origin. In addition, a correlation between respiratory rate and the HF component of HRV observed in some transplanted patients also indicates that a nonneural mechanism may generate a respiration-related rhythmic oscillation."}
{"_id": "WikiPedia_Cardio$$$corpus_1342", "text": "A reduced HRV has been observed consistently in patients with cardiac failure. In this condition characterized by signs of sympathetic activation such as faster heart rates and high levels of circulating catecholamines, a relation between changes in HRV and the extent of left ventricular dysfunction was reported. In fact, whereas the reduction in time domain measures of HRV seemed to parallel the severity of the disease, the relationship between spectral components and indices of ventricular dysfunction appears to be more complex. In particular, in most patients with a very advanced phase of the disease and with a drastic reduction in HRV, an LF component could not be detected despite the clinical signs of sympathetic activation. This reflects that, as stated above, the LF may not accurately reflect cardiac sympathetic tone."}
{"_id": "WikiPedia_Cardio$$$corpus_1343", "text": "Liver  cirrhosis  is associated with decreased HRV. Decreased HRV in patients with cirrhosis has a prognostic value and predicts mortality. Loss of HRV is also associated with higher plasma pro-inflammatory cytokine levels and impaired neurocognitive function in this patient population. [ 68 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1344", "text": "HRV is decreased in patients with sepsis. Loss of HRV has both diagnostic and prognostic value in neonates with sepsis. [ 69 ]  The pathophysiology of decreased HRV in sepsis is not well understood but there is experimental evidence to show that partial uncoupling of cardiac pacemaker cells from autonomic neural control may play a role in decreased HRV during acute systemic inflammation. [ 70 ]  (Decreased HRV is generally lower in inflammatory conditions [ 1 ] )."}
{"_id": "WikiPedia_Cardio$$$corpus_1345", "text": "Patients with chronic complete high cervical spinal cord lesions have intact efferent vagal neural pathways directed to the sinus node. However, an LF component can be detected in HRV and arterial pressure variabilities of some tetraplegic patients. Thus, the LF component of HRV in those without intact sympathetic inputs to the heart represent vagal modulation."}
{"_id": "WikiPedia_Cardio$$$corpus_1346", "text": "Victims of  sudden cardiac death  have been found to have had lower HRV than healthy individuals. [ 71 ] [ 63 ]  HRV can be observed to be depressed prior to the development of SCD, which raises questions about whether or not altered autonomic function plays a role in the development of electrical instability. HRV is also depressed in SCD survivors, who are at high risk for subsequent episodes. [ 72 ]  HRV is markedly decreased prior to both fatal and non-fatal  arrhythmias . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1347", "text": "HRV correlates with the progression of disease and outcome of cancer patients, according to a systematic review of published studies. [ 73 ]  Patients in the early stages of cancer have a significantly higher HRV when compared to patients in the later stages of cancer, suggesting disease severity influences HRV. Different ranges of HRV can be observed between cancer types. [ 74 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1348", "text": "HRV alterations occur in healthy pregnancies as well as similar changes in pregnancies with gestational diabetes that include lower HRV mean values. [ 75 ] [ 76 ] [ 77 ] [ 78 ] [ 79 ] [ 80 ] [ 81 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1349", "text": "Low RMSSD, thought to represent vagal tone, have been associated with major depression. [ 82 ]  Lower SDNN and elevated LF/HF were found in those with bipolar disorder, and in particular those characterized as having greater illness severity due to greater number of episodes, illness duration and whether there had been psychosis. [ 83 ] [ 84 ]  Patients with PTSD also had lower HF, a measure of vagal tone. [ 84 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1350", "text": "Interventions that augment HRV may be protective against cardiac mortality and sudden cardiac death. Although the rationale for changing HRV is sound, it also contains the inherent danger of leading to the unwarranted assumption that modification of HRV translates directly into cardiac protection, which may not be the case. Despite the growing consensus that increases in vagal activity can be beneficial, it is not as yet known how much vagal activity (or HRV as a marker) has to increase in order to provide adequate protection."}
{"_id": "WikiPedia_Cardio$$$corpus_1351", "text": "The data on the effect of \u03b2-blockers on HRV in post-MI patients are surprisingly scant. Despite the observation of statistically significant increases, the actual changes are very modest. In conscious post-MI dogs, \u03b2-blockers do not modify HRV. The unexpected observation that before MI, \u03b2-blockade increases HRV only in the animals destined to be at low risk for lethal arrhythmias after MI may suggest novel approaches to post-MI risk stratification."}
{"_id": "WikiPedia_Cardio$$$corpus_1352", "text": "Data exist for several antiarrhythmic drugs. Flecainide and propafenone but not amiodarone were reported to decrease time domain measures of HRV in patients with chronic ventricular arrhythmia. In another study, propafenone reduced HRV and decreased LF much more than HF. A larger study confirmed that flecainide, also encainide and moricizine, decreased HRV in post-MI patients but found no correlation between the change in HRV and mortality during follow-up. Thus, some antiarrhythmic drugs associated with increased mortality can reduce HRV. However, it is not known whether these changes in HRV have any direct prognostic significance."}
{"_id": "WikiPedia_Cardio$$$corpus_1353", "text": "Low-dose muscarinic receptor blockers, such as atropine and  scopolamine , may produce a paradoxical increase in vagal effects on the heart, as suggested by a decrease in heart rate. In addition, scopolamine and low dose atropine can markedly increase HRV. However, though the heart rate slowing in proportional to the (low) dose of atropine, the increase in HRV varies widely across and within individuals. This suggests that even for vagal activity to the heart, HRV may be a limited marker."}
{"_id": "WikiPedia_Cardio$$$corpus_1354", "text": "The effect of  thrombolysis  on HRV (assessed by pNN50) was reported in 95 patients with acute MI. HRV was higher 90 minutes after thrombolysis in the patients with patency of the infarct-related artery. However, this difference was no longer evident when the entire 24 hours were analyzed."}
{"_id": "WikiPedia_Cardio$$$corpus_1355", "text": "Exercise training may decrease cardiovascular mortality and sudden cardiac death. Regular exercise training is also thought to modify cardiac autonomic control. Individuals who exercise regularly have a 'training bradycardia' (i.e., low resting heart rate) and generally have higher HRV than sedentary individuals. [ 85 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1356", "text": "The technique called  resonant breathing  biofeedback  teaches how to recognize and control involuntary heart rate variability. A randomized study by Sutarto et al. assessed the effect of resonant breathing biofeedback among manufacturing operators; depression, anxiety and stress significantly decreased. [ 86 ]  A first overall meta-analysis by Goessl VC et al. (24 studies, 484 individuals, 2017) indicates ''HRV biofeedback training is associated with a large reduction in self-reported stress and anxiety'', while mentioning that more well-controlled studies are needed. [ 87 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1357", "text": "One study that surveyed the physiological effects of playing  Native American flutes  found a significant HRV increase when playing both low-pitched and high-pitched flutes. [ 88 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1358", "text": "Even though there are no widely accepted standard values for HRV that can be used for clinical purposes, multiple studies have measured and reported normal values for various populations: [ 1 ] [ 89 ] [ 90 ] [ 91 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1359", "text": "Time Domain Analysis Abbreviations"}
{"_id": "WikiPedia_Cardio$$$corpus_1360", "text": "IBI  is InterBeat Interval, the time period between successive heartbeats (Normal-to-Normal interbeat interval, also known as the R\u2013R interval), measured in milliseconds (ms).  SDNN  is Standard Deviation of Normal-to-Normal interbeat intervals measured in milliseconds.  RMSSD  is Root Mean Square of Successive Differences between normal heartbeats measured in milliseconds. [ 89 ] [ 1 ]  The conventional recording time is five minutes. [ 89 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1361", "text": "Spectral Analysis Abbreviations"}
{"_id": "WikiPedia_Cardio$$$corpus_1362", "text": "LF  is Power of the Low Frequency range [ms squared (ms 2 ) or normal units (nu)]  HF  is Power of the High Frequency range [ms squared (ms 2 ) or normal units (nu)]  LF/HF  is the ratio of LF-to-HF power [ 89 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1363", "text": "Heart sounds  are the noises generated by the beating  heart  and the resultant flow of blood through it. Specifically, the sounds reflect the turbulence created when the  heart valves  snap shut. In cardiac  auscultation , an examiner may use a  stethoscope  to listen for these unique and distinct sounds that provide important  auditory  data regarding the condition of the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_1364", "text": "In healthy adults, there are two normal heart sounds, often described as a  lub  and a  dub  that occur in sequence with each heartbeat. These are the  first heart sound  (S 1 ) and  second heart sound  (S 2 ),\nproduced by the closing of the  atrioventricular valves  and  semilunar valves , respectively. In addition to these normal sounds, a variety of other sounds may be present including  heart murmurs ,  adventitious sounds , and  gallop rhythms   S 3  and  S 4 ."}
{"_id": "WikiPedia_Cardio$$$corpus_1365", "text": "Heart murmurs  are generated by turbulent flow of blood and a murmur to be heard as turbulent flow must require pressure difference of at least 30  mm of Hg  between the chambers and the pressure dominant chamber will outflow the blood to non-dominant chamber in diseased condition which leads to  Left-to-right shunt  or  Right-to-left shunt  based on the pressure dominance. Turbulence may occur inside or outside the heart; if it occurs outside the heart then the turbulence is called  bruit  or  vascular murmur . Murmurs may be physiological (benign) or pathological (abnormal). Abnormal murmurs can be caused by  stenosis  restricting the opening of a heart valve, resulting in turbulence as blood flows through it. Abnormal murmurs may also occur with valvular insufficiency ( regurgitation ), which allows backflow of blood when the incompetent valve closes with only partial effectiveness. Different murmurs are audible in different parts of the  cardiac cycle , depending on the cause of the murmur."}
{"_id": "WikiPedia_Cardio$$$corpus_1366", "text": "Normal heart sounds are associated with heart valves closing:"}
{"_id": "WikiPedia_Cardio$$$corpus_1367", "text": "The  first heart sound , or  S 1 , forms the \"lub\" of \"lub-dub\" and is composed of components M 1  (mitral valve closure) and T 1  (tricuspid valve closure). Normally M 1  precedes T 1  slightly. It is caused by the  closure of the atrioventricular  valves , i.e.  tricuspid  and  mitral  (bicuspid), at the beginning of ventricular contraction, or  systole . When the ventricles begin to contract, so do the papillary muscles in each ventricle. The papillary muscles are attached to the cusps or leaflets of the tricuspid and mitral valves via  chordae tendineae  (heart strings). When the papillary muscles contract, the chordae tendineae become tense and thereby prevent the backflow of blood into the lower pressure environment of the atria. The chordae tendineae act a bit like the strings on a parachute, and allow the leaflets of the valve to balloon up into the atria slightly, but not so much as to evert the cusp edges and allow backflow of blood. It is the pressure created from ventricular contraction that closes the valve, not the papillary muscles themselves. The contraction of the ventricle begins just prior to AV valves closing and prior to the opening of the semilunar valves. The sudden tensing of the chordae tendineae and the squeezing of the ventricles against closed semilunar valves, send blood rushing back toward the atria, and the parachute-like valves catch the rush of blood in their leaflets causing the valve to snap shut. The S1 sound results from reverberation within the blood associated with the sudden block of flow reversal by the valves. The delay of T1 even more than normally causes the split S1 which is heard in a  right bundle branch block . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1368", "text": "The  second heart sound , or  S 2 , forms the \"dub\" of \"lub-dub\" and is composed of components A 2  (aortic valve closure) and P 2  (pulmonary valve closure). Normally A 2  precedes P 2  especially during inspiration where a split of S 2  can be heard. It is caused by the closure of the  semilunar valves  (the  aortic valve  and  pulmonary valve ) at the end of ventricular systole and the beginning of ventricular  diastole . As the  left ventricle  empties, its pressure falls below the pressure in the  aorta .  Aortic blood flow quickly reverses back toward the left ventricle, catching the pocket-like cusps of the aortic valve, and is stopped by aortic valve closure.  Similarly, as the pressure in the  right ventricle  falls below the pressure in the  pulmonary artery , the pulmonary valve closes. The  S 2  sound results from reverberation within the blood associated with the sudden block of flow reversal. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1369", "text": "Splitting of S2 , also known as physiological split, normally occurs during inhalation because the decrease in intrathoracic pressure increases the time needed for pulmonary pressure to exceed that of the right ventricular pressure.  A widely split S2 can be associated with several different cardiovascular conditions, and the split is sometimes wide and variable whereas, sometimes wide and fixed. The wide and variable split occurs in  Right bundle branch block ,  pulmonary stenosis , pulmonary hypertension and  ventricular septal defects . The wide and fixed splitting of S2 occurs in  atrial septal defect . Pulmonary S2 (P2) will be accentuated (loud P2) in pulmonary hypertension and pulmonary embolism. S2 becomes softer in aortic stenosis. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1370", "text": "The rarer extra heart sounds form  gallop rhythms  and are heard in both normal and abnormal situations. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1371", "text": "The  third heart sound , or  S 3  is rarely heard, and is also called a protodiastolic gallop, ventricular gallop, or informally the \" Kentucky \" gallop as an  onomatopoeic  reference to the rhythm and stress of S1 followed by S2 and S3 together (S1=Ken; S2=tuck; S3=y). [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1372", "text": "\"lub-dub-ta\" or \"slosh-ing-in\"  If new, indicates heart failure or volume overload. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1373", "text": "It occurs at the beginning of diastole after S2 and is lower in pitch than S1 or S2 as it is not of valvular origin. The third heart sound is benign in youth, some trained athletes, and sometimes in pregnancy but if it re-emerges later in life it may signal cardiac problems, such as a failing left ventricle as in dilated  congestive heart failure  (CHF). S3 is thought to be caused by the oscillation of blood back and forth between the walls of the ventricles initiated by blood rushing in from the atria. The reason the third heart sound does not occur until the middle third of diastole is probably that during the early part of diastole, the ventricles are not filled sufficiently to create enough tension for reverberation. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1374", "text": "It may also be a result of tensing of the chordae tendineae during rapid filling and expansion of the ventricle. In other words, an S3 heart sound indicates increased volume of blood within the ventricle. An S3 heart sound is best heard with the bell-side of the stethoscope (used for lower frequency sounds). A left-sided S3 is best heard in the left lateral decubitus position and at the apex of the heart, which is normally located in the 5th left intercostal space at the midclavicular line. A right-sided S3 is best heard at the lower left sternal border. The way to distinguish between left and right-sided S3 is to observe whether it increases in intensity with inhalation or exhalation. A right-sided S3 will increase on inhalation, while a left-sided S3 will increase on exhalation. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1375", "text": "S3 can be a normal finding in young patients but is generally pathologic over the age of 40. The most common cause of pathologic S3 is congestive heart failure. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1376", "text": "The  fourth heart sound , or  S 4  when audible in an adult is called a presystolic gallop or atrial gallop. This gallop is produced by the sound of blood being forced into a stiff or hypertrophic ventricle. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1377", "text": "\"ta-lub-dub\" or \"a-stiff-wall\""}
{"_id": "WikiPedia_Cardio$$$corpus_1378", "text": "It is a sign of a pathologic state, usually a failing or hypertrophic left ventricle, as in systemic hypertension, severe valvular  aortic stenosis , and  hypertrophic cardiomyopathy . The sound occurs just after atrial contraction at the end of diastole and immediately before S1, producing a rhythm sometimes referred to as the \" Tennessee \" gallop where S4 represents the \"Ten-\" syllable. [ 2 ]  It is best heard at the cardiac apex with the patient in the left lateral decubitus position and holding their breath.  The combined presence of S3 and S4 is a quadruple gallop, also known as the \"Hello-Goodbye\" gallop. At rapid heart rates, S3 and S4 may merge to produce a summation gallop, sometimes referred to as S7. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1379", "text": "Atrial contraction must be present for production of an S4. It is absent in  atrial fibrillation  and in other rhythms in which atrial contraction does not precede ventricular contraction. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1380", "text": "Heart murmurs  are produced as a result of turbulent flow of blood strong enough to produce audible noise. They are usually heard as a whooshing sound. The term murmur only refers to a sound believed to originate within blood flow through or near the heart; rapid blood velocity is necessary to produce a murmur. Most heart problems do not produce any murmur and most valve problems also do not produce an audible murmur. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1381", "text": "Murmurs can be heard in many situations in adults without major congenital heart abnormalities: [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1382", "text": "Though several different  cardiac  conditions can cause heart murmurs, the murmurs can change markedly with the severity of the cardiac disease.  An astute physician can sometimes diagnose cardiac conditions with some accuracy based largely on the murmur, related  physical examination , and experience with the relative frequency of different heart conditions. However, with the advent of better quality and wider availability of  echocardiography  and other techniques, heart status can be recognized and quantified much more accurately than formerly possible with only a stethoscope, examination, and experience. Another advantage to the use of the echocardiogram is that the devices can be handheld. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1383", "text": "Inhalation  decreases intrathoracic pressure which allows more venous blood to return to the right heart (pulling blood into the right side of the heart via a vacuum-like effect). Therefore, right-sided heart murmurs generally increase in intensity with inhalation. The decreased (more negative) intrathoracic pressure has an opposite effect on the left side of the heart, making it harder for the blood to exit into circulation. Therefore, left-sided murmurs generally decrease in intensity during inhalation. Increasing venous blood return to the right side of the heart by raising a patient's legs to a 45-degree while lying supine produces similar effect which occurs during inhalation. Inhalation can also produce a non-pathological  split S2  which will be heard upon auscultation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1384", "text": "With  exhalation , the opposite haemodynamic changes occur: left-sided murmurs generally increase in intensity with exhalation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1385", "text": "There are a number of interventions that can be performed that alter the intensity and characteristics of abnormal heart sounds.  These interventions can differentiate the different heart sounds to more effectively obtain a diagnosis of the cardiac anomaly that causes the heart sound. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1386", "text": "Clicks  \u2013 Heart clicks are short, high-pitched sounds that can be appreciated with modern non-invasive imaging techniques. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1387", "text": "Rubs  \u2013 The pericardial friction rub can be heard in  pericarditis , an  inflammation  of the  pericardium , the sac surrounding the heart. This is a characteristic scratching, creaking, high-pitched sound emanating from the rubbing of both layers of inflamed pericardium. It is the loudest in systole, but can often be heard at the beginning and at the end of diastole. It is very dependent on body position and breathing, and changes from hour to hour. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1388", "text": "The aortic area, pulmonic area, tricuspid area and mitral area are areas on the surface of the chest where the heart is auscultated. [ 6 ] \nHeart sounds result from reverberation within the blood associated with the sudden block of flow reversal by the valves closing. Because of this, auscultation to determine function of a valve is usually not performed at the position of the valve, but at the position to where the sound waves reverberate. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1389", "text": "Using electronic stethoscopes, it is possible to record heart sounds via direct output to an external recording device, such as a  laptop  or  MP3  recorder. The same connection can be used to listen to the previously recorded auscultation through the stethoscope headphones, allowing for a more detailed study of murmurs and other heart sounds, for general research as well as evaluation of a particular patient's condition. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1390", "text": "1G5W ,  1HMR ,  1HMS ,  1HMT ,  2HMB ,  3RSW ,  3WBG ,  3WVM ,  3WXQ ,  4TJZ ,  4TKB ,  4TKH ,  4TKJ ,  4WBK ,  5CE4"}
{"_id": "WikiPedia_Cardio$$$corpus_1391", "text": "2170"}
{"_id": "WikiPedia_Cardio$$$corpus_1392", "text": "14077"}
{"_id": "WikiPedia_Cardio$$$corpus_1393", "text": "ENSG00000121769"}
{"_id": "WikiPedia_Cardio$$$corpus_1394", "text": "ENSMUSG00000028773"}
{"_id": "WikiPedia_Cardio$$$corpus_1395", "text": "P05413"}
{"_id": "WikiPedia_Cardio$$$corpus_1396", "text": "P11404"}
{"_id": "WikiPedia_Cardio$$$corpus_1397", "text": "NM_004102 NM_001320996"}
{"_id": "WikiPedia_Cardio$$$corpus_1398", "text": "NM_010174"}
{"_id": "WikiPedia_Cardio$$$corpus_1399", "text": "NP_001307925 NP_004093"}
{"_id": "WikiPedia_Cardio$$$corpus_1400", "text": "NP_034304"}
{"_id": "WikiPedia_Cardio$$$corpus_1401", "text": "Heart-type fatty acid binding protein  (hFABP) also known as  mammary-derived growth inhibitor  is a  protein   that in humans is encoded by the  FABP3   gene . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1402", "text": "Heart-type Fatty Acid-Binding Protein (H-FABP) is a small cytoplasmic protein (15 kDa) released from cardiac  myocytes  following an  ischemic  episode. [ 7 ]   Like the nine other distinct FABPs that have been identified, H-FABP is involved in active  fatty acid  metabolism where it transports fatty acids from the cell membrane to  mitochondria  for oxidation. [ 7 ]   See  FABP3  for biochemical details."}
{"_id": "WikiPedia_Cardio$$$corpus_1403", "text": "The intracellular fatty acid-binding proteins ( FABPs ) belongs to a multigene family. FABPs are divided into at least three distinct types, namely the hepatic-, intestinal- and cardiac-type. They form 14-15 kDa proteins and are thought to participate in the uptake, intracellular metabolism and/or transport of  long-chain fatty acids . They may also be responsible in the modulation of cell growth and proliferation. Fatty acid-binding protein 3 gene contains four exons and its function is to arrest growth of mammary  epithelial cells . This gene is also a candidate tumor suppressor gene for human  breast cancer . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1404", "text": "FABP3 is known to interact with  TNNI3K  in the context of interacting with cardiac troponin I. [ 8 ]  The protein also interacts with,  VPS28 ,  KIAA159 , [ 9 ]   NUP62 , [ 10 ]   PLK1 ,  UBC , and  Xpo1 . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1405", "text": "In HIV, a synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 downregulates the expression of fatty acid binding protein 3 (FABP3) in peptide-treated PBMCs. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1406", "text": "H-FABP is a sensitive  biomarker  for  myocardial infarction [ 12 ] [ 13 ]  and can be detected in the blood within one to three hours of the pain."}
{"_id": "WikiPedia_Cardio$$$corpus_1407", "text": "The diagnostic potential of the biomarker H-FABP for heart injury was discovered in 1988 by Professor Jan Glatz (Maastricht, Netherlands). [ 14 ]   H-FABP is 20 times more specific to cardiac muscle than  myoglobin , [ 14 ]  it is found at 10-fold lower levels in skeletal muscle than heart muscle and the amounts in the kidney, liver and small intestine are even lower again. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1408", "text": "H-FABP is recommended to be measured with  troponin  to identify myocardial infarction and acute coronary syndrome in patients presenting with chest pain.  H-FABP measured with troponin shows increased sensitivity of 20.6% over troponin at 3\u20136 hours following chest pain onset. [ 17 ]    This sensitivity may be explained by the high concentration of H-FABP in myocardium compared to other tissues, the stability and solubility of H-FABP, its low molecular weight; 15kDa compared to 18, 80 and 37kDa for  MYO ,  CK-MB  and  cTnT  respectively, [ 18 ] [ 19 ] [ 20 ]  its rapid release into plasma after myocardial injury \u2013 60 minutes after an ischemic episode, [ 21 ]  and its relative tissue specificity. [ 22 ]   Similarly this study showed that measuring H-FABP in combination with troponin increased the diagnostic accuracy and with a negative predictive value of 98% could be used to identify those not suffering from MI at the early time point of 3\u20136 hours post chest pain onset. [ 17 ]  The effectiveness of using the combination of H-FABP with troponin to diagnose MI within 6 hours is well reported. [ 23 ] [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1409", "text": "In addition to its diagnostic potential, H-FABP also has prognostic value.  Alongside D-dimer, NT-proBNP and peak troponin T, it was the only cardiac biomarker that proved to be a statistically significant predictor of death or MI at one year.  This prognostic information was independent of troponin T, ECG and clinical examination. [ 24 ]    The risk associated with raised H-FABP is dependent upon its concentration. [ 26 ] [ 27 ]    Patients who were TnI  negative but  H-FABP positive had 17% increased risk of all cause mortality within one year compared to those patients who were TnI positive but H-FABP negative. [ 26 ]   Currently these TnI positive patients are prioritised for angioplasty, and the TnI negative patients are considered to be of a lower priority, yet the addition of the H-FABP test helps identify patients who are currently slipping through the net and allows physicians to more appropriately manage this hidden high risk group.  If both biomarkers were negative, there is 0% mortality at 6 months, in the authors own words this \u201crepresents a particularly worthwhile clinical outcome, especially because it was observed in patients admitted into hospital for suspected ACS.\u201d  H-FABP indicates risk across the ACS spectrum including UA, NSTEMI or STEMI where low H-FABP concentrations confer low risk whereas high H-FABP concentrations indicate patients who are at a much higher risk of future events. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1410", "text": "H-FABP has been proven to significantly predict 30-day mortality in acute  pulmonary embolism . [ 28 ]   H-FABP is more effective than Troponin T in risk stratifying Chronic Heart Failure patients. [ 29 ]   H-FABP is beginning to create interest with researchers who have found emerging evidence that indicates a role in differentiating between different neurodegenerative diseases. [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1411", "text": "To obtain diagnostic and prognostic information a precise and fully quantitative measurement of H-FABP is required. Commercial tests include a Cardiac Array on Evidence MultiStat; and an automated biochemistry assay  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1412", "text": "Heart: A History  is a 2018 book by  Sandeep Jauhar . In the book Jauhar discusses the historical experiments and procedures done in the past and how innovations can be taken for granted. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1413", "text": "The book begins with Jauhar discussing his personal health and family history, focusing on heart-related issues. He gives his opinion and talks about the advances in technology that have come about in the past few decades and how they have shaped the way doctors practice  cardiology  today.  Jauhar also discusses the old views that people had about the heart and why this was the last organ that was operated upon due to cultural perspectives and the level of difficulty.  He further notes several of his personal experiences as a cardiologist and states that the heart is still the center of attention of the body. Jauhar mentions research and experiments conducted on animals and humans, which he sees as unethical by modern standards while stating that without them society would not have the experience or procedures that are currently used."}
{"_id": "WikiPedia_Cardio$$$corpus_1414", "text": "Jauhar also covers the effects of emotions on the heart and how he believes stressors can significantly damage a person's heart. He states that doctors have lowered the risk of dying from a heart attack in a hospital to 3 percent, which he does not believe can be improved much further. He notes the difficulty for physicians to help patients prevent common stressors and that it has become easy to prescribe medicine for cholesterol. Finally, Jauhar advises that  yoga , meditation, and activities that help emotions should be taught in schools and the medical field."}
{"_id": "WikiPedia_Cardio$$$corpus_1415", "text": "Critical reception for the book has been positive, [ 2 ] [ 3 ] [ 4 ]  and received reviews from  The New Statesman ,  The Globe and Mail ,  and  Financial Express . [ 5 ] [ 6 ] [ 7 ]   The Washington Post  and  Business Standard  both wrote favorable reviews, with the former stating that it was \"a fascinating education for those of us who harbor this most hallowed organ but know little about it.\u201d [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1416", "text": "HeartScore  is a cardiovascular disease risk assessment and management tool developed by the  European Society of Cardiology , aimed at supporting clinicians in optimising individual cardiovascular risk reduction."}
{"_id": "WikiPedia_Cardio$$$corpus_1417", "text": "HeartScore is the interactive version of SCORE - Systematic COronary Risk Evaluation  [ 1 ]  - a cardiovascular disease risk assessment system initiated by the European Society of Cardiology, using data from 12 European cohort studies (N=205,178) covering a wide geographic spread of countries at different levels of cardiovascular risks. The SCORE data contains some 3-million person-years of observation and 7,934 fatal cardiovascular events. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1418", "text": "The SCORE risk estimation is based on the following risk factors:  gender ,  age ,  smoking ,  systolic blood pressure , total  cholesterol , and estimates fatal  cardiovascular disease  events over a ten-year period. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1419", "text": "HeartScore is one of the tools developed to implement the  2007 European guidelines on CVD prevention in clinical practice . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1420", "text": "In addition to two European versions for high/low risk countries, HeartScore now counts 13 national versions. HeartScore Sweden was the first national version to be launched in 2005, followed by versions in Germany, Greece, Poland, Spain, Cyprus, Slovakia, Czech Republic and Turkey. Translated versions now exist in Bosnia and Herzegovina, Russia, Romania and Croatia. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1421", "text": "A roll-out plan of additional national versions has been defined for 2009\u20132010 within the framework of the EuroHeart Programme of the European Commission and according to countries specific requests. Further updates will be produced as knowledge evolves (new cohort studies, risk factors, end points) [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1422", "text": "Three formats have been developed to cater for different users\u2019 needs:  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1423", "text": "The  hexaxial reference system , better known as the  Cabrera system , is a convention to present the extremity leads of the 12 lead  electrocardiogram , [ 1 ]  that provides an illustrative logical sequence that helps interpretation of the ECG, especially to determine the heart's electrical axis in the frontal plane.\nThe most practical way of using this is by arranging extremity leads according to the Cabrera system, reversing polarity of lead aVR and presenting ECG complexes in the order (aVL, I, -aVR, II, aVF, III). Then determine the direction the maximal ECG vector is \"pointing\", i.e. in which lead there are most positive amplitude - this direction is the electrical axis - see diagram.\nExample: If lead I has the highest amplitude (higher than aVL or -aVR), the axis is approximately 0\u00b0.\nConversely, if lead III has the most negative amplitude it means the vector is pointing away from this lead, i.e. towards -60\u00b0. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1424", "text": "An alternative use is to locate the most isoelectric (or equiphasic) [ clarification needed ]  lead (I, II, III, aVR, aVL, or aVF) on a diagnostic quality  ECG  with proper lead placement. Then find the corresponding spoke on the hexaxial reference system. The perpendicular spoke will point to the heart's electrical axis. To determine which numerical value should be used, observe the polarity of the perpendicular lead on the  ECG . [ clarification needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1425", "text": "For example, if the most isoelectric (or equiphasic) lead is aVL, the perpendicular lead on the hexaxial reference system is lead II. If lead II is positively deflected on the  ECG , the heart's electrical axis in the frontal plane will be approximately +60\u00b0."}
{"_id": "WikiPedia_Cardio$$$corpus_1426", "text": "High-density lipoprotein  ( HDL ) is one of the five major groups of  lipoproteins . [ 1 ]  Lipoproteins are complex particles composed of multiple proteins which transport all  fat  molecules ( lipids ) around the body within the water outside cells. They are typically composed of 80\u2013100 proteins per particle (organized by one, two or three  ApoA ). HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1427", "text": "Lipoproteins are divided into five subgroups, by density/size (an inverse relationship), which also correlates with function and incidence of cardiovascular events. Unlike the larger lipoprotein particles, which deliver fat molecules to cells, HDL particles remove fat molecules from cells. The lipids carried include  cholesterol ,  phospholipids , and  triglycerides , amounts of each are variable. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1428", "text": "Increasing concentrations of HDL particles are associated with decreasing accumulation of  atherosclerosis  within the walls of arteries, [ 4 ]  reducing the risk of  sudden plaque ruptures ,  cardiovascular disease ,  stroke  and other  vascular diseases . [ 2 ]  HDL particles are commonly referred to as \"good cholesterol\", because they transport fat molecules out of artery walls, reduce  macrophage  accumulation, and thus help prevent or even regress atherosclerosis. [ 5 ]  Higher HDL-C may not necessarily be protective against cardiovascular disease and may even be harmful in extremely high quantities, [ 6 ]  with an increased cardiovascular risk, especially in hypertensive patients. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1429", "text": "Because of the high cost of directly measuring HDL and LDL ( low-density lipoprotein ) protein particles,  blood tests  are commonly performed for the surrogate value, HDL-C, i.e. the cholesterol associated with  ApoA-1 /HDL particles. In healthy individuals, about 30% of blood cholesterol, along with other fats, is carried by HDL. [ 5 ]  This is often contrasted with the amount of cholesterol estimated to be carried within low-density lipoprotein particles,  LDL , and called LDL-C. HDL particles remove fats and cholesterol from cells, including within  artery  wall  atheroma , and transport it back to the liver for excretion or re-utilization; thus the cholesterol carried within HDL particles (HDL-C) is sometimes called \"good cholesterol\" (despite being the same as cholesterol in LDL particles). Those with higher levels of HDL-C tend to have fewer problems with  cardiovascular diseases , while those with low HDL-C cholesterol levels (especially less than 40\u00a0mg/dL or about 1\u00a0mmol/L) have increased rates for heart disease. [ 8 ] [ needs update ]  Higher native HDL levels are correlated with lowered risk of cardiovascular disease in healthy people. [ 9 ] [ needs update ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1430", "text": "The remainder of the serum cholesterol after subtracting the HDL is the  non-HDL cholesterol . The concentration of these other components, which may cause  atheroma , is known as the  non-HDL-C . This is now preferred to LDL-C as a secondary marker as it has been shown to be a better predictor and it is more easily calculated. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1431", "text": "With a size ranging from 5 to 17\u00a0nm, HDL is the smallest of the  lipoprotein  particles. [ 2 ]  It is the densest because it contains the highest proportion of  protein  to  lipids . [ 2 ]  Its most abundant  apolipoproteins  are  apo A-I  and  apo A-II . A rare genetic variant,  ApoA-1 Milano , has been documented to be far more effective in both protecting against and regressing arterial disease,  atherosclerosis ."}
{"_id": "WikiPedia_Cardio$$$corpus_1432", "text": "The liver synthesizes these lipoproteins as complexes of apolipoproteins and phospholipid, which resemble cholesterol-free flattened spherical lipoprotein particles, [ 2 ]  whose NMR structure was published; [ 11 ]  the complexes are capable of picking up cholesterol, carried internally, from cells by interaction with the  ATP-binding cassette transporter A1 (ABCA1) . [ 12 ]  A  plasma  enzyme called  lecithin-cholesterol acyltransferase  (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of the lipoprotein particle, eventually causing the newly synthesized HDL to assume a spherical shape. HDL particles increase in size as they circulate through the blood and incorporate more cholesterol and phospholipid molecules from cells and other lipoproteins, such as by interaction with the  ABCG1  transporter and the  phospholipid transport protein (PLTP) . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1433", "text": "HDL transports cholesterol mostly to the  liver  or  steroidogenic organs  such as  adrenals ,  ovary , and  testes  by both direct and indirect pathways. HDL is removed by HDL receptors such as  scavenger receptor BI  (SR-BI), which mediate the selective uptake of cholesterol from HDL. In humans, probably the most relevant pathway is the indirect one, which is mediated by  cholesteryl ester transfer protein (CETP) . [ 2 ]  This protein exchanges triglycerides of  VLDL  against cholesteryl esters of HDL. As the result, VLDLs are processed to  LDL , which are removed from the circulation by the  LDL receptor  pathway. The triglycerides are not stable in HDL, but are degraded by  hepatic lipase  so that, finally, small HDL particles are left, which restart the uptake of cholesterol from cells. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1434", "text": "The cholesterol delivered to the liver is excreted into the  bile  and, hence,  intestine  either directly or indirectly after conversion into  bile acids . Delivery of HDL cholesterol to adrenals, ovaries, and testes is important for the synthesis of  steroid hormones . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1435", "text": "Several steps in the metabolism of HDL can participate in the transport of cholesterol from lipid-laden  macrophages  of  atherosclerotic   arteries , termed  foam cells , to the liver for secretion into the bile. This pathway has been termed  reverse cholesterol transport  and is considered as the classical protective function of HDL toward atherosclerosis."}
{"_id": "WikiPedia_Cardio$$$corpus_1436", "text": "HDL carries many lipid and protein species, several of which have very low concentrations but are biologically very active. For example, HDL and its protein and lipid constituents help to inhibit  oxidation ,  inflammation ,  activation of the endothelium ,  coagulation , and  platelet aggregation . All these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is not yet known which are the most important. In addition, a small subfraction of HDL lends protection against the protozoan parasite  Trypanosoma brucei  brucei . This HDL subfraction, termed trypanosome lytic factor (TLF), contains specialized proteins that, while very active, are unique to the TLF molecule. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1437", "text": "In the  stress response ,  serum amyloid A , which is one of the  acute-phase proteins  and an apolipoprotein, is under the stimulation of  cytokines  ( interleukin 1 ,  interleukin 6 ), and  cortisol  produced in the  adrenal cortex  and carried to the damaged tissue incorporated into HDL particles. At the inflammation site, it attracts and activates leukocytes. In chronic inflammations, its deposition in the tissues manifests itself as  amyloidosis ."}
{"_id": "WikiPedia_Cardio$$$corpus_1438", "text": "It has been postulated that the concentration of large HDL particles more accurately reflects protective action, as opposed to the concentration of total HDL particles. [ 14 ]  This ratio of large HDL to total HDL particles varies widely and is measured only by more sophisticated lipoprotein assays using either  electrophoresis  (the original method developed in the 1970s) or newer  NMR spectroscopy  methods (See also  nuclear magnetic resonance  and  spectroscopy ), developed in the 1990s."}
{"_id": "WikiPedia_Cardio$$$corpus_1439", "text": "Five subfractions of HDL have been identified.  From largest (and most effective in cholesterol removal) to smallest (and least effective), the types are 2a, 2b, 3a, 3b, and 3c. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1440", "text": "Men tend to have noticeably lower HDL concentrations, with smaller size and lower cholesterol content, than women. Men also have a greater incidence of  atherosclerotic  heart disease. Studies confirm the fact that HDL has a buffering role in balancing the effects of the hypercoagulable state in type 2 diabetics and decreases the high risk of cardiovascular complications in these patients. Also, the results obtained in this study revealed that there was a significant negative correlation between HDL and  activated partial thromboplastin time  (APTT). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1441", "text": "Epidemiological studies have shown that high concentrations of HDL (over 60\u00a0mg/dL) have protective value against  cardiovascular diseases  such as ischemic stroke and  myocardial infarction . Low concentrations of HDL (below 40\u00a0mg/dL for men, below 50\u00a0mg/dL for women) increase the risk for  atherosclerotic  diseases. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1442", "text": "Data from the landmark  Framingham Heart Study  showed that, for a given level of LDL, the risk of heart disease increases 10-fold as the HDL varies from high to low. On the converse, however, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1443", "text": "Even people with very low LDL levels achieved by  statin  treatment are exposed to increased risk if their HDL levels are not high enough. [ 19 ] [ non-primary source needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1444", "text": "Clinical laboratories formerly measured HDL cholesterol by separating other lipoprotein fractions using either ultracentrifugation or chemical precipitation with divalent ions such as Mg 2+ , then coupling the products of a cholesterol oxidase reaction to an indicator reaction. The reference method still uses a combination of these techniques. [ 20 ]  Most laboratories now use automated homogeneous analytical methods in which lipoproteins containing  apo B  are blocked using antibodies to apo B, then a  colorimetric  enzyme reaction measures cholesterol in the non-blocked HDL particles. [ 21 ]   HPLC  can also be used. [ 22 ]  Subfractions (HDL-2C, HDL-3C) can be measured, [ 23 ]  but clinical significance of these subfractions has not been determined. [ 24 ]   The measurement of apo-A reactive capacity can be used to measure HDL cholesterol but is thought to be less accurate. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1445", "text": "The  American Heart Association ,  NIH  and  NCEP  provide a set of guidelines for fasting HDL levels and risk for  heart disease . [ 25 ] [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1446", "text": "High LDL with low HDL level is an additional risk factor for cardiovascular disease. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1447", "text": "As technology has reduced costs and clinical trials have continued to demonstrate the importance of HDL, [ 29 ]  methods for directly measuring HDL concentrations and size (which indicates function) at lower costs have become more widely available and increasingly regarded as important for assessing individual risk for progressive  arterial disease  and treatment methods. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1448", "text": "Since the HDL particles have a net negative charge and vary by density & size, ultracentrifugation combined with  electrophoresis  have been utilized since before 1950 to enumerate the concentration of HDL particles and sort them by size with a specific volume of blood plasma. Larger HDL particles are carrying more cholesterol."}
{"_id": "WikiPedia_Cardio$$$corpus_1449", "text": "Concentration and sizes of lipoprotein particles can be estimated using  nuclear magnetic resonance  fingerprinting. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1450", "text": "The HDL particle concentrations are typically categorized by event rate percentiles based on the people participating and being tracked in the MESA [ 31 ]  trial, a medical research study sponsored by the United States National Heart, Lung, and Blood Institute."}
{"_id": "WikiPedia_Cardio$$$corpus_1451", "text": "The lowest incidence of atherosclerotic events over time occurs within those with both the highest concentrations of total HDL particles (the top quarter, >75%) and the highest concentrations of large HDL particles. Multiple additional measures, including LDL particle concentrations, small LDL particle concentrations, VLDL concentrations, estimations of  insulin resistance  and standard cholesterol lipid measurements (for comparison of the plasma data with the estimation methods discussed above) are routinely provided in clinical testing."}
{"_id": "WikiPedia_Cardio$$$corpus_1452", "text": "While higher HDL levels are correlated with lower risk of cardiovascular diseases, no medication used to increase HDL has been proven to improve health. [ 2 ] [ 32 ]  As of 2017, numerous lifestyle changes and drugs to increase HDL levels were under study. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1453", "text": "HDL lipoprotein particles that bear  apolipoprotein C3  are associated with increased, rather than decreased, risk for  coronary heart disease . [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1454", "text": "Certain changes in diet and exercise may have a positive impact on raising HDL levels: [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1455", "text": "Most  saturated fats  increase HDL cholesterol to varying degrees but also raise total and LDL cholesterol. [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1456", "text": "HDL levels can be increased by  smoking cessation , [ 40 ]  or mild to moderate  alcohol  intake. [ 49 ] [ 50 ] [ 51 ] [ 52 ] [ 53 ] [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1457", "text": "Cannabis  in unadjusted analyses, past and current cannabis use was not associated with higher HDL-C levels. [ 55 ]   A study performed in 4635 patients demonstrated no effect on the HDL-C levels (P=0.78) [the mean (standard error) HDL-C values in control subjects (never used), past users and current users were 53.4 (0.4), 53.9 (0.6) and 53.9 (0.7) mg/dL, respectively]. [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1458", "text": "Exogenous  anabolic androgenic steroids , particularly  17\u03b1-alkylated anabolic steroids  and others administered orally, can reduce HDL-C by 50 percent or more. [ 56 ]  Other  androgen receptor  agonists such as  selective androgen receptor modulators  can also lower HDL. As there is some evidence that the HDL reduction is caused by increased  reverse cholesterol transport , it is unknown if AR agonists' HDL-lowering effect is pro- or anti-atherogenic. [ 57 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1459", "text": "Pharmacological therapy  to increase the level of HDL cholesterol includes use of  fibrates  and  niacin . Fibrates have not been proven to have an effect on overall deaths from all causes, despite their effects on lipids. [ 58 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1460", "text": "Niacin  (nicotinic acid, a form of  vitamin B3 ) increases HDL by selectively inhibiting hepatic  diacylglycerol acyltransferase  2, reducing  triglyceride  synthesis and  VLDL  secretion through a receptor HM74 [ 59 ]  otherwise known as   niacin receptor 2  and HM74A / GPR109A, [ 60 ]   niacin receptor 1 ."}
{"_id": "WikiPedia_Cardio$$$corpus_1461", "text": "Pharmacologic (1- to 3-gram/day) niacin doses increase HDL levels by 10\u201330%, [ 61 ]  making it the most powerful agent to increase HDL-cholesterol. [ 62 ] [ 63 ]  A randomized clinical trial demonstrated that treatment with niacin can significantly reduce atherosclerosis progression and cardiovascular events. [ 64 ]  Niacin products sold as \"no-flush\",  i.e.  not having side-effects such as \"niacin  flush \", do not, however, contain free nicotinic acid and are therefore ineffective at raising HDL, while products sold as \"sustained-release\" may contain free nicotinic acid, but \"some brands are hepatotoxic\"; therefore the recommended form of niacin for raising HDL is the cheapest, immediate-release preparation. [ 65 ]  Both fibrates and niacin increase artery toxic  homocysteine , an effect that can be counteracted by also consuming a multivitamin with relatively high amounts of the B-vitamins, but multiple European trials of the most popular B-vitamin cocktails, trial showing 30% average reduction in homocysteine, while not showing problems have also not shown any benefit in reducing cardiovascular event rates.  A 2011 extended-release niacin (Niaspan) study was halted early because patients adding niacin to their statin treatment showed no increase in heart health, but did experience an increase in the risk of stroke. [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1462", "text": "In contrast, while the use of  statins  is effective against high levels of LDL cholesterol, most have little or no effect in raising HDL cholesterol. [ 62 ]   Rosuvastatin  and  pitavastatin , however, have been demonstrated to significantly raise HDL levels. [ 67 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1463", "text": "Lovaza  has been shown to increase HDL-C. [ 68 ]  However, the best evidence to date suggests it has no benefit for primary or secondary prevention of cardiovascular disease."}
{"_id": "WikiPedia_Cardio$$$corpus_1464", "text": "The  PPAR  modulator  GW501516  has shown a positive effect on HDL-C [ 69 ]  and an antiatherogenic where LDL is an issue. [ 70 ]  However, research on the drug has been discontinued after it was discovered to cause rapid cancer development in several organs in rats. [ 71 ] [ 72 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1465", "text": "The  history of invasive and interventional cardiology  is complex, with multiple groups working independently on similar technologies.  Invasive and interventional  cardiology  is currently closely associated with cardiologists ( physicians  who treat the diseases of the  heart ), though the development and most of its early research and procedures were performed by diagnostic and interventional  radiologists ."}
{"_id": "WikiPedia_Cardio$$$corpus_1466", "text": "The history of invasive cardiology begins with the development of  cardiac   catheterization  in 1711, when  Stephen Hales  placed catheters into the  right  and  left ventricles  of a living horse. [ 1 ]  Variations on the technique were performed over the subsequent century, with formal study of cardiac physiology being performed by  Claude Bernard  in the 1840s. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1467", "text": "The technique of angiography itself was first developed in 1927 by the Portuguese physician  Egas Moniz  at the  University of Lisbon  for cerebral angiography, the viewing of brain vasculature by X-ray radiation with the aid of a contrast medium introduced by catheter.  Cardiac catheterization was first performed when  Werner Forssmann , in 1929, created an incision in one of his left  antecubital  veins and inserted a catheter into his venous system.  He then guided the catheter by  fluoroscopy  into his right atrium.  Subsequently, he walked up a flight of stairs to the radiology department and documented the procedure by having a  chest roentgenogram  performed. [ 3 ]   Over the next year, catheters were placed in a similar manner into the right ventricle, and measurements of pressure and  cardiac output  (using the  Fick principle ) were performed. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1468", "text": "In the early 1940s,  Andr\u00e9 Cournand , in collaboration with  Dickinson Richards , performed more systematic measurements of the  hemodynamics  of the heart. [ 5 ]   For their work in the discovery of cardiac catheterization and hemodynamic measurements, Cournand, Forssmann, and Richards shared the  Nobel Prize in Physiology or Medicine  in 1956. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1469", "text": "In 1958,  Interventional Radiologist , Dr.  Charles Dotter  began working on methods to visualize the coronary anatomy via sequential radiographic films.  He invented a method known as occlusive aortography in an animal model.  Occlusive aortography involved the transient occlusion of the aorta and subsequent injection of a small amount of radiographic contrast agent into the aortic root and subsequent serial x-rays to visualize the coronary arteries. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1470", "text": "Later that same year, while performing an aortic root  aortography ,  Mason Sones , a pediatric cardiologist at the  Cleveland Clinic , noted that the catheter had accidentally entered the patient's right coronary artery.  Before the catheter could be removed, 30cc of  contrast agent  had been injected. [ 8 ]   While the patient went into  ventricular fibrillation , the dangerous arrhythmia was terminated by Dr. Sones promptly performing a  precordial thump  which restored sinus rhythm."}
{"_id": "WikiPedia_Cardio$$$corpus_1471", "text": "Until the 1950s, placing a catheter into either the arterial or venous system involved a \"cut down\" procedure, in which the soft tissues were dissected out of the way until the artery or vein was directly visualized and subsequently punctured by a catheter; this was known as the Sones technique.  The  percutaneous  approach that is widely used today was developed by radiologist  Sven-Ivar Seldinger  in 1953. [ 9 ] [ 10 ]  Percutaneous access of the artery or vein is still commonly known as the  Seldinger technique .  The use of the Seldinger technique for visualizing the coronary arteries was described by Ricketts and Abrams in 1962 and Judkins in 1967. [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1472", "text": "By the late 1960s,  Melvin Judkins  had begun work on creating catheters that were specially shaped to reach the coronary arteries to perform selective coronary angiography.  His initial work involved shaping stiff wires and comparing those shapes to radiographs of the ascending aorta to determine if the shape appeared promising.  Then he would place the stiff wire inside a flexible catheter and use a  heat-fixation  method to permanently shape the catheter.  In the first use of these catheters in humans, each catheter was specifically shaped to match the size and shape of the aorta of the subject.  His work was documented in 1967, and by 1968 the Judkins catheters were manufactured in a limited number of fixed tip shapes. [ 13 ]   Catheters in these shapes carry his name and are still used to this day for selective coronary angiography."}
{"_id": "WikiPedia_Cardio$$$corpus_1473", "text": "The use of tapered Teflon dilating catheters for the treatment of atherosclerotic vascular disease was first described in 1964 by two interventional radiologists, Charles Dotter and Melvin Judkins, when they used it to treat a case of atherosclerotic disease in the  superficial femoral artery  of the left leg. [ 14 ] [ 15 ]   Building on their work and his own research involving balloon-tipped catheters,  Andreas Gruentzig  performed the first success percutaneous transluminal coronary angioplasty (known as PTCA or percutaneous coronary intervention (PCI)) on a human on September 16, 1977 at University Hospital, Zurich. [ 16 ]   The results of the procedure were presented at the  American Heart Association  meeting two months later to a stunned audience of cardiologists.  In the subsequent three years, Dr. Gruentzig performed coronary angioplasties in 169 patients in Zurich, while teaching the practice of coronary angioplasty to a field of budding  interventional cardiologists .  Ten years later, nearly 90 percent of these individuals were still alive. [ 16 ]   By the mid-1980s, over 300,000 PTCAs were being performed on a yearly basis, equalling the number of  bypass surgeries  being performed for coronary artery disease. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1474", "text": "Soon after Andreas Gruentzig began performing percutaneous interventions on individuals with stable coronary artery disease, multiple groups described the use of catheter-delivered  streptokinase  for the treatment of  acute myocardial infarction  (heart attack). [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1475", "text": "From the time of the initial percutaneous balloon angioplasty, it was theorized that devices could be placed inside the arteries as scaffolds to keep them open after a successful balloon angioplasty. [ 14 ]   This did not become a reality in the cardiac realm until  the first intracoronary  stents  were successfully deployed in coronary arteries in 1986. [ 20 ] [ 21 ]   The first stents used were self-expanding Wallstents.  The use of intracoronary stents was quickly identified as a method to treat some complications due to PTCA, [ 20 ]  and their use can decrease the incidence of emergency bypass surgery for acute complications post balloon angioplasty. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1476", "text": "It was quickly realized that restenosis rates were significantly lower in individuals who received an intracoronary stent when compared to those who underwent just balloon angioplasty. [ 23 ]   A damper on the immediate use of intracoronary stents was subacute  thrombosis .  Subacute thrombosis rates with intracoronary stents proved to be about 3.7 percent, higher than the rates seen after balloon angioplasty. [ 21 ]   Post-procedure bleeding was also an issue, due to the intense combination of  anticoagulation  and  anti-platelet agents  used to prevent stent thrombosis. [ medical citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1477", "text": "Stent technology improved rapidly, and in 1989 the Palmaz-Schatz balloon-expandable intracoronary stent was developed. [ 24 ] [ 25 ]   Initial results with the Palmaz-Schatz stents were excellent when compared to balloon angioplasty, with a significantly lower incidence of abrupt closure and peri-procedure heart attack. [ 26 ]   Late restenosis rates with Palmaz-Schatz stents were also significantly improved when compared with balloon angioplasty. [ 27 ] [ 28 ]   However,  mortality  rates were unchanged compared to balloon angioplasty. [ 29 ]   While the rates of subacute thrombosis and bleeding complications associated with stent placement were high, by 1999 nearly 85% of all PCI procedures included intracoronary stenting. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1478", "text": "In recognition of the focused training required by cardiologists to perform percutaneous coronary interventions and the rapid progression in the field of percutaneous coronary interventions, specialized fellowship training in the field of Interventional Cardiology was instituted in 1999. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1479", "text": "Through the 1990s and beyond, various incremental improvements were made in balloon and stent technology, as well as newer devices, some of which are still in use today while many more have fallen into disuse.  As important as balloon and stent technology had been, it was becoming obvious that the anticoagulation and anti-platelet regimen that individuals received post-intervention was at least as important.  Trials in the late 1990s revealed that anticoagulation with  warfarin  was not required post balloon angioplasty or stent implantation, while intense anti-platelet regimens and changes in procedural technique (most importantly, making sure that the stent was well opposed to the walls of the coronary artery) improved short term and long term outcomes. [ 31 ]   Many different antiplatelet regimens were evaluated in the 1990s and the turn of the 21st century, with the optimal regimen in an individual patient still being up for debate."}
{"_id": "WikiPedia_Cardio$$$corpus_1480", "text": "With the high use of intracoronary stents during PCI procedures, the focus of treatment changed from procedural success to prevention of recurrence of disease in the treated area (in-stent restenosis). By the late 1990s, it was generally acknowledged among cardiologists that the incidence of in-stent restenosis was between 15 and 30%, and possibly higher in certain subgroups of individuals. [ 30 ]  Stent manufacturers experimented with (and continue to experiment with) a number of chemical agents to prevent the neointimal hyperplasia that is the cause of in-stent restenosis. [ medical citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1481", "text": "One of the first products of the new focus on preventing late events (such as in stent restenosis and late thrombosis) was the  heparin -coated Palmaz-Schatz stent. [ 32 ]   These coated stents were found to have a lower incidence of subacute thrombosis than bare metal stents. [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1482", "text": "At approximately the same time,  Cordis  (a division of  Johnson & Johnson ) was developing the  Cypher stent , a stent that would release  sirolimus  (a chemotherapeutic agent) over time.  The first study of these individuals revealed an incredible lack of restenosis (zero percent restenosis) at six months. [ 34 ]   This led to the approval for the stent to be used in Europe in April 2002. [ 35 ]   Further trials with the Cypher stent revealed that restenosis did occur in some individuals with high risk features (such as long areas of stenosis or a history of  diabetes mellitus ), but that the restenosis rate was significantly lower than with bare metal stents (3.2 percent compared to 35.4 percent). [ 36 ]   About a year after approval in Europe, the United States  FDA  approved the use of the Cypher stent as the first  drug-eluting stent  for use in the general population in the United States. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1483", "text": "Concurrent with the development of the Cypher stent,  Boston Scientific  started development of the  Taxus stent .  The Taxus stent was the Express2 metal stent, which was in general use for a number of years, [ 38 ]  with a  copolymer  coating of  paclitaxel  that inhibited cell replication.  As with the Cypher stent before it, the first trials of the Taxus stent revealed no evidence of in-stent restenosis at six months after the procedure, [ 39 ]  while later studies showed some restenosis, at a rate much lower than the bare metal counterpart. [ 40 ]  With further study, [ 41 ]  the FDA approved the use of the Taxus stent in the United States in March 2004. [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1484", "text": "By the end of 2004, drug-eluting stents were used in nearly 80 percent of all percutaneous coronary interventions. [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1485", "text": "Another source of controversy in the field of interventional cardiology has been the overlapping roles of PCI and coronary artery bypass surgery for individuals with coronary artery disease compared to the role of intense pharmacologic therapy.  This area has been studied in a number of trials since the early 1990s. [ 44 ] [ 45 ] [ 46 ]  With rapid changes in techniques occurring in both bypass surgery as well as PCI, multiple studies have been conducted with the hope of identifying which individuals do better with PCI and which do better with  coronary artery bypass graft  (CABG) surgery. [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1486", "text": "Several of these studies evaluate the effectiveness of newer techniques, such as  fractional flow reserve  (FFR), and suggest PCI can frequently improve outcomes for patients with clinically significant coronary atherosclerosis. [ 48 ]  The  FAME study  found that the primary endpoint of death, nonfatal myocardial infarction, and repeat revascularization were 5.1% lower after one year in patients whose care was guided by FFR. [ 49 ]  Benefits from PCI have also been shown for those having a heart attack ( ST elevation myocardial infarction , or STEMI), those having a heart attack without EKG changes ( non-ST elevation myocardial infarction , or NSTEMI), and those with angina that is not being controlled with medication. [ 50 ]  In general, each case is individualized to the patient and the relative comfort level of their interventional cardiologist and cardiothoracic surgeon."}
{"_id": "WikiPedia_Cardio$$$corpus_1487", "text": "At the 2007 meeting of the  American College of Cardiology  (ACC), data from the COURAGE trial was presented, suggested that the combination of PCI and intensive (optimal) medical therapy did not reduce the incidence of death, heart attacks, or stroke compared to intensive medical therapy alone. [ 51 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1488", "text": "Research conducted since 2007 has documented ways in which PCI can be an effective treatment in specific instances. Data analysis of COURAGE trial results showed an incremental benefit for patients during the first 12-24 months following treatment using PCI, specifically regarding frequency of angina, physical limitations, and quality-of-life factors. [ 52 ]  Results from a 2019 trial did not show evidence that an initial invasive strategy reduced the risk of ischemic cardiovascular events or death from any cause. However, they did show that for patients with angina, an initial invasive strategy led to more effective relief of angina symptoms, [ 53 ]  and that PCI reduced the risk of spontaneous myocardial infarction when compared with initial conservative management. [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1489", "text": "When results from the first trials of drug-eluting stents were published, there was a general feeling in the interventional cardiology community that these devices would be part of the perfect revascularization regimen for coronary artery disease. With the very low restenosis rates of the RAVEL [ 34 ]  and SIRIUS [ 36 ]  trials, interventions were performed on more complex blockages in the coronary arteries under the assumption that real-life results would mimic the results from the trials. Based on early trials, the advised antiplatelet regimen for drug-eluting stents was a combination of  aspirin  and  clopidogrel  for 3 months when Cypher stents were used, [ 36 ]  and 9 months when Taxus stents were used, [ 55 ]  followed by aspirin indefinitely."}
{"_id": "WikiPedia_Cardio$$$corpus_1490", "text": "Soon, case reports started being published regarding late stent thrombosis. [ 56 ]   At the 2006 ACC annual meeting, preliminary results from the BASKET-LATE trial were presented, which showed a slight increase in late thrombosis associated with drug-eluting stents over bare metal stents. [ 57 ]   However, this increase was not statistically significant, and further data would have to be collected.  Additional data published over the following year had conflicting results, [ 58 ]  making it unclear whether stent thrombosis was truly higher when compared to bare metal stents.  During this time of uncertainty, many cardiologists started extending the dual antiplatelet regimen of aspirin and clopidogrel in individuals with drug-eluting stents, as some data suggested it may prevent late thrombosis. [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1491", "text": "The  FDA Center for Devices and Radiological Health  held a Circulatory System Devices Panel in December 2006 to review data presented by Cordis and Boston Scientific to determine if drug-eluting stents should be considered less safe than bare metal stents. [ 60 ]   It became evident at the meeting that with all the data published, there were varied definitions of late thrombosis and key differences in the types of lesions in different studies, hampering analysis of the data. [ 43 ]   It was also noted that with the advent of drug-eluting stents, interventional cardiologists had started performing procedures on more complex lesions, subsequently using the stents in \"off label\" coronary artery lesions that would otherwise go untreated, or for  bypass surgery . [ 43 ]   The FDA advisory board reiterated the ACC guidelines that clopidogrel should be continued for 12 months after drug-eluting stent placement in individuals who are at low risk for bleeding. [ 61 ] [ 62 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1492", "text": "Since 2006, technology advancements for drug-eluting stents have led to safety improvements. More recent analysis of clinical data note drug-eluting stents can be safely used and can lead to more effective reduction in stent thrombosis than bare metal stents. [ 63 ]  According to a 2018 data analysis, using drug-eluting stents in coronary intervention lowered risk of myocardial infarction, ischemia-driven target lesion revascularization, target vessel revascularization, and stent thrombosis in the first month following stenting. [ 64 ]  Newer generations of drug-eluting stents have been found to reduce the risk of restenosis, myocardial infarction, and death when compared with bare-metal stents. [ 65 ]  Advancements in stent design that include reducing strut thickness have shown further improvements for patients compared to previous generations. [ 65 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1493", "text": "A 2021 study noting a lack of age-specific recommendations for elderly patients with ischemic heart disease found a statistically significant decrease in major cardiovascular events when elderly patients were treated using drug-eluting stents. [ 66 ]  The findings led the study's authors to recommend drug-eluting stents over bare metal stents when treating the elderly. [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1494", "text": "HL7 aECG  (the  HL7  Annotated  Electrocardiogram ) is a standard medical record data format for storing and retrieving electrocardiogram data for a patient.  Like other HL7 formats, it is XML based."}
{"_id": "WikiPedia_Cardio$$$corpus_1495", "text": "The HL7 aECG standard was created in response to the  Food and Drug Administration \u2019s digital electrocardiogram initiative which was introduced November, 2001. [ 1 ]   The FDA initiative required ECG waveforms and annotations submitted to the FDA to have a standard format for the data. At the time, no current ECG waveform standards met all the FDA's needs. As a result, the FDA, sponsors, core laboratories, and device manufactures worked together within HL7 to create a standard to meet the FDA requirements."}
{"_id": "WikiPedia_Cardio$$$corpus_1496", "text": "The aECG standard was created by HL7's Regulated Clinical Research Information Management ( RCRIM ). It passed final balloting in January, 2004, and was accepted by ANSI May, 2004.\n [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1497", "text": "This  computer-storage -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1498", "text": "This  standards - or  measurement -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1499", "text": "Hurst's The Heart  is a  medical   textbook  published by  McGraw-Hill Education . First released in 1966, it is currently in its 15th edition. It covers the field of  cardiology  and is one of the most widely used medical textbooks in the world. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1500", "text": "The first edition of the book, titled  The Heart , was written in 1966 by  John Willis Hurst , who had served as the  cardiologist  of former U.S. President  Lyndon B. Johnson . In 1986, the book was renamed  Hurst's The Heart . [ 1 ]  It is currently in its 15th edition published as Fuster and Hurst's The Heart in June 2022."}
{"_id": "WikiPedia_Cardio$$$corpus_1501", "text": "Hurst's the Heart: Manual of Cardiology  provides a summary of the clinical content of its larger companion textbook. It features a streamlined, quick-access presentation designed for use in emergencies and urgent clinical situations. It is edited by Robert A O'Rourke. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1502", "text": "The book has been described as a \"widely read textbook of cardiology\", [ 3 ]  and a \"standard reference\" work. [ 4 ]  According to  The New York Times ,  Hurst's The Heart  has become one of the most widely used medical textbooks in the world. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1503", "text": "A  hybrid cardiac surgical procedure  in a narrow sense is defined as a procedure that combines a conventional, more invasive surgical part (including a skin incision) with an interventional part, using some sort of  catheter -based procedure guided by  fluoroscopy  (or other, e.g.,  CT  or  MRI ) imaging in a  hybrid operating room (OR)  without interruption. [ 1 ]  The hybrid technique has a reduced risk of surgical complications and has shown decreased recovery time. It can be used to treat numerous heart diseases and conditions and with the increasing complexity of each case, the hybrid surgical technique is becoming more common."}
{"_id": "WikiPedia_Cardio$$$corpus_1504", "text": "A hybrid cardiac surgery can be either a one-stage or two-stage procedure. The difference between the two is the extent of time elapsed between the two components of a hybrid surgery. A one-stage procedure is done in hybrid suite and requires a specialized operating room. In the two-stage procedure, there is a time gap between the catheter intervention and the surgical operation. The time between can vary by minutes or hours, and although unlikely, up to days and weeks. The two-stage procedure is typically done in different locations, beginning in a  catheterization laboratory  followed by a surgical operating room."}
{"_id": "WikiPedia_Cardio$$$corpus_1505", "text": "The first uses of the technical hybrid cardiac surgical procedures were done in the 1990's. However, there have been descriptions of such procedures earlier in the 1970's. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1506", "text": "There are no absolute contraindications to a hybrid cardiac surgery, and the precise circumstances which indicate a hybrid surgery would be most beneficial are uncertain. [ 3 ]   However, several factors should be considered when devising a care plan."}
{"_id": "WikiPedia_Cardio$$$corpus_1507", "text": "Regarding most cardiovascular diseases, high-risk and re-operative patients are ideal candidates for a hybrid surgery. [ 3 ]   Crucial factors to acknowledge are the complexity of the disease and the possible  comorbidities , such as advanced age,  obesity  and decreased pulmonary function. Cardiologists often use the  SYNTAX score  grading system to determine the complexity of the coronary artery disease and the possible surgical outcomes. Other deciding factors may include the patient's suitable vessels for grafting, body mass index,  radiographic contrast  allergies, and response to  antiplatelet therapies . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1508", "text": "Both components of a hybrid surgery have multiple uses and can be used independently to restore cardiac functions. Each component also has risks and complications associated."}
{"_id": "WikiPedia_Cardio$$$corpus_1509", "text": "Cardiac catheterization  is the insertion of a  catheter  into the heart through a blood vessel. The cardiac catheter can then be used to run tests and perform other procedures. Such procedures are  stent placement ,  angioplasty ,  fractional flow reserve ,  intravascular ultrasound (IVUS)  and  cardiac biopsy . [ 4 ]  Conditions indicating the need for a cardiac catheter include the following:  atherosclerosis ,  cardiomyopathy ,  congenital heart disease ,  heart failure , and  heart valve disease . [ 4 ]  The risks associated with cardiac catheterization are bleeding, bruising, pain, blood clot, blood vessel damage, or infection where the catheter was inserted,  heart arrhythmia ,  ischemia , sudden blockage of a  coronary artery , a tear in the lining of an  artery ,  kidney damage  or  stroke .  [ 4 ]  Many of the risks associated with catheterization are also risks when more invasive cardiac procedures are done. Hybrid surgeries involve many of the same risks applied and there is often concern about the success of antiplatelet therapy and bleeding postoperative."}
{"_id": "WikiPedia_Cardio$$$corpus_1510", "text": "Surgical  bypass grafting  and percutaneous coronary artery  revascularization  are traditionally considered isolated options. A simultaneous hybrid approach may allow an opportunity to match the best strategy for a particular anatomic  lesion . Thus  hybrid coronary revascularization  and MIDCAB ( minimally invasive direct coronary artery bypass surgery ) have been developed.  Revascularization  of the  left anterior descending artery  with the  left internal mammary artery  is by far the best treatment option in terms of long-term results. Integrating this therapy with percutaneous coronary  angioplasty  (hybrid procedure) offers multi-vessel revascularization through a  mini-thoracotomy . Particularly in high risk patients,  morbidity  and  mortality  decreases in comparison to conventional  surgery . [ medical citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1511", "text": "For people who undergo  coronary artery bypass grafting , coronary imaging (completion  angiography ) for the routine evaluation of the  bypass grafts  may be reasonable. During the hybrid procedure  angiographs  may be used to monitor and confirm  anastomosis . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1512", "text": "For  congenital  cardiac malformations, even though surgery remains the treatment of choice,  interventional cardiology  approaches are increasingly being used. However, such percutaneous approaches can be challenging or even impossible because of difficult and complex anatomies (such as double-outlet right ventricle, or transposition of the great arteries, acute turns or kinks in the pulmonary arteries of  tetralogy of Fallot  patients) and patient characteristics/ complications (low weight, poor vascular access, induced rhythm disturbances, hemodynamic compromise). [ 5 ] [ 6 ]  Nevertheless, surgery has its limitations, so that combining interventions and surgery into a single therapeutic procedure potentially leads to reduction of complexity,  cardiopulmonary bypass  time, risk, and to improved outcomes.\nAnother important concept in hybrid procedures is completion  angiography , as described above, which in the case of  congenital heart disease  surgery may detect residual structural lesions, thus reduce postoperative complications. Again, 3D imaging using  rotational angiography  should be the concept of choice. [ 7 ]  Completion angiography in a hybrid OR may even induce a reduction of  contrast media  and  ionizing radiation  dose applied to the patient, as it reduces the need for post-operative examination. [ 8 ]  Further dose reduction can be achieved with a combination of intraoperative  rotational angiography  and intraoperative  MRI , when both a fixed C-arm and an MRI system are available in the surgical theatre, and MRI adds functional information. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1513", "text": "The conventional approach for treatment of  aortic valve stenosis  is surgical replacement of the  aortic valve . This procedure has excellent outcomes particularly in younger patients at relatively low-risk and will remain the gold standard for aortic valve replacement in the upcoming years. However,  TAVI  (transcatheter aortic valve implantation) has emerged as a valid alternative for patients in whom conventional surgical techniques are considered too invasive and risky. To put this approach into practice, a hybrid operating room is strongly recommended by a number of professional associations, including the  European Society of Cardiology , the European Association of Cardio-thoracic Surgery, [ 10 ]  the German Society of Cardiology, and the German Society of Cardiac, Thoracic and Vascular Surgery."}
{"_id": "WikiPedia_Cardio$$$corpus_1514", "text": "The repair of a defected mitral valve is a potential future hybrid procedure, that is still dependent on approval of the necessary devices by the U.S.  Food and Drug Administration . Some of these devices also will most likely be used for procedures performed in regular  cath labs . Further prostheses for mitral und  tricuspid valve  replacement are under development and certainly will be available within the next years. Complex hybrid procedures may arise where the various parts of the mitral valve apparatus (e.g.  chordae ,  leaflet  and  ring ) are repaired on a beating heart in combination with purely interventional techniques (e.g. MitralClip). From an imaging modality perspective, fluoroscopy will most likely be combined with 2D and 3D  ultrasound  and a fusion of these modalities may become helpful. The reason is that the metal devices are optimally imaged without artifacts by fluoroscopy whereas the valve itself is better evaluated with  ultrasound . As an alternative to  transesophageal echocardiography , the use of intracardiac 2D and 3D echo may prove useful because it would allow avoiding  general anesthesia  in selected patients. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1515", "text": "For  aneurysms  of the  thoracic aorta ,  thoracic endovascular aortic repair  (TEVAR) has become a valid alternative to open repair. This method may even be applied to  pathologies  of the  aortic arch  and the  distal descending aorta . [ 12 ]  A common complication of  EVAR  are endoleaks. These may be missed by 2D angiographic evaluation. Rotational angiography, providing CT-like 3D imaging with the angiographic C-arm enables the surgeon to diagnose this complication intraoperatively and correct it right away.  An indication that a hybrid technique would be most beneficial and successful is that the patient has had a previous aortic repair. Patients with chronic dissecting aneurysms are not good candidates for the hybrid approach. In the hybrid one-stage procedure the graft can be check immediately after the placement of the stent.  [ 3 ]  In the hybrid two-stage procedure the total operation time is much shorter and decreases postoperative complications, however there is a risk that the aneurysm could rupture between the two stages. [ 3 ]  In cases where the hybrid technique was used to repair an aortic aneurysm complications that have been experiences are  permanent paraplegia , stroke,  spinal cord ischemia  and other neurological complications. [ 3 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1516", "text": "With regards to rhythm disturbances, in particular  atrial fibrillation  (AF), a hybrid procedure involves the combination of the surgical  epicardial  approach with the interventional  endocardial  approach. [ medical citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1517", "text": "In many cases for differing heart diseases and conditions the morbidity rates greatly decreased when a hybrid approach was used. The hybrid cardiac procedures have also shown to decrease post-operative complications. Patients have also had shorter hospital stays post-operative and have had quicker recovery times. [ 1 ] [ 3 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1518", "text": "A  hyperoxia test  is a test that is performed\u2014usually on an infant\u2014to determine whether the patient's  cyanosis  is due to lung disease or a problem with blood circulation. It is performed by measuring the  arterial blood gases  of the patient while they breathe room air, then re-measuring the blood gases after the patient has breathed 100% oxygen for 10 minutes. [ 1 ] :141 [ 2 ] :141 [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1519", "text": "If the cause of the cyanosis is poor oxygen saturation by the lungs, allowing the patient to breathe 100% oxygen will augment the lungs' ability to saturate the blood with oxygen, and the  partial pressure  of oxygen in the arterial blood will rise (usually above 150\u00a0 mmHg [ 3 ] ). However, if the lungs are healthy and already fully saturating the blood that is delivered to them, then supplemental oxygen will have no effect, and the partial pressure of oxygen will usually remain below 100\u00a0mmHg. [ 3 ]  In this case, the cyanosis is most likely due to blood that moves from the systemic veins to the systemic arteries via a  right-to-left shunt  without ever going through the lungs. [ 1 ] :141"}
{"_id": "WikiPedia_Cardio$$$corpus_1520", "text": "This  pediatrics  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1521", "text": "Impella  is a family of medical devices used for temporary  ventricular support  in patients with depressed heart function. Some versions of the device can provide left heart support during other forms of mechanical circulatory support including  ECMO  and Centrimag. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1522", "text": "The device is approved for use in high-risk  percutaneous coronary intervention  (PCI) and  cardiogenic shock  following  heart attack  or  open heart surgery  and is placed through a  peripheral artery . [ 2 ]  From the peripheral artery it pumps blood to the  left  or  right heart  via the  ascending aorta  or  pulmonary artery ."}
{"_id": "WikiPedia_Cardio$$$corpus_1523", "text": "The Impella technology was acquired by  Abiomed  in 2005. [ 3 ]  As of March 2019, the Impella series includes: the Impella 2.5, Impella 5.0/LD, Impella CP and Impella RP. [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1524", "text": "The Impella device is an alternative for  percutaneous  mechanical circulatory support that has been utilized as a bridge to recovery. Used alone or in tandem sets, it utilizes the concept of  magnetic levitation [ clarification needed ]  to reduce moving parts to an absolute minimum, thus reducing  anticoagulation  requirements.  Cardiogenic shock  has been addressed by many devices, most notably the  intraaortic balloon pump  (IABP). The technology deployed by the Impella device similarly alters the fundamental characteristics of the human circulatory system. As the propeller is accelerated to give respite to an acutely injured  myocardium , the circulatory system transitions from a pulsatile mechanism to continuous flow. Cellular response to cardiogenic shock is poorly described by either method ( counterpulsation  or  continuous flow ). Control of directional flow of the device (magnetic vectors) is under investigation for addressing  right - versus  left-sided heart failure . Transseptal intervention in addressing  physiologic mismatch in perfusion  between left- and right-sided heart failure is in experimental status. [ citation needed ] \nHowever, recent studies point to significantly greater in-hospital risks of major bleeding, death, and other adverse events for patients supported by Impella devices, compared with those managed with an IABP. [ 7 ] \nA  propensity-matched  comparison of patients receiving mechanical circulatory support (MCS) for  myocardial infarction \u2013related shock saw a nearly one-third excess in mortality and almost a doubling in risk of major bleeding, both in-hospital endpoints, with use of Impella compared to IABP. \nImpella may provide some of the results similar to venoarterial  extracorporeal life support  and TandemHeart. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1525", "text": "In patients with acute myocardial infarction complicated by cardiogenic shock,  haemodynamic  support with the Impella device had no significant effect on thirty-day mortality as compared with IABP. [ 9 ] \nOverall outcomes in the population, regardless of MCS device, were significantly worse for patients after the 2008 approval of Impella. [ clarification needed ]  Among hospitals using Impella, those using it the most had significantly worse outcomes with Impella than those using it the least. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1526", "text": "Potential complications related to the use of Impella are device related, [ clarification needed ]  peripheral vascular and distal  thrombus  formation with subsequent strokes. The most common complications reported were bleeding requiring  transfusion ,  vascular access  complications, infection,  haemolysis , vascular complications requiring  surgical repair , limb  ischaemia , and bleeding requiring surgical intervention (2.6%). Valvular complications included  aortic  and  mitral valve  injury or  mitral valve regurgitation . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1527", "text": "Impella heart pumps are percutaneous microaxial pumps that act as mechanical circulatory support devices in patients in need of  hemodynamic support . [ 11 ]  The pumps are mounted on support catheters and typically inserted through the  femoral artery , although  axillary  and  subclavian artery  approaches are not uncommon. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1528", "text": "The Impella Device is a generational extension of the Intra aortic balloon pump (IABP) in addressing cardiogenic shock. Tech has allowed a single moving piece floated by magnetically steered mechanisms to deploy an \"Archimedes Pump\" just north of the Aortic Valve that purports to reduce both preload and afterload. The same tech can apparently also be deployed just above the pulmonary (pulmonic) valve as a gate on right sided heart failure."}
{"_id": "WikiPedia_Cardio$$$corpus_1529", "text": "Designed to provide hemodynamic support when the patient's heart is unable to produce sufficient  cardiac output , Impella heart pumps can supply one to five liters per minute of blood flow. [ 13 ]  The physiological consequences of left-sided support are threefold. First, it unloads the left ventricle by reducing left ventricular  end-diastolic volume  and pressure, thereby decreasing ventricular  wall stress ,  work , and myocardial  oxygen demand . [ 14 ] [ 15 ] [ 16 ] [ 17 ]  Second, it increases  mean arterial pressure ,  diastolic pressure , and  cardiac output , improving cardiac  power  output and  cardiac index . [ 15 ]  The combined effects on wall stress and perfusion pressure (especially diastolic pressure) augment coronary perfusion. [ 14 ] [ 18 ]  Lastly, augmented cardiac output and forward flow from the left ventricle decreases  pulmonary capillary wedge pressure  and reduces right ventricular  afterload . [ 19 ] [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1530", "text": "Impella was approved for mechanical circulatory support in 2008, but large-scale, real-world data on its use are lacking. \nIn June 2008, the Impella 2.5 heart pump received  FDA   510(k)  clearance [ 22 ]  for partial circulatory support for periods of up to six hours during cardiac procedures not requiring  cardiopulmonary bypass . In March 2015, it received FDA  premarket approval  for elective and urgent high-risk percutaneous intervention procedures. [ 23 ]  In December 2016, the premarket approval was expanded to include the Impella CP heart pump. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1531", "text": "In April 2009, the Impella 5.0 and Impella LD heart pumps received 510(k) clearance for circulatory support for periods of up to six hours during cardiac procedures not requiring cardiopulmonary bypass. [ 25 ]  In July 2010, the automated Impella controller received FDA 510(k) clearance for use by trained healthcare professionals in healthcare facilities and  medical transport . [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1532", "text": "In January 2015, the Impella RP was granted a  humanitarian device exemption  to provide circulatory assistance for patients with  right heart failure . [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1533", "text": "In February 2018, the FDA approved the sale of the Impella ventricular support systems. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1534", "text": "Deaths and strokes in the data base overall increased after the Impella gained regulatory approval in 2008, compared to\nearlier years; mortality went up 17% and strokes more than tripled. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1535", "text": "In July 2023, the FDA issued a  Class I recall  for all Impella left-sided blood pumps due to risk of motor damage after contact with a  transcatheter aortic valve replacement  stent. [ 29 ] [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1536", "text": "In March 2024, the FDA issued a warning about Impella left-sided blood pumps being linked to 49 deaths due to left ventricular perforation or wall rupture. [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1537", "text": "Instruments used specially in  cardiology   are as follows:"}
{"_id": "WikiPedia_Cardio$$$corpus_1538", "text": "This article related to  medical equipment  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1539", "text": "Intima\u2013media thickness  ( IMT ), also called  intimal medial thickness , is a measurement of the thickness of  tunica intima  and  tunica media , the innermost two layers of the wall of an  artery . The measurement is usually made by external  ultrasound  and occasionally by  internal, invasive ultrasound catheters . Measurements of the total wall thickness of  blood vessels  can also be done using other imaging modalities."}
{"_id": "WikiPedia_Cardio$$$corpus_1540", "text": "Carotid IMT is used to detect the presence of  atherosclerosis  in humans and, more contentiously, to track the regression, arrest or progression of atherosclerosis. [ 1 ]   Ultrasound measurements of carotid IMT were first proposed and validated  in vitro  by Paolo Pignoli in 1984 [ 2 ]  and further details were subsequently published in a highly cited article. [ 3 ]  The use of IMT as a non-invasive tool to track changes in arterial walls has increased substantially  since the mid-1990s. [ 1 ]  Although carotid IMT is predictive of future  cardiovascular events , [ 4 ]  the usefulness of measuring  change  in carotid IMT over time is disputed, as meta-analyses have not found that change in carotid IMT is predictive of cardiovascular events. [ 5 ] [ 6 ]  As such, the use of change in carotid IMT as a  surrogate endpoint  measure of drug efficacy in  clinical trials , or in clinical management of cardiovascular disease, is debated. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1541", "text": "Carotid IMT is occasionally used in clinical practice, but its role is not clear. [ 7 ]  After systematically reviewing the evidence base, the  United States Preventive Services Task Force  found no support for its routine use in stratification of risk for people at intermediate cardiovascular risk. [ 8 ]  However, in 2003 the European Society of Hypertension\u2013 European Society of Cardiology  guidelines for the management of arterial hypertension [ 9 ]  recommended the use of carotid IMT measurements in high-risk patients to help identify target organ damage and in 2010 the  American Heart Association  and the  American College of Cardiology  advocated the use of carotid IMT on intermediate risk patients if usual risk classification was not satisfactory. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1542", "text": "IMT can be measured using external ultrasound in large arteries relatively close to the skin (e.g. the  carotid ,  brachial ,  radial , or  femoral  arteries). External ultrasound methods have the advantage of being non-invasive, comparatively low cost and convenient. Deeper internal arteries, such as the  coronary arteries  require special intravascular catheters employing  ultrasound  or  optical coherence tomography  to measure IMT. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1543", "text": "The carotid artery is the usual site of measurement of IMT and consensus statements for carotid IMT have been published for adults [ 12 ]  and children. [ 13 ]  Often, carotid IMT is measured in three locations: in the common carotid artery (typically at one cm proximal to the flow divider), at the bifurcation, and in the internal carotid artery. [ 14 ] [ 15 ]   IMT measurements of the far (deeper) wall, by ultrasound, are generally considered more reliable than measurements performed on the near (more superficial) wall; [ 14 ]  although measurement of both near and far wall IMT has also been advocated. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1544", "text": "Carotid IMT has been used in many epidemiological and clinical studies and these have shown associations with several risk factors, including  type 2 diabetes , [ 17 ]   familial hypercholesterolemia , [ 18 ]   high-density lipoprotein  cholesterol (HDL-C),  triglycerides , [ 19 ]   rheumatoid arthritis , [ 20 ]   non-alcoholic fatty liver disease , [ 21 ]  and  air pollution . [ 22 ]  Since the 1990s, some  clinical trials  of  lifestyle  and  pharmaceutical  interventions have also used carotid artery IMT as a  surrogate endpoint  for evaluating the regression and/or progression of atherosclerotic cardiovascular disease; [ 23 ]  however the appropriateness of carotid IMT in this context is uncertain. [ 24 ]  Although carotid intima\u2013media thickness is strongly associated with  atherosclerosis , thickening of the intima\u2013media may not always be due to atherosclerosis. Intima\u2013medial thickening is a complex process, depending on a variety of factors, including  blood pressure , [ 25 ]  local  hemodynamics , [ 25 ]   shear stress [ 25 ]  and circumferential  tensile stress . [ 25 ]  Variations in IMT between different locations (e.g. the common carotid artery, the  carotid bulb  and the  internal carotid artery )  may reflect differences in local hemodynamic forces."}
{"_id": "WikiPedia_Cardio$$$corpus_1545", "text": "The  intra-aortic balloon pump  ( IABP ) is a mechanical device that increases  myocardial   oxygen  perfusion and indirectly increases  cardiac output  through  afterload  reduction. It consists of a cylindrical polyurethane balloon that sits in the  aorta , approximately 2 centimeters (0.79\u00a0in) from the left  subclavian artery . [ 1 ]  The balloon inflates and deflates via counter pulsation, meaning it actively deflates in  systole  and inflates in  diastole . Systolic deflation decreases afterload through a vacuum effect and indirectly increases forward flow from the heart. Diastolic inflation increases blood flow to the  coronary arteries  via retrograde flow. These actions combine to decrease myocardial oxygen demand and increase myocardial oxygen supply. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1546", "text": "A computer-controlled mechanism inflates the balloon with  helium  from a cylinder during diastole, usually linked to either an  electrocardiogram  (ECG) or a pressure  transducer  at the  distal  tip of the  catheter ; some IABPs, such as the Datascope System 98XT, allow asynchronous counterpulsation at a set rate, though this setting is rarely used. Helium is used to inflate the balloon as its low density means there is little turbulent flow, so the balloon can inflate quickly and deflate slowly. It is also relatively benign and eliminated quickly if there is a leak or rupture in the balloon. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1547", "text": "The following situations may benefit from this device. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1548", "text": "The following conditions will always exclude patients for treatment: [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1549", "text": "The following conditions make IABP therapy inadvisable except under pressing circumstances: [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1550", "text": "IABP has a beneficiary effect to the struggling heart. It decreases myocardial demand for oxygen and increases coronary flow. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1551", "text": "Since the device is placed in the  femoral artery  and aorta it could provoke  ischemia , and  compartment syndrome . The leg is at highest risk of becoming ischemic if the femoral artery it is supplied by becomes obstructed. Placing the balloon too  distal  from the  aortic arch  may induce occlusion of the  renal artery  and subsequent  kidney failure . Other possible complications are  cerebral embolism  during insertion, infection,  dissection  of the aorta or  iliac artery , perforation of the artery and  bleeding  in the  mediastinum . Mechanical failure of the balloon itself is also a risk which entails vascular surgery to remove under that circumstance. After balloon removal there is also a risk of 'embolic shower' from micro clots that have formed on the surface of the balloon, and can lead to peripheral thrombosis,  myocardial ischemia , hemodynamic decompensation, and late  pseudoaneurysm . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1552", "text": "The first publication of intra-aortic balloon counter-pulsation appeared in the American Heart Journal of May 1962; 63: 669-675 by S. Moulopoulos, S. Topaz and W. Kolff. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1553", "text": "The device and the balloons were then developed for commercial use between 1967 and 1969  heart surgery  by William Rassman at Cornell Medical Center and were manufactured by Datascope Corporation in 1969.  The system was subsequently used clinically by David Bregman in 1976 at  NewYork-Presbyterian Hospital  in  New York City . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1554", "text": "The first clinical implant was performed at  Maimonides Medical Center , Brooklyn, N.Y. in June 1967 by  Dr. Adrian Kantrowitz  and Dr. Steven Phillips. [ 9 ]  The patient, a 48-year-old woman, was in cardiogenic shock and unresponsive to traditional therapy. An IABP was inserted by a cut down on the left  femoral artery . Pumping was performed for approximately 6 hours. Shock reversed and the patient was discharged. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1555", "text": "The size of the original balloon was 15  French  but eventually 9 and 8  French  balloons were developed. [ 6 ]  A second operation removed the balloon. Since 1979 the placement of the balloon has been modified using the Seldinger technique. [ 6 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1556", "text": "An  isochrone map  in  geography  and  urban planning  is a map that depicts the area accessible from a point within a certain time threshold. [ 1 ]  An  isochrone  (iso = equal, chrone = time) is defined as \"a line drawn on a map connecting points at which something occurs or arrives at the same time\". [ 2 ]  In  hydrology  and  transportation planning  isochrone maps are commonly used to depict areas of equal travel time. The term is also used in  cardiology [ 3 ] [ 4 ] [ 5 ]  as a tool to visually detect abnormalities using body surface distribution. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1557", "text": "Early examples of Isochrone maps include the  Galton's   Isochronic Postal Charts  and  Isochronic Passage Charts  of 1881 and 1882, [ 8 ]   Bartholomew's   Isochronic Distance Map and Chart  first published 1889, [ 9 ]  and  Albrecht Penck's   Isochronenkarte  first published 1887. [ 10 ]  Where as Galton and the Bartholomews published maps depicting the days or weeks it took to travel long distances, Albrecht further developed the idea to not only depict long distances and world travel but also smaller areas. Penck also created a series of maps that only depict the travel times of a certain transportation mode, for example  rail transport . Isochrone maps are commonly used in the UK in connection with  development control . [ 11 ] [ 12 ] [ 13 ] [ 14 ]  Isochrones are currently typically computed by via generating  shortest-path trees  on network  graphs , and then generating a  convex hull  around the accessible nodes. Increases in computation, data storage, and improvements in algorithms have facilitated the rapid generation of isochrones. [ 1 ] [ 15 ]  Recent techniques in visualization include linking travel times to network edges to show the paths accessible from a point rather than show the area accessible from a point. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1558", "text": "Isochrone and related maps are used to show the time taken for  runoff  water within a  drainage basin  to reach a lake, reservoir or outlet, assuming constant and uniform effective rainfall. [ 16 ] [ 17 ] [ 18 ] [ 19 ]  An early example of this method was demonstrated by Clark in 1945. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1559", "text": "Isochrone maps have been used in transportation planning since at least 1887. [ 21 ] [ 22 ]  Isochrone maps in the context of transport planning are essentially maps of  accessibility  where travel time is used as the cost metric. Isochrone maps can be created for different  modes of transportation , [ 23 ]  e.g. foot, bicycle, motor vehicle. Put simply, the output of an isochrone map for transport will show how far (in distance) is reachable from a start point, including the parameter of time."}
{"_id": "WikiPedia_Cardio$$$corpus_1560", "text": "Such maps for private motor transport were widely used in a 1972 study into airport accessibility in  Hampshire ,  South East England . [ 24 ]  At that time, their use was disadvantaged by being time-consuming to create. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1561", "text": "The term isodapane map is used to refer to a map were the contour represent transportation  cost  instead of transportation  time . [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1562", "text": "Journey time websites have been built using mapping technologies and  open data . [ 26 ] [ 27 ]  Isochrones can be used by house hunters wishing to evaluate  residential areas . [ 28 ]  An isochrone map of the  London Underground  network was made available in 2007. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1563", "text": "Several digital tools exist which can generate isochrone maps."}
{"_id": "WikiPedia_Cardio$$$corpus_1564", "text": "openstreetmap -based solutions: [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1565", "text": "GTFS-based solutions:"}
{"_id": "WikiPedia_Cardio$$$corpus_1566", "text": "Proprietary data solutions:"}
{"_id": "WikiPedia_Cardio$$$corpus_1567", "text": "The  JUPITER trial  ( J ustification for the  U se of Statins in Primary  P revention: An  I ntervention  T rial  E valuating  R osuvastatin trial) was a  clinical trial  aimed at evaluating whether  statins  reduce  heart attacks  and strokes in people with normal  cholesterol  levels."}
{"_id": "WikiPedia_Cardio$$$corpus_1568", "text": "JUPITER was a  randomized   double-blind   placebo-controlled study  investigating the use of  rosuvastatin  in the  primary prevention  of  cardiovascular disease . The trial focused on patients with normal  low-density lipoprotein  (LDL)  cholesterol  levels but increased levels of  high-sensitivity C-reactive protein  (hs-CRP). JUPITER was the first  clinical trial  to indicate that statin therapy may provide benefit to patients with low-to-normal LDL levels and no known cardiovascular disease. [ 1 ] [ 2 ]  The trial, which began in 2003, was directed by  Paul Ridker  of  Brigham and Women\u2019s Hospital . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1569", "text": "Because half of all vascular events occur in patients with normal or low levels of LDL cholesterol, JUPITER was designed to determine whether hs-CRP testing could identify these patients, and whether statin therapy could prevent cardiovascular events among them. [ 4 ]  Elevated hs-CRP levels are thought to be a  biomarker  of inflammation, and have been  associated  with an increased risk of  myocardial infarction ,  stroke ,  peripheral arterial disease , and  sudden cardiac death . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1570", "text": "The trial analyzed 17,802 patients without evidence of heart disease but with high CRP levels. In 2008, results presented at the  American Heart Association  meeting and published in the  New England Journal of Medicine   (NEJM)  found that patients with low-to-normal LDL cholesterol receiving rosuvastatin had a lower rate of major cardiovascular events. Compared to patients taking a  placebo , patients given rosuvastatin had reductions in LDL and CRP levels, and a reduction of 0.2% to 0.6% in their  absolute risk  of  heart attack ,  stroke , and death at one year. [ 5 ] [ 6 ] [ 7 ]  The study's authors estimated that the  number needed to treat  with rosuvastatin to prevent one cardiovascular event was 95 over two years, extrapolated to 25 over five years. The trial was stopped early, after just 1.9 years median duration, by the study's Independent Data Monitoring Board, because the interim results met the study's predefined stopping criteria (it had been predetermined that it would be unethical to continue the study once it became clear that the patients in one arm of the study had a significantly higher cardiovascular risk than the other arm's patients). [ 1 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1571", "text": "The trial was sponsored by  AstraZeneca , the marketer of Crestor (rosuvastatin). [ 3 ]  The company saw an increase in its share of the U.S. statin drug market following the November 2008  NEJM  publication. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1572", "text": "Reports of serious adverse events within JUPITER were equally distributed between the study's rosuvastatin and placebo arms. There were no significant differences between the treatment groups with respect to muscle pain, muscle weakness, hepatic function, or renal function; however, the researchers noted small but  statistically significant  increases in the rate of physician-reported  diabetes  and  glycated hemoglobin  values in the rosuvastatin group, an effect that has also been seen in studies with other statins. [ 5 ] [ 8 ]  Those latter findings, along with concerns over the safety of very low LDL levels, rosuvastatin's higher cost compared to  generic  statins, and the validity of biomarkers used in the diagnosis of cardiovascular disease, have been cited by those urging caution before expanding indications for statin treatment. [ 10 ] [ 11 ] [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1573", "text": "In 2010, Dr. Michel de Lorgeril, et al., published \"a critical reappraisal\" of the JUPITER Trial in the  Archives of Internal Medicine . The article's authors critiqued what they saw as flaws in the trial, pointing out that the cardiovascular mortality rate and the case-fatality rate for myocardial infarction were much lower than they expected. They also raised concerns about conflict of interest in the trial design and leadership: nine of 14 authors of the main report had financial ties to the sponsor,  AstraZeneca , and the lead investigator held the patent for the C-reactive protein test, whose use in screening would be promoted by the results as reported. [ 14 ]  They also argued that the trial's premature termination may have distorted the results, and raised concerns that AstraZeneca scientists had controlled and managed the raw data.  They concluded that, \"The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.\" [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1574", "text": "In addition, some prior and some subsequent studies have contrasted with the JUPITER trial results.  On the role of C-reactive protein, a 2009 study employing  Mendelian randomization , published in the  Journal of the American Medical Association  suggested that CRP does not play a causal role in cardiovascular disease; the results may argue against CRP's use as a marker of cardiovascular disease risk or for identifying subjects for statin therapy as in JUPITER, and more strongly argue against using CRP as a therapeutic target  per se . [ 15 ]  The discordant results of this subsequent study provoked debate over the role and value of CRP as a biomarker and possible therapeutic target in heart disease. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1575", "text": "Lancisi's sign  is a  clinical sign  in which a large venous wave, or  Giant V wave , is visible in the  jugular vein  in patients with  tricuspid regurgitation . It is caused by blood flowing backwards into the jugular vein through the incompetent  tricuspid valve  during  ventricular systole . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1576", "text": "The sign is named after  Giovanni Maria Lancisi . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1577", "text": "Left ventricular mass  or  LVM  refers to the  mass  of the  left ventricle of the heart ."}
{"_id": "WikiPedia_Cardio$$$corpus_1578", "text": "Left ventricular mass index  or  LVMi  is LVM divided by  body surface area ."}
{"_id": "WikiPedia_Cardio$$$corpus_1579", "text": "LVM is usually estimated using linear measurements obtained from  echocardiography , [ 1 ]  but can also be calculated using  CT  or  MRI  images. [ 2 ]  LVM increases withe  ageing , though ageing related  remodeling  of the left ventricle's geometry can lead to a discordancy between CT and echocardiographic based measurements of LVM. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1580", "text": "Published normal ranges for LVMi are 49\u2013115 g/m 2  for men and 43\u201395 g/m 2  for women. [ 1 ] [ 4 ]   left ventricular hypertrophy  (LVH) is defined as an abnormal increase in LVM, an important independent  risk factor  for  cardiovascular morbidity  and mortality. [ 5 ] [ 6 ] [ 7 ]  LVM is also an independent risk factor for cardiovascular disease even within the normal limits. [ 8 ]   A reduction in LVM following  antihypertensive treatment  or  aortic vale replacement  is associated with a reduced rate of complications. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1581", "text": "Intensive athletic training can cause physiologic changes in the heart (\" athlete's heart \") which include an increase in LVM. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1582", "text": "A  Lewis Lead  (also called the  S5 lead ) is a modified  ECG  lead used to detect  atrial flutter  waves when atrial flutter is suspected clinically, based on signs and symptoms, but is not definitely demonstrated on the standard 12 lead ECG. In order to create the Lewis Lead, the right arm electrode is moved to the  manubrium  adjacent to the  sternum . Then the left arm electrode is moved to the right, fifth intercostal space adjacent to the sternum. The left leg electrode is placed on the right lower costal margin. The Lewis Lead is then read as Lead I on the ECG and, since in most patients it will be roughly perpendicular to the wave of ventricular  depolarization , atrial flutter waves may be more apparent."}
{"_id": "WikiPedia_Cardio$$$corpus_1583", "text": "This article related to  medical imaging  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1584", "text": "Liebermeister's rule  concerns the increment ratio between an adult individual's cardiac frequency and temperature when in fever. Each Celsius grade of  body temperature  increment corresponds to an 8  beats per minute  increase in cardiac frequency, although the exact number of this rule varies significantly across different sources. [ 1 ] [ 2 ]  An exception to this rule by creating a  relative   bradycardia  is known as  Faget sign  (pulse-temperature dissociation) common in some diseases, especially  yellow fever , tularaemia and salmonella typhi. It is named for  Carl von Liebermeister . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1585", "text": "A  lipoprotein  is a  biochemical  assembly whose primary function is to transport  hydrophobic   lipid  (also known as  fat ) molecules in water, as in  blood plasma  or other  extracellular fluids . They consist of a  triglyceride  and  cholesterol  center, surrounded by a  phospholipid  outer shell, with the  hydrophilic  portions oriented outward toward the surrounding water and  lipophilic  portions oriented inward toward the lipid center. A special kind of protein, called  apolipoprotein , is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role."}
{"_id": "WikiPedia_Cardio$$$corpus_1586", "text": "Plasma lipoprotein particles  are commonly divided into five main classes, based on size, lipid composition, and apolipoprotein content:  HDL ,  LDL ,  IDL ,  VLDL  and  chylomicrons . Subgroups of these plasma particles are primary drivers or modulators of  atherosclerosis . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1587", "text": "Many  enzymes ,  transporters , structural proteins,  antigens ,  adhesins , and  toxins  are sometimes also classified as lipoproteins, since they are formed by lipids and proteins."}
{"_id": "WikiPedia_Cardio$$$corpus_1588", "text": "Some transmembrane  proteolipids , especially those found in  bacteria , are referred to as lipoproteins; they are not related to the lipoprotein particles that this article is about. [ 2 ]  Such  transmembrane proteins  are difficult to isolate, as they bind tightly to the lipid membrane, often require lipids to display the proper structure, and can be water-insoluble.  Detergents  are usually required to isolate transmembrane lipoproteins from their associated biological membranes."}
{"_id": "WikiPedia_Cardio$$$corpus_1589", "text": "Because fats are insoluble in water, they cannot be transported on their own in extracellular water, including blood plasma. Instead, they are surrounded by a hydrophilic external shell that functions as a transport vehicle. The role of lipoprotein particles is to transport fat molecules, such as  triglycerides , phospholipids, and cholesterol within the extracellular water of the body to all the cells and tissues of the body. The proteins included in the external shell of these particles, called apolipoproteins, are synthesized and secreted into the extracellular water by both the  small intestine  and  liver  cells. The external shell also contains phospholipids and cholesterol."}
{"_id": "WikiPedia_Cardio$$$corpus_1590", "text": "All  cells  use and rely on fats and cholesterol as building blocks to create the multiple  membranes  that cells use both to control internal water content and internal water-soluble elements and to organize their internal structure and protein enzymatic systems. The outer shell of lipoprotein particles have the hydrophilic groups of phospholipids, cholesterol, and apolipoproteins directed outward. Such characteristics make them soluble in the salt-water-based blood pool.  Triglycerides  and  cholesteryl esters  are carried internally, shielded from the water by the outer shell. The kind of apolipoproteins contained in the outer shell determines the functional identity of the lipoprotein particles. The interaction of these apolipoproteins with enzymes in the blood, with each other, or with specific proteins on the surfaces of cells, determines whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles."}
{"_id": "WikiPedia_Cardio$$$corpus_1591", "text": "Characterization in human plasma [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1592", "text": "Lipoproteins are complex particles that have a central hydrophobic core of non-polar lipids, primarily cholesteryl esters and triglycerides. This hydrophobic core is surrounded by a hydrophilic membrane consisting of phospholipids, free cholesterol, and apolipoproteins. Plasma lipoproteins, found in  blood plasma , are typically divided into five main classes based on size, lipid composition, and apolipoprotein content:  HDL ,  LDL ,  IDL ,  VLDL  and  chylomicrons . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1593", "text": "The handling of lipoprotein particles in the body is referred to as  lipoprotein particle metabolism . It is divided into two pathways,  exogenous  and  endogenous , depending in large part on whether the lipoprotein particles in question are composed chiefly of dietary (exogenous) lipids or whether they originated in the liver (endogenous), through  de novo synthesis  of triglycerides."}
{"_id": "WikiPedia_Cardio$$$corpus_1594", "text": "The  hepatocytes  are the main platform for the handling of triglycerides and cholesterol; the liver can also store certain amounts of  glycogen  and triglycerides. While  adipocytes  are the main storage cells for triglycerides, they do not produce any lipoproteins."}
{"_id": "WikiPedia_Cardio$$$corpus_1595", "text": "Bile  emulsifies fats contained in the  chyme , then  pancreatic lipase  cleaves triglyceride molecules into two fatty acids and one 2-monoacylglycerol.  Enterocytes  readily absorb the small molecules from the chymus. Inside of the enterocytes, fatty acids and  monoacylglycerides  are transformed again into triglycerides. Then these lipids are assembled with  apolipoprotein B-48  into  nascent  chylomicrons . These particles are then secreted into the  lacteals  in a process that depends heavily on apolipoprotein B-48. As they circulate through the  lymphatic vessels , nascent chylomicrons bypass the liver circulation and are drained via the  thoracic duct  into the bloodstream."}
{"_id": "WikiPedia_Cardio$$$corpus_1596", "text": "In the blood stream,  nascent chylomicron particles  interact with HDL particles, resulting in HDL donation of  apolipoprotein C-II  and  apolipoprotein E  to the nascent chylomicron. The chylomicron at this stage is then considered mature. Via apolipoprotein C-II, mature chylomicrons activate  lipoprotein lipase  (LPL), an enzyme on  endothelial cells  lining the blood vessels. LPL catalyzes the  hydrolysis  of triglycerides that ultimately releases glycerol and  fatty acids  from the chylomicrons. Glycerol and fatty acids can then be absorbed in peripheral tissues, especially  adipose  and  muscle , for energy and storage."}
{"_id": "WikiPedia_Cardio$$$corpus_1597", "text": "The hydrolyzed chylomicrons are now called  chylomicron remnants . The chylomicron remnants continue circulating the bloodstream until they interact via apolipoprotein E with chylomicron remnant receptors, found chiefly in the liver. This interaction causes the  endocytosis  of the chylomicron remnants, which are subsequently hydrolyzed within  lysosomes . Lysosomal  hydrolysis  releases glycerol and fatty acids into the cell, which can be used for energy or stored for later use."}
{"_id": "WikiPedia_Cardio$$$corpus_1598", "text": "The liver is the central platform for the handling of lipids: it is able to store glycerols and fats in its cells, the  hepatocytes . Hepatocytes are also able to create triglycerides via de novo synthesis. They also produce the bile from cholesterol. The intestines are responsible for absorbing cholesterol. They transfer it over into the blood stream."}
{"_id": "WikiPedia_Cardio$$$corpus_1599", "text": "In the hepatocytes, triglycerides and cholesteryl esters are assembled with  apolipoprotein B-100  to form  nascent VLDL particles . Nascent VLDL particles are released into the bloodstream via a process that depends upon apolipoprotein B-100."}
{"_id": "WikiPedia_Cardio$$$corpus_1600", "text": "In the blood stream,  nascent VLDL particles  bump with HDL particles; as a result, HDL particles donate  apolipoprotein C-II  and apolipoprotein E to the nascent VLDL particle. Once loaded with apolipoproteins C-II and E, the nascent VLDL particle is considered mature. VLDL particles circulate and encounter LPL expressed on  endothelial cells . Apolipoprotein C-II activates LPL, causing hydrolysis of the VLDL particle and the release of glycerol and fatty acids. These products can be absorbed from the blood by peripheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called  VLDL remnants  or  intermediate-density lipoproteins  (IDLs). VLDL remnants can circulate and, via an interaction between apolipoprotein E and the remnant receptor, be absorbed by the liver, or they can be further hydrolyzed by  hepatic lipase ."}
{"_id": "WikiPedia_Cardio$$$corpus_1601", "text": "Hydrolysis by hepatic lipase releases glycerol and fatty acids, leaving behind  IDL remnants , called  low-density lipoproteins  (LDL), which contain a relatively high cholesterol content [ 5 ]  ( see native LDL structure at 37\u00b0C  on  YouTube ). LDL circulates and is absorbed by the liver and peripheral cells. Binding of LDL to its target tissue occurs through an interaction between the  LDL receptor  and apolipoprotein B-100 on the LDL particle. Absorption occurs through  endocytosis , and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol."}
{"_id": "WikiPedia_Cardio$$$corpus_1602", "text": "Plasma lipoproteins may carry oxygen gas. [ 6 ]  This property is due to the crystalline hydrophobic structure of lipids, providing a suitable environment for O 2  solubility compared to an aqueous medium. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1603", "text": "Inflammation , a biological system response to stimuli such as the introduction of a  pathogen , has an underlying role in numerous systemic biological functions and pathologies. This is a useful response by the immune system when the body is exposed to pathogens, such as bacteria in locations that will prove harmful, but can also have detrimental effects if left unregulated. It has been demonstrated that lipoproteins, specifically HDL, have important roles in the inflammatory process. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1604", "text": "When the body is functioning under normal, stable physiological conditions, HDL has been shown to be beneficial in several ways. [ 8 ]  LDL contains apolipoprotein B (apoB), which allows LDL to bind to different tissues, such as the artery wall if the  glycocalyx  has been damaged by high  blood sugar levels . [ 8 ]  If oxidised, the LDL can become trapped in the proteoglycans, preventing its removal by HDL cholesterol efflux. [ 8 ]  Normal functioning HDL is able to prevent the process of oxidation of LDL and the subsequent inflammatory processes seen after oxidation. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1605", "text": "Lipopolysaccharide , or LPS, is the major pathogenic factor on the cell wall of  Gram-negative bacteria .  Gram-positive bacteria  has a similar component named  Lipoteichoic acid , or LTA. HDL has the ability to bind LPS and LTA, creating HDL-LPS complexes to neutralize the harmful effects in the body and clear the LPS from the body. [ 9 ]  HDL also has significant roles interacting with cells of the immune system to modulate the availability of cholesterol and modulate the immune response. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1606", "text": "Under certain abnormal physiological conditions such as system  infection  or  sepsis , the major components of HDL become altered, [ 9 ] [ 10 ]  The composition and quantity of lipids and apolipoproteins are altered as compared to normal physiological conditions, such as a decrease in HDL cholesterol (HDL-C), phospholipids, apoA-I (a major lipoprotein in HDL that has been shown to have beneficial anti-inflammatory properties), and an increase in  Serum amyloid A . [ 9 ] [ 10 ]  This altered composition of HDL is commonly referred to as acute-phase HDL in an acute-phase inflammatory response, during which time HDL can lose its ability to inhibit the oxidation of LDL. [ 8 ]  In fact, this altered composition of HDL is associated with increased mortality and worse clinical outcomes in patients with sepsis. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1607", "text": "Lipoproteins may be classified as five major groups, listed from larger and lower density to smaller and higher density. Lipoproteins are larger and less dense when the fat to protein ratio is increased. They are classified on the basis of  electrophoresis ,  ultracentrifugation  and  nuclear magnetic resonance spectroscopy  via the  Vantera Analyzer . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1608", "text": "For young healthy research subjects, ~70\u00a0kg (154\u00a0lb), these data represent averages across individuals studied, percentages represent\u00a0% dry weight:"}
{"_id": "WikiPedia_Cardio$$$corpus_1609", "text": "[ 12 ] [ 13 ]  However, these data are not necessarily reliable for any one individual or for the general clinical population."}
{"_id": "WikiPedia_Cardio$$$corpus_1610", "text": "It is also possible to classify lipoproteins as \"alpha\" and \"beta\", according to the classification of proteins in  serum protein electrophoresis . This terminology is sometimes used in describing lipid disorders such as  abetalipoproteinemia ."}
{"_id": "WikiPedia_Cardio$$$corpus_1611", "text": "Lipoproteins, such as LDL and HDL, can be further subdivided into subspecies isolated through a variety of methods. [ 14 ] [ 15 ]  These are subdivided by density or by the protein contents/ proteins they carry. [ 14 ]  While the research is currently ongoing, researchers are learning that different subspecies contain different apolipoproteins, proteins, and lipid contents between species which have different physiological roles. [ 14 ]  For example, within the HDL lipoprotein subspecies, a large number of proteins are involved in general lipid metabolism. [ 14 ]  However, it is being elucidated that HDL subspecies also contain proteins involved in the following functions:  homeostasis ,  fibrinogen ,  clotting cascade , inflammatory and immune responses, including the  complement system ,  proteolysis  inhibitors,  acute-phase response  proteins, and the  LPS-binding protein ,  heme  and iron metabolism,  platelet  regulation, vitamin binding and general transport. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1612", "text": "High levels of lipoprotein(a) are a significant  risk factor  for  atherosclerotic   cardiovascular diseases  via mechanisms associated with  inflammation  and  thrombosis . [ 16 ]  The links of mechanisms between different lipoprotein isoforms and risk for cardiovascular diseases, lipoprotein synthesis, regulation, and metabolism, and related risks for  genetic diseases  are under active research, as of 2022. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1613", "text": "1I71 ,  1JFN ,  1KIV ,  2FEB ,  4BV5 ,  4BV7 ,  4BVC ,  4BVD ,  4BVV ,  4BVW ,  3KIV ,  4KIV"}
{"_id": "WikiPedia_Cardio$$$corpus_1614", "text": "4018"}
{"_id": "WikiPedia_Cardio$$$corpus_1615", "text": "n/a"}
{"_id": "WikiPedia_Cardio$$$corpus_1616", "text": "ENSG00000198670"}
{"_id": "WikiPedia_Cardio$$$corpus_1617", "text": "P08519"}
{"_id": "WikiPedia_Cardio$$$corpus_1618", "text": "NM_005577"}
{"_id": "WikiPedia_Cardio$$$corpus_1619", "text": "Lipoprotein(a)  is a  low-density lipoprotein  variant containing a protein called  apolipoprotein(a) . Genetic and  epidemiological studies  have identified lipoprotein(a) as a risk factor for  atherosclerosis  and related diseases, such as  coronary heart disease  and  stroke . [ 3 ] [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1620", "text": "Lipoprotein(a) was discovered in 1963 by  K\u00e5re Berg . [ 7 ]  The human  gene  encoding apolipoprotein(a) was successfully cloned in 1987. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1621", "text": "Lipoprotein(a) [Lp(a)] consists of an  LDL -like particle and the specific apolipoprotein(a), which is bound covalently to the  apoB  contained in the outer shell of the particle. Lp(a) plasma concentrations are highly heritable [ 9 ] [ 10 ]  and mainly controlled by the  LPA  gene [ 11 ]  located on  chromosome 6q 25.3\u2013q26. [ 12 ]   Apo(a) proteins vary in size due to a size polymorphism [KIV-2  VNTR ], which is caused by a variable number of  kringle  IV repeats in the  LPA  gene. [ 13 ]  This size variation at the gene level is expressed on the protein level as well, resulting in apo(a) proteins with 10 to more than 50 kringle IV repeats (each of the variable kringle IV consists of 114  amino acids ). [ 8 ] [ 14 ]  These variable apo(a) sizes are known as \"apo(a)  isoforms \"."}
{"_id": "WikiPedia_Cardio$$$corpus_1622", "text": "There is a general inverse correlation between the size of the apo(a) isoform and the Lp(a) plasma concentration. [ 15 ]  One theory explaining this correlation involves different rates of protein synthesis. Specifically, the larger the isoform, the more apo(a) precursor protein accumulates  intracellularly  in the  endoplasmic reticulum . Lp(a) is not fully synthesised until the precursor protein is released from the cell, so the slower rate of production for the larger isoforms limits the plasma concentration. [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1623", "text": "Lp(a) concentrations can vary by more than one thousand between individuals, from <0.2 to >200\u00a0mg/dL. This range of concentrations is observed in all populations studied by scientists so far. The mean and median concentrations differ among world populations. Most prominently, there is a two- to threefold higher mean Lp(a) plasma concentration in populations of African descent compared to Asian, Oceanic, or European populations. [ 18 ] [ 19 ]  The general inverse correlation between apo(a) isoform size and Lp(a) plasma concentration is observed in all populations. [ 15 ]  However, it was also discovered that mean Lp(a) associated with certain apo(a) isoforms varies between populations. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1624", "text": "In addition to size effects, mutations in the LPA promoter may lead to a decreased apo(a) production. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1625", "text": "The  Atherosclerosis Risk in Communities  (ARIC) Study is a community-based cohort from 4 geographically diverse US communities. The ARIC Study found that the proportion of Atherosclerotic Cardiovascular Disease cases potentially attributable to elevated Lp(a) was 10.2% among Black adults compared with 4.7% among white adults. The population-attributable fraction ratio for Black adults compared with white adults was 2.30.\nBecause the hazard ratios for ASCVD associated with higher Lp(a) did not significantly differ between races, the ARIC study concluded that these differences appeared to be driven largely by racial differences in the distribution of Lp(a) levels. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1626", "text": "Lp(a) is assembled at the  hepatocyte  cell membrane surface, which is similar to typical LDL particles. However, there are other possible locations of assembly. The particles mainly exist in plasma. [ 22 ] [ 23 ] [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1627", "text": "Lp(a) contributes to the process of  atherogenesis . The structure of apolipoprotein(a) is similar to  plasminogen  and tPA ( tissue plasminogen activator ) and it competes with plasminogen for its binding site, leading to reduced  fibrinolysis . [ 26 ] [ 27 ]  Also, because Lp(a) stimulates secretion of  PAI-1 , it leads to  thrombogenesis . [ 28 ] [ 3 ] [ 29 ]  It also may enhance coagulation by inhibiting the function of tissue factor pathway inhibitor. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1628", "text": "Moreover, Lp(a) carries  atherosclerosis -causing cholesterol and binds atherogenic pro-inflammatory oxidised phospholipids as a preferential carrier of oxidised phospholipids in human plasma, [ 31 ]  which attracts inflammatory cells to vessel walls and leads to smooth muscle cell proliferation. [ 32 ] [ 33 ] [ 34 ]  Moreover, Lp(a) also is hypothesised to be involved in wound healing and tissue repair by interacting with components of the vascular wall and  extracellular matrix . [ 35 ] [ 36 ]  Apo(a), a distinct feature of the Lp(a) particle, binds to immobilized fibronectin and endows Lp(a) with the serine-proteinase-type proteolytic activity. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1629", "text": "Nonetheless, individuals without Lp(a) or with very low Lp(a) levels seem to be healthy. [ citation needed ]  Thus, plasma Lp(a) is not vital, at least under normal environmental conditions. [ citation needed ]  Since apo(a)/Lp(a) appeared rather recently in mammalian evolution \u2014 only  old world monkeys  and humans have been shown to harbour Lp(a) \u2014 its function might not be vital, but just evolutionarily advantageous under certain environmental conditions, e.g. in case of exposure to certain infectious diseases. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1630", "text": "Another possibility, suggested by  Linus Pauling , is that Lp(a) is a primate adaptation to  L-gulonolactone oxidase  (GULO) deficiency, found only in certain lines of mammals. GULO is required for converting  glucose  to  ascorbic acid  (vitamin C), which is needed to repair arteries; following the loss of GULO, those primates who adopted diets less abundant in vitamin C may have used Lp(a) as an ascorbic-acid surrogate to repair arterial walls. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1631", "text": "The half-life of Lp(a) in circulation is approximately three to four days. [ 23 ]  The mechanism and sites of Lp(a) catabolism are largely unknown. The LDL receptor has been reported as a receptor for Lp(a) clearance, but is not a major pathway of Lp(a) metabolism under normal or hypercholesterolemic conditions. [ 29 ] [ 39 ] [ 40 ]  The kidney has been identified as playing a role in Lp(a) clearance from plasma. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1632", "text": "High Lp(a) in blood correlates with  coronary heart disease  (CHD),  cardiovascular disease  (CVD),  atherosclerosis ,  thrombosis , and stroke. [ 42 ]  However, the association between Lp(a) levels and stroke is not as strong as that between Lp(a) and cardiovascular disease. [ 3 ]  Lp(a) concentrations may be affected by disease states (for example kidney failure), but are only slightly affected by diet, exercise, and other environmental factors. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1633", "text": "Most commonly prescribed lipid-reducing drugs have little or no effect on Lp(a) concentration. Results using  statin  medications have been mixed in most trials, although a meta-analysis published in 2012 suggests that  atorvastatin  may be of benefit. [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1634", "text": "Niacin  (Vitamin B 3 ) has been shown to reduce the levels of Lp(a) significantly in individuals with high levels of low-molecular weight Lp(a). [ 44 ] [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1635", "text": "High Lp(a) correlates with early atherosclerosis independently of other cardiac risk factors, including LDL. In patients with advanced cardiovascular disease, Lp(a) indicates a coagulant risk of plaque thrombosis. Apo(a) contains domains that are very similar to plasminogen (PLG). Lp(a) accumulates in the vessel wall and inhibits the binding of PLG to the cell surface, reducing plasmin generation, which increases clotting. This inhibition of PLG by Lp(a) also promotes the proliferation of  smooth muscle  cells. These unique features of Lp(a) suggest that Lp(a) causes generation of clots and atherosclerosis. [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1636", "text": "In one homogeneous tribal population of Tanzania, vegetarians have higher levels of Lp(a) than fish eaters, raising the possibility that pharmacologic amounts of fish oil supplements may help lower the levels of Lp(a). [ 47 ]  Researchers in studies in 1995 and 1998 concluded that regular consumption of moderate amounts of alcohol led to a significant decline in plasma levels of Lp(a). [ 48 ]  Other studies did not report this."}
{"_id": "WikiPedia_Cardio$$$corpus_1637", "text": "Numerous studies confirming a strong correlation between elevated Lp(a) and heart disease have led to the consensus that Lp(a) is an important independent predictor of  cardiovascular disease . [ 3 ]  Animal studies have shown that Lp(a) may directly contribute to atherosclerotic damage by increasing plaque size, inflammation, instability, and smooth muscle cell growth. [ 49 ]  Genetic data also support the theory that Lp(a) causes cardiovascular disease. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1638", "text": "The European Atherosclerosis Society currently recommends that patients with a moderate or high risk of cardiovascular disease should have their Lp(a) levels checked. Any patient with one of the following risk factors should be screened:"}
{"_id": "WikiPedia_Cardio$$$corpus_1639", "text": "If the level is elevated, treatment should be initiated to bring the level below 50\u00a0mg/dL. In addition, the patient's other cardiovascular risk factors (including LDL levels) should be managed optimally. [ 3 ]  Apart from the total Lp(a) plasma concentration, the apo(a) isoform might be an important risk parameter as well. [ 50 ] [ 51 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1640", "text": "Prior studies of the relationship between Lp(a) and ethnicity have shown inconsistent results. Lp(a) levels seem to differ in different populations. For example, in some African populations, Lp(a) levels are higher on average than in other groups, so that using a risk threshold of 30\u00a0mg/dl could classify over 50% of the individuals as higher risk. [ 52 ] [ 53 ] [ 54 ] [ 55 ]  Some part of this complexity may be related to the different genetic factors involved in determining Lp(a) levels.  One recent study showed that in different ethnic groups, different genetic alterations were associated with increased Lp(a) levels. [ 56 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1641", "text": "More recent data suggest that prior studies were underpowered. The  Atherosclerosis Risk in Communities (ARIC)  Study followed 3467 African Americans and 9851 whites for 20 years. The researchers found that an elevated Lp(a) conferred the same risk in each group. African Americans had roughly three times the level of Lp(a), however, and Lp(a) also predicted an increased risk of stroke. [ 57 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1642", "text": "Approximate levels of risk are indicated by the results below, although at present there are a variety of different methods by which to measure Lp(a). A standardized international reference material has been developed and is accepted by the  WHO Expert Committee on Biological Standardization  and the  International Federation of Clinical Chemistry and Laboratory Medicine . Although further standardization is still needed, development of a reference material is an importance step toward standardizing results. [ 58 ] [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1643", "text": "Lipoprotein(a) \u2014 Lp(a) [ 60 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1644", "text": "Lp(a) appears with different isoforms (per kringle repeats) of apolipoprotein; 40% of the variation in Lp(a) levels when measured in mg/dl can be attributed to different isoforms. Lighter Lp(a) are also associated with disease. Thus, a test with simple quantitative results may not provide a complete assessment of risk. [ 61 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1645", "text": "The  US FDA  has  given the Tina-quant\u00ae lipoprotein Lp(a) RxDx assay from Roche, a Breakthrough Device Designation. The assay is designed to identify patients who may benefit from therapies aimed at decreasing Lp(a) levels. [ 62 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1646", "text": "The current simplest treatment for elevated Lp(a) is to take 1\u20133 grams of  niacin  daily, typically in an extended-release form. Niacin therapy may reduce Lp(a) levels by 20\u201330%. [ 63 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1647", "text": "A meta-analysis suggested that atorvastatin may lower Lp(a) levels. [ 43 ]  In severe cases, such as familial hypercholesterolemia or treatment-resistant hypercholesterolemia,  LDL apheresis  may dramatically reduce Lp(a). The goal of the treatment is to reduce levels to below 50\u00a0mg/dL. Cost is prohibitively high. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1648", "text": "A meta-analysis of six clinical trials confirmed that  flaxseed  supplementation modestly lowers Lp(a) levels. [ 64 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1649", "text": "Testosterone is known to reduce Lp(a) levels. [ 65 ]  Testosterone replacement therapy also appears to be associated with lower Lp(a) levels. [ 65 ] [ 66 ]  Estrogen replacement therapy in post-menopausal women will reduce Lp(a). [ 67 ]   Raloxifene  has not been shown to reduce Lp(a), while  tamoxifen  has. [ 68 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1650", "text": "L-carnitine may also reduce Lp(a) levels. A systematic review and meta-analysis found a significant reduction with oral but not intravenous carnitine. [ 69 ]  Other medications that are in various stages of development include thyromimetics, cholesterol-ester-transfer protein (CETP inhibitors), anti-sense oligonucleopeptides (such as  Pelacarsen  and  Olpasiran ), and proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) inhibitors. [ 66 ] [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1651", "text": "The  American Academy of Pediatrics  now recommends that all children between the ages of nine and eleven years old be screened for hyperlipidemia. Lp(a) levels should be considered in particular in children with a family history of early heart disease or high blood cholesterol levels. However, there have not been enough studies to determine which therapies might be beneficial. [ 71 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1652", "text": "Lp(a) has been shown to  interact  with  calnexin , [ 72 ] [ 73 ]   fibronectin , [ 37 ]  and  fibrinogen beta chain . [ 74 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1653", "text": "The following are  medications  commonly prescribed  cardiac pharmaceutical agents .\nThe specificity of the following medications is highly variable, and often are not particularly specific to a given class.\nAs such, they are listed as are commonly accepted."}
{"_id": "WikiPedia_Cardio$$$corpus_1654", "text": "Group of  pharmaceuticals  that are used to suppress abnormally fast rhythms ( tachycardias ), such as  atrial fibrillation ,  supraventricular tachycardia  and  ventricular tachycardia ."}
{"_id": "WikiPedia_Cardio$$$corpus_1655", "text": "Class of  antihypertensives  that work by causing relaxation of blood vessels as well as a decrease in  blood volume , which leads to lower  blood pressure  and decreased  oxygen  demand from the  heart . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1656", "text": "Class of  antihypertensives  that bind to and inhibit the  angiotensin II receptor type 1  and thereby block the  arteriolar contraction  and  sodium retention  effects of  renin\u2013angiotensin system ."}
{"_id": "WikiPedia_Cardio$$$corpus_1657", "text": "Class of medications that are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system."}
{"_id": "WikiPedia_Cardio$$$corpus_1658", "text": "Litten's sign  is a  clinical sign  in which  cotton wool spots  are seen on  fundoscopic  examination of the  retina  in patients with  infective endocarditis . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1659", "text": "The sign is named after  Moritz Litten ."}
{"_id": "WikiPedia_Cardio$$$corpus_1660", "text": "The Louis and Artur Lucian Award in Cardiovascular Diseases  is a prize for cardiovascular medicine conferred by  McGill University . Described as Canada's \"top cardiovascular research prize\", [ 1 ]  it has been awarded annually since 1978, except in 2007. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1661", "text": "Source:  McGill University"}
{"_id": "WikiPedia_Cardio$$$corpus_1662", "text": "This  award -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1663", "text": "Low-density lipoprotein  ( LDL ) is one of the five major groups of  lipoprotein  that transport all  fat  molecules around the body in extracellular water. [ 1 ]  These groups, from least dense to most dense, are  chylomicrons  (aka  ULDL  by the overall density naming convention),  very low-density lipoprotein  (VLDL),  intermediate-density lipoprotein  (IDL), low-density lipoprotein (LDL) and  high-density lipoprotein  (HDL). LDL delivers fat molecules to  cells . LDL has been associated with the progression of  atherosclerosis ."}
{"_id": "WikiPedia_Cardio$$$corpus_1664", "text": "Lipoproteins transfer  lipids  ( fats ) around the body in the  extracellular fluid , making fats available to body cells for  receptor-mediated endocytosis . [ 2 ] [ 3 ]  Lipoproteins are complex particles composed of multiple  proteins , typically 80\u2013100 proteins per particle (organized by a single  apolipoprotein B  for LDL and the larger particles). A single LDL particle is about 220\u2013275  angstroms  in diameter, typically transporting 3,000 to 6,000 fat molecules per particle, and varying in size according to the number and mix of fat molecules contained within. [ 4 ]  The lipids carried include all fat molecules with  cholesterol ,  phospholipids , and  triglycerides  dominant; amounts of each vary considerably. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1665", "text": "A good clinical interpretation of blood lipid levels is that high LDL, in combination with a high amount of triglycerides, which indicates a high likelihood of the LDL being oxidised, is associated with increased risk of  cardiovascular diseases . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1666", "text": "Each native LDL particle enables emulsification, i.e. surrounding the fatty acids being carried, enabling these fats to move around the body within the water outside cells. Each particle contains a single  apolipoprotein  B-100 molecule ( Apo B-100 , a protein that has 4536  amino acid  residues and a mass of 514  kDa ), along with 80 to 100 additional ancillary proteins. Each LDL has a highly hydrophobic core consisting of  polyunsaturated fatty acid  known as  linoleate  and hundreds to thousands (about 1500 commonly cited as an average) of  esterified  and unesterified cholesterol molecules. This core also carries varying numbers of triglycerides and other fats and is surrounded by a shell of phospholipids and unesterified cholesterol, as well as the single copy of Apo B-100. LDL particles are approximately 22\u00a0nm (0.00000087\u00a0in.) to 27.5\u00a0nm in diameter and have a mass of about 3 million daltons. [ 7 ]  Since LDL particles contain a variable and changing number of fatty acid molecules, there is a distribution of LDL particle mass and size. [ 4 ]  Determining the structure of LDL has been difficult for biochemists because of its heterogeneous structure. However, the structure of LDL at human body temperature in native condition, with a resolution of about 16  Angstroms  using  cryogenic electron microscopy , has been described in 2011. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1667", "text": "LDL particles are formed when triglycerides are removed from VLDL by the  lipoprotein lipase  enzyme (LPL) and they become smaller and denser (i.e. fewer fat molecules with same protein transport shell), containing a higher proportion of cholesterol esters. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1668", "text": "When a cell requires additional cholesterol (beyond its current internal  HMGCoA  production pathway), it synthesizes the necessary  LDL receptors  as well as  PCSK9 , a  proprotein convertase  that marks the LDL receptor for degradation. [ 11 ]  LDL receptors are inserted into the plasma membrane and diffuse freely until they associate with  clathrin -coated pits. When LDL receptors bind LDL particles in the bloodstream, the clathrin-coated pits are endocytosed into the cell. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1669", "text": "Vesicles containing LDL receptors bound to LDL are delivered to the  endosome . In the presence of low  pH , such as that found in the endosome, LDL receptors undergo a conformation change, releasing LDL. LDL is then shipped to the  lysosome , where  cholesterol esters  in the LDL are  hydrolysed . LDL receptors are typically returned to the plasma membrane, where they repeat this cycle. If LDL receptors bind to PCSK9, however, transport of LDL receptors is redirected to the lysosome, where they are degraded. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1670", "text": "LDL interferes with the  quorum sensing  system that upregulates genes required for invasive  Staphylococcus aureus  infection. The mechanism of antagonism entails binding apolipoprotein B to a  S. aureus   autoinducer  pheromone, preventing signaling through its receptor. Mice deficient in apolipoprotein B are more susceptible to invasive bacterial infection. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1671", "text": "LDL can be grouped based on its size: large low density LDL particles are described as  pattern A , and small high density LDL particles are  pattern B . [ 14 ]   Pattern B  has been associated by some with a higher risk for  coronary heart disease . [ 15 ] :\u200a1\u201310\u200a  This is thought to be because the smaller particles are more easily able to penetrate the  endothelium  of  arterial walls .  Pattern I , for  intermediate , indicates that most LDL particles are very close in size to the normal gaps in the endothelium (26\u00a0nm). According to one study, sizes 19.0\u201320.5\u00a0nm were designated as pattern B and LDL sizes 20.6\u201322\u00a0nm were designated as pattern A. [ 16 ]  Other studies have shown no such correlation at all. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1672", "text": "Some evidence suggests the correlation between Pattern B and coronary heart disease is stronger than the correspondence between the LDL number measured in the standard lipid profile test. Tests to measure these LDL subtype patterns have been more expensive and not widely available, so the common lipid profile test is used more often. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1673", "text": "There has also been noted a correspondence between higher triglyceride levels and higher levels of smaller, denser LDL particles and alternately lower triglyceride levels and higher levels of the larger, less dense (\"buoyant\") LDL. [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1674", "text": "With continued research, decreasing cost, greater availability and wider acceptance of other  lipoprotein subclass analysis  assay methods, including  NMR spectroscopy , research studies have continued to show a stronger correlation between human clinically obvious cardiovascular events and quantitatively measured particle concentrations. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1675", "text": "Oxidized LDL is a general term for LDL particles with oxidatively modified structural components. As a result, from  free radical  attack, both lipid and protein parts of LDL can be oxidized in the vascular wall. Besides the oxidative reactions taking place in vascular wall, oxidized lipids in LDL can also be derived from oxidized dietary lipids. [ 21 ] [ 22 ]   Oxidized LDL is known to associate with the development of  atherosclerosis , and it is therefore widely studied as a potential risk factor of  cardiovascular diseases . [ 23 ]  Atherogenicity of oxidized LDL has been explained by lack of recognition of oxidation-modified LDL structures by the LDL receptors, preventing the normal metabolism of LDL particles and leading eventually to development of atherosclerotic plaques. [ 23 ]  Of the lipid material contained in LDL, various lipid oxidation products are known as the ultimate atherogenic species. [ 24 ]  Acting as a transporter of these injurious molecules is another mechanism by which LDL can increase the risk of atherosclerosis. [ 22 ] [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1676", "text": "Blood tests  commonly report LDL-C: the amount of cholesterol which is estimated to be contained with LDL particles, on average, using a formula, the  Friedewald equation . In clinical context, mathematically calculated estimates of LDL-C are commonly used as an estimate of how much low density lipoproteins are driving progression of atherosclerosis. The problem with this approach is that LDL-C values are commonly discordant with both direct measurements of LDL particles and actual rates of atherosclerosis progression. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1677", "text": "Direct LDL measurements are also available and better reveal individual issues but are less often promoted or done due to slightly higher costs and being available from only a couple of laboratories in the  United States . In 2008, the  ADA  and  ACC  recognized direct LDL particle measurement by NMR as superior for assessing individual risk of cardiovascular events. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1678", "text": "Chemical measures of lipid concentration have long been the most-used clinical measurement, not because they have the best correlation with individual outcome, but because these lab methods are less expensive and more widely available."}
{"_id": "WikiPedia_Cardio$$$corpus_1679", "text": "The lipid profile does not measure LDL particles. It only estimates them using the Friedewald equation [ 19 ] [ 27 ] \nby subtracting the amount of cholesterol associated with other particles, such as  HDL  and VLDL, assuming a prolonged fasting state, etc.:"}
{"_id": "WikiPedia_Cardio$$$corpus_1680", "text": "There are limitations to this method, most notably that samples must be obtained after a 12 to 14 h fast and that LDL-C cannot be calculated if plasma triglyceride is >4.52\u00a0mmol/L (400\u00a0mg/dL). Even at triglyceride levels 2.5 to 4.5\u00a0mmol/L, this formula is considered inaccurate. [ 28 ]   If both total cholesterol and triglyceride levels are elevated then a modified formula, with quantities in mg/dL, may be used"}
{"_id": "WikiPedia_Cardio$$$corpus_1681", "text": "This formula provides an approximation with fair accuracy for most people, assuming the blood was drawn after fasting for about 14 hours or longer, but does not reveal the actual LDL particle concentration because the percentage of fat molecules within the LDL particles which are cholesterol varies, as much as 8:1 variation. There  are several formulas published addressing the inaccuracy in LDL-C estimation. [ 29 ] [ 30 ] [ 31 ]  The inaccuracy is based on the assumption that VLDL-C (Very low density lipoprotein cholesterol) is always one-fifth of the triglyceride concentration. Another formulae addresses this issue by using an adjustable factor  [ 32 ]  or by using a regression equation. [ 33 ]  There are few studies which have compared the LDL-C values derived from this formula and values obtained by direct enzymatic method. [ 34 ]  Direct enzymatic method are found to be accurate and it has to be the test of choice in clinical situations. In the resource poor settings, the option of using the formula has to be considered. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1682", "text": "However, the concentration of LDL particles, and to a lesser extent their size, has a stronger and consistent correlation with individual clinical outcome than the amount of cholesterol within LDL particles, even if the LDL-C estimation is approximately correct. There is increasing evidence and recognition of the value of more targeted and accurate measurements of LDL particles. Specifically, LDL particle number (concentration), and to a lesser extent size, have shown slightly stronger correlations with atherosclerotic progression and cardiovascular events than obtained using chemical measures of the amount of cholesterol carried by the LDL particles. [ 35 ]  It is possible that the LDL cholesterol concentration can be low, yet LDL particle number high and cardiovascular events rates are high. Correspondingly, it is possible that LDL cholesterol concentration can be relatively high, yet LDL particle number low and cardiovascular events are also low. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1683", "text": "In the US, the  American Heart Association ,  NIH , and  NCEP  provide a set of guidelines for fasting LDL-Cholesterol levels, estimated or measured, and risk for heart disease. As of about 2005, these guidelines were: [ 36 ] [ 37 ] [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1684", "text": "Over time, with more clinical research, these recommended levels keep being reduced because LDL reduction, including to abnormally low levels, was the most effective strategy for reducing cardiovascular death rates in one large  double blind , randomized clinical trial of men with  hypercholesterolemia ; [ 39 ]  far more effective than coronary angioplasty/stenting or bypass surgery. [ 40 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1685", "text": "For instance, for people with known atherosclerosis diseases, the 2004 updated American Heart Association, NIH and NCEP recommendations are for LDL levels to be lowered to less than 70\u00a0mg/dL. This low level of less than 70\u00a0mg/dL was recommended for primary prevention of 'very-high risk patients' and in secondary prevention as a 'reasonable further reduction'. This position was disputed. [ 41 ]  Statin drugs involved in such clinical trials have  numerous physiological effects  beyond simply the reduction of LDL levels."}
{"_id": "WikiPedia_Cardio$$$corpus_1686", "text": "From longitudinal population studies following progression of atherosclerosis-related behaviors from early childhood into adulthood, [ 42 ]  the usual LDL in childhood, before the development of  fatty streaks , is about 35\u00a0mg/dL. However, all the above values refer to chemical measures of lipid/cholesterol concentration within LDL, not measured low-density lipoprotein concentrations, the accurate approach. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1687", "text": "A study was conducted measuring the effects of guideline changes on LDL cholesterol reporting and control for diabetes visits in the US from 1995 to 2004. It was found that although LDL cholesterol reporting and control for diabetes and coronary heart disease visits improved continuously between 1995 and 2004, [ 43 ] [ 44 ]  neither the 1998 ADA guidelines nor the 2001 ATP III guidelines increased LDL cholesterol control for diabetes relative to coronary heart disease. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1688", "text": "There are several competing methods for measurement of lipoprotein particle concentrations and size. The evidence is that the NMR methodology (developed, automated & greatly reduced in costs while improving accuracy as pioneered by  Jim Otvos  and associates) results in a 22-25% reduction in cardiovascular events within one year, [ 46 ]  contrary to the longstanding claims by many in the medical industry that the superiority over existing methods was weak, even by statements of some proponents. [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1689", "text": "Since the later 1990s, because of the development of NMR measurements, it has been possible to clinically measure lipoprotein particles at lower cost [under $80 US (including shipping) & is decreasing; versus the previous costs of >$400 to >$5,000] and higher accuracy. There are two other assays for LDL particles, however, like LDL-C, most only estimate LDL particle concentrations. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1690", "text": "Direct LDL particle measurement by NMR was mentioned by the ADA and ACC, in a 28 March 2008 joint consensus statement, [ 48 ]  as having advantages for predicting individual risk of atherosclerosis disease events, but the statement noted that the test is less widely available, is more expensive [about $13.00 US (2015 without insurance coverage) from some labs which use the Vantera Analyzer [ 49 ] ]. Debate continues that it is \"...unclear whether LDL particle size measurements add value to measurement of LDL-particle concentration\", though outcomes have always tracked LDL particle, not LDL-C, concentrations."}
{"_id": "WikiPedia_Cardio$$$corpus_1691", "text": "Using NMR, the total LDL particle concentrations, in nmol/L plasma, are typically subdivided by percentiles referenced to the 5,382 men and women, not on any lipid medications, who are participating in the MESA trial. [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1692", "text": "LDL particle concentration can also be measured by measuring the concentration of the protein ApoB, based on the generally accepted principle that each LDL or VLDL particle carries one ApoB molecule. [ 51 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1693", "text": "The LDL particle concentrations are typically categorized by percentiles, <20%, 20\u201350%, 50th\u201380th%, 80th\u201395% and >95% groups of the people participating and being tracked in the  MESA trial , a medical research study sponsored by the United States National Heart, Lung, and Blood Institute."}
{"_id": "WikiPedia_Cardio$$$corpus_1694", "text": "The lowest incidence of atherosclerotic events over time occurs within the <20% group, with increased rates for the higher groups.  [ citation needed ]  Multiple other measures, including particle sizes, small LDL particle concentrations, large total and HDL particle concentrations, along with estimations of  insulin resistance  pattern and standard cholesterol lipid measurements (for comparison of the plasma data with the estimation methods discussed above) are also routinely provided."}
{"_id": "WikiPedia_Cardio$$$corpus_1695", "text": "(Per 2004 United States Government Minimum Guidelines [ 52 ] [ 53 ] )"}
{"_id": "WikiPedia_Cardio$$$corpus_1696", "text": "The  mevalonate pathway  serves as the basis for the biosynthesis of many molecules, including cholesterol. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase ( HMG CoA reductase ) is an essential component and performs the first of 37 steps within the cholesterol production pathway, and is present in every animal cell. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1697", "text": "LDL-C is not a measurement of actual LDL particles. LDL-C is only an estimate (not measured from the individual's blood sample) of how much cholesterol is being transported by all LDL particles, which is either a smaller concentration of large particles or a high concentration of small particles. LDL particles carry many fat molecules (typically 3,000 to 6,000 fat molecules per LDL particle); this includes cholesterol, triglycerides, phospholipids and others. Thus even if the hundreds to thousands of cholesterol molecules within an average LDL particle were measured, this does not reflect the other fat molecules or even the number of LDL particles."}
{"_id": "WikiPedia_Cardio$$$corpus_1698", "text": "LDL cholesterol can be lowered through dietary intervention by limiting foods with  saturated fat  and avoiding foods with  trans fat . [ 65 ]  Saturated fats are found in meat products (including poultry), full-fat dairy, eggs, and refined tropical oils like coconut and palm. [ 66 ]  Added trans fat (in the form of partially hydrogenated oils) has been banned in the US since 2021. [ 67 ]  However, trans fat can still be found in red meat and dairy products as it is produced in small amounts by ruminants such as sheep and cows. [ 68 ]  LDL cholesterol can also be lowered by increasing consumption of soluble fiber and plant-based foods. [ 69 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1699", "text": "Another lifestyle approach to reduce LDL cholesterol has been minimizing total body fat, in particular fat stored inside the  abdominal cavity  ( visceral body fat ). Visceral fat, which is more metabolically active than subcutaneous fat, has been found to produce many enzymatic signals, e.g.  resistin , which increase  insulin resistance  and circulating VLDL particle concentrations, thus both increasing LDL particle concentrations and accelerating the development of diabetes mellitus."}
{"_id": "WikiPedia_Cardio$$$corpus_1700", "text": "In 2021, scientists demonstrated that  CRISPR gene editing  can decrease blood levels of LDL cholesterol in  Macaca fascicularis  monkeys for months by 60% via  knockout  of  PCSK9  in the  liver . [ 70 ] [ 71 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1701", "text": "Marden\u2013Walker syndrome  ( MWS ) is a rare  autosomal   recessive   congenital disorder . [ 1 ] [ 2 ]  It is characterized by  blepharophimosis ,  microcephaly ,  micrognathia , multiple  joint   contractures ,  arachnodactyly ,  camptodactyly ,  kyphoscoliosis  and delayed  motor development  and is often associated with  cystic   dysplastic   kidneys ,  dextrocardia ,  Dandy\u2013Walker malformation  and  agenesis of corpus callosum . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1702", "text": "Most of the signs of MWS are present during the neonatal period. The most common signs at this state are multiple congenital joint contractures, dysmorphic features with mask-like face,  blepharophimosis ,  ptosis ,  micrognathia , cleft or high arched palate, low-set ears,  arachnodactyly , chest deformation as pectus,  kyphoscoliosis  and absent deep tendon reflexes are frequent minor malformations have also been described and consist of renal anomalies, cardiovascular abnormalities,  hypospadias ,  omphalomesenteric  duct, hypertrophic pyloric stenosis and duodenal bands, hypoplastic right lower lobe of the lung, displacement of the  larynx  to the right and vertebral abnormalities, cerebral malformations. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1703", "text": "The natural history of MWS is not well known: many patients died in infancy and clinical follow-up has been reported in few surviving adults. However, diagnosis may be more difficult to establish in adults patients, such as:  blepharophimosis ,  contractures ,  growth retardation , and  developmental delay , whereas minor face anomalies are less noticeable as the patient grows older. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1704", "text": "MWS is a  heterogeneous , initially described as a syndrome. But this condition is more on the lines of a  phenotypic  expression of various heterogeneous diseases and belongs to the second group in the classification of  arthrogryposis . Unknown congenital  myopathy  has been suspected to underlie MWS due to muscular involvement, but extension of the  neuromuscular  systems failed to identify a primary myopathy in patients with MWS. Secondary muscle involvement from a CNS lesion may occur. This could lead to congenital weakness with hypoatonia deep tendon reflex. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1705", "text": "MWS is inherited in an autosomal recessive manner. [ 2 ]  This means the defective gene responsible for the disorder is located on an  autosome , and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both  carry  one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1706", "text": "Though the pathomechanism of Marden\u2013Walker syndrome is unknown, it may be caused by a genetic defect which manifests as a  dysfunctional molecular mechanism  in the primary  cilia  structures of the  cell .  These  organelles  are present in many cellular types throughout the  human  body.  The cilia defects adversely affect \"numerous critical developmental signaling pathways\" essential to cellular development. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1707", "text": "The only treatment for MWS is only symptomatic, with multidisciplinary management [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1708", "text": "There have been 30 cases of Marden-Walker Syndrome reported since 1966. The first case of this was in 1966 a female infant was diagnosed with  blepharophimosis ,  joint contractures , arachnodactyly and growth development delay. She ended up dying at 3 months due to pneumonia. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1709", "text": "Multicenter Automatic Defibrillator Implantation Trial [ 1 ]  and MADIT II [ 2 ]   are  implantable cardioverter defibrillator  (or ICD) trials which investigate whether prophylactic ICD therapy in moderately high-risk  coronary  patients (in addition to conventional therapy) would significantly reduce death compared with patients treated with conventional therapy alone."}
{"_id": "WikiPedia_Cardio$$$corpus_1710", "text": "The MADIT II trial started in 1997 and ended in 2001 where the safety committee stopped the study because the benefits were already statistically significant."}
{"_id": "WikiPedia_Cardio$$$corpus_1711", "text": "The study included patients with a prior  myocardial infarction  and an  ejection fraction  less than or equal to 30%."}
{"_id": "WikiPedia_Cardio$$$corpus_1712", "text": "The results were a reduction in mortality of 31% compared to patients receiving conventional therapy alone."}
{"_id": "WikiPedia_Cardio$$$corpus_1713", "text": "This  medical treatment \u2013related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1714", "text": "Myocardial depressant factor  (MDF) or  Myocardial Toxic factor  (MTF) is a low-molecular-weight  peptide [ 1 ]  released from the  pancreas  into the blood in mammals during various  shock  states. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1715", "text": "MDF is a significant mediator of shock pathophysiology, reducing  myocardial  contractility, constricting  splanchnic  arteries and impairing  phagocytosis  by the  reticuloendothelial system . Survival can be improved by preventing its release or blocking its activity, for example using  glucocorticoids ,  prostaglandins ,  aprotinin ,  captopril ,  imidazole  or  lidocaine . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1716", "text": "This  molecular biology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_1717", "text": "Myocardial injury after non-cardiac surgery , also known as  MINS , refers to at least one elevated post-operative  troponin  level presumed to be of an ischemic mechanism. [ 1 ] [ 2 ]  There is an absence of any overt non-ischemic causes to explain this elevation."}
{"_id": "WikiPedia_Cardio$$$corpus_1718", "text": "National Medical Research Center for Cardiology named after academician  Yevgeniy Chazov  of the  Ministry of Health of the Russian Federation  ( Russian :  \u0424\u0413\u0411\u0423 \u00ab\u041d\u0430\u0446\u0438\u043e\u043d\u0430\u043b\u044c\u043d\u044b\u0439 \u043c\u0435\u0434\u0438\u0446\u0438\u043d\u0441\u043a\u0438\u0439 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u0442\u0435\u043b\u044c\u0441\u043a\u0438\u0439 \u0446\u0435\u043d\u0442\u0440 \u043a\u0430\u0440\u0434\u0438\u043e\u043b\u043e\u0433\u0438\u0438 \u0438\u043c\u0435\u043d\u0438 \u0430\u043a\u0430\u0434\u0435\u043c\u0438\u043a\u0430 \u0415.\u0418. \u0427\u0430\u0437\u043e\u0432\u0430\u00bb (\u041d\u041c\u0418\u0426 \u043a\u0430\u0440\u0434\u0438\u043e\u043b\u043e\u0433\u0438\u0438) \u041c\u0438\u043d\u0438\u0441\u0442\u0435\u0440\u0441\u0442\u0432\u0430 \u0437\u0434\u0440\u0430\u0432\u043e\u043e\u0445\u0440\u0430\u043d\u0435\u043d\u0438\u044f \u0420\u043e\u0441\u0441\u0438\u0439\u0441\u043a\u043e\u0439 \u0424\u0435\u0434\u0435\u0440\u0430\u0446\u0438\u0438 )  is one of the leading and oldest specialized medical institutions in Russia, whose activities are aimed at diagnosing, treating and preventing cardiovascular diseases. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1719", "text": "The history of the cardiological complex dates back to 1945, when the Institute of Experimental and Clinical Therapy of the  USSR Academy of Medical Sciences  was organized on the basis of the clinics of the All-Union Institute of Experimental Medicine. The first director of the institute was the therapist, doctor of medical sciences, academician of the Academy of Medical Sciences V. F. Zelenin. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1720", "text": "Three years later, the Institute of Clinical Therapy was reorganized into the Institute of Therapy, and Academician A. L. Myasnikov was appointed director, who, upon taking office, identified priority areas for study:  hypertension  and atherosclerosis. Soon the institute became the leading institution in the Soviet Union dealing with cardiovascular pathologies. However, for further development, the institute needed to expand its staff and territory. This became possible after moving to Petroverigsky Lane. The priority areas of the Institute's activities include  coronary circulation  and its regulation,  renal circulation  and arterial hypertension; research on  atherosclerosis  has also expanded significantly. [ 2 ]  In 1963, the Institute established the first specialized department in the  Soviet Union  for the treatment of  acute myocardial infarction . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1721", "text": "In 1965, after the death of A. L. Myasnikov,  Yevgeniy Chazov  who worked also in the  Kremlin Hospital  became the director. A year later, the institute received the name of the former director and became known as the Research Institute of Therapy named after. A. L. Myasnikov, and a year later changed the name to the Institute of Cardiology. A. L. Myasnikova. At that time, the institute carried out extensive research on the possibilities of diagnosing and treating secondary forms of arterial hypertension. An experimental laboratory for cardiac electrophysiology was also founded, where two antiarrhythmic drugs, ethmozine and ethacizine, were created. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1722", "text": "On May 16, 1973, the first clinical echocardiographic study was carried out at the institute. Yuri Belenkov, an employee of the institute, becomes a pioneer in the development and implementation of this diagnostic method into wide practice. In 1975, by a decree of the  Council of Ministers of the USSR , the All-Union Cardiology Research Center (VKSC) was created, the composition of which was constantly increasing, and by 1981 it included the Research Institute of Cardiology named after. A. L. Myasnikova, Institute of Experimental Cardiology and Institute of Preventive Cardiology. [ 2 ]  On June 5 of the same year, in the Department of Emergency Cardiology of the VKSC, for the first time in the world, a patient with myocardial infarction underwent thrombolysis using intracoronary administration of fibrinolysin at a dose 10 times lower than with intravenous administration, which led to the creation of a new method of treatment -  thrombolytic therapy ."}
{"_id": "WikiPedia_Cardio$$$corpus_1723", "text": "On August 24, 1982 [ 3 ]  The Institute of Clinical Cardiology and the Institute of Experimental Cardiology move to a new complex of 26 buildings on 3rd Cherepkovskaya Street. The work of a group of architects (I.M. Vinogradsky, V.K. Legoshin and others) on this complex of buildings was awarded the USSR State Prize in Literature, Art and Architecture in 1990."}
{"_id": "WikiPedia_Cardio$$$corpus_1724", "text": "In 1984, the Department of Cardiac Surgery was opened, headed by Academician R.S. Akchurin. In 1988, the Institute of Preventive Cardiology was withdrawn from the VKSC, which was later transformed into the Center for Preventive Medicine. In 1996, by an  order  of the  Government of Russia , the center received the name of the Russian Cardiology Research and Production Complex (RKNPC) of the Ministry of Health of Russia. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1725", "text": "In 2016, plans were announced for the reconstruction and expansion of building 9b of the RKNPC, which houses the cardio-reanimation ward [ 4 ]  The reconstruction provides for a change in the space-planning decisions of the building, with placement on the first floor of a therapeutic inpatient department for 30 beds. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1726", "text": "On May 1, 2017, in accordance with the order of the  Minister of Health of the Russian Federation , Corresponding Member of the  Russian Academy of Sciences , Doctor of Medical Sciences, Professor Sergey Boytsov was appointed General Director. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1727", "text": "On July 12, 2017, the RKNPC was renamed the National Medical Research Center for Cardiology."}
{"_id": "WikiPedia_Cardio$$$corpus_1728", "text": "In cardiology  neocardiogenesis  is the  homeostatic  regeneration, repair and renewal of sections of malfunctioning adult cardiovascular tissue.  This includes a combination of  cardiomyogenesis  (the regeneration of  cardiac muscle ) and  angiogenesis  (the regeneration of  blood vessels ). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1729", "text": "The term neocardiogenesis comes from  cardiogenesis , which refers to the development of the heart in the embryo; neocardiogenesis, in turn, means the development of the heart in adults.  The heart has mechanisms already in place that are responsible for small scale repair.  However, these repair mechanisms are not sufficient for large scale repair, made necessary by events such as  myocardial infarctions .  Neocardiogenesis replaces dead cardiac muscle cells with living cells so that both the structure and function of the heart are maintained.  This improves myocardial pumping of fluid around the body. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1730", "text": "The human heart has been thought of as a  postmitotic  organ.  Cardiomyocytes  (muscle cells of the heart) were thought to be terminally differentiated cells that were irreplaceable and thus required to maintain cardiac function throughout life. However it is now known that the heart is able to regenerate new small vessels needed to repair an  ischemic  (lacking blood) myocardium. The belief that humans are born with a fixed number of cardiomyocytes, and that the growth of these cells was directly responsible for the growth of the heart, has also been disproven. [ 3 ]  Reports of the heart's ability to repair itself have started to appear in peer reviewed journals [ 4 ]  and a paper has been published that has shown the potential of bone marrow cells to regenerate myocardium (myogenesis). [ 5 ]  Other studies into the regeneration of myocardium have reported evidence of angiogenesis, [ 6 ]  although such studies have been found to contain discrepancies. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1731", "text": "It has been reported that improvement in heart contractility has occurred as a result of the induction of angiogenesis. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1732", "text": "The activation of cardiac  progenitor cells  (a special type of stem cell with long  telomeres  located in the storage areas of the heart) and circulating stem cells induce cardiomyocytes to  proliferate .  These cells are activated by a mixture of transcriptional factors, genes, growth factors, receptors, the  extracellular matrix  and signalling pathways. The cells then move to affected areas where they can reverse some of the damage by generating a new population of cardiomyocytes. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1733", "text": "The heart has the potential to repair itself when damaged using progenitor and  stem cells . [ 10 ]   Clinical trials have shown that heart muscle has not previously been able to regenerate itself.  New noninvasive drugs, which may make this possible in humans, are required to induce the cardiac myocytes to proliferate.  Studies have been done in an attempt to find such a treatment. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1734", "text": "Neurocardiology  is the study of the  neurophysiological ,  neurological  and  neuroanatomical  aspects of  cardiology , including especially the neurological origins of cardiac disorders. [ 1 ]  The effects of stress on the  heart  are studied in terms of the heart's interactions with both the  peripheral nervous system  and the  central nervous system ."}
{"_id": "WikiPedia_Cardio$$$corpus_1735", "text": "Clinical issues in neurocardiology include  hypoxic \u2013 ischemic  brain injury, neurogenic  stress cardiomyopathy , cerebral  embolism ,  encephalopathy , neurologic sequelae of cardiac and thoracic surgery and cardiac interventions, and cardiovascular findings in patients with primary neurological disease. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1736", "text": "Neurocardiology refers to the pathophysiological interplays of the nervous and cardiovascular systems. [ 3 ]  The constant communication between the heart and the brain have proved invaluable to the interdisciplinary fields of neurological and cardiac diseases. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1737", "text": "The fundamental understanding of the communication between the heart and the brain via the nervous system has led scientists towards an understanding of its elaborate circuitry. The brain emits neurological signals of oscillating frequencies. The neural rhythms provide information on the steady-state conditions of healthy individuals. Variations in the neural rhythms provide evidence that a problem is present regarding physiologic regulation and help physicians to more quickly determine the underlying condition based on the given symptoms. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1738", "text": "The  neurocardiac axis  links the cardiovascular and nervous systems to physiological problems such as arrhythmias, epilepsy and stroke. These problems are related to the fundamental factor of stress on the body. As stated previously, the changes in neural oscillations can contribute to the knowledge of what a steady state in an individual looks like, especially because it changes based on the person, as well as contributing to the imbalance of the nervous system and physiological function. Moreover, the brain can control the heart rate through the sympathetic nervous system. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1739", "text": "The cardiovascular system is regulated by the autonomic nervous system, which includes the sympathetic and parasympathetic nervous systems. A distinct balance between these systems is crucial for the pathophysiology of cardiovascular disease. An imbalance can be caused by  hormone  levels, lifestyle, environmental stressors and injuries. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1740", "text": "The complicated link between the brain and the heart can be mapped out from the complex of higher nervous system influences descending down to the heart. This complex innervates key autonomic structures from the brain's cortex to the heart along the neurocardiac axis. The heart is both the source of life and a source of cardiac arrhythmias and complications. The information originates in the brain's cortex and descends down to the  hypothalamus . The neural signals are then transferred to the  brainstem , followed by the  spinal cord \u2014the location from which the heart receives all its signals. In further detail, the heart receives its neural input through parasympathetic and sympathetic ganglia and the  lateral grey column  of the spinal cord. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1741", "text": "The neurocardiac axis is the link to many problems regarding the physiological functions of the body. This includes cardiac ischemia, stroke, epilepsy, heart arrhythmias and cardiac myopathies. Many of these problems are due to the imbalance of the nervous system, resulting in symptoms that affect both the heart and the brain. [ 6 ] \n The connection between the cardiovascular and nervous system has raised concerns in the training processes for medical students. Neurocardiology is based on an understanding that systems within the body are interconnected. When training within one specialty, doctors are more likely to associate patients' symptoms with their field. Without taking integration into account, doctors can consequently delay a correct diagnosis and treatment for the patient. [ 7 ]  However, by specializing in a field, advancement in medicine continues as new findings come into perspective. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1742", "text": "Cardiovascular systems are regulated by the  autonomic nervous system , which includes the sympathetic and  parasympathetic nervous systems . A distinct balance between these two systems is crucial for the pathophysiology of cardiovascular disease.  Chronic stress  has been widely studied for its effects on the body, resulting in an elevated heart rate (HR), reduced HR variability, elevated sympathetic tone and intensified cardiovascular activity. Consequently, stress promotes an autonomic imbalance in favor of the  sympathetic nervous system . The activation of the sympathetic nervous system contributes to  endothelial  dysfunction,  hypertension ,  atherosclerosis , insulin resistance and increased incidence of arrhythmias. [ 6 ]   An imbalance in the autonomic nervous system has been documented in mood disorders; it is commonly regarded as a mediator between mood disorders and cardiovascular disorders. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1743", "text": "The hypothalamus is the part of the brain that regulates function and responds to stress. When the brain perceives environmental danger, the  amygdala  fires a nerve impulse to the  hypothalamus  to initiate the body's fight-or-flight mode through the sympathetic nervous system. The stress response starts with the hypothalamus stimulating the  pituitary gland , which releases the  adrenocorticotropic hormone . This signals the release of  cortisol , the stress hormone, initiating a multitude of physical effects on the body to aid in survival. A  negative feedback loop  is then needed to return the body to its resting state by signaling the parasympathetic nervous system. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1744", "text": "Prolonged stress leads to many hazards within the nervous system. Various hormones and glands become overworked, and chemical waste is produced, resulting in the degeneration of nerve cells. The result of prolonged stress is the breakdown of the body and the nervous system. Stress alone does not produce potentially deadly arrhythmias in normal healthy hearts; however, studies do appear to show that stress causes cardiac damage that may lead to arrhythmias. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1745", "text": "In a study relating to the relationship between neurocardiology and  arrhythmias  and sudden cardiac death, the authors hypothesized that an individual with a diseased heart has a greater likelihood of experiencing cardiac arrhythmias and sudden cardiac death when the neurocardiac axis is activated. [ 7 ]  An arrhythmia is defined as any disturbance in the cardiac activation sequence or any deviation from accepted limits for the rate or regularity of the normal impulse. The main types of arrhythmias leading to sudden cardiac death are tachyarrhythmias and bradyarrhythmia. Tachyarrhythmias are associated with ventricular fibrillation and  ventricular tachycardia . Bradyarrhythmias are associated with complete atrioventricular blockage and sudden asystole. The underlying cause of sudden cardiac death is unclear, despite the understanding that heart disease causes arrhythmias, which in turn produce sudden cardiac death. [ 7 ]  Lown describes the heart as the target, and the brain as the trigger. If a sudden cardiac death is triggered by an electrical accident, it can be treated with ventricular defibrillation. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1746", "text": "Stroke activates the neurocardiac axis, producing arrhythmias, cardiac damage, and sudden death. In a recent study on patients with already diseased hearts and  electrocardiographic  abnormalities, there was evidence of lost hypothalamic\u2013medullary integration at the midbrain. This resulted in the observation that overactivity in the parasympathetic nervous system may also cause sudden death with  asystole  after stroke.  Catecholamine  medications have been studied for their ability to mediate the effects of electrocardiographic changes and heart damage. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1747", "text": "Sudden death from epilepsy is not very common, with a rate of approximately two cases in every thousand. The present understanding about how sudden cardiac death can result from epilepsy is that the brain stimulates an arrhythmia. Recordings during seizures report that the onset of tachycardia just prior to the seizure is common, with both atrial and ventricular ectopy. [ 7 ]  A sudden epileptic death may be a result of the sympathetic activation or autonomic imbalance of the nervous system, as described earlier. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1748", "text": "The relationship between emotions and their effect on the destabilization of the heart continues to be a mystery. It is considered that both the spatial and temporal patterns of autonomic input to the heart play a key role in altered electrophysiological parameters. The body continually attempts to maintain homeostasis through the  baroreflex . This balance in the autonomic neural input to the heart in response to the pressure and volume changes leads to alterations in the  baroreceptors . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1749", "text": "Drugs with both antidepressant and cardiometabolic actions are in the process of being studied. Most medications work on stressors of the heart and some also work to treat neuropsychiatric diseases. Antidepressant medications have shown to be insufficient to induce the normalization of cardiovascular dysfunctions, which are associated with psychiatric conditions. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1750", "text": "Lifestyle modifications play a crucial role in the management of cardiovascular and neurological diseases. Physical activity and a well-balanced diet favor cardiovascular conditioning and improve performance and capacity. Exercise has a positive effect on the metabolism, which controls glucose levels, especially for stress-related pathology and brain disorders such as depression, which impose a heavy burden on the cardiovascular system. Many studies are currently being conducted to gather more information regarding the common mediators of cardiovascular disease and the central nervous system. The brain\u2013heart interaction is considered bidirectional; however, the central nervous system is often regulated more strongly than the heart and blood vessels. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1751", "text": "Pacemaker crosstalk  results when the  pacemaker -generated electrical event in one  heart chamber  is sensed by the lead in another chamber, resulting in inappropriate inhibition of the pacing artifact in the second chamber. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1752", "text": "Crosstalk can only occur in a dual chamber or  biventricular pacemaker . It happens less often in more recent models of dual chamber pacemakers due to the addition of a  ventricular  blanking period, which coincides with the  atrial  stimulus. This helps to prevent ventricular channel oversensing of atrial output. Newer dual chamber pacemakers also use  bipolar  leads with a smaller pacing spike, and  steroid  eluting leads with lower pacing thresholds. Crosstalk is more common in unipolar systems since they require a larger pacing spike. Crosstalk is sometimes referred to as crosstalk inhibition, far-field sensing, or self-inhibition. In some cases, crosstalk can occur in the  pulse generator   circuit  itself, though more common causes include atrial lead dislodgement into the ventricle, ventricular lead dislodgement into the atrium, high atrial output current, high ventricular sensitivity, and short ventricular blanking period. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1753", "text": "In general, the treatment of crosstalk includes decreasing atrial pacing output, decreasing atrial  pulse width , decreasing ventricular sensitivity, increasing the ventricular blanking period, activating ventricular safety pacing, and new atrial lead  implant  if insulation failure mandates unipolar programming. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1754", "text": "Parachute mitral valve  (or  PMV ) is a rare  congenital heart disease  where the  mitral valve  only has a single papillary muscle from which all  chordae tendineae  originate. It is caused by an embryologic failure of papillary muscles to divide into two normally distinct columns, giving the mitral valve orifice and chordea an irregular, parachute-like appearance. Due to the abnormal anatomy, there are almost always associated mitral valve disorders, and because of its abnormal embryologic origin, PMV almost always coincides in a complex of other congenital heart defects. [ 1 ]  PMV is usually identified during infancy or childhood due to its symptomatic nature, and hardly ever diagnosed during adulthood."}
{"_id": "WikiPedia_Cardio$$$corpus_1755", "text": "As a result of the thickened and shortened chordae, there is a restriction of the inflow of blood to mitral valve annulus and subannulus causing a narrowing known as  mitral stenosis  which increases the pressure gradient through the valve. Also, abnormal closure of the mitral valve leaflets or  mitral valve prolapse  will cause the valve significantly leak during closure known as  mitral valve insufficiency ."}
{"_id": "WikiPedia_Cardio$$$corpus_1756", "text": "Parachute mitral valve is commonly associated with other congenital heart disease.  A 2004 study finds that children with PMV are 68% likely to have aortic coarctation, 54% likely to have an atrial septal defect, 46% likely to have a ventricular septal defect, and 19% likely to have left ventricular hypoplasia. [ 2 ]  Parachute mitral valve is also a part of the congenital complex of  Shone's Syndrome . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1757", "text": "Unfortunately, the overall outcome of the children diagnosed with parachute mitral valve especially with the other likely multilevel left-heart diseases is only somewhat satisfactory. [ 4 ]  However, with increasingly improved technology for mitral valve reconstructions, repairs and replacements procedures, outcomes are expected to improve in the future."}
{"_id": "WikiPedia_Cardio$$$corpus_1758", "text": "ParvE101Q  is an experimental modification of  parvalbumin , designed to delay  calcium  sequestration in heart muscles to enhance contraction. [ 1 ]  The protein parvalbumin has  EF hand  motifs used for calcium binding. [ 2 ]  EF hands are structural helix-loop-helix protein subunits that have a high affinity for calcium ions, and a moderate affinity for  magnesium  ions. [ 3 ]  In muscle, the binding of Ca 2+  by parvalbumin efficiently sequesters it following contraction. This increases the speed of muscle relaxation, allowing the muscle to contract again sooner. [ 1 ]  Although parvalbumin is classified as a  delayed calcium buffer , it quickly sequesters Ca 2+ , usually before the muscle is done fully contracting. [ 4 ]  Large amounts of parvalbumin allow rapid contractions of muscles at a high contractile speed with the trade-off of having relatively lower contraction force. [ 4 ]  This decreased force of contraction is due to the rapid sequestration of Ca 2+ , preventing prolonged contraction which is required for greater force."}
{"_id": "WikiPedia_Cardio$$$corpus_1759", "text": "It has been theorized that expressing a modified version of parvalbumin in the  heart  could have therapeutic use to aid heart contraction, and treat relaxation disorders. [ 5 ]  ParvE101Q is optimized so that relaxation is rapid, but contraction lasts for a sufficient time to fully eject blood. [ 1 ]   Amino acid  substitutions of  glutamine  for  glutamate  on the protein\u2019s 101st amino acid were introduced, followed immediately by a  tryptophan  replacing a  phenylalanine  at site 102, as well as  alanine  replacing  aspartate  at site 51. By introducing these changes, the preferential binding of Ca 2+  and Mg 2+  were reversed. Instead of having high preference for Ca 2+  like parvalbumin, ParvE101Q has a preference for Mg 2+  first, and Ca 2+  second. [ 1 ]  This reversed binding preference allows the normal presence of Mg 2+  to delay the Ca 2+  sequestration of ParvE101Q. This delay allows heart contraction to last long enough to preserve blood ejection, then have the excess Ca 2+  bound and sequestered by ParvE101Q. The resulting increase in contractility is speculated to be due to the increased Mg 2+  binding affinity. By binding Mg 2+  first, ParvE101Q allows more Ca 2+  binding to  Troponin C , which is required for  myocyte  contraction. [ 1 ]  The result of the modification is an increased contractility and quicker relaxation in myocytes with no reported side-effects. [ 1 ]  This modified protein retains the heart\u2019s ability to store calcium in the  sarcoplasmic reticulum , even under the added stress of  caffeine . Additionally, when treated with ParvE101Q,  calcium sparks  (spontaneous releases of Ca 2+  from the sarcoplasmic reticulum) are not different from normal. Other Ca 2+  handling proteins used for sequestration are not affected by ParvE101Q, and the effects are not dependent on temperature changes. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1760", "text": "Clinically, ParvE101Q shows promise in correcting  diastolic heart failure . Diastolic heart failure is a condition where the heart has trouble relaxing efficiently. As a result, less blood is pumped out of the ventricles and the blood trying to enter the heart can back up in the circulation to cause  hypertension , often in the lungs, and  congestive heart failure  develops. [ 6 ]  Additionally, the decreased ability of the heart to eject blood leads to perfusion problems to vital organs such as the heart\u2019s  coronary arteries  and the  brain . ParvE101Q is being investigated for side effects, and optimal delivery mechanisms before moving on to experimental trials to treat conditions such as diastolic heart failure. Parvalbumin has diverse effects on  cell cycles ,  second messengers ,  microtubule  organization, cardiac muscle contraction, and the  nervous system . [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1761", "text": "Pathophysiology  is a study which explains the function of the body as it relates to diseases and conditions. The  pathophysiology of hypertension  is an area which attempts to explain mechanistically the causes of  hypertension , which is a chronic disease characterized by elevation of  blood pressure . Hypertension can be classified by cause as either  essential  (also known as primary or  idiopathic ) or  secondary . About 90\u201395% of hypertension is essential hypertension. [ 1 ] [ 2 ] [ 3 ] [ 4 ]   Some authorities define essential hypertension as that which has no known explanation, while others define its cause as being due to overconsumption of sodium and underconsumption of potassium.  Secondary hypertension  indicates that the hypertension is a result of a specific underlying condition with a well-known mechanism, such as chronic kidney disease, narrowing of the aorta or kidney arteries, or endocrine disorders such as excess  aldosterone ,  cortisol , or  catecholamines . Persistent hypertension is a major risk factor for hypertensive heart disease, coronary artery disease, stroke, aortic aneurysm, peripheral artery disease, and chronic kidney disease. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1762", "text": "Cardiac output  and  peripheral resistance  are the two determinants of  arterial pressure . [ 6 ]  Cardiac output is determined by  stroke volume  and  heart rate ; stroke volume is related to  myocardial contractility  and to the size of the  vascular compartment . Peripheral resistance is determined by functional and anatomic changes in small  arteries  and  arterioles ."}
{"_id": "WikiPedia_Cardio$$$corpus_1763", "text": "Single gene mutations can cause  Mendelian  forms of  high blood pressure ; [ 7 ]  ten genes have been identified which cause these monogenic forms of  hypertension . [ 7 ] [ 8 ]  These mutations affect blood pressure by altering  kidney salt handling . [ 9 ] [ 10 ]  There is greater similarity in  blood pressure  within families than between families, which indicates a form of  inheritance , [ 11 ]  and this is not due to shared environmental factors. [ 12 ]  With the aid of  genetic analysis   techniques , a  statistically significant  linkage of blood pressure to several  chromosomal regions , including regions linked to familial combined  hyperlipidemia , was found. [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ]  These findings suggest that there are many  genetic loci , in the general population, each with small effects on blood pressure. Overall, however, identifiable single-gene causes of hypertension are uncommon, consistent with a multifactorial cause of essential hypertension. [ 2 ] [ 10 ] [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1764", "text": "The  autonomic nervous system  plays a central role in maintaining cardiovascular homeostasis via  pressure ,  volume , and  chemoreceptor  signals. It does this by regulating the peripheral vasculature, and kidney function, which in turn affect  cardiac output ,  vascular resistance , and  fluid retention . Excess activity of the  sympathetic nervous system  increases blood pressure and contributes to hypertension. [ 20 ] [ 21 ] [ 22 ] [ 23 ] [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1765", "text": "The mechanisms of increased sympathetic nervous system activity in hypertension involve alterations in  baroreflex  and  chemoreflex  pathways at both peripheral and central levels.  Arterial baroreceptors  are reset to a higher pressure in hypertensive patients, and this peripheral resetting reverts to normal when arterial pressure is normalized. [ 25 ] [ 26 ] [ 27 ]  Furthermore, there is  central  resetting of the  aortic baroreflex  in hypertensive patients, resulting in suppression of sympathetic inhibition after activation of aortic baroreceptor nerves. This baroreflex resetting seems to be mediated, at least partly, by a central action of  angiotensin II . [ 28 ] [ 29 ] [ 30 ]  Additional small-molecule  mediators  that suppress baroreceptor activity and contribute to exaggerated sympathetic drive in hypertension include  reactive oxygen species  and  endothelin . [ 31 ] [ 32 ]  Some studies have shown that hypertensive patients manifest greater  vasoconstrictor  responses to infused  norepinephrine  than  normotensive  controls. [ 33 ]  And that hypertensive patients do not show the normal response to increased circulating norepinephrine\nlevels which generally induces downregulation of  noradrenergic receptor , and it is believed that this abnormal response is  genetically   inherited . [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1766", "text": "Exposure to  stress  increases sympathetic outflow, and repeated stress-induced vasoconstriction may result in  vascular hypertrophy , leading to progressive increases in  peripheral resistance  and blood pressure. [ 2 ]  This could partly explain the greater incidence of hypertension in  lower socioeconomic groups , since they must endure greater levels of stress associated with daily living. Persons with a family history of hypertension manifest augmented vasoconstrictor and sympathetic responses to laboratory stressors, such as  cold pressor testing  and  mental  stress, that may predispose them to hypertension. This is particularly true of young African Americans. Exaggerated stress responses may contribute to the increased incidence of hypertension in this group. [ 35 ]  For patients having hypertension, higher  heart rate variability  (HRV) is a risk factor for  atrial fibrillation . [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1767", "text": "Resistant hypertension can be treated by electrically stimulating the  baroreflex  with a pacemaker-like device. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1768", "text": "Another system maintaining the  extracellular fluid volume ,  peripheral resistance , and that if disturbed may lead to hypertension, is the  renin\u2013angiotensin\u2013aldosterone system .  Renin  is a circulating  enzyme  that participates in maintaining  extracellular  volume and arterial  vasoconstriction , therefore contributing to regulation of  blood pressure . It performs this function by breaking down ( hydrolysing )  angiotensinogen , secreted from the liver, into the peptide  angiotensin I . Angiotensin I is further cleaved by an enzyme that is located primarily but not exclusively in the  pulmonary circulation  bound to  endothelium ; that enzyme is  angiotensin converting enzyme  (ACE). This cleavage produces  angiotensin II , the most vasoactive peptide. [ 38 ] [ 39 ]  Angiotensin II is a potent constrictor of all blood vessels. It acts on the musculature of arteries, raising peripheral resistance and thereby elevating blood pressure. Angiotensin II also causes the adrenal glands to release  aldosterone , which stimulates the epithelial cells of the kidneys to increase re-absorption of salt and water, leading to raised blood volume and raised blood pressure. So elevated  renin  levels in the blood (normally 1.98-2.46\u00a0ng/ml in the upright position) [ 40 ]  leads to hypertension. [ 2 ] [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1769", "text": "Recent studies claim that obesity is a risk factor for hypertension because of activation of the  renin\u2013angiotensin system  (RAS) in  adipose tissue , [ 42 ] [ 43 ]  and also linked  renin\u2013angiotensin system  with  insulin resistance , and claims that anyone can cause the other. [ 44 ]  Local production of  angiotensin II  in various tissues, including the  blood vessels ,  heart ,  adrenals , and  brain , is controlled by  ACE  and other  enzymes , including the  serine protease   chymase . The activity of local renin\u2013angiotensin systems and alternative pathways of angiotensin II formation may make an important contribution to remodeling of resistance  vessels  and the development of target organ damage (i.e.  left ventricular hypertrophy ,  congestive heart failure ,  atherosclerosis ,  stroke ,  end-stage kidney disease ,  myocardial infarction , and  arterial aneurysm ) in hypertensive persons. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1770", "text": "The  endothelium  of blood vessels produces an extensive range of substances that influence  blood flow  and, in turn, is affected by changes in the blood and the pressure of blood flow. For example, local  nitric oxide  and  endothelin , which are secreted by the endothelium, are the major regulators of vascular tone and blood pressure. In patients with essential hypertension, the balance between the  vasodilators  and the  vasoconstrictors  is upset, which leads to changes in the endothelium and sets up a \" vicious cycle \" that contributes to the maintenance of high blood pressure. In patients with hypertension,  endothelial activation  and damage also lead to changes in  vascular tone , vascular reactivity, and  coagulation  and  fibrinolytic pathways . Alterations in endothelial function are a reliable indicator of target organ damage and atherosclerotic disease, as well as prognosis. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1771", "text": "Evidence suggests that  oxidant stress  alters many functions of the  endothelium , including modulation of  vasomotor tone . Inactivation of  nitric oxide  ( NO ) by  superoxide  and other  reactive oxygen species  ( ROS ) seems to occur in conditions such as  hypertension . [ 46 ] [ 47 ] [ 48 ]  Normally  nitric oxide  is an important regulator and mediator of numerous processes in the  nervous ,  immune  and  cardiovascular systems , including  smooth muscle  relaxation thus resulting in  vasodilation  of the  artery  and increasing  blood flow , suppressor of migration and proliferation of vascular smooth-muscle cells. [ 2 ]  It has been suggested that  angiotensin II  enhances formation of the oxidant superoxide at concentrations that affect blood pressure minimally. [ 49 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1772", "text": "Endothelin  is a potent vasoactive peptide produced by endothelial cells that has both  vasoconstrictor  and vasodilator properties. Circulating endothelin levels are increased in some hypertensive patients, [ 50 ] [ 51 ]  particularly  African Americans  and persons with hypertension. [ 50 ] [ 52 ] [ 53 ] [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1773", "text": "A 2007 review article states that while excessive sodium consumption has long been recognized as contributing to the risk of hypertension, \"potassium, the main intracellular cation, has usually been viewed as a minor factor in the pathogenesis of hypertension. However, abundant evidence indicates that a potassium deficit has a critical role in hypertension and its cardiovascular sequelae.\" The authors state that modern, western, high sodium, low potassium diets result in corresponding changes in intracellular concentration of these, the two most important cations in animal cells.  This imbalance leads to contraction of vascular smooth muscle, restricting blood flow and so driving up blood pressure.  The authors cite studies which show that potassium supplementation is effective in reducing hypertension. [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1774", "text": "Epidemiological support for this hypothesis can be found in a 2014 meta-analysis which states that \"the sodium-to-potassium ratio appears to be more strongly associated with blood pressure outcomes than either sodium or potassium alone in hypertensive adult populations.\". [ 56 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1775", "text": "Basic science discoveries have implicated the immune system as in the development of hypertension in animal models. [ 57 ]  Population studies in humans have reported that higher levels of certain inflammatory cytokines are associated with greater risk of hypertension development. [ 58 ] [ 59 ] [ 60 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1776", "text": "Phidippides cardiomyopathy  refers to the  cardiomyopathic  changes that occur after long periods of  endurance training . This term was coined by Justin E. Trivax, MD, MPH, FACC, FSCAI, FSVM and his colleague  Peter A. McCullough  in 2012 following Dr. Trivax's research of marathon runners.  [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1777", "text": "In 490 BC, during the Greco-Persian War, Persian King Darius I launched an attack on the outnumbered Greeks, prompting the legendary Greek herald,  Phidippides  to run nearly 75 miles to Sparta for military support. Although the Spartans agreed to help, they could not leave immediately due to religious obligations, so Phidippides returned to Marathon, where he learned that the Greeks had defeated the Persians. After running another 26.2 miles to Athens to announce the victory, he collapsed and died after exclaiming, \"We are victorious!\" This was the first account of long-distance running resulting in mortality."}
{"_id": "WikiPedia_Cardio$$$corpus_1778", "text": "It has been proposed by Trivax et al. that strenuous exercise results in a cascade of events starting with the effects of training for long-distance events which may result in left ventricular dilation, left ventricular hypertrophy, and increased left ventricular mass. The acute effects of exercise including increased catecholamines, increased oxygen demand, increased preload and afterload, metabolic derangements, acute kidney injury, dehydration, elevation of troponin, CK, CK-MB, and natriuretic peptides. This results in right atrial and right ventricular strain and dilation, right ventricular hypokinesis and marked diastolic dysfunction. Subacute effects of exercise include increased expression of cardiac fibrotic markers including TGF, fibronectin-1, collagens, MMP-2 and TIMP1. Chronic effects include increased cardiac chamber sizes, patchy areas of fibrosis, atrial and ventricular arrhythmias and increased risk of sudden cardiac death."}
{"_id": "WikiPedia_Cardio$$$corpus_1779", "text": "This has been quoted in the literature multiple times and has been inaccurately thought that Dr. James O'Keefe had coined the term. [ 3 ]  He was speaking about the sudden death of  Micah True , a 58-year-old ultrarunner and cult hero a.k.a. Caballo Blanco who died on a 12-mile training jog in the rugged Gila Wilderness of southwest New Mexico. After an autopsy, the Albuquerque coroner wrote that \u201cMicah True died as a result of cardiomyopathy during exertion\u201d. Since then, multiple websites have warned their readers on the possible damage from prolonged endurance training. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1780", "text": "The suggested etiology for Phidippides cardiomyopathy is the cardiac remodeling from prolonged strenuous exercises. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1781", "text": "The repeated prolonged states of volume overload in the right  atrium  and right  ventricle  from endurance training will lead to chronic structural changes. Long term changes include patches of  cardiac fibrosis  which can allow zones of re-entry for  cardiac arrhythmias . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1782", "text": "It is suggested that  Cardiac MRI  is the best imaging modality [ 1 ]  to investigate this condition."}
{"_id": "WikiPedia_Cardio$$$corpus_1783", "text": "There is not much evidence describing this condition and other than a case report, [ 1 ]  no other studies have corroborated the pathophysiological changes suggested by McCullough."}
{"_id": "WikiPedia_Cardio$$$corpus_1784", "text": "Not all experts agree with Trivax and McCullough.  Many feel that further research is necessary to understand this condition better. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1785", "text": "The  photoplethysmogram  (PPG) measurement made at a peripheral site, such as the finger, ear or forehead represents the volume of blood in the vessel at the site of measurement. The PPG signal consists of pulses that reflect the change in vascular blood volume with each  cardiac  beat. Beat-to-beat fluctuations, known as  photoplethysmogram variability (PPGV)  are found in the signal baseline and  amplitude  which reflects various physiological influences such as  respiration  and regulation of vascular tone by the sympathetic nervous system."}
{"_id": "WikiPedia_Cardio$$$corpus_1786", "text": "The beat-to-beat variation of the PPG in time domain can be represented in the  frequency domain  by means of signal transformation methods, such as  fast Fourier transform  or autoregressive model. The spectrum can be divided into two main bands, that is, low frequency (LF) band ranging from 0.04 to 0.15\u00a0Hz and high frequency (HF) band between 0.15 and 0.6\u00a0Hz. The LF band can be subdivided into a mid-frequency (MF) band from 0.09\u00a0Hz to 0.15\u00a0Hz. [ 1 ]  The integration of the power  spectral density  over the frequency range will give the spectral power.\nLow-frequency oscillation in the PPG is found to reflect the sympathetic control over the peripheral circulation, whilst the high frequency component is related to the mechanical consequence of respiration on venous return. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1787", "text": "The PPGV was found to be useful in detecting blood loss by observing the spectral features of the PPGV. [ 3 ] [ 4 ] [ 5 ] \nLF power, together with other features derived from the PPG waveform, was used to classify patients into different ranges of systemic vascular resistance, which may be used as an indicator of critical illness. [ 6 ] \nIt has been proposed that the PPGV can also be used as an indicator of peripheral circulatory abnormalities in  sepsis  patients. [ 7 ]  The application of PPGV as an indicator of sepsis has been extended by using spectral analysis of the PPGV to classify patients into different severity of sepsis. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1788", "text": "Portsmouth sign  refers to a situation in which the  systolic blood pressure  (SBP) reading (measured in  mmHg ) falls below that of the  heart rate  (HR) (measured in beats per minute). It typically signifies a worrying clinical prognosis, specifically caused by  shock . The sign takes its name from physicians working at  Portsmouth University  who first described the sign in the context of  hypotension . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1789", "text": "Portsmouth sign is most often noted clinically when reviewing observations charts which often plot SBP and HR on the same axis, allowing direct observation of situations in which SBP falls below HR. Patients exhibiting this sign are likely to be significantly fluid depleted and in urgent need of aggressive fluid resuscitation. This sign is part of a number of 'early warning' signs that can be used to promptly detect abnormal physiological states. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1790", "text": "Potassium-sparing diuretics  or  antikaliuretics [ 1 ]  refer to drugs that cause  diuresis  without causing  potassium  loss in the  urine . [ 2 ]  They are typically used as an  adjunct  in management of  hypertension ,  cirrhosis , and  congestive heart failure . [ 3 ]  The steroidal  aldosterone antagonists  can also be used for treatment of  primary hyperaldosteronism .  Spironolactone , a  steroidal   aldosterone antagonist , is also used in management of female  hirsutism  and  acne  from  PCOS  or  other causes . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1791", "text": "Normally, sodium is reabsorbed in the  collecting tubules  of a renal  nephron . This occurs via epithelial sodium channels or ENaCs, located on the luminal surface of principal cells that line the collecting tubules. Positively-charged Na+ entering the cells during reabsorption leads to an electronegative luminal environment causing the secretion of potassium (K + ) into the lumen/ urine in exchange. [ 2 ]  Sodium reabsorption also causes water retention. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1792", "text": "When the kidneys detect low blood pressure, the  renin\u2013angiotensin\u2013aldosterone system  (RAAS) is activated and eventually, aldosterone is secreted. Aldosterone binds to aldosterone receptors (mineralocorticoid receptors) increasing sodium reabsorption in an effort to increase blood pressure and improve fluid status in the body. When excessive sodium reabsorption occurs, there is an increasing loss of K +  in the urine and can lead to clinically significant decreases, termed  hypokalemia . Increased sodium reabsorption also increases water retention. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1793", "text": "Potassium-sparing diuretics act to prevent sodium reabsorption in the collecting tubule by either binding ENaCs (amiloride, triamterene) or by inhibiting aldosterone receptors (spironolactone, eplerenone). This prevents excessive excretion of K +  in urine and decreased retention of water, preventing hypokalemia. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1794", "text": "Because these diuretics are weakly  natriuretic , they do not cause clinically significant blood pressure changes and thus, are not used as primary therapy for hypertension. [ 11 ]  They can be used in combination with other  anti-hypertensives  or drugs that cause hypokalemia to help maintain a  normal range  for potassium. For example, they are often used as an adjunct to  loop diuretics  (usually  furosemide ) to treat fluid retention in  congestive heart failure  and  ascites  in  cirrhosis . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1795", "text": "On their own this group of drugs may raise potassium levels beyond the normal range, termed  hyperkalemia , which risks potentially fatal  arrhythmias . Triamterene, specifically, is a potential nephrotoxin and up to half of the patients on it can have  crystalluria  or  urinary casts . [ 12 ] [ 13 ]  Due to its activity as an androgen receptor antagonist and progesterone receptor agonist, spironolactone causes adverse effects, including gynecomastia or decreased libido in males and menstrual abnormalities in females. [ 14 ]  Spironolactone also causes hyperkalemia [ 15 ]  and renal insufficiency. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1796", "text": "Spironolactone interacts with the following medications: [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1797", "text": "- ACE inhibitors/ARBs: increases hyperkalemia risk"}
{"_id": "WikiPedia_Cardio$$$corpus_1798", "text": "- Alcohol: risk of orthostatic hypotension"}
{"_id": "WikiPedia_Cardio$$$corpus_1799", "text": "- Barbiturates: risk of orthostatic hypotension"}
{"_id": "WikiPedia_Cardio$$$corpus_1800", "text": "- Narcotics: risk of orthostatic hypotension"}
{"_id": "WikiPedia_Cardio$$$corpus_1801", "text": "- NSAIDs: increases hyperkalemia risk and decreases diuretic effect of potassium-sparing diuretics"}
{"_id": "WikiPedia_Cardio$$$corpus_1802", "text": "- Digoxin: increases digoxin plasma concentrations, leading to increased toxicity"}
{"_id": "WikiPedia_Cardio$$$corpus_1803", "text": "In  medicine , the  cardiac examination , also  precordial exam , is performed as part of a  physical examination , or when a patient presents with  chest pain  suggestive of a cardiovascular  pathology . It would typically be modified depending on the  indication  and integrated with other examinations especially the  respiratory examination . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1804", "text": "Like all medical examinations, the cardiac examination follows the standard structure of inspection, palpation and auscultation."}
{"_id": "WikiPedia_Cardio$$$corpus_1805", "text": "The patient is positioned in the  supine position  tilted up at 45 degrees if the patient can tolerate this. The head should rest on a pillow and the arms by their sides. The level of the jugular venous pressure (JVP) should only be commented on in this position as flatter or steeper angles lead to artificially elevated or reduced level respectively. Also, left ventricular failure leads to  pulmonary edema  which increases and may impede breathing if the patient is laid flat."}
{"_id": "WikiPedia_Cardio$$$corpus_1806", "text": "Lighting should be adjusted so that it is not obscured by the examiner who will approach from the right hand side of the patient as is medical custom."}
{"_id": "WikiPedia_Cardio$$$corpus_1807", "text": "The torso and neck should be fully exposed and access should be available to the legs."}
{"_id": "WikiPedia_Cardio$$$corpus_1808", "text": "General Inspection:"}
{"_id": "WikiPedia_Cardio$$$corpus_1809", "text": "Inspect the hands for:"}
{"_id": "WikiPedia_Cardio$$$corpus_1810", "text": "Inspect the head for:"}
{"_id": "WikiPedia_Cardio$$$corpus_1811", "text": "Then inspect the precordium for:"}
{"_id": "WikiPedia_Cardio$$$corpus_1812", "text": "The pulses should be palpated, first the  radial pulse  commenting on rate and rhythm then the brachial pulse commenting on character and finally the  carotid pulse  again for character.\nThe pulses may be:"}
{"_id": "WikiPedia_Cardio$$$corpus_1813", "text": "The valve areas are palpated for abnormal pulsations (palpable  heart murmurs  known as  thrills ) and precordial movements (known as  heaves ).  Heaves are best felt with the heel of the hand at the  sternal  border."}
{"_id": "WikiPedia_Cardio$$$corpus_1814", "text": "The  apex beat  is found approximately in the fifth left  intercostal space  in the  mid-clavicular line . It can be impalpable for a variety of reasons including  obesity ,  emphysema ,  effusion  and rarely  dextrocardia . The apex beat is assessed for size, amplitude, location, impulse and duration. There are specific terms to describe the sensation such as tapping, heaving and thrusting."}
{"_id": "WikiPedia_Cardio$$$corpus_1815", "text": "Often the apex beat is felt diffusely over a large area, in this case the most inferior and lateral position it can be felt in should be described as well as the location of the largest amplitude."}
{"_id": "WikiPedia_Cardio$$$corpus_1816", "text": "Finally the  sacrum  and  ankles  are checked for  pitting edema  which is caused by  right ventricular failure  in isolation or as part of  congestive cardiac failure ."}
{"_id": "WikiPedia_Cardio$$$corpus_1817", "text": "One should comment on"}
{"_id": "WikiPedia_Cardio$$$corpus_1818", "text": "To complete the exam blood pressure should be checked, an  ECG  recorded,  funduscopy  performed to assess for  Roth spots  or  papilledema . A full peripheral circulation exam should be performed."}
{"_id": "WikiPedia_Cardio$$$corpus_1819", "text": "A plot of a system's  pressure versus volume  has long been used to measure the work done by the system and its efficiency. This analysis can be applied to  heat engines  and  pumps , including the  heart . A considerable amount of information on cardiac performance can be determined from the  pressure vs. volume  plot ( pressure\u2013volume diagram ). A number of  methods  have been determined for measuring PV-loop values experimentally."}
{"_id": "WikiPedia_Cardio$$$corpus_1820", "text": "Real-time  left ventricular  (LV) pressure\u2013volume loops provide a framework for understanding cardiac mechanics in experimental animals and humans. Such loops can be generated by real-time measurement of pressure and volume within the left ventricle. Several physiologically relevant  hemodynamic  parameters such as  stroke volume ,  cardiac output ,  ejection fraction ,  myocardial contractility , etc. can be determined from these loops."}
{"_id": "WikiPedia_Cardio$$$corpus_1821", "text": "To generate a PV loop for the left ventricle, the LV pressure is plotted against LV volume at multiple time points during a single  cardiac cycle ."}
{"_id": "WikiPedia_Cardio$$$corpus_1822", "text": "Afterload  is the mean tension produced by a chamber of the heart in order to contract. It can also be considered as the \u2018load\u2019 that the heart must eject blood against. Afterload is, therefore, a consequence of aortic large vessel compliance, wave reflection, and small vessel resistance (LV afterload) or similar pulmonary artery parameters (RV afterload)."}
{"_id": "WikiPedia_Cardio$$$corpus_1823", "text": "Left ventricular afterload is affected by various disease conditions.  Hypertension  increases the afterload, since the LV has to work harder to overcome the elevated arterial peripheral resistance and decreased compliance.  Aortic valve  diseases like  aortic stenosis  and  insufficiency  also increase the afterload, whereas  mitral valve regurgitation  decreases the afterload."}
{"_id": "WikiPedia_Cardio$$$corpus_1824", "text": "Preload  is described as the stretching of a single  cardiac myocyte  immediately prior to contraction and is, therefore, related to the  sarcomere  length. Since sarcomere length cannot be determined in the intact heart, other indices of preload such as ventricular  end-diastolic volume  or pressure are used."}
{"_id": "WikiPedia_Cardio$$$corpus_1825", "text": "As an example, preload increases when venous return is increased. This is because the end-diastolic pressure and volume of the ventricle are increased, which stretches the sarcomeres.\nPreload can be calculated as"}
{"_id": "WikiPedia_Cardio$$$corpus_1826", "text": "Stroke volume  (SV) is the volume of blood ejected by the right/left ventricle in a single contraction. It is the difference between the  end-diastolic volume  (EDV) and the  end-systolic volume  (ESV)."}
{"_id": "WikiPedia_Cardio$$$corpus_1827", "text": "In mathematical terms,  \n \n \n \n \n SV \n \n = \n \n EDV \n \n \u2212 \n \n ESV \n \n \n \n {\\displaystyle {\\text{SV}}={\\text{EDV}}-{\\text{ESV}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_1828", "text": "The stroke volume is affected by changes in preload, afterload, and inotropy (contractility). In normal hearts, the SV is not strongly influenced by afterload, whereas, in failing hearts, the SV is highly sensitive to afterload changes.\nStroke volume relative to EDV is  Ejection Fraction ."}
{"_id": "WikiPedia_Cardio$$$corpus_1829", "text": "Ventricular stroke work (SW) is defined as the work performed by the left or right ventricle to eject the stroke volume into the  aorta  or  pulmonary artery , respectively. The area enclosed by the PV loop is a measure of the ventricular stroke work, which is a product of the stroke volume and the mean aortic or pulmonary artery pressure (afterload), depending on whether one is considering the left or the right ventricle."}
{"_id": "WikiPedia_Cardio$$$corpus_1830", "text": "Cardiac output  (CO) is defined as the amount of blood pumped by the ventricle in unit time."}
{"_id": "WikiPedia_Cardio$$$corpus_1831", "text": "In mathematical terms,  \n \n \n \n \n CO \n \n = \n \n SV \n \n \u00d7 \n \n Heart Rate \n \n \n \n {\\displaystyle {\\text{CO}}={\\text{SV}}\\times {\\text{Heart Rate}}} \n \n ."}
{"_id": "WikiPedia_Cardio$$$corpus_1832", "text": "CO is an indicator of how well the heart is performing its function of transporting blood to deliver oxygen, nutrients, and chemicals to various cells of the body and to remove the cellular wastes. CO is regulated principally by the demand for oxygen by the cells of the body."}
{"_id": "WikiPedia_Cardio$$$corpus_1833", "text": "Diseases of the cardiovascular system, such as  hypertension  and  heart failure , are often associated with changes in CO.  Cardiomyopathy  and  heart failure  cause a reduction in cardiac output, whereas infection and  sepsis  are known to increase cardiac output. Hence, the ability to accurately measure CO is important in physiology, as it provides for improved diagnosis of abnormalities, and can be used to guide the development of new treatment strategies. However, CO is dependent upon loading conditions and is inferior to hemodynamic parameters defined by the PV plane.\nFurther reading: Bramwel's book of physiology"}
{"_id": "WikiPedia_Cardio$$$corpus_1834", "text": "Ejection fraction  (EF) is defined as the fraction of  end-diastolic volume  that is ejected out of the ventricle during each contraction."}
{"_id": "WikiPedia_Cardio$$$corpus_1835", "text": "In mathematical terms,  \n \n \n \n \n EF \n \n = \n \n \n SV \n EDV \n \n \n \n \n {\\displaystyle {\\text{EF}}={\\frac {\\text{SV}}{\\text{EDV}}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_1836", "text": "Healthy ventricles typically have ejection fractions greater than 0.55. However, EF is also dependent on loading conditions and inferior to hemodynamic parameters defined by the PV plane."}
{"_id": "WikiPedia_Cardio$$$corpus_1837", "text": "Myocardial infarction  or  cardiomyopathy  causes damage to the  myocardium , which impairs the heart's ability to eject blood and, therefore, reduces ejection fraction. This reduction in the ejection fraction can manifest itself as heart failure."}
{"_id": "WikiPedia_Cardio$$$corpus_1838", "text": "Low EF usually indicates  systolic dysfunction , and severe heart failure can result in EF lower than 0.2. EF is also used as a clinical indicator of the inotropy (contractility) of the heart. Increasing inotropy leads to an increase in EF, whereas decreasing inotropy decreases EF."}
{"_id": "WikiPedia_Cardio$$$corpus_1839", "text": "These represent the minimum and maximum rate of pressure change in the ventricle. Peak dP/dt has historically been used as an index of ventricular performance. However, it is known to be load-dependent and inferior to hemodynamic parameters defined by the PV plane."}
{"_id": "WikiPedia_Cardio$$$corpus_1840", "text": "An increase in contractility is manifested as an increase in dP/dt max  during isovolumic contraction. However, dP/dt max  is also influenced by preload, afterload, heart rate, and myocardial hypertrophy. Hence, the relationship between ventricular end-diastolic volume and dP/dt is a more accurate index of contractility than dP/dt alone."}
{"_id": "WikiPedia_Cardio$$$corpus_1841", "text": "Likewise, an increase in diastolic function or an increase in relaxation ( lusitropy ) causes increased dP/dt min  during  isovolumic relaxation . Hence, dP/dt min  has been used as a valuable tool in the analysis of isovolumic relaxation. However, studies have shown that this parameter may not be a valid measure of LV relaxation rate, especially during acute alterations in contractility or afterload."}
{"_id": "WikiPedia_Cardio$$$corpus_1842", "text": "Tau represents the exponential decay of the ventricular pressure during  isovolumic relaxation . Several studies have shown that Tau is a preload-independent measure of isovolumic relaxation."}
{"_id": "WikiPedia_Cardio$$$corpus_1843", "text": "The accurate estimation of Tau is highly dependent on the accuracy of ventricular pressure measurements. Thus, high fidelity pressure transducers are required to obtain real time instantaneous ventricular pressures."}
{"_id": "WikiPedia_Cardio$$$corpus_1844", "text": "Calculation of Tau (Glantz method)"}
{"_id": "WikiPedia_Cardio$$$corpus_1845", "text": "P \n \n ( \n \n t \n \n ) \n = \n \n \n P \n \n \n 0 \n \n \n \n e \n \n \n \n \u2212 \n \n t \n \n \n \n \u03c4 \n \n E \n \n \n \n \n \n + \n \n \n P \n \n \n \u03b1 \n \n \n \n \n {\\displaystyle {\\text{P}}({\\text{t}})={\\text{P}}_{0}e^{\\frac {-{\\text{t}}}{\\tau _{E}}}+{\\text{P}}_{\\alpha }}"}
{"_id": "WikiPedia_Cardio$$$corpus_1846", "text": "Due to the load dependency of the previous parameters, more accurate measures of ventricular function are available in the PV plane."}
{"_id": "WikiPedia_Cardio$$$corpus_1847", "text": "End- systolic  pressure volume relationship (ESPVR) describes the maximal pressure that can be developed by the ventricle at any given LV volume. This implies that the PV loop cannot cross over the line defining ESPVR for any given contractile state."}
{"_id": "WikiPedia_Cardio$$$corpus_1848", "text": "The slope of ESPVR (Ees) represents the end-systolic elastance, which provides an index of myocardial contractility. The ESPVR is relatively insensitive to changes in preload, afterload, and  heart rate . This makes it an improved index of systolic function over other hemodynamic parameters like ejection fraction, cardiac output, and stroke volume."}
{"_id": "WikiPedia_Cardio$$$corpus_1849", "text": "The ESPVR becomes steeper and shifts to the left as inotropy (contractility) increases. The ESPVR becomes flatter and shifts to the right as inotropy decreases."}
{"_id": "WikiPedia_Cardio$$$corpus_1850", "text": "End- diastolic  pressure volume relationship (EDPVR) describes the passive filling curve for the ventricle and thus the passive properties of the myocardium. The slope of the EDPVR at any point along this curve is the reciprocal of ventricular compliance (or ventricular stiffness)."}
{"_id": "WikiPedia_Cardio$$$corpus_1851", "text": "For example, if ventricular compliance is decreased (such as in  ventricular hypertrophy ), the ventricle is stiffer. This results in higher ventricular end-diastolic pressures (EDP) at any given end-diastolic volume (EDV). Alternatively, for a given EDP, a less compliant ventricle would have a smaller EDV due to impaired filling."}
{"_id": "WikiPedia_Cardio$$$corpus_1852", "text": "If ventricular compliance increases (such as in  dilated cardiomyopathy  where the ventricle becomes highly dilated without appreciable thickening of the wall), the EDV may be very high but the EDP may not be greatly elevated."}
{"_id": "WikiPedia_Cardio$$$corpus_1853", "text": "The Pressure-volume area (PVA) represents the total  mechanical energy  generated by ventricular contraction. This is equal to the sum of the stroke work (SW), encompassed within the PV loop, and the elastic potential energy (PE)."}
{"_id": "WikiPedia_Cardio$$$corpus_1854", "text": "In mathematical terms,  \n \n \n \n \n PVA \n \n = \n \n PE \n \n + \n \n SW \n \n \n \n {\\displaystyle {\\text{PVA}}={\\text{PE}}+{\\text{SW}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_1855", "text": "also,"}
{"_id": "WikiPedia_Cardio$$$corpus_1856", "text": "PE \n \n = \n \n \n \n \n PES \n \n ( \n \n VES \n \n \u2212 \n \n \n V \n \n \n 0 \n \n \n ) \n \n 2 \n \n \n \u2212 \n \n \n \n \n PED \n \n ( \n \n VED \n \n \u2212 \n \n \n V \n \n \n 0 \n \n \n ) \n \n 4 \n \n \n \n \n {\\displaystyle {\\text{PE}}={\\frac {{\\text{PES}}({\\text{VES}}-{\\text{V}}_{0})}{2}}-{\\frac {{\\text{PED}}({\\text{VED}}-{\\text{V}}_{0})}{4}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_1857", "text": "There is a highly linear correlation between the PVA and cardiac oxygen consumption per beat. This relationship holds true under a variety of loading and contractile conditions. This estimation of myocardial oxygen consumption (MVO 2 ) is used to study the  coupling of mechanical work  and the energy requirement of the heart in various disease states, such as  diabetes ,  ventricular hypertrophy , and  heart failure . MVO 2  is also used in the calculation of cardiac efficiency, which is the ratio of cardiac stroke work to MVO 2 ."}
{"_id": "WikiPedia_Cardio$$$corpus_1858", "text": "Preload recruitable stroke work (PRSW) is determined by the linear regression of stroke work with the end-diastolic volume. The slope of the PRSW relationship is a highly linear index of myocardial contractility that is insensitive to preload and afterload."}
{"_id": "WikiPedia_Cardio$$$corpus_1859", "text": "During heart failure, myocardial contractility is reduced, which decreases the slope of the PRSW relationship. Recent studies also indicate that the volume axis intercept of the PRSW relationship (not the slope) may be a better indicator of the severity of contractile dysfunction."}
{"_id": "WikiPedia_Cardio$$$corpus_1860", "text": "\u201cThe heart will pump what it receives\u201d- Starling\u2019s law of the heart"}
{"_id": "WikiPedia_Cardio$$$corpus_1861", "text": "The  Frank\u2013Starling mechanism  describes the ability of the heart to change its force of contraction (and, hence, stroke volume) in response to changes in venous return. In other words, if the end-diastolic volume increases, there is a corresponding increase in stroke volume."}
{"_id": "WikiPedia_Cardio$$$corpus_1862", "text": "The Frank\u2013Starling mechanism can be explained on the basis of preload. As the heart fills with more blood than usual, there is an increase in the load experienced by each  myocyte . This stretches the muscle fibers, increasing the affinity of  troponin C  to Ca 2+  ions, causing a greater number of  cross-bridges  to form within the muscle fibers. This increases the contractile force of the cardiac muscle, resulting in increased stroke volume."}
{"_id": "WikiPedia_Cardio$$$corpus_1863", "text": "Frank\u2013Starling curves can be used as an indicator of muscle contractility (inotropy). However, there is no single Frank\u2013Starling curve on which the ventricle operates but rather a family of curves, each of which defined by the afterload and inotropic state of the heart. Increased afterload or decreased inotropy shifts the curve down and to the right. Decreased afterload and increased inotropy shifts the curve up and to the left."}
{"_id": "WikiPedia_Cardio$$$corpus_1864", "text": "Arterial elastance (Ea) is a measure of arterial load and is calculated as the simple ratio of ventricular end-systolic pressure to stroke volume."}
{"_id": "WikiPedia_Cardio$$$corpus_1865", "text": "In mathematical terms,  \n \n \n \n \n \n E \n \n \n a \n \n \n = \n \n \n ESP \n SV \n \n \n = \n \n Heart Rate \n \n \u00d7 \n \n Resistance \n \n \n \n {\\displaystyle {\\text{E}}_{\\text{a}}={\\frac {\\text{ESP}}{\\text{SV}}}={\\text{Heart Rate}}\\times {\\text{Resistance}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_1866", "text": "By characterizing both the ventricular and arterial systems in terms of pressure and stroke volume, it is possible to study the ventriculo-arterial coupling (the interaction between the heart and the arterial system)."}
{"_id": "WikiPedia_Cardio$$$corpus_1867", "text": "In  dilated cardiomyopathy , the ventricle becomes dilated without compensatory thickening of the wall. The LV is unable to pump enough blood to meet the metabolic demands of the organism."}
{"_id": "WikiPedia_Cardio$$$corpus_1868", "text": "The end-systolic and diastolic volumes increase and the pressures remain relatively unchanged. The ESPVR and EDPVR curves are shifted to the right."}
{"_id": "WikiPedia_Cardio$$$corpus_1869", "text": "Left ventricular hypertrophy  (LVH) is an increase in the thickness and mass of the myocardium. This could be a normal reversible response to cardiovascular conditioning (athletic heart) or an abnormal irreversible response to chronically increased volume load (preload) or increased pressure load (afterload). Shown is a diagram of pathological hypertrophy reducing EDV and SV."}
{"_id": "WikiPedia_Cardio$$$corpus_1870", "text": "The thickening of the ventricular muscle results in decreased chamber compliance. As a result, LV pressures are elevated, the ESV is increased, and the EDV is decreased, causing an overall reduction in cardiac output."}
{"_id": "WikiPedia_Cardio$$$corpus_1871", "text": "Restrictive cardiomyopathy  includes a group of heart disorders in which the walls of the ventricles become stiff (but not necessarily thickened) and resist normal filling with blood between heartbeats."}
{"_id": "WikiPedia_Cardio$$$corpus_1872", "text": "This condition occurs when heart muscle is gradually infiltrated or replaced by scar tissue or when abnormal substances accumulate in the heart muscle. The ventricular systolic pressure remains normal, diastolic pressure is elevated and the cardiac output is reduced."}
{"_id": "WikiPedia_Cardio$$$corpus_1873", "text": "Aortic valve stenosis  is abnormal narrowing of the aortic valve. This results in much greater LV pressures than the aortic pressures during LV ejection. The magnitude of the pressure gradient is determined by the severity of the stenosis and the flow rate across the valve."}
{"_id": "WikiPedia_Cardio$$$corpus_1874", "text": "Severe aortic stenosis results in"}
{"_id": "WikiPedia_Cardio$$$corpus_1875", "text": "This is a narrowing of the  mitral valve  orifice when the valve is open.  Mitral stenosis  impairs LV filling so that there is a decrease in end-diastolic volume (preload). This leads to a decrease in stroke volume by the Frank\u2013Starling mechanism and a fall in cardiac output and aortic pressure. This reduction in afterload (in particular, aortic diastolic pressure) enables the end-systolic volume to decrease slightly but not enough to overcome the decline in end-diastolic volume. Therefore, because end-diastolic volume decreases more than end-systolic volume decreases, the stroke volume decreases."}
{"_id": "WikiPedia_Cardio$$$corpus_1876", "text": "Aortic insufficiency  (AI) is a condition in which the aortic valve fails to close completely at the end of systolic ejection, causing leakage of blood back through the valve during LV diastole."}
{"_id": "WikiPedia_Cardio$$$corpus_1877", "text": "The constant backflow of blood through the leaky aortic valve implies that there is no true phase of isovolumic relaxation. The LV volume is greatly increased due to the enhanced ventricular filling."}
{"_id": "WikiPedia_Cardio$$$corpus_1878", "text": "When the LV begins to contract and develop pressure, blood is still entering the LV from the aorta (since aortic pressure is higher than LV pressure), implying that there is no true isovolumic contraction. Once the LV pressure exceeds the aortic diastolic pressure, the LV begins to eject blood into the aorta."}
{"_id": "WikiPedia_Cardio$$$corpus_1879", "text": "The increased end-diastolic volume (increased preload) activates the Frank\u2013Starling mechanism to increase the force of contraction, LV systolic pressure, and stroke volume."}
{"_id": "WikiPedia_Cardio$$$corpus_1880", "text": "Mitral regurgitation  (MR) occurs when the mitral valve fails to close completely, causing blood to flow back into the left atrium during ventricular systole."}
{"_id": "WikiPedia_Cardio$$$corpus_1881", "text": "The constant backflow of blood through the leaky mitral valve implies that there is no true phase of isovolumic contraction. Since the afterload imposed on the ventricle is reduced, end-systolic volume can be smaller than normal."}
{"_id": "WikiPedia_Cardio$$$corpus_1882", "text": "There is also no true period of isovolumic relaxation because some LV blood flows back into the left atrium through the leaky mitral valve. During ventricular diastolic filling, the elevated atrial pressure is transmitted to the LV during filling so that LV end-diastolic volume (and pressure) increases. This would cause the afterload to increase if it were not for the reduced outflow resistance (due to mitral regurgitation) that tends to decrease afterload during ejection. The net effect of these changes is that the width of the PV loop is increased (i.e., ventricular stroke volume is increased). However, ejection into the aorta (forward flow) is reduced. The increased ventricular stroke volume in this case includes the volume of blood ejected into the aorta as well as the volume ejected back into the left atrium."}
{"_id": "WikiPedia_Cardio$$$corpus_1883", "text": "Pressure\u2013volume loops  are widely used in  basic and preclinical research . Left ventricular PV loops are considered to be the gold standard for  hemodynamic  assessment and are widely used in research to evaluate cardiac performance. While it has long been possible to measure pressure in real time from the left  ventricle , measuring the volume was technically more difficult."}
{"_id": "WikiPedia_Cardio$$$corpus_1884", "text": "The use of ultrasonic  sonomicrometry  and the development of the conductance catheter triggered renewed interest in PV loops studies. In sonomicrometry, small ultrasonic transducers (usually referred to as \"crystals\") transmit signals to each other, and the distance between them is accurately determined based on the transit-time of the signals. By knowing the long and short axis lengths of the ventricle, ventricular volume is easily and accurately determined. Conductance catheters measure instantaneous conductance in the left ventricle, which is then converted to blood volume using complex formulas and usually after determining and applying various correction factors. Typically only one method is used to perform PV studies in research settings."}
{"_id": "WikiPedia_Cardio$$$corpus_1885", "text": "The miniaturization of sonomicrometer crystals and pressure catheters have made mice PV loop studies feasible and more common."}
{"_id": "WikiPedia_Cardio$$$corpus_1886", "text": "A  sonomicrometer  system is composed of an electronic signal-processing unit that is connected to small ultrasonic transducers (crystals). A computer acting as a data acquisition and display device obtains data in real time from the signal processor unit, while the crystals are implanted in or on the left ventrical. As few as 2 or as many as 6 crystals can be used to perform 1-axis, 2-axis, or 3-axis length measurements of the axial planes of the heart, usually at a rate of 200 to 2000 times per second. A typical sonomicrometer system has a resolution of 12 micrometres, enabling high-resolution measurements of the axial lengths."}
{"_id": "WikiPedia_Cardio$$$corpus_1887", "text": "Ventricular volume is computed directly (either in micro-liters or milli-liters) by combining the axial length measurements in standard spherical or ellipsoidal volume equations:"}
{"_id": "WikiPedia_Cardio$$$corpus_1888", "text": "V \n o \n l \n u \n m \n e \n = \n \n \n 4 \n 3 \n \n \n \u00d7 \n \u03c0 \n \u00d7 \n \n r \n \n 3 \n \n \n \n \n {\\displaystyle Volume={\\frac {4}{3}}\\times \\pi \\times r^{3}} \n \n  (for a single-axis measurement)"}
{"_id": "WikiPedia_Cardio$$$corpus_1889", "text": "V \n o \n l \n u \n m \n e \n = \n \n \n \u03c0 \n 6 \n \n \n \u00d7 \n \n L \n \n 1 \n \n \n \u00d7 \n \n L \n \n 2 \n \n \n 2 \n \n \n \n \n {\\displaystyle Volume={\\frac {\\pi }{6}}\\times L_{1}\\times L_{2}^{2}} \n \n  (for a two-axis measurement, where L1 is the length of the long axis)"}
{"_id": "WikiPedia_Cardio$$$corpus_1890", "text": "V \n o \n l \n u \n m \n e \n = \n \n \n \u03c0 \n 6 \n \n \n \u00d7 \n \n L \n \n 1 \n \n \n \u00d7 \n \n L \n \n 2 \n \n \n \u00d7 \n \n L \n \n 3 \n \n \n \n \n {\\displaystyle Volume={\\frac {\\pi }{6}}\\times L_{1}\\times L_{2}\\times L_{3}} \n \n  (for a three-axis measurement)"}
{"_id": "WikiPedia_Cardio$$$corpus_1891", "text": "When the axial measurements are acquired in terms of millimeters, then the volume units in these equations will be in terms of milliliters."}
{"_id": "WikiPedia_Cardio$$$corpus_1892", "text": "A conductance catheter contains two or more ring-shaped electrodes along its length. When a high-frequency low-amplitude constant current is passed through the outer electrodes to generate an electric field, the potential difference between any pair of inner electrodes is inversely proportional to the amount of conductive material at that site."}
{"_id": "WikiPedia_Cardio$$$corpus_1893", "text": "Conductance  is defined as the applied current divided by the voltage measured between two adjacent electrodes."}
{"_id": "WikiPedia_Cardio$$$corpus_1894", "text": "The conductance catheter technique has no major drawbacks but requires careful  calibration  of conductance signals. Other techniques exist but this article focuses on the well-established conductance catheter technique."}
{"_id": "WikiPedia_Cardio$$$corpus_1895", "text": "(NOTE: For typical catheter configurations the linear relationship of the inverse potential difference to the amount of material is only an approximation. It is only valid for volumes where the diameter of that volume is less than the distance between the measuring electrodes.)"}
{"_id": "WikiPedia_Cardio$$$corpus_1896", "text": "The formula by Baan et al. (1984) for obtaining ventricular volume is as follows:  \n \n \n \n V \n = \n \n \n 1 \n \u03b1 \n \n \n \u00d7 \n \u03c1 \n \u00d7 \n \n L \n \n 2 \n \n \n \u00d7 \n ( \n G \n \u2212 \n \n G \n \n P \n \n \n ) \n \n \n {\\displaystyle V={\\frac {1}{\\alpha }}\\times \\rho \\times L^{2}\\times (G-G^{P})}"}
{"_id": "WikiPedia_Cardio$$$corpus_1897", "text": "The conductance measured by the catheter is actually the conductance of the blood and of the surrounding myocardial tissue. This latter conductance is called the parallel conductance (G P )."}
{"_id": "WikiPedia_Cardio$$$corpus_1898", "text": "From the above equation, it can be seen that the volume measurement requires the knowledge of  \u03b1 ,  \u03c1 ,  L , and  G P ."}
{"_id": "WikiPedia_Cardio$$$corpus_1899", "text": "The equation may be considered to be a straight line of the form y = mx + b, where  m  (the gain) is a combination of the three terms 1/ \u03b1 ,  \u03c1 , and  L 2  and  b  (the offset) is  G P ."}
{"_id": "WikiPedia_Cardio$$$corpus_1900", "text": "L  is available from catheter data sheets, while  \u03c1  can be measured directly using appropriate equipment."}
{"_id": "WikiPedia_Cardio$$$corpus_1901", "text": "Ideally, gain should be determined in every experiment. While  L  is known and  \u03c1  can be measured, the  \u03b1  factor poses more difficulties. Indeed, the only way to obtain a reliable gain (encompassing  \u03b1 ) involves directly measuring cardiac output. Therefore, for most purposes, an educated estimate is used based on values found in the literature."}
{"_id": "WikiPedia_Cardio$$$corpus_1902", "text": "To take into account the parallel conductance,  G P , the most common method involves injection of hypertonic saline into the subject\u2014enough to temporarily reduce blood resistance, and therefore increase preload, but not so much as to alter haemodynamics. The minimum and maximum volumes (V max  and V min ) from each loop in the series of loops are plotted on a graph. V max  and V min  lines are extrapolated and at their point of intersection, where V max  is equal to V min , must be zero\u2014conductance is parallel conductance only. The volume at this point is the correction volume."}
{"_id": "WikiPedia_Cardio$$$corpus_1903", "text": "Admittance  techniques offer an alternative to the saline bolus as a means of determining  G P ."}
{"_id": "WikiPedia_Cardio$$$corpus_1904", "text": "Several parameters can be calculated for each loop (e.g. end-diastolic pressure, end-systolic pressure, ejection and filling intervals, contractility index, stroke volume, and ejection fraction)."}
{"_id": "WikiPedia_Cardio$$$corpus_1905", "text": "More importantly, other interesting  parameters are derived from series of loops  obtained under changing conditions. For example, the end-diastolic pressure-volume relationship (EDPVR) and end-systolic pressure-volume relationship (ESPVR) are derived from series of loops obtained by slowly inflating a balloon to occlude the inferior vena cava, a procedure that reduces  cardiac preload ."}
{"_id": "WikiPedia_Cardio$$$corpus_1906", "text": "EDPVR and ESPVR are valuable because they are load-independent indices of left ventricular function.\nThey also measure left ventricle Compliance/Stiffness (EDPVR) and Contractility (ESPVR) respectively."}
{"_id": "WikiPedia_Cardio$$$corpus_1907", "text": "Other parameters derived from series of loops are:"}
{"_id": "WikiPedia_Cardio$$$corpus_1908", "text": "The  Pravastatin or Atorvastatin Evaluation and Infection Therapy\u2013Thrombolysis in Myocardial Infarction 22  trial, also known as  PROVE-IT \u00a0 TIMI \u00a0 22 , was a   randomized, double-blind ,  clinical trial  that recruited 4,162 people admitted within 10 days of an  acute coronary event  and randomised them to the  lipid-lowering drugs   pravastatin  (40\u00a0mg) or  atorvastatin  (80\u00a0mg) and a 10-day course of the antibiotic  gatifloxacin  or  placebo . [ 1 ]  The participants enrolled at 349 sites across Australia, Europe, and North America between November 2000 and December 2001, and the study concluded that statin treatment for  secondary prevention  reduced  coronary heart disease  (CHD) events and that atorvastatin had a more marked effect than pravastatin. The study was published in  The New England Journal of Medicine  and reported at the  American College of Cardiology  Annual Scientific Session in 2004. [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1909", "text": "Pulmonary angiography  (or  pulmonary arteriography , conventional pulmonary angiography ,  selective pulmonary angiography ) is a medical  fluoroscopic  procedure used to visualize the pulmonary arteries and much less frequently, the pulmonary veins. It is a minimally invasive procedure performed most frequently by an  interventional radiologist  or  interventional cardiologist  to visualise the arteries of the lungs."}
{"_id": "WikiPedia_Cardio$$$corpus_1910", "text": "Pulmonary angiography is useful as the confirmation test where the non-invasive imaging such as  CT pulmonary angiography  is inconclusive on determining the presence of  pulmonary embolism . [ 1 ]  The accuracy of pulmonary angiography may be higher than clinical examination,  arterial blood gas  results, and  ventilation/perfusion scan . [ 2 ]  Pulmonary angiography is also used to confirm  chronic thromboembolic pulmonary hypertension  (CTEPH) and provides a platform for  balloon pulmonary angioplasty  to treat the disease. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1911", "text": "CT pulmonary angiography  has nearly entirely replaced conventional pulmonary angiography in common practice as it is less invasive, faster, safer, and provides most of the same diagnostic information with the added benefit of visualizing the lung tissue as well as other structures. Nevertheless, it is still used in cases where CT angiography is nondiagnostic."}
{"_id": "WikiPedia_Cardio$$$corpus_1912", "text": "Types of catheters that can be used are pigtail catheters and balloon occlusion catheters. Tip of the catheter is advanced through the  inferior vena cava ,   right atrium ,  right ventricle , right ventricular outflow tract, pulmonary trunk, and the tip is parked in the left pulmonary artery. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1913", "text": "Conventional pulmonary angiography was first performed in 1931 by Portuguese angiography pioneers  Lopo de Carvalho ,  Egas Moniz  and colleagues. [ 5 ]  Robb and Steinberg described pulmonary angiography by infusion of peripheral radiocontrast. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1914", "text": "A  pulse duplicator  is a device used to duplicate the pulsing flow of the human heart and the associated  hemodynamics .  It is used to research the conditions of heart disease. [ 1 ] [ 2 ] [ 3 ]  Pulse duplicators can be used to conduct  in vitro  or  ex vivo  testing.  Common uses include testing new  artificial heart valves [ 4 ]  and simulating procedures like  transcatheter aortic valve replacement . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1915", "text": "A pulse duplicator replicates parts of the circulatory system.  Many pulse duplicators model only half the heart, commonly the left atrium and ventricle, in order to test the  mitral  and  aortic valves ."}
{"_id": "WikiPedia_Cardio$$$corpus_1916", "text": "A common design to model the heart uses a  piston  to simulate the contraction and expansion of the heart.  An alternate design uses a flexible plastic heart model, or an ex vivo heart, and applies  hydraulic  pressure to induce contraction and expansion. [ 1 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1917", "text": "The circulatory system blood vessels are typically modeled using tubing. Compliance chambers and narrow tubing can be used to model the  Windkessel effect . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1918", "text": "A pulse duplicator is categorized as a lump parameter model, also known as a Windkessel model, if it uses a limited set of compliance chambers and resistance tubing to model the sum of circulatory compliance and resistance.  A pulse duplicator is a wave propagation model if it physically replicates the circulatory system in a more anatomically correct manner.  [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1919", "text": "A pulse duplicator is filled with a fluid with a similar  viscosity  and  specific gravity  compared to blood. One such blood analog is a mixture of water,  glycerol , and a small amount of  sodium chloride . [ 5 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1920", "text": "Pulse oximetry  is a  noninvasive  method for monitoring blood  oxygen saturation .  Peripheral oxygen saturation  (Sp O 2 ) readings are typically within 2% accuracy (within 4% accuracy in 95% of cases) of the more accurate (and invasive) reading of arterial oxygen saturation (Sa O 2 ) from  arterial blood gas  analysis. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1921", "text": "A standard pulse oximeter passes two wavelengths of  light  through tissue to a  photodetector . Taking advantage of the  pulsate  flow of  arterial blood , it measures the change in  absorbance  over the course of a  cardiac cycle , allowing it to determine the absorbance due to arterial blood alone, excluding unchanging absorbance due to  venous blood , skin, bone, muscle, fat, and, in many cases,  nail polish . [ 2 ]  The two wavelengths measure the quantities of bound (oxygenated) and unbound (non-oxygenated) hemoglobin, and from their ratio, the percentage of bound hemoglobin is computed.\nThe most common approach is  transmissive pulse oximetry . In this approach, one side of a thin part of the patient's body, usually a  fingertip  or  earlobe , is illuminated, and the photodetector is on the other side. Fingertips and earlobes have disproportionately high blood flow relative to their size, in order to keep warm, but this will be lacking in  hypothermic  patients. [ 1 ]  Other convenient sites include an  infant's  foot or an unconscious patient's  cheek  or  tongue ."}
{"_id": "WikiPedia_Cardio$$$corpus_1922", "text": "Reflectance pulse oximetry  is a less common alternative, placing the photodetector on the same surface as the illumination. This method does not require a thin section of the person's body and therefore may be used almost anywhere on the body, such as the forehead, chest, or feet, but it still has some limitations. Vasodilation and pooling of venous blood in the head due to compromised venous return to the heart can cause a combination of arterial and venous pulsations in the forehead region and lead to spurious Sp O 2  results. Such conditions occur while undergoing  anaesthesia  with  endotracheal intubation  and mechanical ventilation or in patients in the  Trendelenburg position . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1923", "text": "A pulse oximeter is a  medical device  that indirectly monitors the oxygen saturation of a patient's  blood  (as opposed to measuring oxygen saturation directly through a blood sample) and changes in blood volume in the skin, producing a  photoplethysmogram  that may be further processed into  other measurements . [ 4 ]  The pulse oximeter may be incorporated into a multiparameter patient monitor. Most monitors also display the pulse rate. Portable, battery-operated pulse oximeters are also available for transport or home blood-oxygen monitoring. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1924", "text": "Pulse oximetry is particularly convenient for  noninvasive  continuous measurement of blood oxygen saturation. In contrast, blood gas levels must otherwise be determined in a laboratory on a drawn blood sample. Pulse oximetry is useful in any setting where a patient's  oxygenation  is unstable, including  intensive care , operating, recovery, emergency and hospital ward settings,  pilots  in unpressurized aircraft, for assessment of any patient's oxygenation, and determining the effectiveness of or need for supplemental  oxygen . Although a pulse oximeter is used to monitor oxygenation, it cannot determine the metabolism of oxygen, or the amount of oxygen being used by a patient. For this purpose, it is necessary to also measure  carbon dioxide  (CO 2 ) levels. It is possible that it can also be used to detect abnormalities in ventilation. However, the use of a pulse oximeter to detect  hypoventilation  is impaired with the use of supplemental oxygen, as it is only when patients breathe room air that abnormalities in respiratory function can be detected reliably with its use. Therefore, the routine administration of supplemental oxygen may be unwarranted if the patient is able to maintain adequate oxygenation in room air, since it can result in hypoventilation going undetected. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1925", "text": "Because of their simplicity of use and the ability to provide continuous and immediate oxygen saturation values, pulse oximeters are of critical importance in  emergency medicine  and are also very useful for patients with respiratory or cardiac problems, [ 7 ]  especially  COPD , or for diagnosis of some  sleep disorders  such as  apnea  and  hypopnea . [ 8 ]  For patients with  obstructive sleep apnea , pulse oximetry readings will be in the 70\u201390% range for much of the time spent attempting to sleep. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1926", "text": "Portable battery-operated pulse oximeters are useful for pilots operating in non-pressurized aircraft above 10,000 feet (3,000\u00a0m) or 12,500 feet (3,800\u00a0m) in the U.S. [ 10 ]  where supplemental oxygen is required. Portable pulse oximeters are also useful for mountain climbers and athletes whose oxygen levels may decrease at high  altitudes  or with exercise. Some portable pulse oximeters employ software that charts a patient's blood oxygen and pulse, serving as a reminder to check blood oxygen levels. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1927", "text": "Connectivity advancements have made it possible for patients to have their blood oxygen saturation continuously monitored without a cabled connection to a hospital monitor, without sacrificing the flow of patient data back to bedside monitors and centralized patient surveillance systems. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1928", "text": "For patients with  COVID-19 , pulse oximetry helps with early detection of  silent hypoxia , in which the patients still look and feel comfortable, but their Sp O 2  is dangerously low. [ 5 ]  This happens to patients either in the hospital or at home. Low Sp O 2  may indicate severe COVID-19-related pneumonia, requiring a ventilator. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1929", "text": "Continuous monitoring with pulse oximetry is generally considered safe for most patients for up to 8 hours. However, prolonged use in certain types of patients can cause burns due to the heat emitted by the infrared LED, which reaches up to 43\u00b0C. Additionally, pulse oximeters occasionally develop electrical faults which causes them to heat up above this temperature. Patients at greater risk include those with delicate or fragile skin, such as infants, particularly premature infants, and the elderly. Additional risks for injury include lack of pain response where the probe is placed, such as having an insensate limb, or being unconscious or under anesthesia, or having communication difficulties. Patients who are at high risk for injury should be have the site of their probe moved frequently, i.e. every hour, whereas patients who are at lower risk should have theirs moved every 2-4 hours. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1930", "text": "Pulse oximetry solely measures hemoglobin saturation, not  ventilation  and is not a complete measure of respiratory sufficiency. It is not a substitute for  blood gases  checked in a laboratory, because it gives no indication of base deficit, carbon dioxide levels, blood  pH , or  bicarbonate  (HCO 3 \u2212 ) concentration. The metabolism of oxygen can readily be measured by monitoring expired CO 2 , but saturation figures give no information about blood oxygen content. Most of the oxygen in the blood is carried by hemoglobin; in severe anemia, the blood contains less hemoglobin, which despite being saturated cannot carry as much oxygen. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1931", "text": "Pulse oximetry also is not a complete measure of circulatory oxygen sufficiency. If there is insufficient  bloodflow  or insufficient hemoglobin in the blood ( anemia ), tissues can suffer  hypoxia  despite high arterial oxygen saturation."}
{"_id": "WikiPedia_Cardio$$$corpus_1932", "text": "Since pulse oximetry measures only the percentage of bound hemoglobin, a falsely high or falsely low reading will occur when hemoglobin binds to something other than oxygen:"}
{"_id": "WikiPedia_Cardio$$$corpus_1933", "text": "A noninvasive method that allows continuous measurement of the  dyshemoglobins  is the pulse  CO-oximeter , which was built in 2005 by Masimo. [ 15 ]  By using additional wavelengths, [ 16 ]  it provides clinicians a way to measure the dyshemoglobins,  carboxyhemoglobin , and  methemoglobin  along with total hemoglobin. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1934", "text": "Because pulse oximeter devices are calibrated for healthy subjects, their accuracy is poor for critically ill patients and preterm newborns. [ 1 ]  Erroneously low readings may be caused by  hypoperfusion  of the extremity being used for monitoring (often due to a limb being cold or from  vasoconstriction  secondary to the use of  vasopressor  agents); incorrect sensor application; highly  calloused  skin; or movement (such as shivering), especially during hypoperfusion. To ensure accuracy, the sensor should return a steady pulse and/or pulse waveform. Pulse oximetry technologies differ in their abilities to provide accurate data during conditions of motion and low perfusion. [ 18 ] [ 19 ]   Obesity ,  hypotension  (low blood pressure), and some  hemoglobin variants  can reduce the accuracy of the results. [ 8 ]  Some home pulse oximeters have low  sampling  rates, which can significantly underestimate dips in blood oxygen levels. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1935", "text": "The accuracy of pulse oximetry deteriorates considerably for readings below 80%. [ 9 ]  Research has suggested that error rates in common pulse oximeter devices may be higher for adults with  dark skin color , leading to claims of encoding  systemic racism  in countries with multi-racial populations  such as the United States . [ 20 ] [ 21 ]  The issue was first identified decades ago; one of the earliest studies on this topic occurred in 1976, which reported reading errors in dark-skinned patients that reflected lower blood oxygen saturation values. [ 22 ]  Further studies indicate that while accuracy with dark skin is good at higher, healthy saturation levels, some devices overestimate the saturation at lower levels, which may lead to hypoxia not being detected. [ 23 ]  A study that reviewed thousands of cases of occult  hypoxemia , where patients were found to have oxygen saturation below 88% per arterial blood gas measurement despite pulse oximeter readings indicating 92% to 96% oxygen saturation, found that black patients were three times as likely as white patients to have their low oxygen saturation missed by pulse oximeters. [ 24 ]  Another research study investigated patients in the hospital with COVID-19 and found that occult hypoxemia occurred in 28.5% of black patients compared to only 17.2% of white patients. [ 25 ]  There has been research to indicate that black COVID-19 patients were 29% less likely to receive supplemental oxygen in a timely manner and three times more likely to have hypoxemia. [ 26 ]  A further study, which used a MIMIC-IV critical care dataset of both pulse oximeter readings and oxygen saturation levels detected in blood samples, demonstrated that black, Hispanic, and Asian patients had higher Sp O 2  readings than white patients for a given blood oxygen saturation level measured in blood samples. [ 27 ]  As a result, black, Hispanic, and Asian patients also received lower rates of supplemental oxygen than white patients. [ 27 ]  It is suggested that melanin can interfere with the absorption of light used to measure the level of oxygenated blood, often measured from a person's finger. [ 27 ]  Further studies and computer simulations show that the increased amounts of melanin found in people with darker skin scatter the photons of light used by the pulse oximeters, decreasing the accuracy of the measurements. As the studies used to calibrate the devices typically oversample people with lighter skin, the parameters for pulse oximeters are set based on information that is not equitably balanced to account for diverse skin colors. [ 28 ]  This inaccuracy can lead to potentially missing people who need treatment, as pulse oximetry is used for the screening of sleep apnea and other types of sleep-disordered breathing, [ 8 ]  which in the United States are conditions more prevalent among minorities. [ 29 ] [ 30 ] [ 31 ]  This bias is a significant concern, as a 2% decrease is important for respiratory rehabilitation, studies of sleep apnea, and athletes performing physical efforts; it can lead to severe complications for the patient, requiring an external oxygen supply or even hospitalization. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1936", "text": "Another concern regarding pulse oximetry bias is that insurance companies and hospital systems increasingly use these numbers to inform their decisions. Pulse oximetry measurements are used to identify candidates for reimbursement. [ 33 ]  Similarly, pulse oximetry data is being incorporated into algorithms for clinicians. Early Warning Scores, which provide a record for analyzing a patient's clinical status and alerting clinicians if needed, incorporate algorithms with pulse oximetry information and can result in misinformed patient records. [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1937", "text": "In addition to pulse oximeters for professional use, many inexpensive \"consumer\" models are available. Opinions vary about the reliability of consumer oximeters; a typical comment is \"The research data on home monitors has been mixed, but they tend to be accurate within a few percentage points\". [ 34 ]  Some smart watches with  activity tracking  incorporate an oximeter function. An article on such devices, in the context of diagnosing  COVID-19  infection, quoted Jo\u00e3o Paulo Cunha of the University of Porto, Portugal: \"these sensors are not precise, that's the main limitation ... the ones that you wear are only for the consumer level, not for the clinical level\". [ 35 ]  Pulse oximeters used for diagnosis of conditions such as COVID-19 should be Class IIB medical grade oximeters. Class IIB oximeters can be used on patients of all skin colors, low pigmentation and in the presence of motion. [ citation needed ]  When a pulse oximeter is shared between two patients, to prevent cross-infection it should be cleaned with alcohol wipes after each use or a disposable probe or finger cover should be used. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1938", "text": "According to a report by iData Research, the US pulse oximetry monitoring market for equipment and sensors was over $700 million in 2011. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1939", "text": "Mobile app  pulse oximeters use the flashlight and the camera of the phone, instead of infrared light used in conventional pulse oximeters. However, apps do not generate as accurate readings because the camera cannot measure the light reflection at two wavelengths, so the oxygen saturation readings that are obtained through an app on a smartphone are inconsistent for clinical use. At least one study has suggested these are not reliable relative to clinical pulse oximeters. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1940", "text": "A blood-oxygen monitor displays the percentage of blood that is loaded with oxygen. More specifically, it uses  light spectrometry  to measure what percentage of  hemoglobin , the protein in blood that carries oxygen, is loaded. Acceptable normal Sa O 2  ranges for patients without pulmonary pathology are from 95 to 99 percent. [ citation needed ]  For a person breathing room air at or near  sea level , an estimate of arterial pO 2  can be made from the blood-oxygen monitor  \"saturation of peripheral oxygen\"  (Sp O 2 ) reading. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1941", "text": "A typical pulse oximeter uses an electronic processor and a pair of small  light-emitting diodes  (LEDs) facing a  photodiode  through a translucent part of the patient's body, usually a fingertip or an earlobe. One LED is red, with  wavelength  of 660\u00a0nm, and the other is  infrared  with a wavelength of 940\u00a0nm. Absorption of light at these wavelengths differs significantly between blood loaded with oxygen and blood lacking oxygen. Oxygenated hemoglobin absorbs more infrared light and allows more red light to pass through. Deoxygenated hemoglobin allows more infrared light to pass through and absorbs more red light. The LEDs sequence through their cycle of one on, then the other, then both off about thirty times per second which allows the photodiode to respond to the red and infrared light separately and also adjust for the ambient light baseline. [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1942", "text": "The amount of light that is transmitted (in other words, that is not absorbed) is measured, and separate normalized signals are produced for each wavelength. These signals fluctuate in time because the amount of arterial blood that is present increases (literally pulses) with each heartbeat. By subtracting the minimum transmitted light from the transmitted light in each wavelength, the effects of other tissues are corrected for, generating a continuous signal for pulsatile arterial blood. [ 40 ]  The ratio of the red light measurement to the infrared light measurement is then calculated by the processor (which represents the ratio of oxygenated hemoglobin to deoxygenated hemoglobin), and this ratio is then converted to Sp O 2  by the processor via a  lookup table [ 40 ]  based on the  Beer\u2013Lambert law . [ 39 ]  The signal separation also serves other purposes: a plethysmograph waveform (\"pleth wave\") representing the pulsatile signal is usually displayed for a visual indication of the pulses as well as signal quality, [ 4 ]  and a numeric ratio between the pulsatile and baseline absorbance (\" perfusion index \") can be used to evaluate perfusion. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1943", "text": "SpO \n \n 2 \n \n \n \n \n \n \n = \n \n \n \n \n HbO \n \n 2 \n \n \n \n \n \n \n \n \n \n HbO \n \n 2 \n \n \n \n \n \n \n + \n Hb \n \n \n \n \n \n {\\displaystyle {\\ce {SpO2}}={\\frac {{\\ce {HbO2}}}{{\\ce {{HbO2}+Hb}}}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_1944", "text": "where HbO 2  is oxygenated hemoglobin ( oxyhemoglobin ) and Hb is deoxygenated hemoglobin."}
{"_id": "WikiPedia_Cardio$$$corpus_1945", "text": "Due to changes in blood volumes in the skin, a  plethysmographic  variation can be seen in the light signal received (transmittance) by the sensor on an oximeter. The variation can be described as a  periodic function , which in turn can be split into a DC component (the peak value) [ a ]  and an AC component (peak minus trough). [ 42 ]  The ratio of the AC component to the DC component, expressed as a percentage, is known as the  (peripheral)  perfusion  index  (Pi) for a pulse, and typically has a range of 0.02% to 20%. [ 43 ]  An earlier measurement called the  pulse oximetry plethysmographic  (POP) only measures the \"AC\" component, and is derived manually from monitor pixels. [ 41 ] [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1946", "text": "Pleth variability index  (PVI) is a measure of the variability of the perfusion index, which occurs during breathing cycles. Mathematically it is calculated as  (Pi max  \u2212 Pi min )/Pi max  \u00d7 100% , where the maximum and minimum Pi values are from one or many breathing cycles. [ 42 ]  It has been shown to be a useful, noninvasive indicator of continuous fluid responsiveness for patients undergoing fluid management. [ 41 ]   Pulse oximetry plethysmographic waveform amplitude  (\u0394POP) is an analogous earlier technique for use on the manually-derived POP, calculated as  (POP max  \u2212 POP min )/(POP max  + POP min )\u00d72 . [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1947", "text": "In 1935, German physician  Karl Matthes  (1905\u20131962) developed the first two-wavelength ear O 2  saturation meter with red and green filters (later red and infrared filters). It was the first device to measure O 2  saturation. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1948", "text": "The original oximeter was made by  Glenn Allan Millikan  in the 1940s. [ 46 ]  In 1943 [ 47 ]  and as published in 1949, [ 48 ]   Earl Wood  added a pressure capsule to squeeze blood out of the ear so as to obtain an absolute O 2  saturation value when blood was readmitted. The concept is similar to today's conventional pulse oximetry, but was difficult to implement because of unstable  photocells  and light sources; today this method is not used clinically. In 1964 Shaw assembled the first absolute reading ear oximeter, which used eight wavelengths of light. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1949", "text": "The first pulse oximetry was developed in 1972 by Japanese bioengineers  Takuo Aoyagi  and Michio Kishi at Japanese medical electronic equipment manufacturer  Nihon Kohden , using the ratio of red to infrared light absorption of pulsating components at the measuring site. Nihon Kohden manufactured the first pulse oximeter, Ear Oximeter OLV-5100. Surgeon Susumu Nakajima and his associates first tested the device in patients, reporting it in 1975. [ 49 ]  However, Nihon Kohden suspended the development of pulse oximetry and did not apply for a basic patent of pulse oximetry except in Japan, which facilitated further development and utilization of pulse oximetry later in U.S. In 1977,  Minolta  commercialized the first finger pulse oximeter OXIMET MET-1471. In the U.S., the first pulse oximetry was commercialized by  Biox  in 1980. [ 49 ] [ 50 ] [ 51 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1950", "text": "By 1987, the standard of care for the administration of a general anesthetic in the U.S. included pulse oximetry. From the operating room, the use of pulse oximetry rapidly spread throughout the hospital, first to  recovery rooms , and then to  intensive care units . Pulse oximetry was of particular value in the neonatal unit where the patients do not thrive with inadequate oxygenation, but too much oxygen and fluctuations in oxygen concentration can lead to vision impairment or blindness from  retinopathy of prematurity  (ROP). Furthermore, obtaining an arterial blood gas from a neonatal patient is painful to the patient and a major cause of neonatal anemia. [ 52 ]  Motion artifact can be a significant limitation to pulse oximetry monitoring, resulting in frequent false alarms and loss of data. This is because during motion and low peripheral  perfusion , many pulse oximeters cannot distinguish between pulsating arterial blood and moving venous blood, leading to underestimation of oxygen saturation. Early studies of pulse oximetry performance during subject motion made clear the vulnerabilities of conventional pulse oximetry technologies to motion artifact. [ 18 ] [ 53 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1951", "text": "In 1995,  Masimo  introduced Signal Extraction Technology (SET) that could measure accurately during patient motion and low perfusion by separating the arterial signal from the venous and other signals. Since then, pulse oximetry manufacturers have developed new algorithms to reduce some false alarms during motion, [ 54 ]  such as extending averaging times or freezing values on the screen, but they do not claim to measure changing conditions during motion and low perfusion. So there are still important differences in performance of pulse oximeters during challenging conditions. [ 19 ]  Also in 1995, Masimo introduced perfusion index, quantifying the amplitude of the peripheral  plethysmograph  waveform. Perfusion index has been shown to help clinicians predict illness severity and early adverse respiratory outcomes in neonates, [ 55 ] [ 56 ] [ 57 ]  predict low superior vena cava flow in very low birth weight infants, [ 58 ]  provide an early indicator of sympathectomy after epidural anesthesia, [ 59 ]  and improve detection of critical congenital heart disease in newborns. [ 60 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1952", "text": "Published papers have compared signal extraction technology to other pulse oximetry technologies and have demonstrated consistently favorable results for signal extraction technology. [ 18 ] [ 19 ] [ 61 ]  Signal extraction technology pulse oximetry performance has also been shown to translate into helping clinicians improve patient outcomes. In one study, retinopathy of prematurity (eye damage) was reduced by 58% in very low birth weight neonates at a center using signal extraction technology, while there was no decrease in retinopathy of prematurity at another center with the same clinicians using the same protocol but with non-signal extraction technology. [ 62 ]  Other studies have shown that signal extraction technology pulse oximetry results in fewer arterial blood gas measurements, faster oxygen weaning time, lower sensor utilization, and lower length of stay. [ 63 ]  The measure-through motion and low perfusion capabilities it has also allow it to be used in previously unmonitored areas such as the general floor, where false alarms have plagued conventional pulse oximetry. As evidence of this, a landmark study was published in 2010 showing that clinicians at Dartmouth-Hitchcock Medical Center using signal extraction technology pulse oximetry on the general floor were able to decrease rapid response team activations, ICU transfers, and ICU days. [ 64 ]  In 2020, a follow-up retrospective study at the same institution showed that over ten years of using pulse oximetry with signal extraction technology, coupled with a patient surveillance system, there were zero patient deaths and no patients were harmed by opioid-induced respiratory depression while continuous monitoring was in use. [ 65 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1953", "text": "In 2007, Masimo introduced the first measurement of the  pleth variability index  (PVI), which multiple clinical studies have shown provides a new method for automatic, noninvasive assessment of a patient's ability to respond to fluid administration. [ 41 ] [ 66 ] [ 67 ]  Appropriate fluid levels are vital to reducing postoperative risks and improving patient outcomes: fluid volumes that are too low (under-hydration) or too high (over-hydration) have been shown to decrease wound healing and increase the risk of infection or cardiac complications. [ 68 ]  Recently, the National Health Service in the United Kingdom and the French Anesthesia and Critical Care Society listed PVI monitoring as part of their suggested strategies for intra-operative fluid management. [ 69 ] [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1954", "text": "In 2011, an expert workgroup recommended newborn screening with pulse oximetry to increase the detection of  critical congenital heart disease  (CCHD). [ 71 ]  The CCHD workgroup cited the results of two large, prospective studies of 59,876 subjects that exclusively used signal extraction technology to increase the identification of CCHD with minimal false positives. [ 72 ] [ 73 ]  The CCHD workgroup recommended newborn screening be performed with motion tolerant pulse oximetry that has also been validated in low perfusion conditions. In 2011, the US Secretary of Health and Human Services added pulse oximetry to the recommended uniform screening panel. [ 74 ]  Before the evidence for screening using signal extraction technology, less than 1% of newborns in the United States were screened. Today,  The Newborn Foundation  has documented near universal screening in the United States and international screening is rapidly expanding. [ 75 ]  In 2014, a third large study of 122,738 newborns that also exclusively used signal extraction technology showed similar, positive results as the first two large studies. [ 76 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1955", "text": "High-resolution pulse oximetry (HRPO) has been developed for in-home sleep apnea screening and testing in patients for whom it is impractical to perform  polysomnography . [ 77 ] [ 78 ]  It stores and records both  pulse rate  and Sp O 2  in 1 second intervals and has been shown in one study to help to detect sleep disordered breathing in surgical patients. [ 79 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1956", "text": "Pump thrombosis  ( PT ) is considered a specific case of a major device malfunction, and is classified as either suspected or confirmed pump  thrombus . Typically, the device is an implanted blood pump such as a  left ventricular assist device . The malfunction is a blockage in the flow of blood anywhere along a vessel (upstream or downstream) and it is mainly due to the bio-incompatible presence of a fairly complex mechanical apparatus. Pump thrombus is dreaded complication of CF LVAD technology [ 1 ]  that can require repeat surgery to replace the pump or lead to death. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1957", "text": "In suspected pump thrombus, the clinical patient condition or pump parameters suggest thrombus on any of the blood-contacting surfaces of the pump (inflow cannula, pump itself, or outflow graft). Confirmed pump thrombus is done by visual inspection (during device exchange, transplantation, autopsy), irrefutable radiographic evidence, or absence of Doppler inflow or outflow signals.Not all ventricular assist devices (VADs) are fully biocompatible, thus device thrombosis has always been a significant complication. Older generation pulsatile VADs were relatively large and it was practically impossible to thrombose the entire pump and cause hemodynamic consequences.Instead, any thrombus created in the pump could be dislodged, possibly resulting in an embolic stroke. In contrast, the newer continuous flow left ventricular assist devices (CF LVAD) are much smaller and have smaller gaps between the various components of the pump. These characteristics predispose CF LVAD to thrombosis of the entire pump where the clot stays in the device, leading to increased hemolysis and device dysfunction. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1958", "text": "Thrombosis of CF LVADSs can occur as a result of various factors, [ 3 ]  which can be divided into three categories: the pump, the patient, and the clinician. Management protocols for VADs are usually institution-dependent and there is a large variability in clinician-related factors. A decrease in anticoagulation thresholds [ 4 ] [ 5 ] [ 6 ]  has been postulated to have resulted in an increase in CF LVAD thrombosis. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1959", "text": "A complex balance exists between over-anticoagulation and under-anticoagulation, in a patient population where the coagulation system response to the CF LVAD device varies greatly between individuals. Common adverse events precipitated by over-anticoagulation include bleeding problems such as gastrointestinal bleeding and intracranial hemorrhage, while common complications due to under-anticoagulation include hemolysis, pump thrombosis and ischemic/embolic strokes. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1960", "text": "Unfortunately, robust and individually-tailored anticoagulation therapy protocols do not exist in most institutions, which usually utilize a \"one size fits all\" approach. One anticoagulation protocol example targets the therapeutic window of  coumadin  of an  international normalized ratio  (INR) goal of 2\u20133 and full-dose aspirin for antiplatelet activity. In the complex dynamics of the interaction of patients' systems, there is no completely safe zone between thrombosis or bleeding, or both."}
{"_id": "WikiPedia_Cardio$$$corpus_1961", "text": "Pump thrombosis is defined as a specific case of a major device malfunction. In turn, device malfunction is as defined by  Interagency Registry for Mechanically Assisted Circulatory Support  (INTERMACS) as a failure of one or more of the components of the mechanical circulatory support systems which either directly causes or could potentially induce a state of inadequate circulatory support (low cardiac output state) or death. A failure that was iatrogenic or recipient-induced will be classified as an Iatrogenic/Recipient-Induced failure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1962", "text": "Device failure should be classified according to which component fails as follows:"}
{"_id": "WikiPedia_Cardio$$$corpus_1963", "text": "The FDA is aware of serious adverse events associated with LVADs. It has received reports and information from a variety of sources indicating an increase in the rate of pump thrombosis events in patients implanted with LVADs. Information also shows that patients are experiencing pump thrombosis events earlier than observed during the clinical trials conducted to support product approvals in 2008 Bridge To Transplant (BTT) and 2010 Destination Therapy (DT). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1964", "text": "Two analyses in scientific literature reported the confirmed (after explant) pump thrombosis rate as high as 8.4% of implanted devices at 3 months (Starling et al, 2013) and 6% of implanted devices at 6 months (Kirklin et al, 2014). This is compared to 1.6% of implanted devices at one year during the BTT clinical trial and 3.8% of implanted devices at 2 years during the DT clinical trial. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1965", "text": "The cause for PT are classified as either pump-related, patient-related, or management-related. But of particular concern is the emergence in some reports of  HIT syndrome  as an etiologic factor in some cases of PT. [ 11 ] [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1966", "text": "Inherent to the technology itself. Examples: Heat generated by pump rotor; Outflow graft kink."}
{"_id": "WikiPedia_Cardio$$$corpus_1967", "text": "Individual conditions that render patient more likely to have thrombotic complications. Examples: Atrial fibrillation; Infection."}
{"_id": "WikiPedia_Cardio$$$corpus_1968", "text": "Criteria should include the presence of hemolysis, presence of heart failure not explained by structural disease, and/or abnormal pump parameters. Imaging and functional studies (ramp) can confirm diagnosis. [ 14 ]  Elevated lactate dehydrogenase (LDH) levels. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1969", "text": "The complication itself, its prevention, or its treatment may lead to PT. Prevention of GI bleeding in VAD patients often includes keeping pump speeds lower to potentially minimize the proliferation of AV malformations."}
{"_id": "WikiPedia_Cardio$$$corpus_1970", "text": "In addition, bleeding, once it occurs, is managed at least temporarily by a halting or decrease in  AC . Efforts to decrease the development of AI in LVAD patients include keeping pump speeds on the lower side as well."}
{"_id": "WikiPedia_Cardio$$$corpus_1971", "text": "Right ventricular dysfunction, particularly in the early postoperative period, is likewise managed with lower pump speeds. Finally, infections and sepsis are known to be associated with a more hypercoagulable state in VAD patients. In the end, the occurrence of any of these complications may thus prove to be a surrogate for a higher risk of PT."}
{"_id": "WikiPedia_Cardio$$$corpus_1972", "text": "While the issue of biocompatibility is always at the forefront of critical issues of new pumps, the field of mechanical circulatory support is first focusing on adopting a standardized approach to this therapy so that valid analyses and comparisons can be made. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1973", "text": "No standardized protocol exist regarding the management of LVAD pump thrombosis. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1974", "text": "No standardized protocol exist regarding therapy of pump thrombosis. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1975", "text": "Beginning in 2011, centers and collaborative groups began to observe a significant increase in the\nincidence of pump thrombosis, which led to pump modifications and the appreciation of more strict control of blood pressure and anticoagulation with this pump design. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1976", "text": "The unexpected abrupt increase in LVAD thrombosis was accompanied by elevated  lactate dehydrogenase  (LDH) levels with outcomes of different management strategies in a multi-institutional study. [ 20 ] [ 21 ] [ 22 ]  Elevation of lactate dehydrogenase during the first month offers an opportunity for early intervention strategies. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1977", "text": "Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% to 8.4% by January 1, 2013. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1978", "text": "Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months, and from March 2011 onward, it was 2.7 months. The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis."}
{"_id": "WikiPedia_Cardio$$$corpus_1979", "text": "While starting in 2011 device failures due to clots forming inside the pumps appeared to rise dramatically, there is some indication that these failures may now be declining, but data analysis and interpretation are complex. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1980", "text": "Computational fluid dynamics  (CFD) is an invaluable tool in the development of VADs, enabling new designs to be tested rapidly and undesirable flow characteristics eliminated in successive versions before prototypes are manufactured. CFD is used for predicting pressure-flow characteristics and efficiency curves, revealing the detailed flow field to help eliminate regions of recirculation or stagnation and for calculating fluid dynamic forces. When combined with models of blood damage CFD has been used for predicting haemolysis and platelet activation by VADs. When combined with shape optimization algorithms it can be used in design optimization. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1981", "text": "The  Randomized Aldactone Evaluation Study  ( RALES ) trial is a landmark clinical study that assessed the impact of  spironolactone , an  aldosterone antagonist , on morbidity and mortality in patients with severe  heart failure  due to systolic dysfunction. [ 1 ]  The findings from this trial significantly influenced the treatment guidelines for heart failure. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1982", "text": "Heart failure, particularly with reduced  ejection fraction  (HFrEF), is a major cause of morbidity and mortality worldwide. Aldosterone, a hormone that promotes sodium retention and potassium excretion, plays a significant role in the pathophysiology of heart failure by contributing to fluid overload, myocardial fibrosis, and vascular damage. Spironolactone, a  potassium-sparing diuretic  and aldosterone antagonist was hypothesized to improve outcomes in patients with severe heart failure. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1983", "text": "RALES trial was a randomized, double-blind, placebo-controlled trial that enrolled 1663 patients from 195 centers in 15 countries from March 1995 to December 1996. The average age of the patients was 65 years. Patients were eligible for enrollment if they had recently been diagnosed with severe heart failure (NYHA class III or IV) and a left ventricular ejection fraction (LVEF) of 35% or less, who were already receiving standard therapy (ACE inhibitors, loop diuretics, and, if tolerated, digoxin). The objective of this trial was to assess the impact of spironolactone on morbidity and mortality in patients with severe heart failure.  Patients were randomized to receive either spironolactone (25 to 50 mg) daily or placebo. Both groups were continued on standard therapy. The primary endpoint was all-cause mortality. Secondary endpoints included hospitalization for heart failure, changes in symptoms of heart failure, and serum potassium levels. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1984", "text": "The trial was stopped early because the beneficial effect of spironolactone on all-cause death exceeded the prespecified discontinuation requirements. Spironolactone reduced the risk of death by 30% compared to placebo. Additionally, there was a 35% reduction in the risk of hospitalization for worsening heart failure in the spironolactone group. Finally, patients treated with spironolactone reported significant improvements in heart failure symptoms. Hyperkalemia was more common in the spironolactone group, but the incidence of severe hyperkalemia was relatively low. Gynecomastia or breast pain occurred in 10% of men treated with spironolactone vs 1% of men in the placebo group, otherwise there were no other differences in safety or adverse events. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1985", "text": "The RALES trial had a profound impact on the management of heart failure. The results led to the inclusion of aldosterone antagonists, such as spironolactone, in treatment guidelines for patients with severe heart failure. Spironolactone has become a standard therapy for reducing mortality and morbidity in patients with severe heart failure with reduced ejection fraction. [ 2 ] [ 3 ]  The RALES trial has then paved the way for further studies on the role of aldosterone antagonists in heart failure and other cardiovascular conditions. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1986", "text": "The RALES trial established spironolactone as a vital component of therapy for patients with severe heart failure, demonstrating significant reductions in mortality and hospitalization and improvements in symptoms. The trial's findings have been instrumental in shaping current heart failure treatment guidelines and improving patient outcomes. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1987", "text": "Reflex syncope  is a brief  loss of consciousness  due to a  neurologically  induced drop in  blood pressure  and/or a  decrease  in  heart  rate. [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 2 ]  Before an affected person passes out, there may be sweating, a decreased ability to see, or  ringing in the ears . [ 1 ]  Occasionally, the person may twitch while unconscious. [ 1 ]  Complications of reflex syncope include injury due to a fall. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1988", "text": "Reflex syncope is divided into three types: vasovagal, situational, and carotid sinus. [ 2 ]  Vasovagal syncope is typically triggered by seeing  blood , pain, emotional stress, or prolonged standing. [ 11 ]  Situational syncope is often triggered by  urination , swallowing, or coughing. [ 2 ]  Carotid sinus syncope is due to pressure on the  carotid sinus  in the neck. [ 2 ]  The underlying mechanism involves the  nervous system  slowing the heart rate and dilating blood vessels, resulting in low blood pressure and thus not enough blood flow to the brain. [ 2 ]  Diagnosis is based on the symptoms after ruling out other possible causes. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1989", "text": "Recovery from a reflex syncope episode happens without specific treatment. [ 2 ]  Prevention of episodes involves avoiding a person's triggers. [ 2 ]  Drinking sufficient fluids, salt, and exercise may also be useful. [ 2 ] [ 4 ]  If this is insufficient for treating vasovagal syncope, medications such as  midodrine  or  fludrocortisone  may be tried. [ 4 ]  Occasionally, a  cardiac pacemaker  may be used as treatment. [ 2 ]  Reflex syncope affects at least 1 in 1,000 people per year. [ 1 ]  It is the most common type of  syncope , making up more than 50% of all cases. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1990", "text": "Episodes of vasovagal syncope are typically recurrent and usually occur when the predisposed person is exposed to a specific trigger. Before losing consciousness, the individual frequently experiences early signs or symptoms such as  lightheadedness , nausea, the feeling of being extremely hot or cold (accompanied by sweating),  ringing in the ears , an uncomfortable feeling in the heart, fuzzy thoughts, confusion, a slight inability to speak or form words (sometimes combined with mild stuttering), weakness and visual disturbances such as lights seeming too bright, fuzzy or tunnel vision, black cloud-like spots in vision, and a feeling of nervousness can occur as well. The symptoms may become more intense over several seconds to several minutes before the loss of consciousness (if it is lost). Onset usually occurs when a person is sitting up or standing. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1991", "text": "When people lose consciousness, they fall down (unless prevented from doing so) and, when in this position, effective blood flow to the brain is immediately restored, allowing the person to regain consciousness. If the person does not fall into a fully flat, supine position, and the head remains elevated above the trunk, a state similar to a  seizure  may result from the blood's inability to return quickly to the brain, and the neurons in the body will fire off and generally cause muscles to twitch very slightly but mostly remain very tense. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1992", "text": "The  autonomic nervous system 's physiological state (see below) leading to loss of consciousness may persist for several minutes, so"}
{"_id": "WikiPedia_Cardio$$$corpus_1993", "text": "Reflex syncope occurs in response to a trigger due to dysfunction of the heart rate and blood pressure regulating mechanism. When heart rate slows or blood pressure drops, the resulting lack of blood to the brain causes fainting. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1994", "text": "Typical triggers include:"}
{"_id": "WikiPedia_Cardio$$$corpus_1995", "text": "Pressing upon a certain spot in the neck. [ 11 ]  This may happen when wearing a tight collar, shaving, or turning the head. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1996", "text": "Regardless of the trigger, the mechanism of syncope is similar in the various vasovagal syncope syndromes. The  nucleus tractus solitarii  of the  brainstem  is activated directly or indirectly by the triggering stimulus, resulting in simultaneous enhancement of  parasympathetic nervous system  ( vagal ) tone and withdrawal of  sympathetic nervous system  tone. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1997", "text": "This results in a spectrum of hemodynamic responses: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_1998", "text": "One account for these physiological responses is the  Bezold-Jarisch reflex ."}
{"_id": "WikiPedia_Cardio$$$corpus_1999", "text": "Vasovagal syncope may be part of an evolved response, specifically, the  fight-or-flight response . [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2000", "text": "In addition to the mechanism described above, a number of other medical conditions may cause  syncope . Making the correct diagnosis for loss of consciousness is difficult. The core of the diagnosis of vasovagal syncope rests upon a clear description of a typical pattern of triggers, symptoms, and time course. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2001", "text": "It is pertinent to differentiate  lightheadedness , seizures,  vertigo , and  low blood sugar  as other causes. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2002", "text": "In people with recurrent vasovagal syncope, diagnostic accuracy can often be improved with one of the following diagnostic tests:"}
{"_id": "WikiPedia_Cardio$$$corpus_2003", "text": "Treatment for reflex syncope focuses on avoidance of triggers, restoring blood flow to the brain during an impending episode, and measures that interrupt or prevent the  pathophysiologic mechanism  described above. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2004", "text": "Types of long-term therapy for vasovagal syncope include [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2005", "text": "Brief periods of unconsciousness usually cause no lasting harm to health. Reflex syncope can occur in otherwise healthy individuals, and has many possible causes, often trivial ones such as prolonged standing with the legs locked. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2006", "text": "The main danger of vasovagal syncope (or dizzy spells from vertigo) is the risk of injury by falling while unconscious. Medication therapy could possibly prevent future vasovagal responses; however, for some individuals medication is ineffective and they will continue to have fainting episodes. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2007", "text": "A  registered cardiovascular invasive specialist  or  RCIS  assists a  cardiologist  with  cardiac catheterization  procedures in the  United States . [ 1 ]   These procedures can determine if a blockage exists in the  blood vessels  that supply the heart muscle and can help diagnose other problems. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2008", "text": "To become registered they have to pass the registry proctored by CCI (Cardiovascular Credentialing International). The exam consists of 170 multiple choice questions.  Some questions involve mathematical computation as well as pictures where one must identify  anatomy  and equipment.  To be registry eligible, they must have worked in the Cardiac Catheterization Laboratory for at least one year or have graduated from a registry\u2013eligible program."}
{"_id": "WikiPedia_Cardio$$$corpus_2009", "text": "Regurgitation  is  blood flow  in the opposite direction from normal, as the backward flowing of blood into the  heart  or between heart chambers. It is the  circulatory  equivalent of  backflow  in engineered systems. It is sometimes called reflux."}
{"_id": "WikiPedia_Cardio$$$corpus_2010", "text": "The various types of heart valve regurgitation via insufficiency are as follows:"}
{"_id": "WikiPedia_Cardio$$$corpus_2011", "text": "Regurgitation in or near the heart is often caused by valvular insufficiency (insufficient function, with incomplete closure, of the  heart valves ); for example,  aortic valve  insufficiency causes regurgitation through that valve, called aortic regurgitation, and the terms  aortic insufficiency  and  aortic regurgitation  are so closely linked as usually to be treated as  metonymically  interchangeable."}
{"_id": "WikiPedia_Cardio$$$corpus_2012", "text": "Regurgitant fraction is the percentage of blood that regurgitates back through the  aortic valve  to the  left ventricle  due to  aortic insufficiency , or through the  mitral valve  to the  atrium  due to  mitral insufficiency . It is measured as the amount of blood regurgitated into a cardiac chamber divided by the  stroke volume ."}
{"_id": "WikiPedia_Cardio$$$corpus_2013", "text": "This fraction affords a quantitative measure of the severity of the valvular lesion. Normally, no blood regurgitates, so the regurgitant fraction is zero. In patients with severe valvular lesions, regurgitant fraction can approach 80%."}
{"_id": "WikiPedia_Cardio$$$corpus_2014", "text": "Tricuspid regurgitation is common and is estimated to occur in 65\u201385% of the population. [ 1 ]  In The  Framingham Heart Study  presence of any severity of tricuspid regurgitation, ranging from trace to above moderate was in 82% of men and in 85.7% of women. [ 2 ]  Mild tricuspid regurgitation tend to be common and benign and in structurally normal tricuspid valve apparatus can be considered a normal variant. [ 1 ]  Moderate or severe tricuspid regurgitation is usually associated with tricuspid valve leaflet abnormalities and/or possibly annular dilation and is usually pathologic which can lead to irreversible damage of  cardiac muscle  and worse outcomes due to chronic prolonged  right ventricular volume overload . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2015", "text": "In a study of 595 male elite football players aged 18\u201338, and 47 sedentary non-athletes, it was found that 58% of the athletes had tricuspid regurgitation vs. 36% in non-athletes and mitral regurgitation was found in 20% football players and 15% in controls. Football players with tricuspid regurgitation had larger tricuspid annulus diameter, compared to athletes without tricuspid regurgitation. Athletes with tricuspid regurgitation also had enlarged right atrium diameter when compared to control group. In athletes with mitral regurgitation it was found they had larger mitral annulus diameter, compared to athletes without regurgitation. Also left atrium diameter was larger in athletes with mitral regurgitation. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2016", "text": "Remnant cholesterol , also known as  remnant lipoprotein  and  triglyceride-rich lipoprotein cholesterol  is an  atherogenic   lipoprotein  composed primarily of  very low-density lipoprotein  (VLDL) and  intermediate-density lipoprotein  (IDL) with  chylomicron  remnants. [ 1 ] [ 2 ] [ 3 ]  Elevated remnant cholesterol is associated with increased risk of atherosclerotic cardiovascular disease and stroke. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2017", "text": "Remnant cholesterol is the cholesterol content of triglyceride-rich lipoproteins, which consist of very low-density lipoproteins and intermediate-density lipoproteins with chylomicron remnants. [ 2 ] [ 5 ]  Remnant cholesterol is primarily chylomicron and VLDL, and each remnant particle contains about 40 times more cholesterol than LDL. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2018", "text": "Remnant cholesterol corresponds to all cholesterol not found in high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C). It is calculated as total cholesterol minus HDL-C and LDL-C. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2019", "text": "Elevated remnant cholesterol is associated with an increased risk of atherosclerotic cardiovascular disease, chronic inflammation,  myocardial infarction  and stroke. [ 4 ] [ 5 ] [ 8 ] [ 9 ]  Remnant cholesterol is especially predictive of  coronary artery disease  in patients with normal total cholesterol. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2020", "text": "High plasma remnant cholesterol is associated with increased plasma triglyceride levels. [ 12 ]   Hypertriglyceridemia  is characteristic of high plasma remnant cholesterol, but persons with high plasma triglycerides without high remnant cholesterol rarely have coronary artery disease. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2021", "text": "Remnant cholesterol has about twice the association with  ischemic heart disease  as LDL cholesterol. [ 14 ]  Although remnant cholesterol tends to be higher in people who are overweight (high  body mass index ), normal-weight persons with high remnant cholesterol tend to have a higher risk of myocardial infarction. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2022", "text": "Vupanorsen, an  ANGPTL3  inhibitor has been shown to lower remnant cholesterol up to 59%. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2023", "text": "Restenosis  is the recurrence of  stenosis , a narrowing of a  blood vessel , leading to restricted blood flow. Restenosis usually pertains to an  artery  or other large  blood vessel  that has become narrowed, received treatment to clear the blockage, and subsequently become re-narrowed. This is usually restenosis of an  artery , or other blood vessel, or possibly a vessel within an  organ ."}
{"_id": "WikiPedia_Cardio$$$corpus_2024", "text": "Restenosis is a common adverse event of endovascular procedures. Procedures frequently used to treat vascular damage from  atherosclerosis  and related narrowing and re-narrowing (restenosis) of blood vessels include  vascular surgery ,  cardiac surgery , and  angioplasty . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2025", "text": "When a stent is used and restenosis occurs, this is called  in-stent restenosis  or  ISR . [ 2 ]  If it occurs following balloon angioplasty, this is called post-angioplasty restenosis or  PARS . The diagnostic threshold for restenosis in both ISR  and PARS is \u226550% stenosis. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2026", "text": "If restenosis occurs after a procedure, follow-up imaging is not the only way to initially detect compromised blood flow. Symptoms may also suggest or signal restenosis, but this should be confirmed by imaging. For instance, a coronary stent patient who develops restenosis may experience recurrent chest pain ( angina ) or have a minor or major heart attack ( myocardial infarction ), though they may not report it. This is why it is important that a patient comply with follow-up screenings and the clinician follows through with a thorough clinical assessment. But it is also important to note that not all cases of restenosis lead to clinical symptoms, nor are they asymptomatic. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2027", "text": "Surgery to widen or unblock a  blood vessel  usually has a long-lasting beneficial effect on the patient. However, in some cases, the procedure itself can cause further narrowing of the vessel, or restenosis.  Angioplasty , also called  percutaneous transluminal coronary angioplasty  (PTCA), is commonly used to treat blockages of the  coronary  or  peripheral arteries  (such as in the limbs). The balloon inserted into the narrowing 'smashes' the  cholesterol  plaques ( atherosclerosis ) against the  artery walls , thus widening the size of the  lumen  and increasing blood flow. However the action damages the artery walls, and they respond by using  physiological  mechanisms to repair the damage. (See physiology below.)  [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2028", "text": "A  stent  is a mesh, tube-like structure often used in conjunction with  angioplasty  to permanently hold open an artery, allowing for unrestricted blood flow, or to support a weakness in the artery wall called an  aneurysm . The artery can react to the stent, perceive it as a foreign body, and respond by mounting an  immune system  response which leads to further narrowing near or inside the stent. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2029", "text": "Damage to the blood vessel wall by angioplasty triggers a physiological response that can be divided into two stages. The first stage that occurs immediately after tissue  trauma , is  thrombosis . A  blood clot  forms at the site of damage and further hinders blood flow. This is accompanied by an inflammatory  immune response . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2030", "text": "The second stage tends to occur 3\u20136 months after surgery and is the result of the  proliferation of cells  in the media, a smooth muscle wall in the vessel. This is also known as  Neointimal Hyperplasia  (NIHA). [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2031", "text": "Vessel restenosis is typically detected by  angiography , but can also be detected by duplex  ultrasound  and other imaging techniques. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2032", "text": "Late loss  is synonymous with  restenosis  and means loss of the  lumen   after  a procedure intended to open the vessel. It measures either the percent (relative) or absolute change in minimum luminal diameter (MLD) over the months following a  vascular procedure , such as the implantation of a stent graft. Late loss is one metric that is useful in determining the effectiveness of vascular interventions in clinical trials for either an individual patient or a group of patients. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2033", "text": "However  late loss  is only part of the terminology in describing the outcomes of vascular interventions. For instance, the implantation of a stent graft will first provide an  acute gain  in lumen diameter. In other words, there is an immediate gain in lumen size because the implanted stent opens up the vessel. However, over time, the body's inflammatory immune response (described below in the \"Causes\" section) reacts to the stent graft via smooth muscle proliferation, etc., which pushes the stent graft back, narrowing the vessel and  losing  at least a percentage of what was previously  gained , or  late loss. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2034", "text": "The  net gain  of lumen diameter is the difference between  acute gain  and  late loss  and is a measure of stent-graft effectiveness. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2035", "text": "Percent diameter restenosis (or just percent diameter stenosis) is a measure observed in individual patients and is typically calculated as the difference between the minimal (or minimum) luminal diameter (MLD) from the target reference vessel diameter (RVD), divided by the RVD, and multiplied by 100 to get the percentage of stenosis. It is an important measure needed to calculate binary restenosis (see Binary Restenosis section below). The RVD is typically calculated by averaging the MLD of the healthy part of the vessel both proximal and distal to the vessel lesion. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2036", "text": "There is some controversy over the accuracy of observing the lesion MLD itself, since many atherosclerotic lesions may create uneven \"hills and valleys\" within the lumen, making a true MLD difficult to obtain or estimate. Some research indicates calculating \"area stenosis\" is also a valid measure of actual vessel stenosis compared to diameter stenosis alone, but this requires additional analysis because a tracing of the lumen border must be performed. However, there are computer programs available to automatically perform this function. It may be helpful to obtain both percent diameter and area percent stenosis, especially since the two percentages may not always correlate with each other. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2037", "text": "An  occlusion , or the blocking of all blood flow through a vessel, is considered 100% percent diameter stenosis."}
{"_id": "WikiPedia_Cardio$$$corpus_2038", "text": "Binary restenosis is traditionally defined as a reduction in the percent diameter stenosis of 50% or more (\u226550%). It is also known as just \"binary stenosis\". [ 10 ]  The term \"binary\" means that patients are placed in 2 groups, those who have \u226550% stenosis and those who have <50% stenosis. Binary restenosis is an epidemiological method of analyzing percent diameter stenosis for observing not only an individual patient, but also performing statistical techniques on a group of patients to determine averages (descriptive measures of central tendency) or as a predictive variable. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2039", "text": "In the first stage of restenosis, administering anti- platelet  drugs (called IIb/IIIa inhibitors) immediately after surgery greatly reduces the chance of a  thrombosis  occurring. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2040", "text": "Drug-eluting stents , coated with  pharmaceuticals  that inhibit tissue growth and thus reduce the risk of restenosis from scar tissue and cell proliferation, are now widely used. [ 11 ]  These  stents  reduce the occurrence of restenosis, with clinical studies showing an incidence rate of 5% or lower. [ 3 ] [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2041", "text": "If restenosis occurs without a  stent , it is usually treated with more  angioplasty . [ citation needed ]  This treatment is also used if restenosis occurs at either the proximal or distal end of the  stent . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2042", "text": "If restenosis occurs within a  stent  (also known as in-stent stenosis), it may be treated with repeated  angioplasty  and insertion of another stent inside the original, often with a drug-eluting stent. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2043", "text": "Over the past 5 years, ISR has been increasingly treated with a  drug-coated balloon  (DCB), which is a balloon coated with the same anti-cancer drugs that prevent restenosis, such as  Paclitaxel . [ 15 ] [ 16 ]  The balloon avoids the need for a double layer of metal which is used when an in-stent restenosis is treated with another stent within the original stent. Additionally, DCB treatment does not leave an implant in the body and is designed for faster drug delivery."}
{"_id": "WikiPedia_Cardio$$$corpus_2044", "text": "Alternative treatments include  brachytherapy , or intracoronary radiation. The radiation kills cells and inhibits tissue growth (similar to a patient undergoing cancer therapy). [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2045", "text": "Rates of restenosis differ between devices (e.g., stent-grafts, balloon angioplasty, etc.) and location of procedure (i.e., centrally located in the heart, such as the coronary artery, or in peripheral vessels such as the popliteal artery in the leg, the pudendal artery in the pelvis, or the carotid artery in the neck). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2046", "text": "In cardiac procedures, balloon angioplasty without stent implantation has been associated with a high incidence of restenosis, with rates ranging from 25% to 50%, and the majority of these patients need further angioplasty within 6 months. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2047", "text": "A 2010 study in India comparing coronary  drug-eluting stents  (DES) with coronary  bare-metal stents  (BMS) reported that restenosis developed in 23.1% of DES patients vs 48.8% in BMS patients, and female sex was found to be a statistically significant risk factor for developing restenosis. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2048", "text": "However, in newer-generation DES and BMS the restenosis rates are much lower. For example, the NORSTENT trial, presented in 2016, reports target-lesion revascularization rates of 5.3% and 10.3% for DES and BMS respectively. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2049", "text": "In peripheral procedures, rates are still high. A 2003 study of selective and systematic stenting for limb-threatening ischemia reported restenosis rates at 1year follow-up in 32.3% of selective stenting patients and 34.7% of systematic stenting patients. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2050", "text": "The 2006 SIROCCO trial compared the sirolimus drug-eluting stent with a bare nitinol stent for atherosclerotic lesions of the  subsartorial artery , reporting restenosis at 2 year follow-up was 22.9% and 21.1%, respectively. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2051", "text": "A 2009 study compared bare nitinol stents with percutaneous transluminal angioplasty (PTA) in  subsartorial artery  disease. At 1 year follow-up, restenosis was reported in 34.4% of stented patients versus 61.1% of PTA patients. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2052", "text": "Return of spontaneous circulation  ( ROSC ) is the resumption of a sustained  heart rhythm  that perfuses the body after  cardiac arrest . It is commonly associated with significant respiratory effort. Signs of return of spontaneous circulation include breathing, coughing, or movement and a palpable pulse or a measurable blood pressure. Someone is considered to have sustained return of spontaneous circulation when circulation persists and  cardiopulmonary resuscitation  has ceased for at least 20 consecutive minutes. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2053", "text": "There are multiple factors during cardiopulmonary resuscitation (CPR) and  defibrillation  that are associated with success of achieving return of spontaneous circulation. One of the factors in CPR is the chest compression fraction, which is a measure of how much time during cardiac arrest are chest compressions performed. A study measured the effects of chest compression fraction on return of spontaneous circulation in out-of-hospital cardiac arrest patients with a non-ventricular fibrillation arrhythmia and it showed a trend to achieving return of spontaneous circulation with an increased chest compression fraction. [ 2 ]  Another study highlighted the benefits of minimizing chest compression intervals before and after shocking a patient's rhythm, which would in turn increase chest compression fraction. [ 3 ]  A  coronary perfusion pressure  of 15 mmHg is thought to be the minimum necessary to achieve ROSC. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2054", "text": "Pertaining to defibrillation, the presence of a shockable rhythm ( ventricular fibrillation  or pulseless  ventricular tachycardia ) is associated with increased chances of return of spontaneous circulation. [ 5 ]  Although a shockable rhythm increases chances for return of spontaneous circulation, a cardiac arrest can present with  pulseless electrical activity  or  asystole , which are non-shockable cardiac rhythms. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2055", "text": "Return of spontaneous circulation can be achieved through cardiopulmonary resuscitation and defibrillation. Though ROSC is necessary for survival, it is not, itself, a predictor of a favorable medium- or long-term outcome. [ 7 ]  Patients have died not long after their circulation has returned. One study showed that those who had had an out-of-hospital cardiac arrest and had achieved return of spontaneous circulation, 38% of those people had a cardiac re-arrest before arriving at the hospital with an average time of 3 minutes to re-arrest. [ 8 ]  Patients with sustained ROSC generally present with  post-cardiac arrest syndrome  (PCAS). Longer time-to-ROSC is associated with a worse presentation of PCAS. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2056", "text": "Lazarus phenomenon  is the rare spontaneous return of circulation after cardiopulmonary  resuscitation  attempts have stopped in someone with cardiac arrest. This phenomenon most frequently occurs within 10 minutes of cessation of resuscitation, thus passive monitoring is recommended for 10 minutes following CPR cessation. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2057", "text": "Rhythm interpretation  is an important part of healthcare in Emergency Medical Services ( EMS ). Trained medical personnel can determine different treatment options based on the  cardiac rhythm  of a patient.  There are many common heart rhythms that are part of a few different categories,  sinus arrhythmia , atrial arrhythmia,  ventricular arrhythmia .   Rhythms can be evaluated by measuring a few key components of a rhythm strip, the  PQRST  sequence, which represents one cardiac cycle, the  ventricular rate , which is the rate at which the  ventricles  contract, and the  atrial rate , which is the rate at which the atria contract."}
{"_id": "WikiPedia_Cardio$$$corpus_2058", "text": "The 5 deviations from the base line on a rhythm strip make up the  PQRST sequence .  There are a few key intervals that must be measured for proper analysis of a heart rhythm,  The  PR  interval is the interval between the end of the  P wave  and the beginning of the  Q wave .  This represents the conduction of the atria of the heart, the speed at which they are able to conduct an electrical impulse.  The  QRS complex  represents the conduction of the ventricles of the heart, the speed at which they are able to conduct an  electrical impulse .  The interval between each  R wave  represents the heart rate, which is critical for determining different rhythms within the defined categories. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2059", "text": "There are 6 different sinus arrhythmia. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2060", "text": "A normal heart should have a  normal sinus rhythm , this rhythm can be identified by a ventricular rate of 60-100 bpm, at a regular rate, with a normal PR interval (0.12 to 0.20 second) and a normal QRS complex (0.12 second and less)."}
{"_id": "WikiPedia_Cardio$$$corpus_2061", "text": "Sinus bradycardia   is another regular rhythm however the ventricular rate is only between 40 and 60 bpm, with a normal PR interval and a normal QRS complex."}
{"_id": "WikiPedia_Cardio$$$corpus_2062", "text": "Sinus tachycardia   is another regular rhythm however the ventricular rate is quicker, between 100 - 160 bpm, with a normal PR interval and normal QRS complex."}
{"_id": "WikiPedia_Cardio$$$corpus_2063", "text": "Sinus arrhythmia   is an irregular rhythm with a ventricular rate of 60 - 100 normally, however a slow rhythm can be distinguished when the rate is less than 60, the PR interval and QRS complex are normal."}
{"_id": "WikiPedia_Cardio$$$corpus_2064", "text": "Sinus pause  is a regular rhythm however a sudden pause occurs in the rhythm which makes it miss a few beats, if the rhythm resumes on time after the pause then this is known as a  sinus block , if the rhythm does not resume on time after the pause this is known as a  sinus arrest."}
{"_id": "WikiPedia_Cardio$$$corpus_2065", "text": "There are 5 different atrial arrhythmias. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2066", "text": "A  wandering atrial pacemaker  can be either normal or irregular in rate, much like a sinus arrhythmia the rate is normally between 60 - 100 bpm when it is normal and less than 60 when it is slow, the distinguishing feature of this rhythm is a p wave that varies in size, shape, and direction, the PR interval can either be normal or irregular depending on the location of conduction of the PR interval, the QRS complex is normal."}
{"_id": "WikiPedia_Cardio$$$corpus_2067", "text": "A  premature atrial pacemaker  has a regular underlying rhythm however there is a premature beat which can be identified by an irregular p wave with a different size, shape, and direction often found within a T wave, the PR interval is generally normal however can be hard to measure, the QRS complex is premature for the PAC, but is generally normal."}
{"_id": "WikiPedia_Cardio$$$corpus_2068", "text": "Paroxysmal  atrial tachycardia  has a regular rate, however a high rate of about 140-250 bpm, p waves are generally hidden and the PR interval is not measurable."}
{"_id": "WikiPedia_Cardio$$$corpus_2069", "text": "Atrial flutter  has an atrial rate of 250-400 and can be identified by p waves with saw tooth deflections."}
{"_id": "WikiPedia_Cardio$$$corpus_2070", "text": "Atrial fibrillation  has an atrial rate of 400+ and is distinguishable due to its irregular ventricular rate and wavy deflections."}
{"_id": "WikiPedia_Cardio$$$corpus_2071", "text": "Ventricular arrhythmias are some of the most dangerous heart rhythms requiring  cardiopulmonary resuscitation  ( CPR ) and defibrillation in cases of symptomatic  ventricular tachycardia  and  ventricular fibrillation ."}
{"_id": "WikiPedia_Cardio$$$corpus_2072", "text": "There are 5 different ventricular arrhymia. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2073", "text": "Ventricular tachycardia  is a regular rhythm with a rate of 140-250 bpm, there are no P waves and the main feature is a wide QRS complex (0.12 and greater)"}
{"_id": "WikiPedia_Cardio$$$corpus_2074", "text": "Ventricular fibrillation  has no p waves or QRS complexes, there are only wavy irregular deflections throughout the heart rhythm, at this point the heart would have a rate of 0 and be supplying no blood through the body."}
{"_id": "WikiPedia_Cardio$$$corpus_2075", "text": "Idioventricular rhythm  this is a regular rhythm identifiable by a wide QRS complex with absent P waves, and a rate between 30 and 40 bpm."}
{"_id": "WikiPedia_Cardio$$$corpus_2076", "text": "Accelerated idioventricular rhythm  is a regular rhythm with a wide QRS complex and absent P waves, and a rate between 50 and 100 bpm."}
{"_id": "WikiPedia_Cardio$$$corpus_2077", "text": "The final rhythm is  ventricular standstill  this rhythm will appear as a flat line, but may have a few non conducted p waves, the heart rate of this will be 0 and be supplying no blood through the body like ventricular fibrillation."}
{"_id": "WikiPedia_Cardio$$$corpus_2078", "text": "The  Roseto effect  is the phenomenon by which a close-knit community experiences a reduced rate of heart disease.  The effect is named for  Roseto, Pennsylvania .  The Roseto effect was first noticed in 1961 when the local Roseto doctor encountered  Stewart Wolf , then head of Medicine of the  University of Oklahoma , and they discussed, over a couple of beers, the unusually low rate of  myocardial infarction  in the  Italian American  community of Roseto compared with other locations. [ 1 ] [ 2 ] [ 3 ]   Many studies followed, including a 50-year study comparing Roseto to nearby  Bangor .  As the original authors had predicted, as the Roseto cohort shed their Italian social structure and became more Americanized in the years following the initial study, heart disease rates increased, becoming similar to those of neighboring towns. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2079", "text": "From 1954 to 1961, Roseto had nearly no heart attacks for the otherwise high-risk group of men 55 to 64, and men over 65 had a death rate of 1% while the national average was 2%.  Widowers outnumbered widows, as well. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2080", "text": "These statistics were at odds with a number of other factors observed in the community.  They smoked unfiltered  stogies , drank  wine  \"with seeming abandon\" in lieu of  milk  and  soft drinks , skipped the  Mediterranean diet  in favor of meatballs and sausages fried in lard with hard and soft cheeses.  The men worked in the  slate  quarries where they contracted illnesses from gases and dust. [ 5 ]   Roseto also had very little crime, and very few applications for public assistance. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2081", "text": "Wolf attributed Rosetans' lower heart disease rate to lower stress.  \"'The community,' Wolf says, 'was very cohesive. There was no  keeping up with the Joneses . Houses were very close together, and everyone lived more or less alike.'\"  Elders were revered and incorporated into community life.  Housewives were respected, and fathers ran the families. [ 2 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2082", "text": "The  San Francisco Syncope Rule  (SFSR) is a rule for evaluating the risk of adverse outcomes in patients presenting with  fainting  or  syncope ."}
{"_id": "WikiPedia_Cardio$$$corpus_2083", "text": "The mnemonic for features of the rule is CHESS:"}
{"_id": "WikiPedia_Cardio$$$corpus_2084", "text": "\u2022  C  - History of  congestive heart failure"}
{"_id": "WikiPedia_Cardio$$$corpus_2085", "text": "\u2022  H  -  Hematocrit  < 30%"}
{"_id": "WikiPedia_Cardio$$$corpus_2086", "text": "\u2022  E  - Abnormal  ECG"}
{"_id": "WikiPedia_Cardio$$$corpus_2087", "text": "\u2022  S  - Shortness of breath"}
{"_id": "WikiPedia_Cardio$$$corpus_2088", "text": "\u2022  S  - Triage systolic  blood pressure  < 90"}
{"_id": "WikiPedia_Cardio$$$corpus_2089", "text": "A patient with any of the above measures is considered at high risk for a serious outcome such as death,  myocardial infarction ,  arrhythmia ,  pulmonary embolism ,  stroke ,  subarachnoid hemorrhage , significant  hemorrhage , or any condition causing a return Emergency Department visit and hospitalization for a related event. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2090", "text": "SFSR was retrospectively found to have 98% sensitivity and specificity of 56% for serious causes of syncope. [ 1 ]  However, external prospective validation of the criteria found sensitivity to be 74%, substantially lower than the initial study. [ 2 ]  This means that in patients with none of the above criteria, potentially serious causes of syncope were missed in over a quarter of patients. Syncope accounts for 1-2%  emergency department  visits. Half are hospitalized and of these, 50% have unclear diagnosis and 85% will be simply monitored. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2091", "text": "SATRO-EKG  - a  computer program  analysing electro-cardiology signals. It is based on the  SFHAM model . It facilitates the evaluation of electrical activity of myocardium, and therefore, early detection of  ischemic changes in the heart ."}
{"_id": "WikiPedia_Cardio$$$corpus_2092", "text": "The reference tests of the SATRO-ECG method in relation to  perfusive scintigraphy SPECT  conducted in Military Medical Institute in  Warsaw  and  Medical University of Wroclaw  proved the possibility to use this method to detect  coronary heart disease (CHD) .  A very high  Sensitivity and specificity  in detecting this disease were obtained. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2093", "text": "Sensitivity (Se), specificity (Sp),  predictive value of positive values results  (PV(+)) and  negative values results  (PV(-)) are presented in the grid below: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2094", "text": "Comparison of SATRO-ECG results -  SPECT  (exercise) for particular parts of the cardiac muscle is presented in the grid below:  [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2095", "text": "The results of the tests prove a high correlation the between SATRO-ECG results and  SPECT  in the case of detection of  coronary heart disease (CHD)   [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2096", "text": "An advantage of this method is a fast and precise analysis of the ECG results in the rest, which enables:  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2097", "text": "The method is a diagnostic element of the Program of Universal Prevention and Therapy of Ischemic Heart Disease in the international project developed for  United Nations Economic and Social Council   [ 2 ] ."}
{"_id": "WikiPedia_Cardio$$$corpus_2098", "text": "The  Scandinavian Simvastatin Survival Study  (also known as the  4S  study), was a multicentre,  randomized, double-blind ,  placebo-controlled clinical trial , which provided the initial data that supported the use of the  cholesterol-lowering drug ,  simvastatin , in people with a moderately raised  cholesterol  and  coronary heart disease  (CHD); that is people who had previously had a  heart attack  or  angina . The study was sponsored by the pharmaceutical company  Merck  and enrolled 4,444 people from 94 centres in  Scandinavia . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2099", "text": "Before the 4S study, it was not proven that lowering cholesterol could prolong life in people who had CHD. [ 3 ]  The study concluded that  secondary prevention  with simvastatin in a high risk group with CHD reduced overall mortality by 30%. [ 3 ]  Published in  The Lancet  in 1994, it is considered a \"landmark paper\". [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2100", "text": "The 4S multicentre,  randomized, double-blind ,  placebo-controlled clinical trial  enrolled 4,444 people chosen from 7,027 people who had been followed up for two months after being given dietary advice. [ 2 ]  The objective of the study was to assess the effect of a  cholesterol-lowering drug  called  simvastatin  on  mortality  and morbidity in people with a history of a previous  heart attack  or  angina , who also had a moderately  raised cholesterol ; between 5.5 and 8.0\u00a0mmol/L. [ 1 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2101", "text": "A second objective was to investigate whether the incidence of major coronary artery disease events (fatal and nonfatal myocardial infarction and sudden death) could be reduced with simvastatin. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2102", "text": "The participants, all at high risk of death from CHD and death in general, [ 5 ]  were selected from 94 clinical centers in Denmark, Finland, Iceland, Norway, and Sweden from 1988 to 1989, and were aged between 35 and 70 years, with the average age being 59. [ 2 ] [ 7 ]  Of the 4,444 people enrolled in the study, 3,617 were men and 827 women, [ 5 ]  2,223 were randomly assigned a  placebo  and 2,221 were given 20 to 40\u00a0mg of simvastatin daily. [ 1 ]  The plan was to follow the participants for a minimum of three years or until such a time as total mortality reached 440 deaths. [ 2 ] [ 5 ]  In practice, the study carried for a median period of 5.4 years. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2103", "text": "After 5.4 years, compared to the group that were given placebo, the simvastatin group demonstrated a 35% reduction in  LDL-C  and 30% reduction in overall mortality. [ 1 ] [ 3 ]  The risk of hospital-verified non-fatal myocardial infarction reduced by 37% and fatal and non-fatal  cerebrovascular events  ( stroke  and  TIA ) lessened by 28%. [ 1 ]  30 people would need to be treated with simvastatin for about five years, to prevent one death;  number needed to treat  around 30. [ 3 ]  There were no extra deaths from other non-cardiac causes such as  cancer  or trauma. [ 3 ] [ 9 ]  The trial also showed benefits in diabetes, women and older people. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2104", "text": "A follow-up of treatment with simvastatin for up to eight years was published in 2000. [ 7 ]  Ten years after the start of the 4S trial, a follow-up study published on 28 August 2004 in  The Lancet , revealed that of those 2,221 people who continued to take simvastatin, there was a further reduction in number of deaths from CHD when compared to those who had switched from placebo to statin at the five year mark. [ 7 ] [ 10 ]  The overall mortality also reduced by 15% at the 10 year mark. [ 3 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2105", "text": "The study concluded that  secondary prevention  with simvastatin in a high risk group with CHD reduced overall mortality by 30%. Non-fatal CHD events and fatal and non-fatal cerebrovascular events were reduced without an increase in risk of cancer. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2106", "text": "Published in  The Lancet  in 1994, the 4S trial, had an immediate influence on medical opinion, [ 9 ]  and is considered a \"landmark paper\". [ 3 ] [ 4 ] [ 11 ]  Several other large multicenter clinical trials followed, leading to widespread use of simvastatin. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2107", "text": "Data from the 4S trial has frequently been used to analyse the cost-effectiveness of simvastatin in secondary prevention. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2108", "text": "SCP-ECG , which stands for  Standard communications protocol for computer assisted electrocardiography , is a standard for  ECG  traces, [ 1 ]  annotations, and  metadata , that specifies the interchange format and a messaging procedure for  ECG  cart-to-host communication and for retrieval of SCP-ECG records from the host to the ECG cart.   It is defined in the joint  ANSI / AAMI  standard EC71:2001  and in the  CEN  standard EN 1064:2005."}
{"_id": "WikiPedia_Cardio$$$corpus_2109", "text": "The SCP Standard was first developed between 1989 and 1991 during a European AIM R&D project. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2110", "text": "DICOM ,  HL7 aECG , MFER (ISO 22077) [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2111", "text": "The  Sensei X robotic catheter  is a medical  robot  designed to enhance a physician\u2019s ability to perform complex  operations  using a small flexible tube called a  catheter . As open surgical procedures that require large incisions have given way to minimally invasive surgeries in which the surgeon gains access to the target organs through small incisions using specialized surgical tools.  One important tool used in many of these procedures is a catheter used to deliver many of things a surgeon needs to do his work, to impact target tissue and deliver a variety of medicines or disinfecting agents to treat disease or infection."}
{"_id": "WikiPedia_Cardio$$$corpus_2112", "text": "Manufactured by  Hansen Medical , Sensei X is a specialized robotic catheter system that is controlled by a physician and is designed for accurate positioning, manipulation and stable control of catheter and catheter-based technologies during  cardiovascular procedures . The Sensei system obtained U.S.  Food and Drug Administration  (FDA) clearance in 2007, after which the  Cleveland Clinic 's  electrophysiology  program, then directed by Dr. Andrea Natale, received the first placement. The  Sensei Robotic Catheter System  and Artisan Extend Control Catheter allow physicians to navigate flexible catheters with greater stability and control during complex  cardiac arrhythmia  procedures. Hansen Medical has related co-development agreements with the following industry leaders:  St. Jude Medical ,  GE Healthcare ,  Siemens Healthcare , and  Philips  Medical Systems."}
{"_id": "WikiPedia_Cardio$$$corpus_2113", "text": "Hansen Medical was founded by Dr. Frederic Moll, who had also co-founded Intuitive Surgical, manufacturer of the Da Vinci Surgical System, whose use has propelled medicinal robotics to the forefront of patient care. The Sensei system is indicated for use during the cardiac mapping phase of cardiac arrhythmia treatment in the US. Meanwhile, it has CE mark approval for facilitating the navigation of ablation catheters within the atria of the heart during complex arrhythmia procedures such as Atrial Fibrillation (AF)."}
{"_id": "WikiPedia_Cardio$$$corpus_2114", "text": "In November 2010, Hansen Medical received unconditional Investigational Device Exemption (IDE) approval from the FDA initiating  a clinical trial to investigate the use of the Sensei X Robotic Catheter System and the Artisan Control Catheter for treatment of AF, the most common cardiac arrhythmia. The Principal Investigator of the ARTISAN AF Trial is Dr. Andrea Natale, executive medical director for Texas Cardiac Arrhythmia Institute (TCAI). The first case in the trial was completed by Dr. Joseph Gallinghouse, an electrophysiologist, at the TCAI at St. David's Medical Center. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2115", "text": "By the end of 2010, nearly 100\u00a0Sensei systems have been shipped worldwide since its 2007 release. The system has been used to perform almost 5,000\u00a0procedures. [ 2 ]  The Sensei system operates by guiding standard catheters through a manipulated robotically steerable sheath (hollow tube) in the patient's vasculature. The doctor performs the procedure at a control station with a technology called \"IntelliSense\" to proximally measure the forces applied along the shaft of the catheter as a result of catheter tissue contact. The Artisan catheter has two robotically controlled segments which provides six degrees of freedom and 270\u00a0degrees of bend articulation which can assist physicians in accessing  hard-to-reach cardiac anatomy. The open lumen Artisan catheter accommodates 8F percutaneous EP catheters. Centers have reported acute and long term success rates consistent with manual procedures. [ 3 ] [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2116", "text": "Although the Sensei system was initially tested in a range of ablation procedures including SVT and typical atrial flutter, [ 7 ] [ 8 ]  there is most excitement about its role in complex ablation procedures  such as for atrial fibrillation (AF), where the ability to manipulate catheters to precise locations within the heart and keep them stable in the desired position is crucial. Achieving adequate tissue contact, ideally with a small amount of pressure being applied by the catheter during ablation, is also essential to effectively destroy the heart tissue responsible for arrhythmia. The ability to titrate catheter contact force using the Sensei system\u2019s built-in pressure sensor technology (called intellisense) may allow operators to maximise the chance of creating effective burns across the thickness of the atrial wall, whilst minimising the risk of complication. [ 9 ]  Intracardiac echocardiography has also demonstrated that greater catheter stability is achieved with robotic compared to manual catheter delivery. [ 10 ]  Consequently, there is evidence that robotic ablation causes more effective and more efficient burns. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2117", "text": "Use of robotic navigation for  catheter ablation  was also designed to allow  Electrophysiology  to perform most of the procedure without being exposed to X-rays (or radiation). The radiation dose to the operator during a conventional manual ablation procedure is relatively small, although there is cumulative exposure that becomes an important consideration for operators performing procedures on a daily basis. By performing procedures a few metres away using a robotic system and seated in the leaded anteroom, the operator is shielded from X-rays and is less vulnerable to operator fatigue, which may affect operator performance in long complex cases. Use of robotic navigation has been shown to reduce fluoroscopy times in  catheter ablation  of AF, resulting in reduced X-ray exposure for patients and other health care professionals present in the catheter laboratory. [ 12 ] [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2118", "text": "The system has been the subject of several  clinical trials  in the USA and Europe, particularly for the catheter ablation of AF. There were early safety concerns after the \u2018first-in-human\u2019 studies suggested high complication rates. Wazni et al. reported experience with the first 71 catheter ablations for AF in their centre using the Hansen robotic navigation system starting from 2005. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2119", "text": "These early studies have allowed others to incorporate changes to their technique, [ 16 ]  and hence recent work has produced complication rates for catheter ablation of AF comparable to procedures performed manually. [ 17 ] [ 18 ] [ 19 ]  The field of robotic ablation is growing and evolving rapidly, and randomised controlled trials comparing robotic to manual ablation are ongoing in Europe and the USA to see if these potential advantages will translate into better clinical outcomes. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2120", "text": "Since there are no completed randomised controlled trials comparing robotic ablation to manual ablation, comparing the modalities remains difficult. Techniques, complication rates and clinical results vary widely between centres for both manual and robotic procedures, making registry data difficult to compare. Typical ranges for procedures performed manually are: major complication rates of 3-5%, and success rates of approximately 80-90% for paroxysmal AF and 70-75% for persistent AF (depending on the length of follow-up). [ 20 ] [ 21 ]  The following are recent reports in medical journals detailing experience of the Sensei system in the catheter ablation of AF, and demonstrate approximate success and complication rates at the time of writing:"}
{"_id": "WikiPedia_Cardio$$$corpus_2121", "text": "All paroxysmal"}
{"_id": "WikiPedia_Cardio$$$corpus_2122", "text": "(Freedom from AF )"}
{"_id": "WikiPedia_Cardio$$$corpus_2123", "text": "86% after 21 patients had a repeat procedure"}
{"_id": "WikiPedia_Cardio$$$corpus_2124", "text": "135 paroxysmal\n55 persistent\n6 long-lasting persistent"}
{"_id": "WikiPedia_Cardio$$$corpus_2125", "text": "127 paroxysmal\n55 persistent\n11 long-lasting persistent"}
{"_id": "WikiPedia_Cardio$$$corpus_2126", "text": "Paroxysmal AF 90%\nPersistent AF 71%\nLong-lasting 100% (of only 6)"}
{"_id": "WikiPedia_Cardio$$$corpus_2127", "text": "Paroxysmal AF 85%\nPersistent AF 73%\nLong lasting 67%"}
{"_id": "WikiPedia_Cardio$$$corpus_2128", "text": "(Freedom from AF)"}
{"_id": "WikiPedia_Cardio$$$corpus_2129", "text": "Paroxysmal 43\nPersistent 22"}
{"_id": "WikiPedia_Cardio$$$corpus_2130", "text": "(remainder completed manually)"}
{"_id": "WikiPedia_Cardio$$$corpus_2131", "text": "76% Paroxysmal\n78% persistent"}
{"_id": "WikiPedia_Cardio$$$corpus_2132", "text": "Tamponade 1.5%"}
{"_id": "WikiPedia_Cardio$$$corpus_2133", "text": "Paroxysmal 29\nPersistent 11"}
{"_id": "WikiPedia_Cardio$$$corpus_2134", "text": "Tamponade 5% (nil else)"}
{"_id": "WikiPedia_Cardio$$$corpus_2135", "text": "SFHAM (single fibre based heart activity model)  is a physical model describing the electric activity of the  left ventricle  of the heart during its  depolarisation . It facilitates a precise analysis of  electric potentials  of different parts of the ventricle. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2136", "text": "The  SFHAM model  is based on the following principles: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2137", "text": "The model constitutes a theoretical basis for  SATRO-ECG  being a system to  non-invasive diagnosing  facilitating early detection  ischemic changes in the heart . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2138", "text": "Samin K. Sharma  (born May 28, 1955) is an American  philanthropist  of Indian descent and an  interventional cardiologist [ 1 ] [ 2 ]  who co-founded the Eternal Heart Care Centre and Research Institute in  Jaipur  (EHCC). [ 3 ]  Sharma has served on New York State\u2019s Cardiac Advisory Board since 2004. As of 2021, he is Senior Vice-President, Operations & Quality at The  Mount Sinai Hospital  in New York [ 4 ]  and runs the  Dr. Samin K. Sharma Family Foundation Cardiac  Catheterization  Laboratory . [ 5 ]  As of 2018, he is Chairman Board of Trustees, Association of Indians in America (AIA). [ 6 ]  As of 2022, he has been an investigator on 86 grants and multi-center trials and authored 486 peer-reviewed articles that have been cited 21,734 times."}
{"_id": "WikiPedia_Cardio$$$corpus_2139", "text": "Sharma was born to a  Brahmin  family in  Alwar , India. [ 7 ]  He graduated from Rajgarh Higher Secondary School in  Alwar . In 1972, he received his bachelor of science degree from University  Maharaja College  then his MBBS degree from  SMS  Medical Department of  Pharmacy , Jaipur in 1978."}
{"_id": "WikiPedia_Cardio$$$corpus_2140", "text": "Sharma traveled to New York in 1983 [ 8 ]  for a three-year residency in  internal medicine  at the  NY Infirmary-Beekman Downtown Hospital  (1983-1986), a two-year fellowship in cardiology at  Elmhurst Hospital  in Queens (1986-1988). He trained with Mount Sinai's chief of cardiology, Dr.  Valent\u00edn Fuster . He was concurrently an emergency department physician in  Queens  and was later hired to Mount Sinai's cardiology department. He is the director of the  Mount Sinai Hospital   Cardiac Catheterization  Laboratory. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2141", "text": "Sharma specializes in the non-surgical treatment of  mitral  and  aortic stenosis . [ 11 ] [ 12 ]  He reportedly performed 3,722  angioplasties  over three years (2005-2007) according to a study by the  New York State Department of Health . [ 13 ]  He also performs rotational  atherectomy , an alternative to angioplasty for complex, calcified coronary lesions. [ 14 ]  \u00a0He has published extensively on the procedure [ 15 ]  and he is a principal investigator (PI) on scores of clinical trials and research grants analyzing and contrasting forms of interventional cardiology. In 2009, he performed a coronary  angiography  and angioplasty procedure on Indian Prime Minister  Shri Manmohan Singh ."}
{"_id": "WikiPedia_Cardio$$$corpus_2142", "text": "As of 2022, Sharma participated as an investigator on more than 80 grants and  multi-center trials . Recent and current trials focus on  transcatheter aortic valve replacement , protracted  percutaneous coronary interventions , outcomes of moderate to severely calcified coronary lesions, best practices, the performance of self-expanding vs balloon-expandable  transcatheter   aortic valve  replacement, post-market device and procedural outcomes, refractory  angina  and rotational  atherectomy . [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2143", "text": "A partial listing of his awards and recognition includes  Businessman of the Year  by national  Republican Congressional Committee  for 2001-2002, Rajasthan Gaurav award in Jaipur by Rajasthan Government, India (2002),  Rajive Gandhi  Memorial Award for outstanding community service and medical excellence for India (2005), Governor\u2019s award of excellence for outstanding contribution to Medicine, New York State (2006),  Ellis Island Medal of Honor  (2011). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2144", "text": "Sharma co-founded the Eternal Heart Care Center in 2004 [ 22 ]  with his wife, Manju Sharma. This 250-bed tertiary   multidisciplinary hospital offers care to patients of any  socioeconomic  status. The plan for this hospital was conceived in 2007 when the Sharmas met then-Chief Minister of  Rajasthan ,  Vasundhara Raje . Sharma is as of 2021 documented as one of the organization's directors. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2145", "text": "Under Sharma\u2019s leadership, the cardiac catheterization lab at Mount Sinai has been implicated in allegations of Medicaid fraud, coaching emergency room patients to say they were having symptoms of a heart attack in order to receive reimbursement for advance scheduled interventional procedures. He has also been accused of inflating procedural numbers to unattainable records by having trainees perform his procedures without supervision. He received $4.8 million from billing for these procedures himself in 2012. [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2146", "text": "According to  ResearchGate , Sharma published 165 articles while affiliated with Icahn School of Medicine. According to Scopus, he has 486 publications as of 2022 that were cited 21,734 times across 18,988 documents. His h-index is listed as 60. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2147", "text": "A  sinus rhythm  is any  cardiac rhythm  in which  depolarisation  of the  cardiac muscle  begins at the  sinus node . [ 1 ]   It is necessary, but not sufficient, for normal electrical activity within the  heart . [ 2 ]  On the  electrocardiogram  (ECG), a sinus rhythm is characterised by the presence of  P waves  that are normal in morphology. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2148", "text": "The term  normal sinus rhythm  ( NSR ) is sometimes used to denote a specific type of sinus rhythm where all other measurements on the ECG also fall within designated normal limits, giving rise to the characteristic appearance of the ECG when the  electrical conduction system of the heart  is functioning normally; however, other sinus rhythms can be entirely normal in particular patient groups and clinical contexts, so the term is sometimes considered a misnomer and its use is sometimes discouraged. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2149", "text": "Other types of sinus rhythm that can be normal include  sinus tachycardia ,  sinus bradycardia , and  sinus arrhythmia . Sinus rhythms may be present together with various other  cardiac arrhythmias  on the same ECG."}
{"_id": "WikiPedia_Cardio$$$corpus_2150", "text": "In humans, for an ECG to be described as showing a sinus rhythm, the shape of the P wave in each of the 12 standard  ECG leads  should be consistent with a \"typical P  vector \" of +50\u00b0 to +80\u00b0. [ 2 ]  This means that the P wave should be:"}
{"_id": "WikiPedia_Cardio$$$corpus_2151", "text": "If the P waves do not meet these criteria, they must be originating from an abnormal site elsewhere in the atria and not from the sinus node; the ECG cannot, therefore, be classed as showing a sinus rhythm. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2152", "text": "In general, each P wave in a sinus rhythm is followed by a QRS complex, and the sinus rhythm therefore gives rise to the whole heart's depolarization. Exceptions to this include  complete heart block  and certain ventricular  artificial pacemaker  rhythms, where the P waves may be completely normal in shape, but ventricular depolarization bears no relation to them; in these cases, the speed of the \"sinus rhythm of the atria\" and the speed of the ventricular rhythm must be calculated separately. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2153", "text": "By convention, the term \"normal sinus rhythm\" is taken to imply that not only are the P waves (reflecting activity of the sinus node itself) normal in morphology but that all other ECG measurements are also normal. [ 3 ] [ 5 ]  Criteria therefore include:"}
{"_id": "WikiPedia_Cardio$$$corpus_2154", "text": "A  sonographer  is an  allied healthcare professional  who specializes in the use of  ultrasonic  imaging devices to produce diagnostic images, scans, videos or three-dimensional volumes of anatomy and diagnostic data. The requirements for clinical practice vary greatly by country. Sonography requires specialized education and skills to acquire, analyze and optimize information in the image. Due to the high levels of decisional latitude and diagnostic input, sonographers have a high degree of responsibility in the diagnostic process. Many countries require medical sonographers to have professional certification. Sonographers have core knowledge in ultrasound physics, cross-sectional anatomy, physiology, and pathology."}
{"_id": "WikiPedia_Cardio$$$corpus_2155", "text": "A  sonologist  is a  medical doctor  who has undergone additional  medical ultrasound  training to diagnose and treat diseases. [ 1 ] [ 2 ]  Sonologist is licensed to perform and write ultrasound imaging reports independently or verifies a sonographer's report, prescribe medications and medical certificates, and give clinical consultations."}
{"_id": "WikiPedia_Cardio$$$corpus_2156", "text": "A sonologist may practice in multiple modalities or specialize in only one field, such as  obstetric ,  gynecology ,  heart ,  emergency  and  vascular  ultrasound."}
{"_id": "WikiPedia_Cardio$$$corpus_2157", "text": "Prior to 1970, many individuals performed sonography for research purposes and those assisting with the imaging were considered technicians or technologists, and in 1973 in the United States the occupation of diagnostic medical technology was established as sonography become more widely used within healthcare settings. [ 3 ]  Today,  sonographer  is the preferred term for the  allied healthcare professionals  who perform  diagnostic medical sonography , or diagnostic  ultrasound . The alternative term \"ultrasonographer\" is much less commonly used. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2158", "text": "The  Australasian Sonographers Association (ASA)  was formed in 1992 in response to the desire of sonographers across Australia for an organisation that represents and considers issues important to sonographers in the Australian healthcare environment. The ASA has more than 5000 individual member sonographers from Australia and New Zealand, and about 30 corporate partners. The ASA has pledged to pursue high standards within the practice of medical sonography, and has a structure of a board of directors and multiple representative branches in all Australian states and New Zealand. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2159", "text": "Australian sonographers must be accredited by the Australian Sonographers Accreditation Registry (ASAR), whose brief is to accredit and reaccredit on a regular basis, postgraduate ultrasound programs offered by Australian universities, and to establish the criteria against which those programs and any other future Australian and New Zealand programs are to be judged. In addition, a register of accredited medical sonographers  and accredited student sonographers  is maintained and their continuing professional development activities monitored and recorded. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2160", "text": "The Health Insurance Commissison in association with the ASAR introduced in 2002 a program of accreditation and continuing professional education for sonographers. The ASAR recognises registration with the Australian Orthoptic Board as appropriate accreditation for  orthoptists  to undertake sonography in relation to ocular structures. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2161", "text": "The vast majority of Canadian sonographers have received their education through an accredited sonography program. Many programs are available across the country and may include direct-entry programs for degrees, advanced diplomas, and second-discipline graduate certificate programs. Sonography Canada registers sonographers in three credentials: generalist, cardiac, and vascular. To become registered, eligible candidates must successfully meet Sonography Canada's clinical (Canadian Clinical Skills Assessment) and academic requirements. Sonography Canada-credentialed sonographers must also document their continuing education by maintaining a minimum 40 continuing professional development credits every three years. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2162", "text": "The  Nova Scotia Society of Diagnostic Medical Sonographers  is currently working with the  Nova Scotia Association of Medical Radiation Technologists  to add diagnostic ultrasound as a new discipline in the proposed college. This means that diagnostic sonography would become a self-regulated profession in Nova Scotia, along with radiography, nuclear medicine, magnetic resonance imaging, and radiation therapy. The Department of Health is now considering their application; the appropriate act and associated regulations have been drafted, and the associations are aiming for approval at the spring 2012 session of the legislature."}
{"_id": "WikiPedia_Cardio$$$corpus_2163", "text": "In the UK, sonographers are also responsible for the interpretation of the images and issue diagnostic reports. They are educated to a high level, and their training is delivered as a MSc/PGDip/PGCert by the universities and overseen by the Consortium for Accreditation of Sonographic Education; as training is delivered at postgraduate level, all sonographers must have a bachelor's degree or equivalent prior to undertaking this specialty, and this means training can take a minimum of 4 years. Currently, no requirement exists for a sonographer to be state registered in the UK, although the majority are registered with the  Health and Care Professions Council  (HCPC) as a radiographer. State registration of sonographers in their own right is being eagerly sought by the profession. However, the HCPC has previously sought to require statutory registration of sonographers, a motion supported by a number of professional bodies, and the HCPC was rejected by the Department of Health. [ 6 ]  The rationale for this rejection remains controversial, but a voluntary registry is currently maintained by the  College of Radiographers . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2164", "text": "Within the United Kingdom, sonographers are employed by hospitals within the  National Health Service  and by private companies offering healthcare services."}
{"_id": "WikiPedia_Cardio$$$corpus_2165", "text": "The profession is subdivided in specialties such as  cardiac , obstetrical, vascular, and general sonographers. General sonographers are registered in abdominal and/or obstetric and gynecologic sonography. [ 8 ]  Around 1 1/2 years may be needed to get a degree in diagnostic medical sonography. [ 9 ]  In the United States, the most widely accepted sonographic education is provided by CAAHEP/JRC-DMS accredited programs."}
{"_id": "WikiPedia_Cardio$$$corpus_2166", "text": "The American Society of Ultrasound Technical Specialists, now the  Society of Diagnostic Medical Sonography , was founded in 1970 as the primary professional society for sonographers. [ 3 ]   The two credentialing bodies in the United States for sonographers are the Cardiovascular Credentialing International established in 1968 and the American Registry for Diagnostic Medical Sonography (ARDMS) established in 1975. Accreditation is granted through the American National Standards Institute. Recognition of ARDMS programs in providing credentials has also earned the ARDMS accreditation with the  National Commission for Certifying Agencies , which is the accrediting arm of the National Organization for Competency Assurance (NOCA). Established in 1977 as a nonprofit organization, NOCA sets quality standards for certifying organizations. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2167", "text": "In 2009, New Mexico and Oregon became the first two states to require licensure of sonographers, and as of 2023, licensure is also required in New Hampshire and North Dakota. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2168", "text": "The occupational risk associated with performing sonography was reported as early as 1985, [ 11 ]  but it wasn't until the mid-1990's those work-related injuries were widely recognized as a significant problem among sonographers that persists today. [ 12 ]  During their careers, up to 90% of sonographers report experiencing some form of work-related musculoskeletal discomfort. [ 13 ] [ 14 ]  Work-related musculoskeletal injuries are most common in the hand, shoulder, and neck. [ 15 ] [ 16 ]  Injuries are often due to scanning in compromised positions, incorrect gripping of the transducer, spending too much time manipulating the transducer on technically difficult exams such as obese or large pregnant patients, and a lack of upper body fitness, [ 17 ] [ 18 ]  but injuries also result from various organizational, administrative, equipment and other factors that are outside of the sonographer's control. [ 19 ] [ 20 ]   Implementation of ergonomic principles, including adjustments to equipment, to perform imaging tasks in low-strain postures is critical to reducing the risk of injury. [ 21 ]  Additionally, stretching and exercise protocols have been suggested to be a useful tool in reducing the risk of musculoskeletal injury, pain, and repetitive strain injury in sonographers. [ 22 ] [ 23 ]  Finally, sonographer health requires representation and acknowledgment of challenges facing the workforce across the entire work organization to promote the development and implementation of supportive policies and administrative procedures within the work setting, such as allowance for regular work breaks, uninterrupted workflow, and supervisor support. [ 14 ] [ 24 ] [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2169", "text": "Multiple professional societies have developed guidelines to address the pervasive problem of work-related injuries among sonographers. The first of these actions was a consensus conference held in 2003 and repeated in 2016 by the  Society of Diagnostic Medical Sonography  that resulted in the development of Industry Standards for the Prevention of Work-Related Musculoskeletal Disorders in Sonography. [ 27 ]  These standards primarily focused on the ergonomic design of equipment and the responsibilities of employers and employees in addressing injury prevention. [ 27 ]  The  American Institute of Ultrasound in Medicine  has also released guidelines that extend these standards by describing imaging exam-specific recommendations and discussing the role of quality improvement practices by healthcare organizations. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2170", "text": "In 2019, an alliance of eight professional societies, credentialing bodies, and accreditation organizations in the United States came together to create the  Work-Related Musculoskeletal Disorder (WRMSD) Grand Challenge  with a goal to stop WRMSDs resulting from the performance of diagnostic medical ultrasound. This alliance has supported design challenges and the creation of a research registry of sonographers to monitor the status of work-related injuries in the profession, examine risk factors, and develop solutions to remediate the pervasive issue. [ 14 ] [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2171", "text": "A  split S2  is a finding upon auscultation of the  S2 heart sound . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2172", "text": "It is caused when the closure of the  aortic valve  (A 2 ) and the closure of the  pulmonary valve  (P 2 ) are not synchronized during inspiration. The second heart sound (S2) is caused by the closure of the aortic and pulmonic valves, which causes vibration of the valve leaflets and the adjacent structures. The aortic valve closes slightly before the pulmonic, and this difference is accentuated during inspiration when S2 splits into two distinct components (physiological splitting). During expiration, the pulmonic valve closes at nearly the same time as the aortic, and splitting of S2 cannot be heard."}
{"_id": "WikiPedia_Cardio$$$corpus_2173", "text": "Exercise increases the intensity of both the aortic and pulmonic components of S2, whereas deep inspiration increases the intensity of the pulmonic component only."}
{"_id": "WikiPedia_Cardio$$$corpus_2174", "text": "During inspiration , the chest wall expands and causes the intrathoracic pressure to become more negative (akin to a vacuum).  The increased negative pressure allows the lungs to fill with air and expand.  While doing so, it also induces an increase in venous blood return from the body into the right atrium via the superior and inferior venae cavae, and into the right ventricle by increasing the pressure gradient (blood is being pulled by the vacuum from the body and towards the right side of the heart).  Simultaneously, there is a reduction in blood volume returning from the lungs into the left atrium (the blood wants to stay in the lungs because of the vacuum surrounding the lungs, and  PVR  is lower because of lung expansion). Since there is an increase in blood volume in the right ventricle during inspiration, the pulmonary valve (P 2  component of S 2 ) stays open longer during ventricular systole due to an increase in ventricular emptying time, whereas the aortic valve (A 2  component of S 2 ) closes slightly earlier due to a reduction in left ventricular volume and ventricular emptying time. Thus the P 2  component of S 2  is delayed relative to that of the A 2  component. This delay in P 2  versus A 2  is heard as a slight broadening or even \"splitting\" of the second heart sound; though it is usually only heard in the pulmonic area of the chest because the P 2  is soft and not heard in other areas. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2175", "text": "During expiration , the chest wall collapses and decreases the negative intrathoracic pressure (compared to inspiration).  Therefore, there is no longer an increase in blood return to the right ventricle versus the left ventricle and the right ventricle volume is no longer increased.  This allows the pulmonary valve to close earlier such that it overlaps the closing of the aortic valve, and the split is no longer heard. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2176", "text": "It is physiologically normal to hear a \"splitting\" of the second heart tone in younger people, during inspiration and in the \"pulmonary area\", i.e. the second ICS (intercostal space) at the left edge of the sternum."}
{"_id": "WikiPedia_Cardio$$$corpus_2177", "text": "According to Harrison's Principles of Internal Medicine, \"Normally, blood pressure falls during inspiration (equal or less than 10 mmHg), due to an increase in blood flow into the right ventricle with displacement of the interventricular septum to the left, decreasing left ventricular filling and cardiac output\". [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2178", "text": "The pressure in the right ventricle tries to open the pulmonary valve. The pressure in the pulmonary artery tries to close the pulmonary valve.  The higher pressure will \"win\". Hence, the closure of the pulmonary valve (P 2 ) will be delayed since the pressure in the right ventricle is increased in inspiration, opposing the pressure in the pulmonary artery and keeping it open longer than in expiration. The change in A 2  is not that evident. Thus P 2  appears after A 2  in inspiration. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2179", "text": "The different types of split S 2  can be associated with medical conditions:"}
{"_id": "WikiPedia_Cardio$$$corpus_2180", "text": "When the pulmonary valve closes  before  the aortic valve, this is known as a \"paradoxically split S 2 \". [ 6 ]  On physical exam, paradoxical splitting is appreciated as increased splitting on expiration relative to inspiration, versus normal splitting where inspiration will increase splitting. It is seen in conditions that delay left ventricular emptying (e.g., aortic stenosis, left bundle branch block)."}
{"_id": "WikiPedia_Cardio$$$corpus_2181", "text": "Sports cardiology  is an emerging subspecialty field of  Cardiology . [ 1 ] [ 2 ] [ 3 ]  It may also be considered a subspecialty field of  Sports medicine  (or Sport & Exercise Medicine), or alternatively a hybrid subspecialty that spans cardiology and  sports medicine .  Emergency medicine  is another medical specialty that has some overlap with Sports Cardiology. Sports cardiology is now considered to be a distinct subspecialty in Europe and the USA, with a core curriculum developed in both regions. [ 4 ] [ 5 ] [ 6 ]  In Europe it has traditionally been grouped under Preventive Cardiology, but the subspecialty of Sports Cardiology is now considered a distinct field. In the USA, it has developed from being a special interest area to a distinct subspecialty as well."}
{"_id": "WikiPedia_Cardio$$$corpus_2182", "text": "Sports cardiology can be roughly divided into two areas itself:"}
{"_id": "WikiPedia_Cardio$$$corpus_2183", "text": "The preventive aspect of Sports Cardiology aligns slightly more with the speciality of  Sports Medicine  (doctors who look after athletes and exercising people), acute response with  Emergency medicine , whereas the management of athletes with known heart disease is more aligned with the  Cardiology  side of Sports Cardiology.\nSports Cardiology as a cardiology subspecialty overlaps with  Electrophysiology , Cardiac Stress Testing,  Echocardiography  and other cardiac imaging,  Genetic testing , and  Cardiomyopathy ."}
{"_id": "WikiPedia_Cardio$$$corpus_2184", "text": "Formal education for doctors is now available in Sports Cardiology, such as a Masters Degree in Sports Cardiology at St George's, University of London [ 7 ]  and at the University of Padua, in Italy (director prof. Domenico Corrado). [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2185", "text": "Sudden cardiac death  (SCD) is a very rare event but particularly tragic affecting apparently healthy young or early middle-aged people. Sudden cardiac death occurs in approximately one per 100,000 young athletes per year, generally in matches or training, but also occasionally at rest. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2186", "text": "Common categories of sudden cardiac death causes are: [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2187", "text": "Cardiomyopathies and conduction diseases are responsible for the majority of sudden cardiac death in young athletes (< 30 years old), whereas Coronary artery disease (often latent in a relatively young person) increases in risk with age and is by far the most common cause of sudden cardiac death in an athlete >35 years old.  Commotio cordis  is less common but caused by an external force rather than an intrinsic abnormality of the heart. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2188", "text": "Sports have been classified into varying risks for Sudden Cardiac Death for competitive athletes. [ 12 ] [ 13 ]  Sports with high static and dynamic forces are those that present the greatest risk, bearing in mind that for individual athletes playing in these sports the risks are still very small. Rowing, cycling and basketball are amongst the sports with the highest annual risk. [ 14 ]  Football (soccer) provides the highest number of young athletes who suffer cardiac arrest, being a medium risk sport that is played extensively worldwide. The risk is higher in male athletes than female athletes. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2189", "text": "Screening of athletes to prevent SCD is a controversial area. Generally, medical screening is considered to be potentially valuable for conditions or diseases that are relatively common and not useful for conditions that are rare, due to the likely high number of false positives. SCD is rare and hence screening necessarily has a high rate of false positives (that is, athletes flagged as being potentially unsafe to participate in high-level sport but who would not die if they did continue to play sport). Nevertheless, because of the fear of SCD and occupational requirement to train and compete at extremely high intensity in professional and elite sport, screening is established as a standard of care in many countries of the world. [ 17 ] \nThe country with the most established program of screening for cardiac disease in athletes is Italy, which requires this to be done by law. Over many decades the rate of SCD in Italy has reduced, probably due to nationwide screening. [ 18 ]  Some experts question whether the rate may have been reduced through other means, and whether the disqualification of many young people from playing vigorous sport annually is worth it. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2190", "text": "International guidelines have been agreed to regarding what constitutes a normal and abnormal athletic ECG when screening asymptomatic athletes. [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2191", "text": "In Europe, the UK and Australia, [ 22 ]  the standard of care is generally to include an ECG as part of the standard screening program. Whilst ECGs are done for many athletes in the USA, the standard of care is more likely to be an annual history & physical examination, with an ECG only performed if any item of concern with the clinical presentation. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2192", "text": "A major charity in the UK is  Cardiac Risk in the Young (CRY)  which performs regular screenings."}
{"_id": "WikiPedia_Cardio$$$corpus_2193", "text": "In theory, cardiac arrest at a sporting event whilst very rare can be predicted and hence the survival rate from arrest should be higher if a good emergency management plan has been implemented. Not all stadia and athletic fields have  AEDs  present, particularly at amateur level. And not all events have well-trained event staff (doctors, paramedics and staff qualified in basic life support). Finally, even with AEDs and staff present, because of the rarity of cardiac arrest in the community especially in young people, event staff may not be well or recently trained to respond, or may not be concentrating at the time of an arrest. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2194", "text": "Event planning is therefore a key component of Sports Cardiology, even though event planning would not normally be a concern of a medical speciality. Making sure that there are sufficiently trained medical, paramedical and other trained staff or volunteers at sporting events, ready availability of AEDs or ambulances or both, and that those qualified people are ready to respond to an arrest, probably leads to a greater lowering of the rates of sudden cardiac death in sport than any other measure. Hence, having an excellent understanding of the parameters of safe event planning is a core subject in Sports Cardiology. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2195", "text": "Hypertrophic cardiomyopathy (HCM) or HOCM (O = obstructive) is considered the most common cause of sudden cardiac death in young athletes that may be preventable. However, the difficulty is that it overlaps with the more  Athlete Heart syndrome  and vast majority of discovered cases are mild, making it unclear about whether it is safe to continue playing intense sport. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2196", "text": "Arrhythmogenic right ventricular cardiomyopathy (ARVC) is less common than HCM but usually more clearly progressive, associated with intense activity and usually has more clear indication to avoid highly intense sporting activities. It is more common in certain genetic backgrounds. Much of the reduction in deaths in Italy since the advent of nationwide screening has been thought to be due to ARVC reduction. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2197", "text": "Long QT syndrome is a familial condition that is uncommon but is a known source of sudden death in young people. It can cause cardiac arrest during athletic activity but also when doing other activities that raise heart rate. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2198", "text": "Brugada syndrome is a familial condition that is also very uncommon, and also a known source of sudden death in young people. Many of the deaths occur when inactive and it is less commonly a cause of sudden death playing sport. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2199", "text": "Atrial fibrillation  (AF) is more common in the inactive, elderly population than the inactive young population. There is a reverse J-shaped curve, however, in that elite athletes doing very arduous sport have a higher rate of AF than moderately active people. Whereas the AF that occurs in the inactive elderly population is known to be associated with increased risk of stroke, it is unknown whether athletic AF increases the risk of sudden death or stroke. AF in athletes can be treated with a minimally-invasive procedure known as ablation. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2200", "text": "Wolff\u2013Parkinson\u2013White syndrome (WPW) syndrome is a known cause of arrhythmia in young people. It causes supraventricular tachycardia during exercise. Most of the time this causes cessation of exercise when the SVT occurs. It can lead to cardiac arrest but generally does not. It can also be successfully treated by a minimally-invasive procedure known as ablation. [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2201", "text": "An Implantable cardioverter-defibrillators (ICD device) can be used in an athlete who has either had a previous cardiac arrest or is known to be at very high risk for cardiac arrest to trigger an internal shock to cardiovert the heart in the event of a fatal rhythm occurring. [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2202", "text": "Still ' s murmur  (also known as  vibratory murmur ) is a common type of benign or \"innocent\"  functional heart murmur  that is not associated with any sort of cardiac disorder or any other medical condition. [ 1 ]   It can occur at any age although it is most common among children two to seven years of age and it is rare in adulthood. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2203", "text": "Still's murmur was initially described by  Dr. George Frederic Still , England's first professor of childhood medicine at the  Great Ormond Street Hospital for Children .  In his pediatric textbook Common Disorders and Diseases of Childhood (published 1909) Dr. Still noted:"}
{"_id": "WikiPedia_Cardio$$$corpus_2204", "text": "\u201cI should like to draw attention to a particular bruit which has somewhat of a musical character, but is neither of sinister omen nor does it indicate endocarditis of any sort.  \u2026its characteristic feature is a twangy sound, very like that made by twanging a piece of tense string...  Whenever may be its origin, I think it is clearly functional, that is to say, not due to any organic disease of the heart either congenital or acquired.\u201d [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2205", "text": "Still's murmur is detected via auscultation with a  stethoscope . It has a peculiar \"musical\", \"resonant\" or \"vibratory\" quality that is quite unique. [ 1 ] [ 2 ]  It is generally most easily heard at the left middle or lower sternal border and the right upper sternal border, often with radiation to the carotid arteries, although other locations are common. The murmur is usually louder in the  supine position  and may only be audible in the supine position. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2206", "text": "The Still's murmur can be differentiated from pathological murmurs by this musical quality and lack of extra snaps or  clicks  in the heart sounds."}
{"_id": "WikiPedia_Cardio$$$corpus_2207", "text": "Because the Still's murmur has never been associated with any sort of cardiac disorder, it has no associated symptoms. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2208", "text": "Heart murmurs are sounds generated by blood flowing through the structures of the heart.  The location of the Still's murmur on examination suggests resonation of blood in the left ventricular outflow tract and  aorta , and this is supported by studies that have shown that the murmur is more intense over the  aortic valve  than the  pulmonary valve . [ 4 ]    There has been conjecture that the vibratory or musical quality of the murmur is caused by vibration of \u201cfalse chordae\u201d of the left ventricle, which are a common finding in normal individuals, but no relationship between the two has been proven. [ 5 ]    There is some evidence that a smaller aorta with higher peak flow velocities are associated with Still's murmur, [ 6 ] [ 7 ] [ 8 ]  which certainly fits in well with the concept that the murmur is a musical phenomenon. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2209", "text": "Still's murmur is diagnosed in the course of a physical examination of the patient, usually using a  stethoscope .  The murmur has a vibratory quality that can be detected as a regular frequency on  phonocardiography , [ 9 ]  although this type of testing is now rarely used.  Additional testing including  electrocardiography  (ECG or EKG) or  echocardiography  may be helpful in ruling out other conditions, particularly if the physical examination is not completely characteristic of Still's murmur.  When additional testing is done in the setting of Still's murmur the results are normal, since Still's murmur is not associated with any sort of cardiovascular pathology. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2210", "text": "Still's murmur does not represent any sort of disorder and does not present a health risk, so no treatment is necessary. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2211", "text": "Still's murmurs may occur in as many as a third of all children.  This type of murmur occurs most often in children two to seven years of age, but can occur in younger or older children.  In most cases, the innocent Still's murmur is present on and off during childhood and resolves on its own by young adulthood. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2212", "text": "The Still's murmur is a harmless finding that does not suggest any medical disorder.  In most cases, Still's murmur disappears around adolescence without medical intervention. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2213", "text": "However, families are often anxious when told their child has a heart murmur.  Parents of children diagnosed with Still's murmur may experience significantly greater anxiety than the children themselves. In a study conducted on the families impacted by Still's murmur, the parents were worried about a variety of issues.  Their concerns included: the need for medicine (49%), facing sports restrictions (41%), the need for  heart surgery  (29%), other offspring also having Still's murmur (20%), and early death (13%). Mothers worried that they did something during pregnancy that caused the murmur (19%). Even after being reassured by the child's physician, 17% of parents were still anxious. After hearing from a  cardiologist  that the children would be fine, only 7% of the parents were still nervous. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2214", "text": "A  string galvanometer  is a sensitive fast-responding measuring instrument that uses a single fine filament of wire suspended in a strong magnetic field to measure small currents. In use, a strong light source is used to illuminate the fine filament, and the optical system magnifies the movement of the filament allowing it to be observed or recorded by photography. \nThe principle of the string galvanometer remained in use for  electrocardiograms  until the advent of electronic vacuum-tube amplifiers in the 1920s. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2215", "text": "Submarine cable telegraph systems of the late 19th century used a  galvanometer  to detect pulses of electric current, which could be observed and transcribed into a message. The speed at which pulses could be detected by the galvanometer was limited by its mechanical inertia, and by the inductance of the multi-turn coil used in the instrument.  Cl\u00e9ment Adair, a French engineer, replaced the coil with a much faster wire or \"string\" producing the first string galvanometer. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2216", "text": "For most telegraphic purposes it was sufficient to detect the existence of a pulse. In 1892  Andr\u00e9 Blondel  described the dynamic properties of an instrument that could measure the wave shape of an electrical impulse, an  oscillograph . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2217", "text": "Augustus Waller had discovered electrical activity from the heart and produced the first electrocardiogram in 1887. [ 3 ]  But his equipment was slow. Physiologists worked to find a better instrument. In 1901,  Willem Einthoven  described the science background and potential utility of a string galvanometer, stating \"Mr. Adair has already built an instrument with a wires stretched between poles of a magnet. It was a telegraph receiver.\" [ 4 ]  Einthoven developed a sensitive form of string galvanomter that allowed photographic recording of the impulses associated with the heartbeat. He was a leader in applying the string galvanometer to physiology and medicine, leading to today's electrocardiography. [ 5 ]   Einthoven was awarded the 1924  Nobel prize in Physiology or Medicine  for his work. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2218", "text": "Previous to the string galvanometer, scientists were using a machine called the capillary  electrometer  to measure the heart\u2019s electrical activity, but this device was unable to produce results of a diagnostic level. [ 7 ]   Willem Einthoven  adapted  the string galvanometer at  Leiden University  in the early 20th century, publishing the first registration of its use to record an electrocardiogram in a  Festschrift  book in 1902. The first human electrocardiogram was recorded in 1887; however, it was not until 1901 that a quantifiable result was obtained from the string galvanometer. [ 8 ]  In 1908, the physicians  Arthur MacNalty , M.D. Oxon, and  Thomas Lewis  teamed to become the first of their profession to apply electrocardiography in medical diagnosis. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2219", "text": "Einthoven's galvanometer consisted of a silver-coated  quartz  filament of a few centimeters length (see picture on the right) and negligible mass that conducted the electrical currents from the heart. This filament was acted upon by powerful  electromagnets  positioned either side of it, which caused sideways displacement of the filament in proportion to the current carried due to the  electromagnetic field . The movement in the filament was heavily magnified and projected through a thin slot onto a moving photographic plate. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2220", "text": "The filament was originally made by drawing out a filament of glass from a crucible of molten glass. To produce a sufficiently thin and long filament an  arrow  was shot across the room so that it dragged the filament from the molten glass. The filament so produced was then coated with  silver  to provide the conductive pathway for the current. [ 11 ]  By tightening or loosening the filament it is possible to very accurately regulate the sensitivity of the galvanometer. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2221", "text": "The original machine required water cooling for the powerful electromagnets, required 5 operators [ 12 ]  and weighed some 600\u00a0lb. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2222", "text": "Patients are seated with both arms and left leg in separate buckets of saline solution. These buckets act as electrodes to conduct the current from the skin's surface to the filament. The three points of electrode contact on these limbs produces what is known as  Einthoven's triangle , a principle still used in modern-day ECG recording. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2223", "text": "A  stromuhr  (literally:  German  for  stream clock ) was a medical instrument designed by  Carl Ludwig  in 1867 to measure the strength of flow in major arteries and veins [ 1 ]  by means of animal experiments. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2224", "text": "For this purpose, the arteries were cut across and the stromuhr was attached between the proximal and distal stumps. The stromuhr had to be filled with the whole blood of the test animal or with a blood substitute solution beforehand. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2225", "text": "Subcutaneous implantable cardioverter defibrillator , or  S-ICD,  is an implantable medical device for detecting and terminating   ventricular tachycardia  and  ventricular fibrillation  in patients at risk of sudden cardiac arrest. [ 1 ]  It is a type of  implantable cardioverter defibrillator  but unlike the transvenous ICD, the S-ICD lead is placed just under the skin, leaving the heart and veins untouched."}
{"_id": "WikiPedia_Cardio$$$corpus_2226", "text": "The S-ICD was developed to reduce the risk of complications associated with transvenous leads. [ 2 ]  Potential complications, such as infections in the bloodstream and the need to remove or replace the leads in the heart, are minimised or entirely eliminated with the S-ICD system."}
{"_id": "WikiPedia_Cardio$$$corpus_2227", "text": "The generator is smaller than the S-ICD generator, which may result in a less visible implanted device. This could improve the time needed to get used to the implantable device, although this is subjective. The procedure can usually be done under local anesthesia and light sedation. The transvenous ICD is capable of  pacing  for  bradycardia  and delivering  antitachycardia pacing  (ATP).   However, device-related complications were numerically more frequent in patients with transvenous ICDs, inappropriate shocks are less frequent that in those with subcutaneous ICDs. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2228", "text": "The leads go into the vein and heart and will grow into the heart wall over time. This may increase the chance of complications if the leads need to be removed or replaced, as the procedure to extract an intracardiac leads can be a challenge. Because the leads need to go into the heart they need to be relatively thin and flexible, since they have to pass through (and remain in) the heart valve(s) and need to flex with every heartbeat. This makes the leads more vulnerable to lead fracture (and therefore complications). It has been demonstrated that  device-related complications were numerically more frequent in patients with transvenous ICDs. [ 3 ]  Due to the position of the pulse generator under the collarbone, it can be more visible with clothing with low neckline."}
{"_id": "WikiPedia_Cardio$$$corpus_2229", "text": "Patients who are relatively older, who need ICD for secondary prevention, or who have concomitant bradycardia requiring pacing, or heart failure requiring  cardiac resynchronisation therapy  are more suitable for transvenous ICD implantation. An older patient with ischemic cardiomyopathy and documented symptomatic ventricular tachycardia is a typical example. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2230", "text": "The lead does not go into the heart, which means it leaves the veins and the heart completely intact. This reduces chance of complications (e.g. systemic infections). Because the lead does not go into the heart it can be thicker and more robust. This minimizes / reduces the chance of lead fracture. In the event the system needs to be explanted, the procedure is a relatively simple surgical procedure."}
{"_id": "WikiPedia_Cardio$$$corpus_2231", "text": "The pulse generator is larger than most transvenous ICD pulse generators. This could result in a longer time needed to get used to it, although this is subjective. Depending on the physique of a person, the S-ICD may be more visible with bare chest. The procedure usually requires deep sedation or general anaesthesia, as creating a larger pocket between the muscles and tunnelling the lead over the sternum, as well as performing defibrillation threshold testing, can be quite painful. The S-ICD can deliver only temporary post-shock pacing, but cannot otherwise address bradycardia and cannot deliver anti-tachycardia pacing.  Inappropriate shocks were numerically more frequent in those with subcutaneous ICDs. [ 3 ]  Defibrillation testing has traditionally been considered mandatory in patients with subcutaneous implantable cardioverter\u2013defibrillator to confirm appropriate ventricular fibrillation detection. [ 5 ]  However, PRAETORIAN-DFT  randomised clinical trial  is aiming to demonstrate non-inferiority of omitting DFT in patients undergoing S-ICD implantation in which the S-ICD system components are optimally positioned by calculated PRAETORIAN score. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2232", "text": "Patients who are relatively younger, who need ICD for primary prevention, and who do not require pacing or cardiac resynchronisation therapy, are more suitable for S-ICD implantation. A young survivor of aborted  sudden cardiac death  is a typical example."}
{"_id": "WikiPedia_Cardio$$$corpus_2233", "text": "SynCardia Systems, LLC , headquartered in  Tucson, Arizona , was founded in 2001 and is the sole manufacturer and provider of the world's only clinically proven and commercially approved Total Artificial Heart. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2234", "text": "The SynCardia temporary  Total Artificial Heart  (TAH) has been in clinical use for more than 35 years. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2235", "text": "SynCardia was founded in 2001 by cardiothoracic surgeon  Jack G. Copeland , MD; biomedical engineer Richard G. Smith, MSEE, CCE; and interventional cardiologist Marvin J. Slepian, MD; with Steven Langford BSEE, as General Manager.  Today, SynCardia is a wholly owned subsidiary of Picard Medical and remains the sole manufacturer and provider of the world\u2019s only commercially approved Total Artificial Heart. In clinical use for more than 35 years, the SynCardia temporary Total Artificial Heart (TAH-t) is the most widely used and extensively studied Total Artificial Heart in the world."}
{"_id": "WikiPedia_Cardio$$$corpus_2236", "text": "In 2004, the  FDA  approved the SynCardia TAH (formerly known as the \"CardioWest temporary Total Artificial Heart\u201d) as a bridge to donor  heart transplant [ 1 ]  in cardiac transplant-eligible candidates at risk of imminent death from end-stage biventricular failure. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2237", "text": "SynCardia's products include the original 70cc TAH; the newer, smaller 50cc TAH, designed to fit patients of smaller stature, including more women and adolescents; the Companion 2 (C2) Hospital Driver, which provides pneumatic power to the TAH from implant through patient recovery in the hospital; and the Freedom Portable Driver, a smaller, portable pneumatic pump for the TAH that allows stable patients who meet discharge criteria to enjoy life at home while they wait for a matching donor heart. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2238", "text": "In addition to its being used as a bridge to transplant in the U.S., Canada and Europe, the 70cc TAH has supported several patients as a  destination therapy  in adult patients who are not eligible for transplant. The longest patient supported by the SynCardia Total Artificial Heart on a person who became not eligible for transplant was over 6 years and 9 months. He lived a near normal lifestyle at home with his wife. The smaller 50cc TAH is currently approved for use as a bridge to transplant for both pediatric and adult patients. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2239", "text": "In September 2016, SynCardia was acquired by Versa Capital Management, LLC, a Philadelphia-based private equity investment firm and then was acquired by Piccard Medical in September 2021, which has provided additional financial and operational resources. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2240", "text": "A documentary about the SynCardia TAH was released in 2016. [ 5 ]  Patrick Schnegelsberg was named CEO of SynCardia. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2241", "text": "Testosterone and the cardiovascular system  are the effects that the male hormone  testosterone  has on the  cardiovascular system ."}
{"_id": "WikiPedia_Cardio$$$corpus_2242", "text": "The predominant androgen in men, testosterone, has shown to substantially decline throughout the  aging process . [ 1 ] [ 2 ]  The decline in both serum and total testosterone with age have been linked to several disease states in men. [ 1 ] [ 3 ] [ 4 ]  In particular,  cardiac failure  and  ischemic heart disease  have been linked to this natural biochemical decline in testosterone. [ 5 ] [ 6 ] [ 7 ]  Previously, the higher cardiovascular risk in men has been attributed in part to the negative effects of systemic testosterone, however, more recent research has highlighted the protective nature of testosterone against cardiovascular disease. [ 5 ]  The magnitude and mechanism of action by which low testosterone in men is influential in the pathogenesis of cardiovascular risk and the potential benefits of testosterone therapy has yet to be fully determined. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2243", "text": "Low testosterone is associated with an increased risk for  coronary artery disease  through the promotion of a pro-atherosclerotic environment. [ 5 ] [ 8 ] [ 9 ]  Some research has identified testosterone as a  vasodilator  and an  endothelium -repairing hormone within many regions in the body, including the coronary arteries. [ 10 ] [ 11 ]  Recent research depicts testosterone as important in decreasing the production of inflammatory cytokines such as  tumor necrosis factor alpha ,  interleukin-1beta  and  interleukin-6 , which are influential in atherosclerotic profiles. [ 10 ] [ 12 ]  Although it is believed that the reduction in inflammatory cytokines is related to a decreased atherosclerotic profile, the full explanation of this mechanism requires further research. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2244", "text": "Testosterone has also shown to be effective as an anti-atherosclerotic through preventing aortic  cholesterol  deposition in both rabbits fed high cholesterol diets and mice with low-density lipoprotein gene knockout. [ 10 ] [ 14 ]  Fatty deposition within the aorta associated with low endogenous testosterone has been determined to be independent of the androgen receptor. [ 10 ]  Although the mechanism has yet to be fully determined, aromatase activity and the activation of estrogen receptor alpha is partially responsible for the atherosclerotic profile characteristic of low testosterone. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2245", "text": "Decreased systemic testosterone in men has also been reported in men with heart failure, whereby the severity of the disease is proportional to the reduction in systemic testosterone levels. [ 5 ]  Although a direct mechanism of action is not fully understood, some research attribute low testosterone to advancing side effects of heart failure, such as decreased exercise ability, decreased muscle mass, fatigue/ dyspnea  and  cachexia . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2246", "text": "Physiological testosterone is crucial for normal functionality in men. Long-term administration of physiological testosterone in mouse models has shown to be atheroprotective by increasing the HDL portion of cholesterol (the anti-atherosclerotic cholesterol). [ 10 ] [ 15 ]  The beneficial action of testosterone in elevating the HDL fraction can be attributed to its conversion via aromatase activity in adipose tissue into 17-beta estradiol and its subsequent activation of estrogen alpha-receptors; thus, more testosterone leads to greater conversion into estrogen and thus a healthier lipid profile. [ 10 ]  This understanding has been determined in several studies, although results of these studies are contradictory. [ 10 ] [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2247", "text": "Testosterone replacement therapy  in men diagnosed with pre-existing heart disease has been related to an increased risk of myocardial infarction. [ 18 ]  Furthermore, recent research has linked testosterone replacement therapy to an increase in deaths and other cardiovascular occurrences in men whom document a history of coronary artery disease. [ 19 ]  Further research is required to determine the full extent to which testosterone replacement therapy in aging men plays a role in the risk and/or advantage of cardiovascular occurrences. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2248", "text": "However, when given to men with  hypogonadism  in the short- and medium-term, testosterone replacement therapy does not increase the risk of cardiovascular events (including strokes and heart attacks and other heart diseases). The long-term safety of the therapy for this condition is not known yet. [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2249", "text": "The  third heart sound  or  S 3  is a rare extra  heart sound  that occurs soon after the normal two \"lub-dub\" heart sounds (S 1  and S 2 ). S 3  is associated with  heart failure ."}
{"_id": "WikiPedia_Cardio$$$corpus_2250", "text": "It occurs at the beginning of the middle third of  diastole , approximately 0.12 to 0.18 seconds after S 2 . [ 1 ]  This produces a rhythm classically compared to the cadence of the word \" Kentucky \" with the final syllable (\" -CKY [ 2 ] \") [ 3 ]  representing S 3 . One may also use the phrase \"Slosh\u2019-ing- IN \" to help with the cadence (Slosh S 1 , -ing S 2 , -in S 3 ), as well as the pathology of the S 3  sound, [ 4 ]  or any other number of local variants."}
{"_id": "WikiPedia_Cardio$$$corpus_2251", "text": "S 3  may be normal in people under 40 years of age and some trained athletes but should disappear before middle age.  Re-emergence of this sound late in life is abnormal [ 5 ]  and may indicate serious problems such as  heart failure .  The sound of S 3  is lower in pitch than the normal sounds, usually faint, and best heard with the  bell  of the  stethoscope . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2252", "text": "It has also been termed a  ventricular gallop  or a  protodiastolic gallop  because of its place in early diastole. It is a type of  gallop rhythm  by virtue of having an extra sound; the other gallop rhythm is called  S 4 . The two are quite different, but they may sometimes occur together forming a  quadruple gallop . If the  heart rate  is also very fast ( tachycardia ), it can become difficult to distinguish between S 3  and S 4  thus producing a single sound called a  summation gallop . S 3  is a dull, low-pitched sound best heard with the bell placed over the cardiac apex with the patient lying in the left lateral decubitus position. This heart sound when present in a child or young adult implies the presence of a supple ventricle that can undergo rapid filling. Conversely, when heard in a middle-aged or older adult, an S 3  is often a sign of disease, indicating increased ventricular filling due to congestive  heart failure  or severe mitral or tricuspid regurgitation. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2253", "text": "S 3  is thought to be caused by the undulation of blood back and forth between the walls of the ventricles initiated by the inflow of blood from the atria. The reason the third heart sound does not occur until the middle third of diastole is probably that, during the early part of diastole, the ventricles are not filled sufficiently to create enough tension for reverberation. It may also be a result of tensing of the  chordae tendineae  during rapid filling and expansion of the  ventricle . [ citation needed ]  Recent research suggests that  mitral valve  annulus diameter is one of the more important factors in producing the S3 sound. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2254", "text": "It is associated with  heart failure , [ 8 ]  caused by conditions which have:"}
{"_id": "WikiPedia_Cardio$$$corpus_2255", "text": "S3 can also be due to tricuspid regurgitation, and could indicate hypertensive heart disease. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2256", "text": "In conditions affecting the  pericardium  or diseases that primarily affect the heart muscle ( restrictive cardiomyopathies ) a similar sound can be heard, but is usually more high-pitched and is called a 'pericardial knock'.The S3 can also be confused with a widely split S2, or a mitral opening snap, but these sounds are typically of much higher pitch and occur closer to the onset of S2. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2257", "text": "The condition itself does not need to be treated, but rather the underlying cause requires correction. Depending on the  etiology  the gallop rhythm may resolve spontaneously. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2258", "text": "U.S. National STEMI Receiving Centers  are medical centers that specialize in receiving ST segment elevation  myocardial infarction  (STEMI) cases. These myocardial infarctions, or heart attacks, are due to fully blocked  coronary arteries . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2259", "text": "Since 2006, the  American College of Cardiology  and the  American Heart Association  have worked to implement a national designation of \"STEMI Receiving Center\" across the U.S., much like the certifications of trauma centers. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2260", "text": "STEMI patients account for over 400,000 of all Americans with MI. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2261", "text": "The Utstein Style  is a set of guidelines for uniform reporting of  cardiac arrest . The Utstein Style was first proposed for  emergency medical services  in 1991.  The name derives from a 1990 conference of the  European Society of Cardiology , the European Academy\nof Anesthesiology, the European Society for Intensive Care Medicine, and related national societies, held at the  Utstein Abbey  on the island of  Moster\u00f8y, Norway ."}
{"_id": "WikiPedia_Cardio$$$corpus_2262", "text": "Examples of cardiac arrest registries based on the Utstein Style include the  Cardiac Arrest Registry to Enhance Survival ,  Resuscitation Outcomes Consortium ,  Save Hearts in Arizona Registry and Education , and the  National Registry of CardioPulmonary Resuscitation ."}
{"_id": "WikiPedia_Cardio$$$corpus_2263", "text": "VA conduction , also named  Ventriculoatrial conduction  and sometimes referred to as  Retrograde conduction , is the conduction backward phenomena in the  heart , where the conduction comes from the  ventricles  or from the  AV node  into and through the  atria . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2264", "text": "Retrograde VA conduction results in many different  symptoms , primarily those symptoms result from the delayed, nonphysiologic timing of  atrial  contraction in relation to  ventricular   contraction . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2265", "text": "A  vagal maneuver  is an action used to stimulate the parasympathetic nervous system by activating the  vagus nerve . The vagus nerve is the longest nerve of the  autonomic nervous system  and helps regulate many critical aspects of human physiology, including heart rate, blood pressure, sweating, and digestion through the release of  acetylcholine . Common maneuvers that activate the vagus nerve include the  Valsalva maneuver  and  carotid sinus massage , which can serve diagnostic or therapeutic functions."}
{"_id": "WikiPedia_Cardio$$$corpus_2266", "text": "There are both diagnostic and therapeutic indications for the use of vagal maneuvers in clinical practice."}
{"_id": "WikiPedia_Cardio$$$corpus_2267", "text": "Diagnostic:"}
{"_id": "WikiPedia_Cardio$$$corpus_2268", "text": "Therapeutic:"}
{"_id": "WikiPedia_Cardio$$$corpus_2269", "text": "While many physical maneuvers can elicit autonomic responses, only some are appropriate for use in a clinical setting. The vagal maneuvers most often used for diagnostic or therapeutic purposes are those that can be reliably performed at bedside or in an office setting with minimal risk. A list of vagal maneuvers are listed below: [ 12 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2270", "text": "Other less clinically useful physical maneuvers that elicit a similar autonomic response through stimulation of the vagus nerve include:"}
{"_id": "WikiPedia_Cardio$$$corpus_2271", "text": "Vagal maneuvers serve to stimulate the  vagus nerve  ( cranial nerve X ) through various mechanisms. The longest nerve in the body, the vagus nerve serves both motor and sensory functions through afferent and efferent signaling to and from the brain. The vagus nerve releases the neurotransmitter acetylcholine, [ 13 ]  and is a main mediator for the parasympathetic nervous system."}
{"_id": "WikiPedia_Cardio$$$corpus_2272", "text": "The vagus nerve exits the skull through the  jugular foramen , moving down through the  carotid sheath  and dividing many times to influence multiple organ systems and directly innervating the pharynx, larynx, esophagus, heart, lung, and GI tract. Due to this wide nerve distribution, many physiologic process may be influenced through its stimulation, including heart rate and blood pressure. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2273", "text": "Stimulation of the vagus nerve through vagal maneuvers is thought to effect afferent fibers that carry sensory information from its distribution throughout the body to the  nucleus tractus solitarii  (NTS) in the dorsal medullary complex, where it is then relayed to other areas of the brain. This stimulation can also be done more directly through a therapy called  Vagus Nerve Stimulation (VNS) , which utilizes an implanted neuro-stimulator device and is approved clinically for controlling seizures in epilepsy patients and drug resistant depression. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2274", "text": "Vagal maneuvers make use of the vagus nerve's afferent and efferent bifunctional role, triggering reflexes (like the  baroreceptor reflex ,  chemoreceptor reflex ) and utilizing those afferent nerve fibers to increase nerve activity. This results in increased parasympathetic signaling through its efferent distribution and is mediated by the chemical messenger acetylcholine. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2275", "text": "A  ventricular assist device  ( VAD ) is an  electromechanical  device that provides support for cardiac pump function, which is used either to partially or to completely replace the function of a failing  heart . VADs can be used in patients with acute (sudden onset) or chronic (long standing)  heart failure , which can occur due to  coronary artery disease ,  atrial fibrillation ,  valvular disease , and other conditions. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2276", "text": "VADs may be used to manage a variety of cardiac diseases and can be categorized based on which ventricle the device is assisting, and whether the VAD will be temporary or permanent."}
{"_id": "WikiPedia_Cardio$$$corpus_2277", "text": "Ventricular Assistance"}
{"_id": "WikiPedia_Cardio$$$corpus_2278", "text": "First, VADs can be categorized based on whether they are designed to assist the right  ventricle  (RVAD) or the left ventricle (LVAD) or to both ventricles (BiVAD). The type of VAD implanted depends on the type of underlying  heart disease  (e.g. patients with right ventricular failure from  pulmonary arterial hypertension  may require an RVAD, versus those with left ventricular failure from a  myocardial infarction  may require an LVAD). The LVAD is the most common device applied to a defective heart (it is sufficient in most cases; the right side of the heart is then often able to make use of the heavily increased blood flow), but when the pulmonary arterial resistance is high, then an (additional) right ventricular assist device (RVAD) might be necessary to resolve the problem of cardiac circulation. If both an LVAD and an RVAD are needed a BiVAD is normally used, rather than a separate LVAD and RVAD. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2279", "text": "Duration"}
{"_id": "WikiPedia_Cardio$$$corpus_2280", "text": "VADs can further be divided by the duration of their use (i.e. temporary versus permanent). Some VADs are for short-term use, [ 3 ]  typically for patients recovering from  myocardial infarction  (heart attack) and for patients recovering from  cardiac surgery ; some are for long-term use (months to years to perpetuity), typically for patients with advanced  heart failure [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2281", "text": "Temporary use of VADs may vary in scale (e.g. days to months) depending on a patient's condition. Certain types of VADS may be used in patients with signs of acute (sudden onset) heart failure or cardiogenic shock as a result of an infarction, valvular disease, among other causes. [ 4 ]  In patients with acute signs of heart failure, small  percutaneous  (introduced to the heart through the skin into a blood vessel rather than through an incision) VADs such as the  Impella  5.5, Impella RP, and others can be introduced to either the left or right ventricle (depending on the patient-specific needs) using a wire and that is introduced through the arteries or veins of the neck, axilla, or groin. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2282", "text": "Long-term use of VADs may also vary in its scale (i.e. months to permanently). VADs that are intended for long term use are also termed \"durable\" VADS, due to their design to function for longer periods of time compared to short term VADs (e.g. Impella, etc.). The long-term VADs can be used in a variety of scenarios. First, VADs may be used as  bridge to transplantation  (BTT) \u2013 keeping the patient alive, and in reasonably good condition, and able to await heart transplant outside of the hospital. Other \"bridges\" include bridge to candidacy (used when a patient has a  contraindication  to heart transplantation but is expected to improve with the VADs support) , bridge to decision (used to support a patient while their candidacy status is decided), and bridge to recovery (used until a patient\u2019s native heart function improves after which the device would be removed). [ 6 ]  In some instances, VADs are also used as  destination therapy  (DT) which indicates that the VAD will remain implanted indefinitely. VADs as destination therapy are used in circumstances where patients are not candidates for transplantation and will thus rely on the VAD for the remainder of their life. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2283", "text": "Other Cardiac Support Devices"}
{"_id": "WikiPedia_Cardio$$$corpus_2284", "text": "Some devices are designed to support the heart and its various components/function but are not considered VADs, below are some common examples."}
{"_id": "WikiPedia_Cardio$$$corpus_2285", "text": "Pacemakers  and Internal Cardiac Defibrillators (ICDs) \u2013  the function of a VAD differs from that of an  artificial cardiac pacemaker  in that a VAD pumps  blood , whereas a pacemaker delivers electrical impulses to the heart muscle."}
{"_id": "WikiPedia_Cardio$$$corpus_2286", "text": "Total Artificial Heart \u2013  VADs are distinct from  artificial hearts , which are designed to assume cardiac function, and generally require the removal of the patient's heart. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2287", "text": "Extracorporeal Membrane Oxygenation (ECMO) \u2013 is a form of mechanical circulatory support typically used in critically ill patients in cardiogenic shock that is established by introducing cannula into the arteries and or veins of the neck, axilla or groin. Generally, a venous cannula pulls deoxygenated blood from the patient's veins into an oxygenating device at the patient's bedside, after which a motor powered pump moves the oxygenated blood is back to the body (either into a vein or the arterial system, typically the aorta). There are different ECMO configurations (venoarterial ECMO, venovenous ECMO, etc.) the end goal remains the same; to oxygenate blood and return it to the body. [ 10 ]  In this sense, the ECMO circuit bypasses one or both ventricles and is therefore not in contact with the patient's native ventricle and is generally not considered a type of VAD."}
{"_id": "WikiPedia_Cardio$$$corpus_2288", "text": "The  pumps  used in VADs can be divided into two main categories \u2013 pulsatile pumps, [ 11 ]  which mimic the natural pulsing action of the heart, and continuous-flow pumps. [ 12 ]  Pulsatile VADs use  positive displacement pumps . [ 13 ] [ 14 ] [ 15 ]  In some pulsatile pumps (that use compressed air as an energy source [ 16 ] ), the volume occupied by blood varies during the pumping cycle. If the pump is contained inside the body then a vent tube to the outside air is required."}
{"_id": "WikiPedia_Cardio$$$corpus_2289", "text": "Continuous-flow VADs are smaller and have proven to be more durable than pulsatile VADs. [ 17 ]  They normally use either a  centrifugal pump  or an  axial flow pump . Both types have a central rotor containing permanent magnets. Controlled electric currents running through coils contained in the pump housing apply forces to the magnets, which in turn cause the rotors to spin. In the centrifugal pumps, the rotors are shaped to accelerate the blood circumferentially and thereby cause it to move toward the outer rim of the pump, whereas in the axial flow pumps the rotors are more or less cylindrical with blades that are helical, causing the blood to be accelerated in the direction of the rotor's axis. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2290", "text": "An important issue with continuous flow pumps is the method used to suspend the rotor. Early versions used solid bearings; however, newer pumps, some of which are approved for use in the EU, use either  magnetic levitation  (\"maglev\") [ 19 ] [ 20 ] [ 21 ]  or  hydrodynamic suspension ."}
{"_id": "WikiPedia_Cardio$$$corpus_2291", "text": "The first left ventricular assist device (LVAD) system was created by  Domingo Liotta  at Baylor College of Medicine in Houston in 1962. The first LVAD was implanted in 1963 by Liotta and E. Stanley Crawford. The first successful implantation of an LVAD was completed in 1966 by Liotta along with Dr.  Michael E. DeBakey . The patient was a 37-year-old woman, and a paracorporeal (external) circuit was able to provide mechanical support for 10 days after the surgery. [ 23 ]  The first successful long-term implantation of an LVAD was conducted in 1988 by Dr.  William F. Bernhard  of  Boston Children's Hospital  Medical Center and Thermedics, Inc. of Woburn, MA, under a  National Institutes of Health  (NIH) research contract which developed HeartMate, an electronically controlled assist device. This was funded by a three-year $6.2 million contract to Thermedics and Children's Hospital, Boston, MA, from the  National Heart, Lung, and Blood Institute , a program of the NIH. [ 24 ]  The early VADs emulated the heart by using a \"pulsatile\" action where blood is alternately sucked into the pump from the left ventricle then forced out into the aorta. Devices of this kind include the HeartMate IP LVAS, which was approved for use in the US by the  Food and Drug Administration  (FDA) in October 1994. These devices began to gain acceptance in the late 1990s as heart surgeons including  Eric Rose ,  O. H. Frazier  and  Mehmet Oz  began popularizing the concept that patients could live outside the hospital. Media coverage of outpatients with VADs underscored these arguments. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2292", "text": "More recent work has concentrated on continuous-flow pumps, which can be roughly categorized as either centrifugal pumps or  axial flow   impeller  driven pumps. These pumps have the advantage of greater simplicity resulting in smaller size and greater reliability. These devices are referred to as second-generation VADs. A side effect is that the user will not have a  pulse , [ 26 ] \nor that the pulse intensity will be seriously reduced. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2293", "text": "A very different approach in the early stages of development was the use of an inflatable cuff around the aorta. Inflating the cuff contracts the aorta and deflating the cuff allows the aorta to expand \u2013 in effect the aorta becomes a second left ventricle. A proposed refinement is to use the patient's skeletal muscle, driven by a  pacemaker , to power this device \u2013 which would make it truly self-contained. However, a similar operation ( cardiomyoplasty ) was tried in the 1990s with disappointing results. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2294", "text": "At one time  Peter Houghton  was the longest surviving recipient of a VAD for permanent use. He received an experimental Jarvik 2000 LVAD in June 2000. Since then, he completed a 91-mile charity walk, published two books, lectured widely, hiked in the Swiss Alps and the American West, flew in an ultra-light aircraft, and traveled extensively around the world. He died of  acute kidney injury  in 2007 at the age of 69. [ 28 ] [ 29 ]   Since then, patient Lidia Pluhar has exceeded Houghton's longevity on a VAD, having received a HeartMate II in March 2011 at age 75, and currently continues to use the device.  In August 2007 the International Consortium of Circulatory Assist Clinicians (ICCAC) was founded by Anthony \"Tony\" Martin, a nurse practitioner (NP) and clinical manager of the mechanical circulatory support (MCS) program at Newark Beth Israel Medical Center, Newark, N.J. The ICCAC was developed as a 501c3 organization, dedicated to the development of best practices and education related to the care of individuals requiring MCS as a bridge to heart transplantation or as destination therapy in those individuals who don't meet the criteria for heart transplantation. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2295", "text": "The majority of VADs on the market today are somewhat bulky. The smallest device approved by the FDA, the HeartMate II, weighs about 1 pound (0.45\u00a0kg) and measures 3 inches (7.6\u00a0cm). This has proven particularly important for women and children, for whom alternatives would have been too large. [ 45 ]  As of 2017, HeartMate III has been approved by the FDA. It is smaller than its predecessor HeartMate II and uses a full maglev impeller instead of the cup-and-ball bearing system found in HeartMate II. [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2296", "text": "The HeartWare HVAD works similarly to the VentrAssist\u2014albeit much smaller and not requiring an abdominal pocket to be implanted into. The device has obtained CE Mark in Europe, and FDA approval in the U.S.  The HeartWare HVAD could be implanted through limited access without  sternotomy , however in 2021 Medtronic discontinued the device. [ 47 ] [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2297", "text": "In a small number of cases left ventricular assist devices, combined with drug therapy, have enabled the heart to recover sufficiently for the device to be able to be removed ( explanted ). [ 7 ] [ 8 ]  Several surgical approaches, including interventional decommissioning, off-pump explantation using a custom-made plug and complete LVAD removal through redo sternotomy, have been described with a 5-year survival of up to 80%. [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2298", "text": "A series of studies involving the use of the HeartMate II LVAD have proven useful in establishing the viability and risks of using LVADs for bridge-to-transplantation and destination therapy."}
{"_id": "WikiPedia_Cardio$$$corpus_2299", "text": "The Harefield Recovery Protocol Study (HARPS) is a clinical trial to evaluate whether advanced heart failure patients requiring VAD support can recover sufficient myocardial function to allow device removal (known as explantation). HARPS combines an LVAD (the HeartMate XVE) with conventional oral heart failure medications, followed by the novel \u03b22 agonist  clenbuterol . This opens the possibility that some advanced heart failure patients may forgo heart transplantation. [ 57 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2300", "text": "The REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) clinical trial began in May 1998 and ran through July 2001 in 20 cardiac transplant centers around the USA. The trial was designed to compare long-term implantation of left ventricular assist devices with optimal medical management for patients with end-stage heart failure who require, but do not qualify to receive cardiac transplantation. As a result of the clinical outcomes, the device received FDA approval for both indications, in 2001 and 2003, respectively. [ 58 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2301", "text": "According to a retrospective cohort study comparing patients treated with a left ventricular assist device versus inotrope therapy while awaiting heart transplantation, the group treated with LVAD had improved clinical and metabolic function at the time of transplant with better blood pressure, sodium, blood urea nitrogen, and creatinine. After transplant, 57.7% of the inotrope group had  kidney failure  versus 16.6% in the LVAD group; 31.6% of the inotrope group had right heart failure versus 5.6% in the LVAD group; and event-free survival was 15.8% in the inotrope group versus 55.6% in the LVAD group. [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2302", "text": "There are a number of potential risks associated with VADs. The most common of these are bleeding events, stroke, pump thrombosis, and infections. [ 60 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2303", "text": "Bleeding"}
{"_id": "WikiPedia_Cardio$$$corpus_2304", "text": "Because the VADs generally result in blood flowing over a non-biologic surface (e.g. metal, synthetic polymers, etc.) this can result in formation of blood clots, also referred to as  thrombosis . Due to these  clotting  abnormalities,  anticoagulation  medications are used to decrease the risk of thrombosis. One device, the HeartMate XVE, is designed with a biologic surface derived from  fibrin  and does not require long term anticoagulation (except aspirin); unfortunately, this biologic surface may also predispose the patient to infection through selective reduction of certain types of leukocytes, however this device was phased out of use starting in 2009 in favor of newer devices. [ 61 ] [ 62 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2305", "text": "Due to the use of anticoagulation, bleeding is the most common postoperative early complication after implantation or explantation of VADs, necessitating reoperation in up to 60% of recipients. [ 63 ] [ 64 ]  Most commonly bleeding occurs in the gastrointestinal tract resulting in dark or bright red stools, [ 65 ]  however if trauma to the head occurs, intracranial bleeding may also occur. [ 66 ]  Bleeding events may require massive blood transfusions and incur certain risks including infection, pulmonary insufficiency, increased costs, right heart failure, allosensitization, and viral transmission, which can prove fatal or preclude transplantation. [ 64 ]  When bleeding occurs, it impacts the one year Kaplan-Meier mortality. [ 63 ]  In addition to complexity of the patient population and the complexity of these procedures contributing to bleeding, the devices themselves may contribute to the severe coagulopathy that can ensue when these devices are implanted. [ 67 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2306", "text": "Ischemic Stroke and Pump Thrombosis"}
{"_id": "WikiPedia_Cardio$$$corpus_2307", "text": "In patients with VADs, ischemic strokes and pump thrombosis occur when there is inadequate anticoagulation to counter act the blood's tendency to form blood clots when exposed to the foreign materials in a VAD. Stroke risk varies based on the type of VAD in place and other risk factors. [ 60 ]  Both atrial fibriliation and high blood pressure may increase risk of stroke and high blood pressure can increase a patient's risk of stroke in the setting of VAD use. [ 68 ]  However, it is difficult to measure blood pressure in LVAD patients using standard blood pressure monitoring and the current practice is to measure by  Doppler ultrasonography  in  outpatients  and invasive  arterial blood pressure  monitoring in  inpatients . [ 69 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2308", "text": "Infections"}
{"_id": "WikiPedia_Cardio$$$corpus_2309", "text": "Infections in VAD patients occur because the artificial surfaces of the devices serve as a surface for bacterial and or fungal growth. [ 70 ]  Most infections are classified as driveline infections, which are infections that occur where the device's power cord enters the skin (usually in the upper abdomen) [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2310", "text": "VAD-related infection can be caused by a large number of different organisms: [ 71 ] [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2311", "text": "Other immune system related problems include  immunosuppression . Some of the  polyurethane  components used in the devices cause the deletion of a subset of  immune cells  when blood comes in contact with them. This predisposes the patient to  fungal  and some  viral  infections necessitating appropriate  prophylactic therapy . [ 72 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2312", "text": "Considering the multitude of risks and lifestyle modifications associated with ventricular assist device implants, [ 73 ]  it is important for prospective patients to be informed prior to decision making. [ 74 ]  In addition to physician consult, various Internet-based patient directed resources are available to assist in patient education. [ 75 ] [ 76 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2313", "text": "This is a partial list and may never be complete \n Referenced additions are welcome"}
{"_id": "WikiPedia_Cardio$$$corpus_2314", "text": "A  ventricular outflow tract  is a portion of either the  left ventricle   or  right ventricle  of the  heart  through which  blood  passes in order to enter the  great arteries . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2315", "text": "The right ventricular outflow tract ( RVOT ) is an  infundibular  extension of the ventricular cavity that connects to the  pulmonary artery . The left ventricular outflow tract ( LVOT ), which connects to the  aorta , is nearly indistinguishable from the rest of the ventricle. The outflow tract is derived from the secondary heart field, during cardiogenesis. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2316", "text": "Both the left and right outflow tract have their own term. The right outflow tract is called \"conus arteriosus\" from the outside, and infundibulum from the inside. In the left ventricle the outflow tract is the \"aortic vestibule\". They both possess smooth walls, and are derived from the embryonic bulbus cordis [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2317", "text": "In both left and right ventricle there are specific structures separating the inflow and outflow of blood. In the right ventricle, the inflow and outflow is separated by the supraventricular crest. In the left ventricle, the anterior cusp of the mitral valve is responsible for separating the flow of blood. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2318", "text": "A form of  ventricular tachycardia  originating from this anatomical structure is called RVOT tachycardia. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2319", "text": "The RVOT is pathophysiologically affected in  Brugada syndrome . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2320", "text": "Wave intensity analysis [ 1 ]  provides a method to calculate the properties of arterial waves that give rise to  arterial blood pressure , based on measurements of pressure, P, and velocity, U, waveforms ( Figure 1 ). Wave intensity analysis is applicable to the evaluation of circulatory physiology and quantifying the pathophysiology of disorders such as coronary artery disease.\nThe method is based on discrete, successive wave fronts (wavelets) and is carried out in the time domain. These wavelets travel forward and backwards in the arteries with amplitudes  \n \n \n \n \u0394 \n P \n \n \n {\\textstyle \\Delta P} \n \n  and  \n \n \n \n \u0394 \n U \n \n \n {\\textstyle \\Delta U} \n \n . The wave intensity,  \n \n \n \n \u0394 \n I \n \n \n {\\textstyle \\Delta I} \n \n , of a particular wavelet is defined as \n \n \n \n \u0394 \n I \n = \n \u0394 \n P \n \u0394 \n U \n \n \n {\\displaystyle \\Delta I=\\Delta P\\Delta U} \n \n It is related to  sound intensity  in acoustics and describes the power per unit area carried by the wavelet. From the theory discussed below, there is a relationship between the pressure amplitude and the velocity amplitude of a wavelet \n \n \n \n \u0394 \n \n P \n \n \u00b1 \n \n \n = \n \n \n 1 \n 2 \n \n \n ( \n \u0394 \n \n P \n \n \u00b1 \n \n \n \u00b1 \n \u03c1 \n c \n \u0394 \n \n U \n \n \u00b1 \n \n \n ) \n \n \n {\\displaystyle \\Delta P_{\\pm }={\\frac {1}{2}}(\\Delta P_{\\pm }\\pm \\rho c\\Delta U_{\\pm })} \n \n where \u03c1 is the density of blood and c is the wave speed of the wavelet. From these equations, generally known as the  water hammer  equations, it follows that the wave intensity for forward wavelets  \n \n \n \n \u0394 \n \n I \n \n + \n \n \n > \n 0 \n \n \n {\\textstyle \\Delta I_{+}>0} \n \n  and for backward wavelets  \n \n \n \n \u0394 \n \n I \n \n \u2212 \n \n \n < \n 0 \n \n \n {\\textstyle \\Delta I_{-}<0} \n \n . The ability to determine the direction of a wavelet from its sign is the basis of the practical utility of wave intensity analysis."}
{"_id": "WikiPedia_Cardio$$$corpus_2321", "text": "The pressure amplitude of a wavelet can be positive (compression) or negative (decompression) and the velocity amplitude can be positive (acceleration) or negative (deceleration). The measured changes  \n \n \n \n \u0394 \n P \n \n \n {\\displaystyle \\Delta P} \n \n  and  \n \n \n \n \u0394 \n U \n \n \n {\\displaystyle \\Delta U} \n \n  are the sums of the amplitudes of the forward and backward wavelets arriving at the measurement site at the time of the measurement and so the wave intensity  \n \n \n \n \u0394 \n I \n \n \n {\\displaystyle \\Delta I} \n \n  is sometimes called net wave intensity. The  \n \n \n \n \u0394 \n I \n \n \n {\\displaystyle \\Delta I} \n \n  in the Figure 2 shows the normal pattern in the aorta and illustrates four important features:"}
{"_id": "WikiPedia_Cardio$$$corpus_2322", "text": "Departures from this pattern of wave intensity is usually indicative of pathology."}
{"_id": "WikiPedia_Cardio$$$corpus_2323", "text": "The additivity of the forward and backward wavelets coinciding at the site of measurement at a particular time can be combined algebraically with the water-hammer equations  to calculate the magnitudes of the two wavelets [ 2 ] \n \n \n \n \u0394 \n \n P \n \n \u00b1 \n \n \n = \n \n \n 1 \n 2 \n \n \n ( \n \u0394 \n \n P \n \n \u00b1 \n \n \n \u00b1 \n \u03c1 \n c \n \u0394 \n \n U \n \n \u00b1 \n \n \n ) \n \n \n {\\displaystyle \\Delta P_{\\pm }={\\frac {1}{2}}(\\Delta P_{\\pm }\\pm \\rho c\\Delta U_{\\pm })} \n \n This method assumes that the wave speed is constant. In general, the wave speed is a function of the pressure. A more complex method of separation involving integrals along the characteristics is available. [ 3 ]  The forward and backward waveforms follow from summing the magnitudes of the sequential wavelets \n \n \n \n \n P \n \n \u00b1 \n \n \n = \n \u03a3 \n \u0394 \n \n P \n \n \u00b1 \n \n \n \n \n {\\displaystyle P_{\\pm }=\\Sigma \\Delta P_{\\pm }} \n \n The pressure shown in Figure 1 is separated into its forward and backward components in Figure 3. This separation is carried out in the time domain and can be applied to irregular, non-periodic data. For periodic heart beats this separation coincides closely with the separation obtained using Fourier analysis methods. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2324", "text": "Wave intensity analysis is based on the 1-D equations for the conservation of mass and momentum of the blood in the elastic arteries (first published by   Euler  in 1775) and a relationship between the cross-sectional area of the artery and the pressure within it (generally called a 'tube law'). The resultant equations are hyperbolic in form and can be solved using the  method of characteristics . The method is based on the identification of 'characteristic' directions along which the partial differential equations reduce to ordinary differential equations. For the arteries these characteristic directions were ( \n \n \n \n x \n \u00b1 \n c \n t \n \n \n {\\textstyle x\\pm ct} \n \n ) where  \n \n \n \n c \n \n \n {\\displaystyle c} \n \n  is the wave speed \n \n \n \n c \n = \n \n \n 1 \n \n \u03c1 \n \n \n D \n \n \n \n \n \n \n \n {\\displaystyle c={\\frac {1}{\\sqrt {\\rho {\\mathcal {D}}}}}} \n \n where  \n \n \n \n \n \n D \n \n \n = \n \n \n 1 \n A \n \n \n \n \n \n d \n A \n \n \n d \n P \n \n \n \n \n \n {\\displaystyle {\\mathcal {D}}={\\frac {1}{A}}{\\frac {dA}{dP}}} \n \n  is the distensibility of the artery wall. These characteristic directions describe the path of the wavelets in  \n \n \n \n ( \n x \n , \n t \n ) \n \n \n {\\displaystyle (x,t)} \n \n . The derivation of an equation for the local wave speed is a significant advantage of the method of characteristics."}
{"_id": "WikiPedia_Cardio$$$corpus_2325", "text": "A method for estimating local wave speed from clinically measurable data is important in wave intensity analysis. The most common approach is referred to as the 'P-U loop' method. During the initial compression wave at the start of systole when the forward wave is dominant the local wave speed is estimated from the slope of the P-U loop \n \n \n \n c \n \u2248 \n \n \n 1 \n \u03c1 \n \n \n \n \n | \n \n \n \n d \n P \n \n \n d \n U \n \n \n \n | \n \n \n i \n n \n i \n t \n i \n a \n l \n \n s \n y \n s \n t \n o \n l \n e \n \n \n \n \n {\\displaystyle c\\approx {\\frac {1}{\\rho }}\\left|{\\frac {dP}{dU}}\\right|_{initial\\;systole}} \n \n In cases where there is no period during the cardiac cycle when it is obvious that forward waves dominate another method, generally called the 'sum of squares' method [ 5 ]  is applicable: \n \n \n \n c \n \u2248 \n \n \n 1 \n \u03c1 \n \n \n \n \n \n \n \u03a3 \n \u0394 \n \n P \n \n 2 \n \n \n \n \n \u03a3 \n \u0394 \n \n U \n \n 2 \n \n \n \n \n \n \n \n \n {\\displaystyle c\\approx {\\frac {1}{\\rho }}{\\sqrt {\\frac {\\Sigma \\Delta P^{2}}{\\Sigma \\Delta U^{2}}}}} \n \n Here the sums are taken over a complete cardiac period. This estimation has been used extensively in the wave intensity analysis of measurements in the coronary arteries. [ 6 ]  It should be remembered that both of these estimates are approximations and should be used with caution."}
{"_id": "WikiPedia_Cardio$$$corpus_2326", "text": "Wave intensity analysis was developed at an era when intra-arterial pressure and velocity waveforms were measured most commonly in the clinic. Other methods of clinical measurements have emerged (e.g. ultrasound and magnetic resonance imaging) and wave intensity analysis has been recast in terms of the parameters that are measured. No systematic notation has been developed to distinguish the different variants. This is a possible source of confusion."}
{"_id": "WikiPedia_Cardio$$$corpus_2327", "text": "Although wave intensity has some clinical applications, its main influence has been on the basic understanding of arterial  hemodynamics . The first publication pointed out that the deceleration of blood in the aorta during late systole is mainly due to forward deceleration waves rather than backward reflections from the periphery. [ 9 ]  Backward wavelets are present as indicated by the negative wave intensity during mid-systole but most of the deceleration is caused by forward decompression waves generated when the contraction of the ventricle can not keep up with the flow of blood established by the initial contraction wave."}
{"_id": "WikiPedia_Cardio$$$corpus_2328", "text": "Various studies have looked at the magnitudes of the forward and backward peaks of wave intensity in various pathologies. [ 7 ]  In the 1990s, Aloka introduced clinical ultrasound scanners that measured the instantaneous wave intensity directly from simultaneous measurements of diameter (by B-mode) and blood velocity (by Doppler). Recent studies suggest that wave intensity calculated from catheter measurements in the pulmonary artery can be used to differentiate between  pulmonary arterial hypertension  and  chronic thromboembolic pulmonary hypertension . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2329", "text": "Wave intensity analysis is frequently used in the study of coronary artery hemodynamics where impedance analysis is seldom, if ever, used. [ 11 ]  It played an important role in the development of the  Instantaneous Wave-free Ratio  as a measure of the functional effect of  stenoses  in the coronary arteries. This method informs an interventional cardiologist if stenting is required by measuring the ratio of downstream and upstream pressures during a period in mid-diastole when the net wave intensity is minimal. Large scale clinical trials have shown that this index is \"at least as good as\" the Functional Flow Resistance Index which requires the injection of a potent  vasodilator ."}
{"_id": "WikiPedia_Cardio$$$corpus_2330", "text": "A  wearable cardioverter defibrillator  ( WCD ) is a non-invasive, external device for patients at risk of  sudden cardiac arrest  (SCA). [ 1 ]  It allows physicians time to assess their patient's arrhythmic risk and see if their ejection fraction improves before determining the next steps in patient care. It is a leased device. A summary of the device, its technology and indications was published in 2017 and reviewed by the EHRA Scientific Documents Committee. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2331", "text": "A wearable cardioverter defibrillator (WCD) is an external device with a built-in  defibrillator . The WCD is worn directly on the body by patients who are at transient risk for  sudden cardiac death  (SCD) for short-term risk mitigation and it does not require surgery for use. A WCD is also a temporary therapeutic option in case an  implantable cardioverter defibrillator  (ICD) cannot be implanted immediately. The WCD enables patients to continue their normal life without constantly worrying about their risk for SCD."}
{"_id": "WikiPedia_Cardio$$$corpus_2332", "text": "The WCD is a non-invasive medical device. It consists of a fabric garment, electrodes located in the fabric garment for sensing and delivering an electrical shock, and a battery-powered device that monitors the patient and connects to the electrodes and defibrillation pads. The WCD is worn under the clothing during the entire day. The WCD should only be removed when taking a shower or bath. The electrodes lie directly on the skin. The monitoring device constantly records heart rate and rhythm. [ 3 ]  If life-threatening  cardiac arrhythmias , such as  ventricular tachycardia  (VT) or  ventricular fibrillation  (VF) are detected, the defibrillator delivers one or more treatment shock(s) in order to restore a normal heart rhythm. Since the time between a cardiac arrest and defibrillation is directly linked to survival, [ 4 ] [ 5 ]  a treatment shock must be delivered within a few minutes after an event to be effective. With every passing minute without treatment, the chances of patient survival is reduced by 7-10%. [ 6 ] [ 7 ]  From detecting a life-threatening cardiac arrhythmia to automatically delivering a treatment shock, the WCD usually needs less than a minute. The first treatment shock success rate for resuscitating patients from SCD is 98%. [ 8 ]  Intervention from bystanders or emergency personnel is not required for the WCD to work."}
{"_id": "WikiPedia_Cardio$$$corpus_2333", "text": "The use of the WCD is recommended for the prevention of SCD in the 2006 international joint guidelines from the American College of Cardiology, American Heart Association, and European Society of Cardiology (ACC/AHA/ESC), [ 9 ]  European Society of Cardiology (ESC) guidelines from 2015 [ 10 ]  and 2021, [ 11 ]  and American Heart Association, American College of Cardiology, Heart Rhythm Society (AHA/ACC/HRS) guidelines from 2017. [ 12 ] [ 13 ]  The International Society for Heart and Lung Transplantation (ISHLT) recommends wearable external defibrillators as a bridge therapy for patients waiting for a heart transplant in their Guidelines for the Care of Cardiac Transplant Candidates. [ 14 ]  In the United Kingdom (UK) the WCD LifeVest\u00ae from ZOLL is available for temporary use on a monthly rental basis since 2017. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2334", "text": "The WCD is a temporary therapeutic option for patients waiting for an ICD, patients with an ICD that had to be removed (e.g., due to infection), or patients who can't have an ICD but are at transient risk for SCD. [ 16 ]   The WCD allows physicians time to assess their patient's cardiac arrhythmic risk, make appropriate treatment plans and monitor cardiac output before or after an invasive cardiac procedure (such as bypass surgery, stent placement or heart transplant) or in patients at high risk for SCD after myocardial infarction (MI). [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2335", "text": "Usual wearing time of a WCD is about 3 months but depends on the patient's needs and the prescription of the treating physician."}
{"_id": "WikiPedia_Cardio$$$corpus_2336", "text": "The use of cardiac defibrillation started in 1947 - first in an open chest and ten years later through a closed chest with high energy levels. In 1972, cardiac defibrillation with intracardiac electrodes delivering much less energy of as low as 30 joules was established, following the development of portable units delivering high energy levels of up to 1000 volt. At Johns Hopkins University, doctors Mirowski, Mower and colleagues started developing implantable cardioverter defibrillators (ICD), and were able to implant an ICD in the first human by 1980. Over the years, the ICD was further improved and is now a standard outpatient procedure. [ 19 ] [ 20 ]  There are limiting factors for direct prophylactic implantation of an ICD. For example, a diagnosed high risk for SCD may be temporary, which would oppose an implantation intended for lifetime use. Per current guidelines (e.g., the ESC guidelines from 2015 and 2021) a patient has to wait at least 40 to 90 days after the cardiac event (e.g., myocardial infarction or newly diagnosed heart failure with reduced left ventricular function) before the decision to implant an ICD should be made. [ 21 ]  An external, wearable cardioverter-defibrillator with defibrillation features similar to an ICD could be a solution to be used as \u201cbridge\u201d to protect these patients from SCD."}
{"_id": "WikiPedia_Cardio$$$corpus_2337", "text": "In 1986, M. Stephen Heilman and Larry Bowling founded LIFECOR and started the development of the first wearable cardioverter defibrillator (WCD). It was named LifeVest\u00ae. This WCD was extensively tested for three years in multi-centre and multinational clinical trials (WEARIT and BIROAD) in the United States and Europe. The results were used to improve the WCD and were also the basis for FDA approval in 2001 for use of the WCD for adult patients who are at high risk for SCD, who are not suitable candidates for an ICD or who refuse to have one. [ 22 ] [ 23 ]  14 years later (2015), FDA approval was received for the use of the WCD in children, who are at high risk for SCD and are not candidates for an ICD or do not receive one due to lack of parental consent. [ 24 ]  In 2000, prior to the FDA approvals, the WCD had already received the European CE-certification. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2338", "text": "In 1986,  M. Stephen Heilman  and Larry Bowling founded Lifecor and along with a team of former Intec employees who developed the first  implantable cardioverter defibrillator  (ICD) began development of the WCD. The WCD was extensively tested for three years in 17 major medical centers across the United States and Europe. The clinical data collected from those trials [ 26 ]  allowed Lifecor to obtain FDA approval for use of the WCD in the United States. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2339", "text": "In 2001, the FDA approved the LifeVest wearable cardioverter defibrillator (model 2000). [ 27 ] [ 28 ] [ 29 ]  The Lifecor business was acquired by ZOLL Medical Corporation in 2006 and Asahi Kasei in 2012. As of 2015, the LifeVest was available in the United States, Europe, Japan, Australia, Israel and Singapore. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2340", "text": "The WCD LifeVest is marketed in the United Kingdom, United States, Europe, Japan, and several other countries worldwide. According to ZOLL, the LifeVest has been prescribed to more than 200,000 patients worldwide. In July 2021, the FDA approved a second WCD product for the market developed by Kestra Medical Technologies, Inc. This new device has an alternative fabric and garment style specifically for women. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2341", "text": "The WCD is covered by most health plans in the United States, including commercial, state, and federal plans as Durable Medical Equipment (DME) for those patients at high risk of cardiac arrest, including: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2342", "text": "The WCD uses dry, non-adhesive ECG electrodes to continuously monitor the patient's heart rhythm. Three defibrillation electrodes are placed in the fabric garment, one on the chest (approximately at the level of the apex of the heart) and two on the back (between the shoulder blades). The ECG electrodes are placed inside the fabric garment on the chest providing two independent ECG leads. Prior to delivering a therapeutic shock, the dry defibrillator electrodes automatically deploy conductive gel to protect the skin from possible injury from the treatment. The WCD can deliver up to five consecutive shocks per sequence. Life-saving therapy typically occurs within a minute of the onset of an arrhythmia. The patient is warned when a treatment sequence has been started, e.g. by siren alarms and spoken information. Through interaction with the WCD, an unjustified shock delivery can be prevented by the patient as long as she/he is conscious. If the patient fails to respond, e.g., because the patient has lost consciousness due to an arrhythmia, gel is automatically ejected from under the defibrillation electrodes. If the arrhythmia resolves on its own, no treatment shock is delivered. Action from bystanders is not required, but they are warned by voice information not to touch the patient during defibrillation and to call emergency services. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2343", "text": "In the electrode belt, four dry, non-adhesive ECG electrodes continuously monitor the patient's heart rhythm. Three defibrillation electrodes are placed in the vest, one on the chest (approximately at the level of the apex of the heart) and two on the back (between the shoulder blades). The ECG electrodes are placed at inside of the vest on the chest providing two independent ECG leads. Prior to delivering a therapeutic shock, the dry defibrillator electrodes automatically deploy conductive gel to protect the skin from possible injury from the treatment. The WCD can deliver up to five consecutive shocks per sequence. Life-saving therapy typically occurs within a minute of the onset of an arrhythmia.The patient is warned when a treating sequence has been started e.g. by siren alarms and spoken information. By pressing two response buttons on the monitor simultaneously, an unjustified shock delivery can be prevented by the patient as long as she/he is conscious. If the patient fails to respond, e.g., because the patient has lost consciousness due to an arrhythmia, gel is automatically ejected from under the defibrillation electrodes. If the arrhythmia resolves on its own, no treatment shock is delivered. Action from bystanders is not required, but they are warned by voice information not to touch the patient during defibrillation and to call the emergency doctor."}
{"_id": "WikiPedia_Cardio$$$corpus_2344", "text": "The patient receives two rechargeable batteries for the WCD. One will be used to operate the monitoring device, the other is charged for daily replacement. Conspicuous ECG sequences or treatments are automatically transmitted to a secure server. The treating physician can view and analyze them via password-protected access. Before a WCD is handed to a patient, the WCD is fitted to the patient for accurate ECG signal detection and the patient receives detailed training to ensure correct handling of the WCD. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2345", "text": "The efficacy and effectiveness of the WCD has been tested in clinical trials and several international post-marketing studies. If the WCD is worn correctly and ECG signal detection is optimal, the success rate of the first shock is approximately 98%. [ 33 ]  Hence, the WCD is as effective as an ICD in treating VT and VF. [ 34 ]  Long term follow-up studies showed that approximately 90% of all patients treated with the WCD are still alive one year after the heart failure incident. [ 35 ] \nSince the WCD is a non-invasive garment, no injuries or scars remain after use and shock delivery. For effective protection, the WCD should be worn 24 hours a day and should only be removed for personal hygiene."}
{"_id": "WikiPedia_Cardio$$$corpus_2346", "text": "Automated external defibrillators (AED) are portable electronic devices designed to analyze the heart rhythm and inform the operator whether defibrillation is required. They are intended for people of the general population with an unknown risk for heart failure and are usually available in public places and first responder ambulances. AEDs are designed for use by laypersons and provide simple audio and visual instructions for the operator to follow. Electrode pads, placed by an operator on the chest of the patient, are for monitoring and defibrillation. [ 36 ]  In contrast to the ICD and WCD, an AED needs the immediate activity of a bystander in order to prevent the SCD."}
{"_id": "WikiPedia_Cardio$$$corpus_2347", "text": "WCDs are intended for patients with a known transient risk for SCD and meant for temporary use as described above.The WCD is the ideal therapeutic option to prevent SCD in patients until it is clear that a patient's heart issues are indeed permanent and long-term protection with an ICD must be applied.[36]"}
{"_id": "WikiPedia_Cardio$$$corpus_2348", "text": "Implantable cardioverter-defibrillators (ICD) are electronic devices implanted in the chest with a lead to the right ventricle of the heart. They are intended for patients with permanent risk for SCD. An ICD is, like a WCD, designed to detect and terminate cardiac arrhythmias by emergency defibrillation. [ 37 ]  An extensive invasive surgery is necessary for implantation of the ICD, which is associated with a number of risks and morbidity. Therefore, the decision for an ICD should be carefully taken. [ 38 ]  The WCD is the ideal therapeutic option to prevent SCD in patients until it is clear that a patient's heart issues are indeed permanent and long-term protection with an ICD must be applied. [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2349", "text": "The WCD allows patients at high risk for SCD who are discharged from the hospital to return to most of the normal daily activities without constantly worrying about their heart issues and possible fatal outcomes. A retrospective study investigating quality of life in patients who had been fitted with a WCD found that the majority did not feel any impairment in terms of mobility (68%), self-care (83%), daily routine (75%), pain (64%) and mental health (57%). [ 40 ]  Another prospective study evaluating depression and anxiety in patients eligible for WCD found a trend for better improvement of depression scores in patients who actually received the WCD. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2350", "text": "Currently a study on the use of the WCD started in the UK."}
{"_id": "WikiPedia_Cardio$$$corpus_2351", "text": "In case of questions concerning which activities are possible, the manufacturer recommends consulting with the treating physician. The manufacturer also advises to avoid activities in loud and/or high vibration environments due to the possibility of missing an alert from WCD."}
{"_id": "WikiPedia_Cardio$$$corpus_2352", "text": "The WCD is generally recommended as temporary therapy for all patients who are at risk of SCD and can be prescribed in the UK as a monthly rental device."}
{"_id": "WikiPedia_Cardio$$$corpus_2353", "text": "According to the international guidelines of ACC/AHA/ESC in 2006, the ESC in 2015 and 2021 as well as AHA/ACC/HRS in 2017  [ 42 ] [ 43 ] [ 44 ] [ 45 ]  patients that may benefit from a WCD include:"}
{"_id": "WikiPedia_Cardio$$$corpus_2354", "text": "Patients with reduced left ventricular pump systolic function (LVEF) of \u2264 35%"}
{"_id": "WikiPedia_Cardio$$$corpus_2355", "text": "Newly diagnosed Ischemic Heart Failure Patient with Reduced Ejection Fraction (HFrEF)"}
{"_id": "WikiPedia_Cardio$$$corpus_2356", "text": "Patients with ventricular fibrillation (VF) or sustained ventricular tachycardia (VT)"}
{"_id": "WikiPedia_Cardio$$$corpus_2357", "text": "Patients on the waiting list for a heart transplantation"}
{"_id": "WikiPedia_Cardio$$$corpus_2358", "text": "Bridging the waiting time for patients"}
{"_id": "WikiPedia_Cardio$$$corpus_2359", "text": "Newly diagnosed non-ischemic heart failure patient with reduced ejection fraction, including dilated cardiomyopathies (DCM) and New York Heart Association (NYHA) stage II-III heart failure patients"}
{"_id": "WikiPedia_Cardio$$$corpus_2360", "text": "Patients in a risk phase of pregnancy cardiomyopathy (peripartum CM/PPCM)"}
{"_id": "WikiPedia_Cardio$$$corpus_2361", "text": "The ISHLT has listed the WCD as a class I recommendation in its Guidelines for the Care of Cardiac Transplant Candidates since 2006. [ 46 ]  This means that patients waiting for a heart transplantation who are discharged from hospital should receive a wearable defibrillator to bridge the waiting time until receiving the transplant. The WCD is one of the procedures or treatments for which there is evidence and general agreement that it is beneficial, useful and effective in the given condition. [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2362", "text": "WCD has also been used in the specific circumstance where patients have an ICD but require temporary explantation for radiotherapy in the location of the ICD generator. [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2363", "text": "After European CE-certification and FDA approval of WCD (LifeVest), a number of retrospective and prospective registries verified the efficacy and safety of the WCD. Data from more than 30,000 patients who have used the WCD are published for an expansive variety of indications. In the following only an excerpt is presented."}
{"_id": "WikiPedia_Cardio$$$corpus_2364", "text": "Meta-analyses"}
{"_id": "WikiPedia_Cardio$$$corpus_2365", "text": "A meta-analysis of 11 comparable studies with approximately 20,000 non-overlapping patients in different indications was published by Nguyen et al. [ 49 ]  They found an overall mortality rate of 1.4%, a VT/VF rate of 2.6% and a VT/VF-related mortality rate of only 0.2% across all patients. 1.7% of the patients (9.1 patients/100 patient years) had received an appropriate treatment, which was successful in 96%. The inappropriate shock rate was <1.0%."}
{"_id": "WikiPedia_Cardio$$$corpus_2366", "text": "A systematic cross-indication review and meta-analysis of studies reporting treatment rates of WCD was conducted by Masri et al. in 2019. [ 50 ]  They analysed 28 studies and over 30,000 patients. Over a period of 3 months, 5 per 100 patients received appropriate WCD treatment shocks, and only 2 per 100 patients received inappropriate treatment shocks. Analyses of selection or publication bias (e.g., Egger-test) revealed, that there were no differences between independent and manufacturer-sponsored studies, and no differences between prospective and retrospective studies. According to the authors, the rate of patients, who were appropriately treated with the WCD over 3 months of follow-up, was substantial and much higher in observational studies compared to the RCT included in the analysis. The mortality rate was very low at 0.7 per 100 patients over 3 months."}
{"_id": "WikiPedia_Cardio$$$corpus_2367", "text": "Randomized controlled trial data"}
{"_id": "WikiPedia_Cardio$$$corpus_2368", "text": "[ 51 ] [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2369", "text": "The first and to this date only randomized controlled trial (RCT) on WCD use with post-MI patients is the VEST Trial, which was first published by Olgin et al. in 2018. [ 53 ]  In total 2,302 patients were included in the intention-to-treat (ITT) analysis. The primary outcome of the VEST-study, arrhythmic mortality, was 1.6% in the WCD group vs. 2.4% in the control group. The difference was not significant despite a 33% relative risk reduction (RRR). The secondary outcome of the VEST-study, all-cause mortality, was 3.1% in the WCD group and 4.9% in the control group. The difference was significant with a 36% reduction in mortality (RRR). Notably, in this study the average daily wearing time was only 14 to 18 hours/day, hence much lower than supposed according to observational studies. An additional as-treated analysis (ATT) provided as supplemented appendix to the original publication, revealed statistical significance in all mortality endpoints, thus positive results for the use of the WCD. In a per protocol analysis (PPA) published in 2020, [ 54 ]  the reduction in arrhythmic mortality was 62% and in all-cause mortality 75%, both significant results, which is comparable to the results shown in the ATT analysis."}
{"_id": "WikiPedia_Cardio$$$corpus_2370", "text": "These results indicated that the WCD is highly effective in reducing mortality rates in patients with a high risk for SCD. Essential factors in successful WCD therapy in everyday clinical practice are high wearing compliance and the use of the monitoring system provided by the manufacturer (ZPM Network)."}
{"_id": "WikiPedia_Cardio$$$corpus_2371", "text": "Health technology assessments (HTA)"}
{"_id": "WikiPedia_Cardio$$$corpus_2372", "text": "Aidelsburger and colleagues published the results of an HTA in 2020. [ 55 ]  The authors analysed data from 49 studies and concluded the WCD is a safe and effective intervention in cases of sudden cardiac arrest during the time needed for determination of long-term risk management strategies, that the WCD is reliable in detecting VT/VF events and shows a high rate of appropriate shocks which lead to a high rate of successful VT/VF terminations.\nCortesi and colleagues published the results from another HTA in 2021. [ 56 ]  They focused on cost-efficacy comparing the WCD to \u201cstandard of care\u201d in patients at risk for SCD after MI or ICD explantation. The authors found that the WCD is a cost-effective treatment option in patients after MI using the data from the VEST study. In patients after ICD explantation the WCD provided even a cost saving of \u20ac1,782 compared to 3 weeks hospitalization in a low intensity hospital (standard of care) using data from the Italian NHS. The authors concluded that for the Italian NHS the WCD use contributes to a more effective utilization of resources and to the improvement of patient care in clinical practice. [ 57 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2373", "text": "Currently an HTA is planned to be conducted in the UK."}
{"_id": "WikiPedia_Cardio$$$corpus_2374", "text": "The  West of Scotland Coronary Prevention Study  (also known as  WOSCOPS ) was a landmark [ 1 ]   randomized controlled trial , published in 1995, that investigated the effects of  pravastatin , a  cholesterol-lowering drug , on  primary prevention  of  coronary heart disease  (CHD) in men with  hypercholesterolemia . Conducted in the early 1990s, this study provided critical evidence on the benefits of statins in reducing cardiovascular events in individuals without a history of CHD. It concluded that statin treatment reduced CHD events by 31% after nearly five years of treatment. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2375", "text": "Cardiovascular disease, particularly CHD, is a leading cause of death globally. High  low-density lipoprotein  (LDL) cholesterol levels are a well-established risk factor for developing CHD. While previous studies [ 3 ] [ 4 ] [ 5 ]  had demonstrated the benefits of lipid-lowering agents in patients with existing CHD, the WOSCOPS was one of the first large-scale trials to evaluate the efficacy of statins for primary prevention in individuals without a prior history of cardiovascular events. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2376", "text": "WOSCOPS was a multicenter, randomized, double-blind, placebo-controlled trial conducted in Scotland. The study enrolled 6,595 men aged 45 to 64 years (average 55 years) with elevated total cholesterol levels (average 272 mg/dl) and LDL cholesterol levels (average 192 mg/dL) and no previous history of myocardial infarction. The enrollment period was from February 1989 through September 1991. Participants were randomly assigned to receive either pravastatin (40 mg daily) or a placebo. The primary endpoint was the incidence of nonfatal myocardial infarction and death from CHD. Secondary endpoints included all-cause mortality, coronary revascularization procedures, and stroke. The patients were followed an average of 4.9 years after enrollment. Patient medical records and the national death registry were used to determine clinical results. [ 2 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2377", "text": "The results of the WOSCOPS, published in 1995, [ 2 ]  demonstrated several significant benefits of pravastatin therapy for the primary prevention of CHD:"}
{"_id": "WikiPedia_Cardio$$$corpus_2378", "text": "The findings of the WOSCOPS had substantial implications for the prevention of CHD. This trial added to the evidence that the incidence of CHD can be reduced with statin therapy. [ 7 ]  Long-term follow-up demonstrated a sustained reduction in death and coronary events. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2379", "text": "The WOSCOPS was a pivotal trial that contributed to the broader acceptance and use of statins in the primary prevention of cardiovascular disease. Its findings have been corroborated by subsequent studies and meta-analyses, reinforcing the role of statins in reducing the risk of CHD in various populations. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2380", "text": "Windkessel effect  (German: Windkesseleffekt) is a term used in  medicine  to account for the shape of the  arterial blood pressure  waveform in terms of the interaction between the  stroke volume  and the  compliance  of the aorta and large  elastic arteries  (Windkessel vessels) and the  resistance  of the smaller arteries and  arterioles .  Windkessel when loosely translated from  German  to English means 'air chamber', [ 1 ] [ 2 ]  but is generally taken to imply an  elastic reservoir . [ 3 ]  The walls of large elastic arteries (e.g.  aorta ,  common carotid ,  subclavian , and  pulmonary arteries  and their larger branches) contain elastic fibers, formed of  elastin .  These arteries distend when the  blood pressure  rises during  systole  and recoil when the blood pressure falls during  diastole .  Since the rate of blood entering these elastic arteries exceeds that leaving them via the  peripheral resistance , there is a net storage of blood in the aorta and large arteries during systole, which discharges during diastole. The compliance (or  distensibility ) of the aorta and large elastic arteries is therefore analogous to a  capacitor  (employing the  hydraulic analogy ); to put it another way, these arteries collectively act as a  hydraulic accumulator ."}
{"_id": "WikiPedia_Cardio$$$corpus_2381", "text": "The Windkessel effect helps in  damping  the fluctuation in  blood pressure  ( pulse pressure ) over the  cardiac cycle  and assists in the maintenance of organ  perfusion  during diastole when cardiac ejection ceases. The idea of the Windkessel was alluded to by  Giovanni Borelli , although  Stephen Hales  articulated the concept more clearly and drew the analogy with an air chamber used in  fire engines  in the 18th century. [ 4 ]   Otto Frank , an influential German physiologist, developed the concept and provided a firm mathematical foundation. [ 2 ]  Frank's model is sometimes called a two-element Windkessel to distinguish it from more recent and more elaborate Windkessel models (e.g. three- or four-element and non-linear Windkessel models). [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2382", "text": "Windkessel physiology remains a relevant yet dated description of important clinical interest. The historic mathematical definition of systole and diastole in the model are obviously not novel but are here elementally staged to four degrees. Reaching five would be original work. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2383", "text": "It is assumed that the ratio of pressure to volume is constant and that outflow from the Windkessel is proportional to the fluid pressure. Volumetric inflow must equal the sum of the volume stored in the capacitive element and volumetric outflow through the resistive element. This relationship is described by a  differential equation : [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2384", "text": "I \n ( \n t \n ) \n = \n \n \n \n P \n ( \n t \n ) \n \n R \n \n \n + \n C \n \n \n \n d \n P \n ( \n t \n ) \n \n \n d \n t \n \n \n \n \n \n {\\displaystyle I(t)={P(t) \\over R}+C{dP(t) \\over dt}}"}
{"_id": "WikiPedia_Cardio$$$corpus_2385", "text": "I(t)  is volumetric inflow due to the pump (heart) and is measured in volume per unit time, while  P(t)  is the pressure with respect to time measured in force per unit area,  C  is the ratio of volume to pressure for the Windkessel, and  R  is the resistance relating outflow to fluid pressure. This model is identical to the relationship between current,  I(t) , and  electrical potential ,  P(t) , in an electrical circuit equivalent of the two-element Windkessel model. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2386", "text": "In the blood circulation, the passive elements in the circuit are assumed to represent elements in the  cardiovascular system . The resistor,  R , represents the total peripheral resistance and the capacitor,  C , represents total arterial compliance. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2387", "text": "During  diastole  there is no blood inflow since the aortic (or pulmonary valve) is closed, so the Windkessel can be solved for  P(t)  since  I(t) = 0:"}
{"_id": "WikiPedia_Cardio$$$corpus_2388", "text": "P \n ( \n t \n ) \n = \n P \n ( \n \n t \n \n d \n \n \n ) \n \n e \n \n \n \n \u2212 \n ( \n t \n \u2212 \n \n t \n \n d \n \n \n ) \n \n \n ( \n R \n C \n ) \n \n \n \n \n \n \n {\\displaystyle P(t)=P(t_{d})e^{-(t-t_{d}) \\over (RC)}}"}
{"_id": "WikiPedia_Cardio$$$corpus_2389", "text": "where  t d  is the time of the start of  diastole  and  P(t d )  is the blood pressure at the start of diastole. This model is only a rough approximation of the arterial circulation; more realistic models incorporate more elements, provide more realistic estimates of the blood pressure waveform and are discussed below."}
{"_id": "WikiPedia_Cardio$$$corpus_2390", "text": "The three-element Windkessel improves on the two-element model by incorporating another resistive element to simulate resistance to blood flow due to the characteristic resistance of the aorta (or pulmonary artery). The  differential equation  for the 3-element model is: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2391", "text": "( \n 1 \n + \n \n \n \n R \n \n 1 \n \n \n \n R \n \n 2 \n \n \n \n \n ) \n I \n ( \n t \n ) \n + \n C \n \n R \n \n 1 \n \n \n \n \n \n d \n I \n ( \n t \n ) \n \n \n d \n t \n \n \n \n = \n \n \n \n P \n ( \n t \n ) \n \n \n R \n \n 2 \n \n \n \n \n + \n C \n \n \n \n d \n P \n ( \n t \n ) \n \n \n d \n t \n \n \n \n \n \n {\\displaystyle (1+{R_{1} \\over R_{2}})I(t)+CR_{1}{dI(t) \\over dt}={P(t) \\over R_{2}}+C{dP(t) \\over dt}}"}
{"_id": "WikiPedia_Cardio$$$corpus_2392", "text": "where  R 1  is the characteristic resistance (this is assumed to be equivalent to the characteristic impedance), [ 7 ]  while  R 2  represents the peripheral resistance. This model is widely used as an acceptable model of the circulation. [ 5 ]  For example it has been employed to evaluate blood pressure and flow in the aorta of a chick embryo  [ 8 ]  and the pulmonary artery in a pig [ 8 ]  as well as providing the basis for construction of physical models of the circulation providing realistic loads for experimental studies of isolated hearts. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2393", "text": "The three-element model overestimates the compliance and underestimates the characteristic impedance of the circulation. [ 7 ]   The four-element model includes an  inductor ,  L , which has units of mass per length, ( \n \n \n \n \n \n M \n \n l \n \n 4 \n \n \n \n \n \n \n {\\displaystyle {M \\over l^{4}}} \n \n ), into the proximal component of the circuit to account for the  inertia  of blood flow. This  is neglected in the two- and three- element models. The relevant  equation is:"}
{"_id": "WikiPedia_Cardio$$$corpus_2394", "text": "( \n 1 \n + \n \n \n \n R \n \n 1 \n \n \n \n R \n \n 2 \n \n \n \n \n ) \n I \n ( \n t \n ) \n + \n ( \n \n R \n \n 1 \n \n \n C \n + \n \n \n L \n \n R \n \n 2 \n \n \n \n \n ) \n \n \n \n d \n I \n ( \n t \n ) \n \n \n d \n t \n \n \n \n + \n L \n C \n \n \n \n \n d \n \n 2 \n \n \n I \n ( \n t \n ) \n \n \n d \n \n t \n \n 2 \n \n \n \n \n \n = \n \n \n \n P \n ( \n t \n ) \n \n \n R \n \n 2 \n \n \n \n \n + \n C \n \n \n \n d \n P \n ( \n t \n ) \n \n \n d \n t \n \n \n \n \n \n {\\displaystyle (1+{R_{1} \\over R_{2}})I(t)+(R_{1}C+{L \\over R_{2}}){dI(t) \\over dt}+LC{d^{2}I(t) \\over dt^{2}}={P(t) \\over R_{2}}+C{dP(t) \\over dt}}"}
{"_id": "WikiPedia_Cardio$$$corpus_2395", "text": "These models relate blood flow to blood pressure through parameters of  R, C ( and, in the case of the four-element model,  L) . These equations can be easily solved (e.g. by employing MATLAB and its supplement SIMULINK) to either find the values of pressure given flow and  R, C, L  parameters, or find values of  R, C, L  given flow and pressure. An example for the two-element model is shown below, where  I(t)  is depicted as an input signal during systole and diastole. Systole is represented by the  sin  function, while flow during diastole is zero.  s  represents the duration of the cardiac cycle, while  Ts  represents the duration of systole, and  Td  represents the duration of diastole (e.g. in seconds). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2396", "text": "I \n ( \n t \n ) \n = \n \n I \n \n o \n \n \n sin \n \u2061 \n [ \n \n \n \n ( \n \u03c0 \n \u2217 \n \n \n t \n s \n \n \n ) \n \n \n T \n s \n \n \n \n ] \n \n \u00a0for\u00a0 \n \n \n \n t \n s \n \n \n \u2264 \n T \n s \n \n \n {\\displaystyle I(t)=I_{o}\\sin[{(\\pi *{t \\over s}) \\over Ts}]{\\text{ for }}{t \\over s}\\leq Ts}"}
{"_id": "WikiPedia_Cardio$$$corpus_2397", "text": "I \n ( \n t \n ) \n = \n 0 \n \n \u00a0for\u00a0 \n \n T \n s \n < \n ( \n T \n d \n + \n T \n s \n ) \n \n \n {\\displaystyle I(t)=0{\\text{ for }}Ts<(Td+Ts)}"}
{"_id": "WikiPedia_Cardio$$$corpus_2398", "text": "The 'Windkessel effect' becomes diminished with age as the elastic arteries become less compliant, termed  hardening of the arteries  or  arteriosclerosis , probably secondary to fragmentation and loss of elastin. [ 10 ]  The reduction in the Windkessel effect results in increased  pulse pressure  for a given  stroke volume .  The increased pulse pressure results in elevated systolic pressure ( hypertension ) which increases the risk of  myocardial infarction ,  stroke ,  heart failure  and a variety of other cardiovascular diseases. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2399", "text": "Although the Windkessel is a simple and convenient concept, it has been largely superseded by more modern approaches that interpret arterial pressure and flow waveforms in terms of wave propagation and reflection. [ 12 ]  Recent attempts to integrate wave propagation and Windkessel approaches through a reservoir concept, [ 13 ]  have been criticized [ 14 ] [ 15 ]  and a recent consensus document highlighted the wave-like nature of the reservoir. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2400", "text": "Wireless ambulatory electrocardiography (ECG)  is a type of ambulatory  electrocardiography  with recording devices that use wireless technology, such as Bluetooth and smartphones, for at-home  cardiac monitoring  (monitoring of heart rhythms). These devices are generally recommended to people who have been previously diagnosed with  arrhythmias  and want to have them monitored, or for those who have suspected arrhythmias and need to be monitored over an extended period of time in order to be diagnosed. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2401", "text": "Wireless ambulatory ECGs work in a way similar to a regular ECG by measuring the electrical potential of the heart through the skin.  The data is saved on an application on a smartphone, and then uploaded to a computer through Bluetooth or  cloud technologies .  The information can also be sent through these technologies or through email to a doctor or cardiac technician. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2402", "text": "Wireless ambulatory ECGs are able to provide voice alarm messages when cardiac abnormalities occur, such as  bradycardia , and can record this information and provide a screen prompt for the patient to view the data.  The devices can also store mass amounts of ECG data on the phone, replay the ECG readings at a high speed, and have a low-voltage alarm function to not waste the battery life.  These characteristics of the devices are seen as benefits in comparison to current ambulatory ECG monitoring equipment such as the  Holter monitor . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2403", "text": "1. CardioSecur ACTIVE is a smartphone based 15-lead mobile ECG for patients. While conventional ECG systems use ten electrodes to depict twelve standard leads, CardioSecur requires only four electrodes. CardioSecur's four-electrode technology has been clinically validated and is an alternative to ten electrode systems. [ 4 ] \nIt provides an instant and personalized evaluation of ECG recordings and offers patients an immediate recommendation to act according to the applicable guidelines of professional cardiological associations. CardioSecur ACTIVE allows cardiovascular patients to gain more certainty about their cardiac activity. Additionally, it enables physicians to diagnose heart diseases faster as treating physicians can access their patients' ECG recordings through a secure database to which the recordings are automatically uploaded. Furthermore, the ECGs can be easily shared via  iMessage , email,  AirDrop  or  AirPrint . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2404", "text": "2.  Alivecor  heart monitors are currently available in the United States, the UK, and Ireland.  The device is a small handheld single-channel ECG recording device that immediately sends information to a smartphone. Recordings can then be sent to a cardiac technician or a certified cardiologist for a small cost. [ 6 ]   AliveCor obtains ECG traces through sensing plates, which can also be purchased through AliveCor. [ 7 ]   The plates are placed on fingers or the chest and the scan takes 30 seconds to complete. [ 8 ]   One of the benefits of AliveCor is the ability to record notes of how the patient was feeling prior to taking the ECG so that the physician has a clear picture of what the patterns indicate. [ 9 ]   Studies on the algorithm used in the technology have indicated that the device provides sufficiently accurate data to be able to diagnose atrial fibrillations. [ 10 ]   The accuracy has been found to be similar to Lead 1 data of a regular 12-lead ECG. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2405", "text": "3. iHealth created a wireless ECG monitor that is placed on the chest under clothing, and the data are sent to mobile phones and is readily available for healthcare professionals. [ 12 ]   The device is small and lightweight, making it easy to participate in daily activities.  It uses Bluetooth technology to send the information to cell phones, but it can also be connected to a computer via USB cable. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2406", "text": "4.  Qardio  created a wearable ECG monitor that wirelessly sends data to the smartphone for the user and health practitioners. The device can be worn every day to track heart health in real life. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2407", "text": "5.  Beurer  produces a single-channel ECG monitor without dedicated electrodes that transmits data via Bluetooth to a smartphone. It is very small and easy to carry around, but is not designed to continuously measure data. The device returns a preliminary analysis of the ECG recording, and detailed data can be later on shown to a physician. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2408", "text": "6. Lithuanian company  ZIVE , created a single-channel ECG monitor (3 channel optional), that transmits data to  iOS or Android phone. Live ECG and full ECG analysis options are available. Device is Class II CE EU certified.  [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2409", "text": "World Hypertension Day  ( WHD ) is a day designated and initiated by  The World Hypertension League  (WHL), which is itself an umbrella to organizations of 85 national hypertension societies and leagues. The day was initiated to increase the awareness of  hypertension . This was especially important because of the lack of appropriate knowledge among hypertensive patients. [ 1 ]   The WHL launched its first WHD on May 14, 2005. Since 2006, the WHL has been dedicating May 17 of every year as WHD. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2410", "text": "In 2005, as the inaugural effort, the theme was simply \"Awareness of  high blood pressure \". [ 3 ]  The 2006 theme was \"Treat to goal\", with a focus on keeping blood pressure under control. [ 1 ]  The recommended blood pressures are less than 140/90 mmHg for the general population and for the hypertensive population without any other complications, and less than 130/80 mmHg for those with  diabetes mellitus  or  chronic kidney disease . These are the cut-off values recommended by international and Canadian guidelines. [ 4 ] [ 5 ]  The 2007 WHD theme was \" Healthy diet , healthy  blood pressure \". Through such specific themes, the WHL intends to raise awareness not only of hypertension, but also of factors contributing to an increase in the incidence of hypertension and on ways to prevent it. [ 1 ]  In an effort to empower the public, the theme for 2008 was \"Measure your blood pressure\u2026at home\". Recent reports confirm the ease, accuracy and safety of blood pressure measurements using home monitors. [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2411", "text": "For the five-year period 2013-2018, the theme of WHD was \"Know Your Numbers\" with the goal of increasing high blood pressure awareness in all populations around the world. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2412", "text": "Cardiac electrophysiology  is a branch of  cardiology  and  basic science  focusing on the electrical activities of the  heart . The term is usually used in clinical context, to describe studies of such phenomena by invasive (intracardiac) catheter recording of spontaneous activity as well as of cardiac responses to  programmed electrical stimulation  -  clinical cardiac electrophysiology . However, cardiac electrophysiology also encompasses  basic research  and  translational research  components. Specialists studying cardiac electrophysiology, either clinically or solely through research, are known as cardiac electrophysiologists."}
{"_id": "WikiPedia_Cardio$$$corpus_2413", "text": "Electrophysiological (EP) studies are performed to assess complex  arrhythmias , elucidate symptoms, evaluate abnormal  electrocardiograms , assess risk of developing arrhythmias in the future, and design treatment.  These procedures include therapeutic methods (typically  radiofrequency ablation , or  cryoablation ) in addition to diagnostic and prognostic procedures.  Other therapeutic modalities used in this field include  antiarrhythmic drug  therapy and implantation of  pacemakers ,  implantable cardioverter-defibrillators  and  cardiac resynchronisation therapy  devices.   [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2414", "text": "The cardiac electrophysiology (EP) study typically measures the response of myocardium to programmed electrical stimulation (PES) on specific pharmacological regimens in order to assess the likelihood that the regimen will successfully prevent potentially fatal sustained  ventricular tachycardia (VT)  or  ventricular fibrillation VF  (VF) in the future. Sometimes a  series  of EP study drug trials must be conducted to enable the cardiologist to select the one regimen for long-term treatment that best prevents or slows the development of VT or VF following PES. Such studies may also be conducted in the presence of a newly implanted or newly replaced cardiac pacemaker or ICD. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2415", "text": "A specialist in cardiac electrophysiology is known as an electrophysiologist, or \"heart electrician\" in layman' terms. Cardiac electrophysiology is a subspecialty of  cardiology  in most countries and usually requires two or more years of EP  fellowship  training after a general cardiology residency. In early 2011, the  Centers for Medicare and Medicaid Services  promoted cardiac electrophysiology to its own specialty category in the United States. Cardiac electrophysiologists are trained to perform interventional cardiac electrophysiology studies and cardiac rhythm management device implantations. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2416", "text": "Cardiac electrophysiologists specialize in a sub-area of  electrophysiology , which in turn is a sub-area of  physiology . This specialization usually requires education at the doctoral (PhD, DSc, or MD/DO) level to become a  principal investigator  for research projects. The area of research is often multi-disciplinary involving chemistry, bioelectrics, biology, and biomedical engineering. The flagship tools used by cardiac electrophysiologists overlap with the toolbox of the neuroscientist including  patch clamp  and  optical mapping . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2417", "text": "Mapping specialists (EP techs, EP physiologists) are typically educated up to the Bachelor's or Master's level and are employed by either a cardiac electrophysiology company or department. Often international certification such as Certified Electrophysiology Specialist (CEPS) by the International Board of Heart Rhythm Examiners (IBHRE) or EHRA Certified Electrophysiology Specialist (ECES) or equivalent is required."}
{"_id": "WikiPedia_Cardio$$$corpus_2418", "text": "Cardiac electrophysiology is a relatively young subdiscipline of cardiology and internal medicine. It was developed during the mid-1970s by  Hein J. J. Wellens , professor of medicine at the  University of Maastricht  in the  Netherlands  and attending cardiologist at the Academic Hospital in  Maastricht . In 1980 the first microprocessor based stimulator was developed there."}
{"_id": "WikiPedia_Cardio$$$corpus_2419", "text": "The author of the definitive textbook in the field is by the late  Mark E. Josephson , former Robinette Professor of Medicine and chief of cardiology at the  University of Pennsylvania School of Medicine  in  Philadelphia, Pennsylvania , professor of medicine at  Harvard Medical School , and attending cardiologist at  Beth Israel Deaconess Medical Center  in  Boston, Massachusetts . [ 4 ]  The most recent published edition of  Clinical Cardiac Electrophysiology: Techniques and Interpretations  is the 6th edition in 2020. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2420", "text": "The  Heart Rhythm Society , founded in 1979, promotes education and advocacy for cardiac arrhythmia professionals (including cardiac electrophysiologists) and patients. European Heart Rhythm Association, a part of  European Society of Cardiology , is active in Europe. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2421", "text": "Founded in 1985 as NASPExAM, the International Board of Heart Rhythm Examiners (IBHRE) offers knowledge based board exams for physicians and allied health professionals working in the field of cardiac electrophysiology and cardiac rhythm device management. [ 7 ]  European Heart Rhythm Association (EHRA) provides knowledge and practical competency based certification to physicians and allied health professionals [ 8 ]  as well as accreditation of cardiac electrophysiology training centres [ 9 ]  in Europe and neighbouring countries."}
{"_id": "WikiPedia_Cardio$$$corpus_2422", "text": "Electroanatomic mapping uses electric and magnetic fields to create three dimensional models of heart structures using specialized catheters."}
{"_id": "WikiPedia_Cardio$$$corpus_2423", "text": "Afterdepolarizations  are abnormal  depolarizations  of  cardiac myocytes  that interrupt phase 2, phase 3, or phase 4 of the  cardiac action potential  in the  electrical conduction system of the heart . Afterdepolarizations may lead to  cardiac arrhythmias . Afterdepolarization is commonly a consequence of  myocardial infarction ,  cardiac hypertrophy , or  heart failure . [ 1 ]  It may also result from congenital mutations associated with  calcium channels  and sequestration. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2424", "text": "Early afterdepolarizations (EADs) occur with abnormal depolarization during phase 2 or phase 3, and are caused by an increase in the frequency of abortive  action potentials  before normal repolarization is completed. [ 1 ]  EADs most commonly originate in mid- myocardial  cells and  Purkinje fibers , but can develop in other cardiac cells that carry an action potential. Phase 2 may be interrupted due to augmented opening of calcium channels, while phase 3 interruptions are due to the opening of  sodium channels . Early afterdepolarizations can result in  torsades de pointes ,  tachycardia , and other  arrhythmias . [ 3 ]  EADs can be triggered by  hypokalemia  and drugs that prolong the  QT interval , including class Ia and III  antiarrhythmic agents , as well as  catecholamines . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2425", "text": "Afterhyperpolarizations can also occur in cortical pyramidal neurons. There, they typically follow an action potential and are mediated by voltage gated sodium or chloride channels. This phenomenon requires potassium channels to close quickly to limit repolarization. It is responsible for the difference between regular spiking and intrinsically bursting pyramidal neurons. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2426", "text": "Delayed afterdepolarizations (DADs) begin during phase 4, after repolarization is completed but before another action potential would normally occur via the normal conduction systems of the heart. They are due to elevated cytosolic  calcium  concentrations, classically seen with  digoxin  toxicity. [ 5 ] [ 6 ]  The overload of the sarcoplasmic reticulum may cause spontaneous Ca 2+  release after repolarization, causing the released Ca 2+  to exit the cell through the 3Na + /Ca 2+ -exchanger. This results in a net depolarizing current. The classical feature is Bidirectional  ventricular tachycardia . Also seen in  catecholaminergic polymorphic ventricular tachycardia  (CPVT). Delayed afterdepolarization is also seen in myocardial infarction. Purkinje fibers which survive myocardial infarction remain partially depolarized due to its high concentration of cations. [ 7 ]  Partially depolarized tissue fires rapidly resulting in delayed after depolarization. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2427", "text": "Antiarrhythmic agents , also known as  cardiac dysrhythmia medications , are a class of  drugs  that are used to suppress abnormally fast rhythms ( tachycardias ), such as  atrial fibrillation ,  supraventricular tachycardia  and  ventricular tachycardia ."}
{"_id": "WikiPedia_Cardio$$$corpus_2428", "text": "Many attempts have been made to classify antiarrhythmic agents. Many of the antiarrhythmic agents have multiple modes of action, which makes any classification imprecise."}
{"_id": "WikiPedia_Cardio$$$corpus_2429", "text": "The cardiac myocyte has two general types of action potentials: conduction system and working myocardium. The action potential is divided into 5 phases and shown in the diagram. The sharp rise in voltage (\"0\") corresponds to the influx of sodium ions, whereas the two decays (\"1\" and \"3\", respectively) correspond to the sodium-channel inactivation and the repolarizing efflux of potassium ions. The characteristic plateau (\"2\") results from the opening of voltage-sensitive  calcium channels . Each phase utilizes different channels and it is useful to compare these phases to the most common classification system \u2014 Vaughan Williams \u2014 described below."}
{"_id": "WikiPedia_Cardio$$$corpus_2430", "text": "The  Vaughan Williams classification [ 1 ]  was introduced in 1970 by  Miles Vaughan Williams . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2431", "text": "Vaughan Williams was a pharmacology tutor at  Hertford College , Oxford. One of his students,  Bramah N. Singh , [ 3 ]  contributed to the development of the classification system. The system is therefore sometimes known as the  Singh-Vaughan Williams classification ."}
{"_id": "WikiPedia_Cardio$$$corpus_2432", "text": "The five main classes in the Vaughan Williams classification of antiarrhythmic agents are:"}
{"_id": "WikiPedia_Cardio$$$corpus_2433", "text": "With regard to management of atrial fibrillation, classes I and III are used in rhythm control as medical cardioversion agents, while classes II and IV are used as rate-control agents."}
{"_id": "WikiPedia_Cardio$$$corpus_2434", "text": "Class Ia drugs prolong the action potential and has an intermediate effect on the 0 phase of depolarization."}
{"_id": "WikiPedia_Cardio$$$corpus_2435", "text": "Class Ib drugs shorten the action potential of myocardial cell and has a weak effect on the initiation of phase 0 of depolarization"}
{"_id": "WikiPedia_Cardio$$$corpus_2436", "text": "Class Ic drugs do not affect action potential duration and have the strongest effect on the initiation phase 0 of depolarization"}
{"_id": "WikiPedia_Cardio$$$corpus_2437", "text": "Sotalol  is also a  beta blocker [ 5 ] \n Amiodarone  has mostly Class III activity, but also I, II, & IV activity [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2438", "text": "The class I antiarrhythmic agents  interfere with the sodium channel .\nClass I agents are grouped by what effect they have on the Na +  channel, and what effect they have on cardiac  action potentials ."}
{"_id": "WikiPedia_Cardio$$$corpus_2439", "text": "Class I agents are called membrane-stabilizing agents, \"stabilizing\" referring to the decrease of excitogenicity of the plasma membrane which is brought about by these agents. (Also noteworthy is that a few class II agents like propranolol also have a  membrane stabilizing effect .)"}
{"_id": "WikiPedia_Cardio$$$corpus_2440", "text": "Class I agents are divided into three groups (Ia, Ib, and Ic) based upon their effect on the length of the action potential. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2441", "text": "Class II agents are conventional  beta blockers . They act by blocking the effects of  catecholamines  at the  \u03b2 1 -adrenergic receptors , thereby decreasing sympathetic activity on the heart, which reduces intracellular cAMP levels and hence reduces Ca 2+  influx. These agents are particularly useful in the treatment of  supraventricular tachycardias . They decrease conduction through the  AV node ."}
{"_id": "WikiPedia_Cardio$$$corpus_2442", "text": "Class II agents include  atenolol ,  esmolol ,  propranolol , and  metoprolol ."}
{"_id": "WikiPedia_Cardio$$$corpus_2443", "text": "Class III agents predominantly  block the potassium channels , thereby prolonging repolarization. [ 12 ]  Since these agents do not affect the sodium channel, conduction velocity is not decreased. The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias. (The re-entrant rhythm is less likely to interact with tissue that has become refractory). The class III agents exhibit reverse-use dependence (their potency increases with slower heart rates, and therefore improves maintenance of sinus rhythm). Inhibiting potassium channels results in slowed atrial-ventricular myocyte repolarization. Class III agents have the potential to prolong the QT interval of the EKG, and may be proarrhythmic (more associated with development of polymorphic VT)."}
{"_id": "WikiPedia_Cardio$$$corpus_2444", "text": "Class III agents include:  bretylium ,  amiodarone ,  ibutilide ,  sotalol ,  dofetilide ,  vernakalant , and  dronedarone ."}
{"_id": "WikiPedia_Cardio$$$corpus_2445", "text": "Class IV agents are slow  non-dihydropyridine   calcium channel blockers . They decrease conduction through the  AV node , and shorten phase two (the plateau) of the  cardiac action potential . They thus reduce the contractility of the heart, so may be inappropriate in heart failure. However, in contrast to beta blockers, they allow the body to retain adrenergic control of heart rate and contractility. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2446", "text": "Class IV agents include  verapamil  and  diltiazem ."}
{"_id": "WikiPedia_Cardio$$$corpus_2447", "text": "Since the development of the original Vaughan Williams classification system, additional agents have been used that do not fit cleanly into categories I through IV. Such agents include:"}
{"_id": "WikiPedia_Cardio$$$corpus_2448", "text": "The initial classification system had 4 classes, although their definitions different from the modern classification. Those proposed in 1970 were: [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2449", "text": "Another approach, known as the \"Sicilian gambit\", placed a greater approach on the underlying mechanism. [ 20 ] [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2450", "text": "It presents the drugs on two axes, instead of one, and is presented in tabular form. On the Y axis, each drug is listed, in roughly the Singh-Vaughan Williams order. On the X axis, the channels, receptors, pumps, and clinical effects are listed for each drug, with the results listed in a grid. It is, therefore, not a true classification in that it does not aggregate drugs into categories. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2451", "text": "A recent publication (2018) has now emerged with a fully modernised drug classification. [ 24 ]  This preserves the simplicity of the original Vaughan Williams framework while capturing subsequent discoveries of sarcolemmal, sarcoplasmic reticular and cytosolic biomolecules. The result is an expanded but pragmatic classification that encompasses approved and potential anti-arrhythmic drugs. This will aid our understanding and clinical management of cardiac arrhythmias and facilitate future therapeutic developments. It starts by considering the range of pharmacological targets, and tracks these to their particular cellular electrophysiological effects. It retains but expands the original Vaughan Williams classes I to IV, respectively covering actions on Na+ current components, autonomic signalling, K +  channel subspecies, and molecular targets related to Ca 2+  homeostasis. It now introduces new classes incorporating additional targets, including:"}
{"_id": "WikiPedia_Cardio$$$corpus_2452", "text": "It also allows for multiple drug targets/actions and adverse pro-arrhythmic effects. The new scheme will additionally aid development of novel drugs under development and is illustrated here."}
{"_id": "WikiPedia_Cardio$$$corpus_2453", "text": "Asian Heart Institute  is a  cardiology  and  cardiac surgery  hospital in  Mumbai , India, which was founded in 2002 by  Ramakanta Panda . Over the last two decades, Asian Heart Institute has treated more than 450,000 patients."}
{"_id": "WikiPedia_Cardio$$$corpus_2454", "text": "Some of the cases operated at the Asian Heart Institute, led by a team of doctors under the leadership of Dr.  Ramakanta Panda , include:"}
{"_id": "WikiPedia_Cardio$$$corpus_2455", "text": "The hospital added a sports medicine facility in 2007 as a number of hospitals across the country expanded their services in that practice area prior to the  2010 Commonwealth Games . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2456", "text": "As of July 2012, it was one of the two private hospitals in  Mumbai ,  India  to participate in a government insurance scheme to provide coverage for the poor. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2457", "text": "In April 2013, through its Pediatric Cardiac Center, AHI committed to providing free heart surgery for  impoverished children  who have congenital heart disease. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2458", "text": "\"Medgate Today\" honoured Dr. Ramakanta Panda, the Chief Consultant Cardiovascular Thoracic Surgery and the Vice Chairman and managing director of Asian Heart Institute, as the No1 cardiac surgeon and one of the 25 living legends in the Healthcare of India. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2459", "text": "Asian Heart Institute is also the health partner of the Mumbai Marathon. [ 15 ]  AHI has been the Official Medical Partner for this event since its inception in 2004 and maintains First Aid stations and provides emergency medical services all along the 42-kilometer route. A contingent of AHI patients always runs in the marathon, each one having undergone a bypass surgery at AHI. [ 16 ]  Many complete the entire marathon. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2460", "text": "In  electrocardiography , the  atrial action potential  are  action potentials  that occur in the  heart atrium . They are similar to  ventricular action potential  with the exception of having a more narrow phase 2 (plateau phase) due to a smaller calcium influx. Also, in comparison to the ventricular action potential, atrial action potentials have a more gradual  repolarization  period. This indicates that the atria's repolarization currents are not very large and they do not undergo a large repolarization peak. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2461", "text": "Cardiac action potential"}
{"_id": "WikiPedia_Cardio$$$corpus_2462", "text": "This  muscle  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_2463", "text": "An  automated external defibrillator or automatic electronic defibrillator  ( AED )  is a portable electronic device that automatically diagnoses the life-threatening  cardiac   arrhythmias  of  ventricular fibrillation  (VF) and  pulseless ventricular tachycardia , [ 1 ]  and is able to treat them through  defibrillation , the application of electricity which stops the arrhythmia, allowing the heart to re-establish an effective rhythm."}
{"_id": "WikiPedia_Cardio$$$corpus_2464", "text": "With simple audio and visual commands, AEDs are designed to be simple to use for the layperson, and the use of AEDs is taught in many  first aid ,  certified first responder , and  basic life support  (BLS) level  cardiopulmonary resuscitation  (CPR) classes. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2465", "text": "The portable version of the defibrillator was invented in the mid-1960s by  Frank Pantridge  in  Belfast ,  Northern Ireland  and the first automatic, public-use defibrillator was produced by the Cardiac Resuscitation Company in the late 1970s. The unit was launched under the name Heart-Aid. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2466", "text": "An automated external  defibrillator  is used in cases of life-threatening cardiac  arrhythmias  which lead to sudden  cardiac arrest , which is not the same as a heart attack. The rhythms that the device will treat are usually limited to:"}
{"_id": "WikiPedia_Cardio$$$corpus_2467", "text": "In each of these two types of shockable  cardiac arrhythmia , the heart is electrically active, but in a dysfunctional pattern that does not allow it to pump and circulate blood. In ventricular tachycardia, the heart beats too fast to effectively pump blood. Ultimately, ventricular tachycardia leads to ventricular fibrillation. In ventricular fibrillation, the electrical activity of the heart becomes chaotic, preventing the  ventricle  from effectively pumping blood. The fibrillation in the heart decreases over time, and will eventually reach  asystole ."}
{"_id": "WikiPedia_Cardio$$$corpus_2468", "text": "AEDs, like all defibrillators, are not designed to shock asystole ('flat line' patterns) as this will not have a positive clinical outcome. The asystolic patient only has a chance of survival if, through a combination of CPR and  cardiac stimulant  drugs, one of the shockable rhythms can be established, which makes it imperative for CPR to be carried out prior to the arrival of a defibrillator."}
{"_id": "WikiPedia_Cardio$$$corpus_2469", "text": "Uncorrected, these cardiac conditions (ventricular tachycardia, ventricular fibrillation, asystole) rapidly lead to irreversible  brain damage  and death, once cardiac arrest takes place. After approximately three to five minutes in cardiac arrest, [ 4 ]  irreversible brain/tissue damage may begin to occur. For every minute that a person in cardiac arrest goes without being successfully treated (by defibrillation), the chance of survival decreases by 7 percent per minute in the first three minutes, and decreases by 10 percent per minute as time advances beyond ~three minutes. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2470", "text": "AEDs are designed to be used by laypersons who ideally should have received AED training. However, sixth-grade students have been reported to begin defibrillation within 90 seconds, as opposed to a trained operator beginning within 67 seconds. [ 6 ]  This is in contrast to more sophisticated manual and semi-automatic defibrillators used by health professionals, which can act as a  pacemaker  if the heart rate is too slow ( bradycardia ) and perform other functions which require a skilled operator able to read  electrocardiograms ."}
{"_id": "WikiPedia_Cardio$$$corpus_2471", "text": "Bras with a metal  underwire  and piercings on the torso must be removed before using the AED on someone to avoid interference. [ 7 ] [ 8 ]  The American television show  MythBusters  found evidence that use of a defibrillator on a woman wearing an underwire bra can lead to arcing or fire but only in unusual and unlikely circumstances. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2472", "text": "In a study analyzing the effects of having AEDs immediately present during Chicago's Heart Start program over a two-year period, of 22 individuals, 18 were in a cardiac arrhythmia which AEDs can treat. Of these 18, 11 survived. Of these 11 patients, 6 were treated by bystanders with absolutely no previous training in AED use. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2473", "text": "Automated external defibrillators are generally either kept where health professionals and first responders can use them (health facilities and ambulances) as well as public access units which can be found in public places including corporate and government offices, shopping centres, restaurants, public transport, and any other location where people may congregate."}
{"_id": "WikiPedia_Cardio$$$corpus_2474", "text": "In order to make them highly visible, public access AEDs are often brightly coloured and are mounted in protective cases near the entrance of a building. When these protective cases are opened or the defibrillator is removed, some will sound a buzzer to alert nearby staff to their removal, though this does not necessarily summon emergency services; trained AED operators should know to phone for an ambulance when sending for or using an AED.  In September 2008, the  International Liaison Committee on Resuscitation  issued a 'universal AED sign' to be adopted throughout the world to indicate the presence of an AED, and this is shown on the right. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2475", "text": "A trend that is developing is the purchase of AEDs to be used in the home, particularly by those with known existing heart conditions. [ 13 ]  The number of devices in the community has grown as prices have fallen to affordable levels. There has been some concern among medical professionals that these home users do not necessarily have appropriate training, [ 14 ]  and many advocate the more widespread use of community responders, who can be appropriately trained and managed."}
{"_id": "WikiPedia_Cardio$$$corpus_2476", "text": "Typically, an AED kit will contain a  face shield  for providing a barrier between patient and first aider during rescue breathing; a pair of  nitrile rubber  gloves; a pair of  trauma shears  for cutting through a patient's clothing to expose the chest; a small towel for wiping away any moisture on the chest, and a razor for shaving those with very hairy chests. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2477", "text": "Most manufacturers recommend checking the AED before every period of duty or on a regular basis for fixed units. Some units need to be switched on in order to perform a self check; other models have a self check system built in with a visible indicator."}
{"_id": "WikiPedia_Cardio$$$corpus_2478", "text": "All manufacturers mark their electrode pads with an expiration date, and it is important to ensure that the pads are in date. The typical life expectancy of AED pads are between 18 and 30 months. [ 16 ]  This is usually marked on the outside of the pads. Some models are designed to make this date visible through a 'window', although others will require the opening of the case to find the date stamp. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2479", "text": "It is also important to ensure that the AED unit's batteries have not expired.  The AED manufacturer will specify how often the batteries should be replaced. Each AED has a different recommended maintenance schedule outlined in the user manual. Common checkpoints on every checklist, however, also include a monthly check of the battery power by checking the green indicator light when powered on, condition and cleanliness of all cables and the unit, and check for the adequate supplies. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2480", "text": "An AED is \"automatic\" because of the unit's ability to autonomously analyse the patient's condition. To assist this, the vast majority of units have spoken prompts, and some may also have visual displays to instruct the user."}
{"_id": "WikiPedia_Cardio$$$corpus_2481", "text": "\"External\" refers to the fact that the operator applies the electrode pads to the bare  chest  of the victim (as opposed to  internal defibrillators , which have  electrodes  surgically implanted inside the body of a patient)."}
{"_id": "WikiPedia_Cardio$$$corpus_2482", "text": "When turned on or opened, the AED will instruct the user to connect the electrodes (pads) to the patient. Once the pads are attached, everyone should avoid touching the patient so as to avoid false readings by the unit. The pads allow the AED to examine the electrical output from the heart and determine if the patient is in a shockable rhythm (either ventricular fibrillation or ventricular tachycardia). If the device determines that a shock is warranted, it will use the battery to charge its internal  capacitor  in preparation to deliver the shock. The device system is not only safer - charging only when required, but also allows for a faster delivery of the electric current."}
{"_id": "WikiPedia_Cardio$$$corpus_2483", "text": "When charged, the device instructs the user to ensure no one is touching the patient and then to press a button to deliver the shock; human intervention is usually required to deliver the shock to the patient in order to avoid the possibility of accidental injury to another person (which can result from a responder or bystander touching the patient at the time of the shock). Depending on the manufacturer and particular model, after the shock is delivered most devices will analyze the patient and either instruct CPR to be performed, or prepare to administer another shock."}
{"_id": "WikiPedia_Cardio$$$corpus_2484", "text": "Many AED units have an 'event memory' which store the ECG of the patient along with details of the time the unit was activated and the number and strength of any shocks delivered. Some units also have voice recording abilities [ 18 ]  to monitor the actions taken by the personnel in order to ascertain if these had any impact on the survival outcome. All this recorded data can be either downloaded to a computer or printed out so that the providing organisation or responsible body is able to see the effectiveness of both CPR and defibrillation. Some AED units even provide feedback on the quality of the compressions provided by the rescuer. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2485", "text": "The first commercially available AEDs were all of a monophasic type, which gave a high-energy shock, up to 360 to 400  joules  depending on the model. This caused increased cardiac injury and in some cases second and third-degree burns around the shock pad sites.  Newer AEDs (manufactured after late 2003) have tended to utilise biphasic algorithms which give two sequential lower-energy shocks of 120\u2013200 joules, with each shock moving in an opposite polarity between the pads.  Others may give a stepped approach to energy delivery, usually in a 200J, a second 200J, then 300J, and finally 360J shock, with any further shocks also being 360 Joules. This lower-energy waveform has proven more effective in clinical tests, as well as offering a reduced rate of complications and reduced recovery time. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2486", "text": "Unlike regular  defibrillators , an automated external defibrillator (AED) requires minimal training to be used (or even no training). That is possible because all AEDs approved for use in the  United States  and many other countries use an electronic voice to prompt users through each step. Many AEDs now include visual prompts in case of a  hearing impaired  user. Most units are designed for use by non-medical operators. Their ease of use has given rise to the notion of public access defibrillation (PAD)."}
{"_id": "WikiPedia_Cardio$$$corpus_2487", "text": "An AED automatically diagnoses the heart rhythm and determines if a shock is needed. Automatic models will administer the shock without the user's command. Semi-automatic models will tell the user that a shock is needed, but the user must tell the machine to do so, usually by pressing a button. In most circumstances, the user cannot override a \"no shock\" advisory by an AED. Some AEDs may be used on children \u2013 those under 55\u00a0lbs (25\u00a0kg) in weight or under age 8. If a particular model of AED is approved for pediatric use,  all that is required is the use of more appropriate pads [ failed verification ] . [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2488", "text": "Observational studies have shown that in out of hospital cardiac arrest, public access defibrillators when used were associated with 40% median survival. When operated by non-dispatched lay first responders they have the highest likelihood of leading to survival. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2489", "text": "Automated external defibrillators are now easy enough to use that most states in the United States include the \"good faith\" use of an AED by any person under  Good Samaritan laws . [ 24 ]  \"Good faith\" protection under a Good Samaritan law means that a volunteer responder (not acting as a part of one's occupation) cannot be held civilly liable for the harm or death of a victim by providing improper or inadequate care, given that the harm or death was not intentional and the responder was acting within the limits of their training and in good faith. In the United States, Good Samaritan laws provide some protection for the use of AEDs by trained and untrained responders. [ 25 ]  AEDs create little liability if used correctly; [ 26 ]  NREMT-B and many state  Emergency Medical Technician  (EMT) training and many CPR classes incorporate or offer AED education as a part of their program."}
{"_id": "WikiPedia_Cardio$$$corpus_2490", "text": "In addition to Good Samaritan laws, Ontario, Canada also has the \" Chase McEachern  Act (Heart Defibrillator Civil Liability), 2007 (Bill 171 \u2013 Subsection N)\", passed in June, 2007, [ 27 ]  which protects individuals from liability for damages that may occur from their use of an AED to save someone's life at the immediate scene of an emergency unless damages are caused by gross negligence."}
{"_id": "WikiPedia_Cardio$$$corpus_2491", "text": "Legislation in Australia varies by state, with separate liability issues relating to providing and using AED equipment.  \nEach state and territory has enacted \"Good Samaritan\" laws that offer legal protection to a person who gives assistance in a medical emergency - the standard of care expected corresponds to their training (or lack of training). [ 28 ] \nIn New South Wales, the Work Health and Safety Regulation (2011) requires an employer to use a risk assessment to ensure that there is adequate provision for first aid; when there is a sufficient risk it warrants providing a defibrillator. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2492", "text": "In 2012, AED's (automated external defibrillators) were under scrutiny by the U.S.  Food and Drug Administration  (FDA) which considered reclassifying AEDs as class III  premarket approval  devices. Technical malfunctions likely contributed to more than 750 deaths in the 5-year period between 2004 and 2009, in most cases by component failures or design errors. During the same period, up to 70 types of AEDs were recalled, including recalls from every AED manufacturer in the world. \n [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2493", "text": "In January and February 2015, the FDA issued this news release: \"The FDA issued a final order that will require AED manufacturers to submit premarket approval applications (PMAs), which undergo a more rigorous review than what was required to market these devices in the past. The agency's strengthened review will focus on the critical requirements needed to ensure the safety and reliability of AEDs and their necessary accessories, including batteries, pad electrodes, adapters and hardware keys for pediatric use.\" [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2494", "text": "In the United Kingdom there is concern that poor maintenance may make public defibrillators unreliable.  The  Henley Standard  reported on 21 July 2017 that more than half the defibrillators in  Henley-on-Thames  and the surrounding area were at risk of failing, either because of low battery power or because adhesive pads had deteriorated. [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2495", "text": "The first use of an external defibrillator on a human was in 1947 by Claude Beck. [ 34 ]  The portable version of the external defibrillator was invented in 1957 by  Frank Pantridge  in  Belfast ,  Northern Ireland , a pioneer in emergency medical treatment. [ 35 ] [ 36 ]  Pantridge's defibrillator required a trained operator to perform the shock procedure and charted a course for many new innovations in external defibrillation. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2496", "text": "In the late 1970s the Heart-Aid was developed as the first truly automated external defibrillator that was designed for the public. The principles of ABC assessment and a human voice relaying instructions helped bystanders respond to a sudden cardiac event while waiting for the first responders to get to scene. [ 3 ]  Many of the early innovations in the Heart-Aid model are still part of the current generation of AEDs, although some innovations, like the airway electrode have fallen from use."}
{"_id": "WikiPedia_Cardio$$$corpus_2497", "text": "In a study published in 2017, researchers in Poland selected the main entrances of buildings which had AEDs, although the researchers themselves did not know the exact locations of the devices.  In drills of pretend heart attack, the average time to bring the AED to the patient was 96 seconds, with a time that ranged from 52 to 144 seconds.  This met the three minute goal.  In some cases, the use of the AED required the continuous presence of building personnel.  Future improvements include more obvious signage and public-access AEDs which do not require a staff member of the building to either retrieve or use the device. [ 38 ] \n [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2498", "text": "The  ballistocardiograph  ( BCG ) is a measure of  ballistic  forces generated by the heart. [ 1 ]  The downward movement of blood through the  descending aorta  produces an  upward recoil , moving the body upward with each heartbeat. [ 2 ]  As different parts of the aorta expand and contract, the body continues to move downward and upward in a repeating pattern. [ 3 ]  Ballistocardiography is a technique for producing a graphical representation of repetitive motions of the human body arising from the sudden ejection of blood into the great vessels with each heart beat. [ 4 ]    It is a  vital sign  in the 1\u201320  Hz   frequency  range which is caused by the mechanical movement of the  heart  and can be recorded by  noninvasive  methods from the surface of the  body . It was shown for the first time, after an extensive research work by Dr.  Isaac Starr , that the effect of main heart malfunctions can be identified by observing and analyzing the BCG signal. [ 5 ]  Recent [ when? ]  work also validates BCG could be monitored using camera in a non-contact manner. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2499", "text": "One example of the use of a BCG is a ballistocardiographic scale, which measures the recoil of the persons body who is on the scale. A BCG scale is able to show a person's heart rate as well as their weight. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2500", "text": "The term ballistocardiograph originated from the Roman  ballista , which is derived from the  Greek  word  ballein  (to throw), a machine for launching missiles, plus the Greek words for heart and writing. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2501", "text": "The  bidomain model  is a  mathematical model  to define the electrical activity of the  heart . It consists in a continuum (volume-average) approach in which the cardiac microstructure is defined in terms of muscle fibers grouped in sheets, creating a complex  three-dimensional  structure with anisotropical properties. Then, to define the electrical activity, two interpenetrating domains are considered, which are the  intracellular  and  extracellular  domains, representing respectively the space inside the cells and the region between them. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2502", "text": "The bidomain model was first proposed by  Schmitt  in 1969 [ 2 ]  before being formulated mathematically in the late 1970s. [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2503", "text": "Since it is a continuum model, rather than describing each cell individually, it represents the average properties and behaviour of group of cells organized in complex structure. Thus, the model results to be a complex one and can be seen as a generalization of the  cable theory  to higher dimensions and, going to define the so-called  bidomain equations . [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2504", "text": "Many of the interesting properties of the bidomain model arise from the condition of unequal anisotropy ratios. The  electrical conductivity  in anisotropic tissues is not unique in all directions, but it is different in parallel and perpendicular direction with respect to the fiber one.\nMoreover, in tissues with unequal anisotropy ratios, the ratio of conductivities parallel and perpendicular to the fibers are different in the intracellular and extracellular spaces. For instance, in cardiac tissue, the anisotropy ratio in the  intracellular space  is about 10:1, while in the  extracellular space  it is about 5:2. [ 13 ] \nMathematically, unequal anisotropy ratios means that the effect of anisotropy cannot be removed by a change in the distance scale in one direction. [ 14 ] \nInstead, the anisotropy has a more profound influence on the electrical behavior. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2505", "text": "Three examples of the impact of unequal anisotropy ratios are"}
{"_id": "WikiPedia_Cardio$$$corpus_2506", "text": "The bidomain domain is principally represented by two main regions: the cardiac cells, called intracellular domain, and the space surrounding them, called extracellular domain. Moreover, usually another region is considered, called extramyocardial region. \nThe intracellular and extracellular domains, which are separate by the  cellular membrane , are considered to be a unique physical space representing the heart ( \n \n \n \n \n H \n \n \n \n {\\displaystyle \\mathbb {H} } \n \n ), while the extramyocardial domain is a unique physical space adjacent of them ( \n \n \n \n \n T \n \n \n \n {\\displaystyle \\mathbb {T} } \n \n ). The extramyocardial region can be considered as a fluid bath, especially when one wants to simulate experimental conditions, or as a  human torso  to simulate physiological conditions. [ 12 ] \nThe boundary of the two principal physical domains defined are important to solve the bidomain model. Here the heart boundary is denoted as  \n \n \n \n \u2202 \n \n H \n \n \n \n {\\displaystyle \\partial \\mathbb {H} } \n \n  while the torso domain boundary is  \n \n \n \n \u2202 \n \n T \n \n . \n \n \n {\\displaystyle \\partial \\mathbb {T} .} \n \n [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2507", "text": "The unknowns in the bidomain model are three, the intracellular potential  \n \n \n \n \n v \n \n i \n \n \n \n \n {\\displaystyle v_{i}} \n \n , the extracellular potential  \n \n \n \n \n v \n \n e \n \n \n \n \n {\\displaystyle v_{e}} \n \n  and the  transmembrane potential   \n \n \n \n v \n \n \n {\\displaystyle v} \n \n , which is defined as the difference of the potential across the cell membrane  \n \n \n \n v \n = \n \n v \n \n i \n \n \n \u2212 \n \n v \n \n e \n \n \n \n \n {\\displaystyle v=v_{i}-v_{e}} \n \n . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2508", "text": "Moreover, some important parameters need to be taken in account, especially the intracellular conductivity tensor matrix  \n \n \n \n \n \n \u03a3 \n \n \n i \n \n \n \n \n {\\displaystyle \\mathbf {\\Sigma } _{i}} \n \n ,  the extracellular conductivity tensor matrix  \n \n \n \n \n \n \u03a3 \n \n \n e \n \n \n \n \n {\\displaystyle \\mathbf {\\Sigma } _{e}} \n \n .  The transmembrane current flows between the intracellular and extracellular regions and it is in part described by the corresponding ionic current over the membrane per unit area  \n \n \n \n \n I \n \n ion \n \n \n \n \n {\\displaystyle I_{\\text{ion}}} \n \n . \nMoreover, the membrane capacitance per unit area  \n \n \n \n \n C \n \n m \n \n \n \n \n {\\displaystyle C_{m}} \n \n  and the surface to volume ratio of the cell membrane  \n \n \n \n \u03c7 \n \n \n {\\displaystyle \\chi } \n \n  need to be considered to derive the bidomain model formulation, which is done in the following  section . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2509", "text": "The bidomain model is defined through two  partial differential equations  (PDE) the first of which is a  reaction diffusion equation  in terms of the  transmembrane potential , while the second one computes the extracellular potential starting from a given transmembran potential distribution. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2510", "text": "Thus, the bidomain model can be formulated as follows:\n \n \n \n \n \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n + \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n e \n \n \n \n ) \n \n = \n \u03c7 \n \n ( \n \n \n C \n \n m \n \n \n \n \n \n \u2202 \n v \n \n \n \u2202 \n t \n \n \n \n + \n \n I \n \n \n i \n o \n n \n \n \n \n \n ) \n \n \u2212 \n \n I \n \n \n s \n \n 1 \n \n \n \n \n \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n + \n \n \n \u03a3 \n \n \n e \n \n \n \n ) \n \n \u2207 \n \n v \n \n e \n \n \n \n ) \n \n = \n \u2212 \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n + \n \n I \n \n \n s \n \n 2 \n \n \n \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{alignedat}{2}&\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right)+\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v_{e}\\right)=\\chi \\left(C_{m}{\\frac {\\partial v}{\\partial t}}+I_{\\mathrm {ion} }\\right)-I_{s_{1}}\\\\[1ex]&\\nabla \\cdot \\left(\\left(\\mathbf {\\Sigma } _{i}+\\mathbf {\\Sigma } _{e}\\right)\\nabla v_{e}\\right)=-\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right)+I_{s_{2}}\\end{alignedat}}} \n \n \nwhere  \n \n \n \n \n I \n \n \n s \n \n 1 \n \n \n \n \n \n \n {\\displaystyle I_{s_{1}}} \n \n  and  \n \n \n \n \n I \n \n \n s \n \n 2 \n \n \n \n \n \n \n {\\displaystyle I_{s_{2}}} \n \n  can be defined as applied external stimulus currents. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2511", "text": "The ionic current is usually represented by an  ionic model  through a system of  ordinary differential equations  (ODEs). Mathematically, one can write  \n \n \n \n \n I \n \n ion \n \n \n = \n \n I \n \n ion \n \n \n ( \n v \n , \n \n w \n \n ) \n \n \n {\\displaystyle I_{\\text{ion}}=I_{\\text{ion}}(v,\\mathbf {w} )} \n \n  where  \n \n \n \n \n w \n \n \n \n {\\displaystyle \\mathbf {w} } \n \n  is called ionic variable. Then, in general, for all  \n \n \n \n t \n > \n 0 \n \n \n {\\displaystyle t>0} \n \n , the system reads [ 19 ] \n \n \n \n \n \n \n { \n \n \n \n \n \n \n \n \u2202 \n \n w \n \n \n \n \u2202 \n t \n \n \n \n \n = \n \n F \n \n ( \n v \n , \n \n w \n \n ) \n \n \n \n in\u00a0 \n \n \n H \n \n \n \n \n \n \n w \n \n ( \n t \n = \n 0 \n ) \n = \n \n \n w \n \n \n 0 \n \n \n \n \n \n in\u00a0 \n \n \n H \n \n \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{cases}{\\dfrac {\\partial \\mathbf {w} }{\\partial t}}=\\mathbf {F} (v,\\mathbf {w} )&{\\text{in }}\\mathbb {H} \\\\\\mathbf {w} (t=0)=\\mathbf {w} _{0}&{\\text{in }}\\mathbb {H} \\end{cases}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_2512", "text": "Different ionic models have been proposed: [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2513", "text": "In some cases, an extramyocardial region is considered. This implies the addition to the bidomain model of an equation describing the potential propagation inside the extramyocardial domain. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2514", "text": "Usually, this equation is a simple generalized  Laplace equation  of type [ 12 ] \n \n \n \n \n \u2212 \n \u2207 \n \u22c5 \n ( \n \n \n \u03a3 \n \n \n 0 \n \n \n \u2207 \n \n v \n \n 0 \n \n \n ) \n = \n 0 \n \n \n x \n \n \u2208 \n \n T \n \n \n \n {\\displaystyle -\\nabla \\cdot (\\mathbf {\\Sigma } _{0}\\nabla v_{0})=0\\quad \\mathbf {x} \\in \\mathbb {T} } \n \n \nwhere  \n \n \n \n \n v \n \n 0 \n \n \n \n \n {\\displaystyle v_{0}} \n \n  is the potential in the extramyocardial region and  \n \n \n \n \n \n \u03a3 \n \n \n 0 \n \n \n \n \n {\\displaystyle \\mathbf {\\Sigma } _{0}} \n \n  is the corresponding conductivity tensor."}
{"_id": "WikiPedia_Cardio$$$corpus_2515", "text": "Moreover, an isolated domain assumption is considered, which means that the following boundary conditions are added\n \n \n \n \n ( \n \n \n \u03a3 \n \n \n 0 \n \n \n \u2207 \n \n v \n \n 0 \n \n \n ) \n \u22c5 \n \n \n n \n \n \n 0 \n \n \n = \n 0 \n \n \n x \n \n \u2208 \n \u2202 \n \n T \n \n , \n \n \n {\\displaystyle (\\mathbf {\\Sigma } _{0}\\nabla v_{0})\\cdot \\mathbf {n} _{0}=0\\quad \\mathbf {x} \\in \\partial \\mathbb {T} ,} \n \n \n \n \n \n \n \n \n n \n \n \n 0 \n \n \n \n \n {\\displaystyle \\mathbf {n} _{0}} \n \n  being the unit normal directed outside of the extramyocardial domain. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2516", "text": "If the extramyocardial region is the human torso, this model gives rise to the  forward problem of electrocardiology . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2517", "text": "The bidomain equations are derived from the  Maxwell's equations  of the electromagnetism, considering some simplifications. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2518", "text": "The first assumption is that the intracellular current can flow only between the intracellular and extracellular regions, while the intracellular and extramyocardial regions can comunicate between them, so that the current can flow into and from the extramyocardial regions but only in the extracellular space. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2519", "text": "Using  Ohm's law  and a quasi-static assumption, the gradient of a scalar potential field  \n \n \n \n \u03c6 \n \n \n {\\displaystyle \\varphi } \n \n  can describe an electrical field  \n \n \n \n \n E \n \n \n \n {\\displaystyle \\mathbf {E} } \n \n , which means that [ 12 ] \n \n \n \n \n \n E \n \n = \n \u2212 \n \u2207 \n \u03c6 \n . \n \n \n {\\displaystyle \\mathbf {E} =-\\nabla \\varphi .}"}
{"_id": "WikiPedia_Cardio$$$corpus_2520", "text": "Then, if  \n \n \n \n J \n \n \n {\\displaystyle J} \n \n  represent the current density of the electric field  \n \n \n \n \n E \n \n \n \n {\\displaystyle \\mathbf {E} } \n \n , two equations can be obtained [ 12 ] \n \n \n \n \n \n \n \n \n \n J \n \n i \n \n \n \n \n \n = \n \u2212 \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n i \n \n \n \n \n \n \n \n J \n \n e \n \n \n \n \n \n = \n \u2212 \n \n \n \u03a3 \n \n \n e \n \n \n \u2207 \n \n v \n \n e \n \n \n . \n \n \n \n \n \n \n {\\displaystyle {\\begin{alignedat}{2}J_{i}&=-\\mathbf {\\Sigma } _{i}\\nabla v_{i}\\\\J_{e}&=-\\mathbf {\\Sigma } _{e}\\nabla v_{e}.\\end{alignedat}}} \n \n \nwhere the subscript  \n \n \n \n i \n \n \n {\\displaystyle i} \n \n  and  \n \n \n \n e \n \n \n {\\displaystyle e} \n \n  represent the intracellular and extracellular quantities respectively. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2521", "text": "The second assumption is that the heart is isolated so that the current that leaves one region need to flow into the other. Then, the current density in each of the intracellular and extracellular domain must be equal in magnitude but opposite in sign, and can be defined as the product of the surface to volume ratio of the cell membrane and the transmembrane ionic current density  \n \n \n \n \n I \n \n m \n \n \n \n \n {\\displaystyle I_{m}} \n \n  per unit area, which means that [ 12 ] \n \n \n \n \n \u2212 \n \u2207 \n \u22c5 \n \n J \n \n i \n \n \n = \n \u2207 \n \u22c5 \n \n J \n \n e \n \n \n = \n \u03c7 \n \n I \n \n m \n \n \n . \n \n \n {\\displaystyle -\\nabla \\cdot J_{i}=\\nabla \\cdot J_{e}=\\chi I_{m}.}"}
{"_id": "WikiPedia_Cardio$$$corpus_2522", "text": "By combining the previous assumptions, the conservation of current densities is obtained, namely [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2523", "text": "from which, summing the two equations [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2524", "text": "This equation states exactly that all currents exiting one domain must enter the other. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2525", "text": "From here, it is easy to find the second equation of the bidomain model subtracting  \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n e \n \n \n ) \n \n \n {\\displaystyle \\nabla \\cdot (\\mathbf {\\Sigma } _{i}\\nabla v_{e})} \n \n  from both sides. In fact, [ 12 ] \n \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n i \n \n \n ) \n \u2212 \n \u2207 \n \u22c5 \n ( \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n e \n \n \n ) \n = \n \u2212 \n \u2207 \n \u22c5 \n ( \n \n \n \u03a3 \n \n \n e \n \n \n \u2207 \n \n v \n \n e \n \n \n ) \n \u2212 \n \u2207 \n \u22c5 \n ( \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n e \n \n \n ) \n \n \n {\\displaystyle \\nabla \\cdot (\\mathbf {\\Sigma } _{i}\\nabla v_{i})-\\nabla \\cdot (\\mathbf {\\Sigma } _{i}\\nabla v_{e})=-\\nabla \\cdot (\\mathbf {\\Sigma } _{e}\\nabla v_{e})-\\nabla \\cdot (\\mathbf {\\Sigma } _{i}\\nabla v_{e})} \n \n  \nand knowing that the transmembral potential is defined as  \n \n \n \n v \n = \n \n v \n \n i \n \n \n \u2212 \n \n v \n \n e \n \n \n \n \n {\\displaystyle v=v_{i}-v_{e}} \n \n [ 12 ] \n \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n ) \n = \n \u2212 \n \u2207 \n \u22c5 \n ( \n ( \n \n \n \u03a3 \n \n \n i \n \n \n + \n \n \n \u03a3 \n \n \n e \n \n \n ) \n \u2207 \n \n v \n \n e \n \n \n ) \n . \n \n \n {\\displaystyle \\nabla \\cdot (\\mathbf {\\Sigma } _{i}\\nabla v)=-\\nabla \\cdot ((\\mathbf {\\Sigma } _{i}+\\mathbf {\\Sigma } _{e})\\nabla v_{e}).} \n \n  \nThen, knowing the transmembral potential, one can recover the extracellular potential."}
{"_id": "WikiPedia_Cardio$$$corpus_2526", "text": "Then, the current that flows across the cell membrane can be modelled with the  cable equation , [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2527", "text": "Combining equations ( 1 ) and ( 2 ) gives [ 12 ] \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n i \n \n \n \n ) \n \n = \n \u03c7 \n \n ( \n \n \n C \n \n m \n \n \n \n \n \n \u2202 \n v \n \n \n \u2202 \n t \n \n \n \n + \n \n I \n \n i \n o \n n \n \n \n \n ) \n \n . \n \n \n {\\displaystyle \\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v_{i}\\right)=\\chi \\left(C_{m}{\\frac {\\partial v}{\\partial t}}+I_{ion}\\right).} \n \n \nFinally, adding and subtracting  \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n e \n \n \n ) \n \n \n {\\displaystyle \\nabla \\cdot (\\mathbf {\\Sigma } _{i}\\nabla v_{e})} \n \n  on the left and rearranging  \n \n \n \n v \n = \n \n v \n \n i \n \n \n \u2212 \n \n v \n \n e \n \n \n \n \n {\\displaystyle v=v_{i}-v_{e}} \n \n , one can get the first equation of the bidomain model [ 12 ] \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n + \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n e \n \n \n \n ) \n \n = \n \u03c7 \n \n ( \n \n \n C \n \n m \n \n \n \n \n \n \u2202 \n v \n \n \n \u2202 \n t \n \n \n \n + \n \n I \n \n \n i \n o \n n \n \n \n \n \n ) \n \n , \n \n \n {\\displaystyle \\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right)+\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v_{e}\\right)=\\chi \\left(C_{m}{\\frac {\\partial v}{\\partial t}}+I_{\\mathrm {ion} }\\right),} \n \n \nwhich describes the evolution of the transmembrane potential in time."}
{"_id": "WikiPedia_Cardio$$$corpus_2528", "text": "The final formulation described in the  standard formulation  section is obtained through a generalization, considering possible external stimulus which can be given through the external applied currents  \n \n \n \n \n I \n \n \n s \n \n 1 \n \n \n \n \n \n \n {\\displaystyle I_{s_{1}}} \n \n  and  \n \n \n \n \n I \n \n \n s \n \n 2 \n \n \n \n \n \n \n {\\displaystyle I_{s_{2}}} \n \n . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2529", "text": "In order to solve the model, boundary conditions are needed. The more classical boundary conditions are the following ones, formulated by Tung. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2530", "text": "First of all, as state before in the  derive  section, there ca not been any flow of current between the intracellular and extramyocardial domains. This can be mathematically described as [ 12 ] \n \n \n \n \n ( \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n i \n \n \n ) \n \u22c5 \n \n n \n \n = \n 0 \n \n \n x \n \n \u2208 \n \u2202 \n \n H \n \n \n \n {\\displaystyle (\\mathbf {\\Sigma } _{i}\\nabla v_{i})\\cdot \\mathbf {n} =0\\quad \\mathbf {x} \\in \\partial \\mathbb {H} } \n \n \nwhere  \n \n \n \n \n n \n \n \n \n {\\displaystyle \\mathbf {n} } \n \n  is the vector that represents the outwardly unit normal to the myocardial surface of the heart.\nSince the intracellular potential is not explicitily presented in the bidomain formulation, this condition is usually described in terms of the transmembrane and extracellular potential, knowing that  \n \n \n \n v \n = \n \n v \n \n i \n \n \n \u2212 \n \n v \n \n e \n \n \n \n \n {\\displaystyle v=v_{i}-v_{e}} \n \n , namely [ 12 ] \n \n \n \n \n ( \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n ) \n \u22c5 \n \n n \n \n = \n \u2212 \n ( \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n e \n \n \n ) \n \u22c5 \n \n n \n \n \n \n x \n \n \u2208 \n \u2202 \n \n H \n \n . \n \n \n {\\displaystyle (\\mathbf {\\Sigma } _{i}\\nabla v)\\cdot \\mathbf {n} =-(\\mathbf {\\Sigma } _{i}\\nabla v_{e})\\cdot \\mathbf {n} \\quad \\mathbf {x} \\in \\partial \\mathbb {H} .}"}
{"_id": "WikiPedia_Cardio$$$corpus_2531", "text": "For the extracellular potential, if the myocardial region is presented, a balance in the flow between the extracellular and the extramyocardial regions is considered [ 12 ] \n \n \n \n \n \n ( \n \n \n \n \u03a3 \n \n \n e \n \n \n \u2207 \n \n v \n \n e \n \n \n \n ) \n \n \u22c5 \n \n \n n \n \n \n e \n \n \n = \n \u2212 \n \n ( \n \n \n \n \u03a3 \n \n \n 0 \n \n \n \u2207 \n \n v \n \n 0 \n \n \n \n ) \n \n \u22c5 \n \n \n n \n \n \n 0 \n \n \n \n \n x \n \n \u2208 \n \u2202 \n \n H \n \n . \n \n \n {\\displaystyle \\left(\\mathbf {\\Sigma } _{e}\\nabla v_{e}\\right)\\cdot \\mathbf {n} _{e}=-\\left(\\mathbf {\\Sigma } _{0}\\nabla v_{0}\\right)\\cdot \\mathbf {n} _{0}\\quad \\mathbf {x} \\in \\partial \\mathbb {H} .} \n \n \nHere the normal vectors from the perspective of both domains are considered, thus the negative sign are necessary. Moreover, a perfect transmission of the potential on the cardiac boundary is necessary, which gives [ 12 ] \n \n \n \n \n \n v \n \n e \n \n \n = \n \n v \n \n 0 \n \n \n \n \n x \n \n \u2208 \n \u2202 \n \n H \n \n . \n \n \n {\\displaystyle v_{e}=v_{0}\\quad \\mathbf {x} \\in \\partial \\mathbb {H} .}"}
{"_id": "WikiPedia_Cardio$$$corpus_2532", "text": "Instead, if the heart is considered as isolated, which means that no myocardial region is presented, a possible boundary condition for the extracellular problem is [ 12 ] \n \n \n \n \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n \u22c5 \n \n n \n \n = \n \u2212 \n \n ( \n \n ( \n \n \n \u03a3 \n \n \n i \n \n \n + \n \n \n \u03a3 \n \n \n e \n \n \n ) \n \u2207 \n \n v \n \n e \n \n \n \n ) \n \n \u22c5 \n \n n \n \n \n \n x \n \n \u2208 \n \u2202 \n \n H \n \n . \n \n \n {\\displaystyle \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right)\\cdot \\mathbf {n} =-\\left((\\mathbf {\\Sigma } _{i}+\\mathbf {\\Sigma } _{e})\\nabla v_{e}\\right)\\cdot \\mathbf {n} \\quad \\mathbf {x} \\in \\partial \\mathbb {H} .}"}
{"_id": "WikiPedia_Cardio$$$corpus_2533", "text": "By assuming equal anisotropy ratios for the intra- and extracellular domains, i.e.  \n \n \n \n \n \n \u03a3 \n \n \n i \n \n \n = \n \u03bb \n \n \n \u03a3 \n \n \n e \n \n \n \n \n {\\displaystyle \\mathbf {\\Sigma } _{i}=\\lambda \\mathbf {\\Sigma } _{e}} \n \n  for some scalar  \n \n \n \n \u03bb \n \n \n {\\displaystyle \\lambda } \n \n , the model can be reduced to one single equation, called  monodomain equation \n \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \u03a3 \n \n \u2207 \n v \n ) \n = \n \u03c7 \n \n ( \n \n \n C \n \n m \n \n \n \n \n \n \u2202 \n v \n \n \n \u2202 \n t \n \n \n \n + \n \n I \n \n \n i \n o \n n \n \n \n \n \n ) \n \n \u2212 \n \n I \n \n s \n \n \n \n \n {\\displaystyle \\nabla \\cdot (\\mathbf {\\Sigma } \\nabla v)=\\chi \\left(C_{m}{\\frac {\\partial v}{\\partial t}}+I_{\\mathrm {ion} }\\right)-I_{s}} \n \n \nwhere the only variable is now the transmembrane potential, and the conductivity tensor  \n \n \n \n \n \u03a3 \n \n \n \n {\\displaystyle \\mathbf {\\Sigma } } \n \n  is a combination of  \n \n \n \n \n \n \u03a3 \n \n \n i \n \n \n \n \n {\\displaystyle \\mathbf {\\Sigma } _{i}} \n \n  and  \n \n \n \n \n \n \u03a3 \n \n \n e \n \n \n . \n \n \n {\\displaystyle \\mathbf {\\Sigma } _{e}.} \n \n [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2534", "text": "If the heart is considered as an isolated tissue, which means that no current can flow outside of it, the final formulation with boundary conditions reads [ 12 ] \n \n \n \n \n \n \n { \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n + \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n e \n \n \n \n ) \n \n = \n \u03c7 \n \n ( \n \n \n C \n \n m \n \n \n \n \n \n \n \u2202 \n v \n \n \n \u2202 \n t \n \n \n \n \n + \n \n I \n \n \n i \n o \n n \n \n \n \n \n ) \n \n \u2212 \n \n I \n \n \n s \n \n 1 \n \n \n \n \n \n \n \n x \n \n \u2208 \n \n H \n \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n + \n \n \n \u03a3 \n \n \n e \n \n \n \n ) \n \n \u2207 \n \n v \n \n e \n \n \n \n ) \n \n = \n \u2212 \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n + \n \n I \n \n \n s \n \n 2 \n \n \n \n \n \n \n \n x \n \n \u2208 \n \n H \n \n \n \n \n \n \n \n \u03a3 \n \n \n i \n \n \n ( \n \u2207 \n v \n + \n \u2207 \n \n v \n \n e \n \n \n ) \n \u22c5 \n \n n \n \n = \n 0 \n \n \n \n x \n \n \u2208 \n \u2202 \n \n H \n \n \n \n \n \n \n [ \n \n \n \n \u03a3 \n \n \n i \n \n \n ( \n \u2207 \n v \n + \n \u2207 \n \n v \n \n e \n \n \n ) \n + \n \n \n \u03a3 \n \n \n e \n \n \n \u2207 \n \n v \n \n e \n \n \n \n ] \n \n \u22c5 \n \n n \n \n = \n 0 \n \n \n \n x \n \n \u2208 \n \u2202 \n \n H \n \n \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{cases}\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right)+\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v_{e}\\right)=\\chi \\left(C_{m}{\\dfrac {\\partial v}{\\partial t}}+I_{\\mathrm {ion} }\\right)-I_{s_{1}}&\\mathbf {x} \\in \\mathbb {H} \\\\[1ex]\\nabla \\cdot \\left(\\left(\\mathbf {\\Sigma } _{i}+\\mathbf {\\Sigma } _{e}\\right)\\nabla v_{e}\\right)=-\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right)+I_{s_{2}}&\\mathbf {x} \\in \\mathbb {H} \\\\[1ex]\\mathbf {\\Sigma } _{i}(\\nabla v+\\nabla v_{e})\\cdot \\mathbf {n} =0&\\mathbf {x} \\in \\partial \\mathbb {H} \\\\[1ex]\\left[\\mathbf {\\Sigma } _{i}(\\nabla v+\\nabla v_{e})+\\mathbf {\\Sigma } _{e}\\nabla v_{e}\\right]\\cdot \\mathbf {n} =0&\\mathbf {x} \\in \\partial \\mathbb {H} \\end{cases}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_2535", "text": "There are various possible techniques to solve the bidomain equations. Between them, one can find  finite difference schemes ,  finite element schemes  and also  finite volume schemes . Special considerations can be made for the numerical solution of these equations, due to the high time and space resolution needed for numerical convergence. [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2536", "text": "A  biological pacemaker  is one or more types of cellular components that, when \"implanted or injected into certain regions of the heart,\" produce specific electrical stimuli that mimic that of the body's natural  pacemaker cells . [ 1 ]  Biological pacemakers are indicated for issues such as  heart block ,  slow heart rate , and  asynchronous heart ventricle contractions . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2537", "text": "The biological pacemaker is intended as an alternative to the  artificial cardiac pacemaker  that has been in human use since the late 1950s. Despite their success, several limitations and problems with artificial pacemakers have emerged during the past decades such as  electrode  fracture or damage to  insulation ,  infection , re-operations for  battery  exchange, and  venous thrombosis . The need for an alternative is most obvious in children, including premature  newborn babies , where size mismatch and the fact that pacemaker leads do not grow with children are a problem. [ 1 ]   A more biological approach has been taken in order to mitigate many of these issues. However, the implanted biological pacemaker cells still typically need to be supplemented with an artificial pacemaker while the cells form the necessary electrical connections with cardiac tissue. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2538", "text": "The first successful experiment with biological pacemakers was carried out by  Arjang Ruhparwar  's group at  Hannover Medical School  in Germany using transplanted  fetal  heart  muscle cells . The process was first introduced at the scientific sessions of the  American Heart Association  in  Anaheim  in 2001, and the results were published in 2002. [ 4 ]  A few months later, Eduardo Marban's group from  Johns Hopkins University  published the first successful gene-therapeutic approach towards the generation of pacemaking activity in otherwise non-pacemaking adult  cardiomyocytes  using a  guinea pig  model. [ 5 ]  The investigators postulated latent pacemaker capability in normal  heart muscle  cells. This potential ability is suppressed by the  inward-rectifier potassium current  Ik1 encoded by the  gene  Kir2 which is not expressed in  pacemaker cells . By specific inhibition of Ik1 below a certain level, spontaneous activity of cardiomyocytes was observed with resemblance to the action potential pattern of genuine pacemaker cells."}
{"_id": "WikiPedia_Cardio$$$corpus_2539", "text": "Meanwhile, other genes and cells have been discovered, including heart muscle cells derived from  embryonic stem cells , \"HCN\" genes which encode the  wild type  pacemaker current I(f). Michael Rosen's group demonstrated that transplantation of HCN2-transfected human mesenchymal  stem cells  (hMSCs) leads to expression of functional HCN2 channels  in vitro  and  in vivo , mimicking overexpression of HCN2 genes in cardiac  myocytes . [ 6 ]  In 2010, Ruhparwar's group again demonstrated a type of biological pacemaker, this time showing that by injection of the \"Adenylate Cyclase\" gene into the heart muscle a biological cardiac pacemaker can be created. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2540", "text": "In 2014, a gene called  TBX18  has been non-invasively applied to speed up heart rates caused by heart block. [ 2 ]  More recent studies in 2015, has been experimented  optogenetic  approach in the rats heart, where a light sensitive  transgene  ( Channelrhodopsin -2) injected to several sites of rat's  ventricular , which, furthermore, can simultaneously stimulate the injection sites by a blue light irradiation. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2541", "text": "Biotronik  (BIOTRONIK  SE  & Co.  KG ; [ 1 ] [ 2 ]  Biotronik Worldwide) is a  limited partnership [ 1 ]  multi-national  cardiovascular   biomedical  research and technology company, headquartered in  Berlin , Germany."}
{"_id": "WikiPedia_Cardio$$$corpus_2542", "text": "The company offers equipment for diagnosis, treatment, and therapy support in the areas of  cardiac rhythm  management,  electrophysiology , and  vascular  intervention. [ 3 ]   In the area of cardiac rhythm management, Biotronik Home Monitoring uses tele-monitoring technology to provide doctors with up-to-date information for implant patients. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2543", "text": "Biotronik employs more than 9,000 people worldwide in over 100 countries, with  research and development  activities in Europe, North America, and Singapore.  It produces all critical components of its products in-house.  One in every five employees at its Berlin headquarters works in research and development (R&D). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2544", "text": "BIOTRONIK began with the development of the first German implantable  pacemaker  (Biotronik IP-03) in 1963.  The pacemaker was developed at  Technische Universit\u00e4t Berlin  by physicist Professor. Dr.  Max Schaldach  (1936\u20132001 [ 5 ] ), [ 6 ] [ 7 ]  a professor of biomedical technology at the Friedrich-Alexander- University of Erlangen-Nuremberg  (FAU), [ 8 ]  and electrical engineer Otto Franke.  In the early years, the company worked to improve pacemakers' capacity and battery life, and secure the connections among electrodes, pacemakers, and the heart.  Since its start, more than 19 million BIOTRONIK devices in over 100 countries have been implanted. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2545", "text": "In 1976, the company moved to Sieversufer 8 in  Berlin-Neuk\u00f6lln .  In 1979, a US production site in  Lake Oswego, Oregon  was built.  This subsidiary resulted from the acquisition of the American pacemaker producer Stimulation Technology, Inc.  At the same time, with the development and production of advanced hybrid circuitry and structural components for the medical technology industry, the company also began to develop circuits for pacemakers.  In the 1980s, the  dual-chamber stimulation method  (DDD) was developed, leading to the manufacturing of a pacemaker that could read and react to spontaneous contractions of the atrium, and better respond to them of its own accord.  To this end, BIOTRONIK developed the Diplos 03, a multi-programme DDD pacemaker with bilateral telemetry, which made it a European market leader and increased its presence in South America and Asia."}
{"_id": "WikiPedia_Cardio$$$corpus_2546", "text": "In 1987, the firm moved its headquarters to Woermannkehre 1, next door to its previous location.  In 1993, BIOTRONIK produced the first German implantable cardioverter defibrillator (ICD), among them the Phylax 06.  Closed loop stimulation (CLS), which integrates the pacemaker into the body's own regulatory system, thereby allowing it to react to patients\u2019 changing physical and emotional activity, was introduced in the 1990s.  Also in 1993, BIOTRONIK developed fractal coating for implantable electrodes.  This coating optimises the electrically active surface of the electrode, thereby improving its perception and stimulation properties.  BIOTRONIK remains the only manufacturer of fractal-coated electrodes."}
{"_id": "WikiPedia_Cardio$$$corpus_2547", "text": "In 1994 and 1995 respectively, BIOTRONIK began offering a full spectrum of  electrophysiology  products and vascular intervention products.  BIOTRONIK also develops and produces  balloon catheters  and  stents  for the treatment of  coronary artery disease .  With Philos, the company has offered a complete pacemaker family with telemetry since 2000, when it received  CE Mark  approval for the product, and also successfully implanted the first pacemaker with Home Monitoring ( remote patient monitoring ).  Home Monitoring has shown significant clinical benefits, including over a 50% reduction in mortality of heart failure patients. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2548", "text": "With the Lumax 540 VR-T DX in 2010, BIOTRONIK launched the first and only single-chamber defibrillator with comprehensive atrial diagnostics worldwide.  Additionally, the company entered into an exclusive international distribution partnership with the Swiss medical technology company  Endosense  to distribute their ablation catheter TactiCath with optical contact force.  The following year, BIOTRONIK released Orsiro to the market, the world's first hybrid drug-eluting stent with a bio-absorbable coating, adding to innovative treatment options combatting coronary artery disease. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2549", "text": "In 2011, BIOTRONIK was the subject of an investigation by the  United States Department of Justice  (US DoJ) into payments made to doctors in  Nevada , United States, who use the company's products in their practices. [ 10 ]   The case was settled in 2014. [ 11 ]   In 2013, a similar investigation began and was settled involving payments to physicians in  Oregon . [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2550", "text": "In 2012, the company acquired the old  Postfuhramt , a historical brick postal building on Berlin's  Oranienburger Strasse  in the sub-neighbourhood of  Spandauer Vorstadt , in the district of  Mitte . [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2551", "text": "The following year, BIOTRONIK launched BioMonitor, a type of mini  ECG  device that offers continuous monitoring and daily remote data collection.  In addition, BIOTRONIK also developed the world's first series of implantable defibrillators that enable patients, including those suffering heart failure, to undergo  MRI scans  under certain conditions.  BIOTRONIK's ProMRI\u00ae technology includes systems approved for 1.5 T and 3.0 T MR scanning, as well as full-body scanning.  The company offers the broadest portfolio of pacemakers, defibrillators, and therapies approved to undergo MRIs, with more than 1,000,000 ProMRI\u00ae devices and leads implanted worldwide. [ 15 ]   To navigate through this portfolio, BIOTRONIK invented two online tools in 2016 and 2017; the  ProMRI\u00aeSystemCheck  and  ProMRI\u00aeConfigurator , correspondingly."}
{"_id": "WikiPedia_Cardio$$$corpus_2552", "text": "For radiation protection, BIOTRONIK distributes the Zero-Gravity Radiation Protection System, which consists of a movable suspended body and head shield.  The shield material has a significantly higher lead equivalency than traditional radiation apparel, thereby reducing radiation exposure by 87\u2013100%. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2553", "text": "Indicated to treat peripheral artery disease in the lower limbs, BIOTRONIK released the Passeo-18 Lux in 2014 as the first peripheral drug-coated balloon.  The year following, CardioMessenger Smart was launched, its new patient device for Home Monitoring, [ 17 ]  and BioMonitor 2, the second-generation insertable cardiac monitor. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2554", "text": "In February 2016, BIOTRONIK Inc. opened an Education and Innovation Center, a training facility and meeting location in New York City. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2555", "text": "In 2007, BIOTRONIK was given the EuroPCR 2007 Novelty Award for its innovative absorbable metal stents (AMS) by the European Association of Percutaneous Cardiovascular Interventions (EAPCI).  In 2009, it was nominated for the German Future Prize for its Home Monitoring system by the German Federal Ministry of Education and Research.  In 2010, BIOTRONIK endowed the  Berlin-Brandenburg Academy of Sciences and Humanities ' Technical Science Prize, first awarded to Till Schl\u00f6sser.  The CARDIOSTIM Innovation Award for Practice Improvement was granted to BIOTRONIK for its MRI AutoDetect. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2556", "text": "BIOTRONIK collaborates with the EPIC Alliance, a global network of female electrophysiologists. The alliance aims to enhance collaboration and support for women in the field of electrophysiology."}
{"_id": "WikiPedia_Cardio$$$corpus_2557", "text": "In 2014, Biotronik faced allegations regarding kickback payments to cardiologists, leading to a settlement of nearly five million dollars. [ 21 ] [ 22 ] [ 23 ] [ 24 ]  Currently, another case is ongoing in the California Central District Court. Additionally,"}
{"_id": "WikiPedia_Cardio$$$corpus_2558", "text": "In a landmark case from New Mexico in 2016, a jury found Biotronik negligent for unnecessarily implanting a pacemaker in Tommy Sowards due to an alleged conspiracy involving the company, a salesman, a hospital, and a cardiologist. The lawsuit exposed a scheme where Biotronik paid kickbacks to the cardiologist, significantly inflating his earnings per procedure. Despite later advice from medical professionals that the pacemaker was not needed, it could not be removed without risking heart damage. As a result, the jury awarded Sowards $2.3 million in compensatory damages and $65 million in punitive damages. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2559", "text": "Biotronik is under investigation in the Netherlands, with inquiries initiated in autumn 2020. This investigation, reported by Der Spiegel and the Dutch newspaper NRC Handelsblad, focuses on suspicions that medical specialists received millions of euros to promote Biotronik products. [ 26 ]  Over ten residences have been searched, and assets worth 3.1 million euros belonging to medical specialists have been confiscated. Biotronik has not provided comments on these allegations."}
{"_id": "WikiPedia_Cardio$$$corpus_2560", "text": "In July 2022, Biotronik resolved a prolonged legal dispute in the USA by agreeing to a multimillion dollar settlement. The case involved allegations from two whistleblowers, who were former independent sales representatives, concerning a kick-back scheme. According to the whistleblowers the scheme entailed treating cardiologists to lavish dinners, winery tours, baseball games, strip club visits, and golf outings, sometimes including their spouses or employees. [ 27 ]  Additionally, cardiologists were allegedly compensated for making brief appearances at international conferences or provided with business class flights. Another aspect of the scheme involved a trainee program where Biotronik employees observed cardiologists during the implantation of ICDs, for which the cardiologists were paid $400. [ 28 ] [ 27 ]  Despite concerns raised by the compliance department, the payments continued. The alleged kick-back system, intended to encouraged the use of Biotronik products, occurred between 2013 and 2021. Although Biotronik denied the allegations, they settled with the US authorities without admitting guilt, paying nearly $13 million. [ 29 ] [ 30 ] [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2561", "text": "The  Bueno-Orovio\u2013Cherry\u2013Fenton model , also simply called  Bueno-Orovio model , is a minimal  ionic model  for human  ventricular   cells . [ 1 ]  It belongs to the category of  phenomenological models , because of its characteristic of describing the  electrophysiological  behaviour of  cardiac muscle cells  without taking into account in a detailed way the underlying  physiology  and the specific mechanisms occurring inside the cells. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2562", "text": "This  mathematical model  reproduces both single  cell  and important  tissue -level properties, accounting for physiological  action potential  development and  conduction velocity  estimations. [ 1 ]  \nIt also provides specific parameters choices, derived from parameter-fitting algorithms of the  MATLAB   Optimization Toolbox , for the modeling of epicardial,  endocardial  and  myd-myocardial  tissues. [ 1 ]  \nIn this way it is possible to match the action potential morphologies, observed from experimental data, in the three different regions of the human ventricles. [ 1 ] \nThe Bueno-Orovio\u2013Cherry\u2013Fenton model is also able to describe reentrant and  spiral wave  dynamics, which occurs for instance during  tachycardia  or other types of  arrhythmias . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2563", "text": "From the mathematical perspective, it consists of a system of four  differential equations . [ 1 ]  One  PDE , similar to the  monodomain model , for an adimensional version of the  transmembrane potential , and three  ODEs  that define the evolution of the so-called  gating variables , i.e.  probability density functions  whose aim is to model the fraction of open  ion channels  across a  cell membrane . [ 1 ] [ 4 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2564", "text": "The  system  of four differential equations reads as follows: [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2565", "text": "where  \n \n \n \n \u03a9 \n \n \n {\\displaystyle \\Omega } \n \n  is the spatial domain and  \n \n \n \n T \n \n \n {\\displaystyle T} \n \n  is the final time. The initial conditions are  \n \n \n \n \n u \n \n 0 \n \n \n = \n 0 \n \n \n {\\displaystyle u_{0}=0} \n \n ,  \n \n \n \n \n v \n \n 0 \n \n \n = \n 1 \n \n \n {\\displaystyle v_{0}=1} \n \n ,  \n \n \n \n \n w \n \n 0 \n \n \n = \n 1 \n \n \n {\\displaystyle w_{0}=1} \n \n ,  \n \n \n \n \n s \n \n 0 \n \n \n = \n 0 \n \n \n {\\displaystyle s_{0}=0} \n \n . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2566", "text": "H \n ( \n x \n \u2212 \n \n x \n \n 0 \n \n \n ) \n \n \n {\\displaystyle H(x-x_{0})} \n \n  refers to the  Heaviside function  centered in  \n \n \n \n \n x \n \n 0 \n \n \n \n \n {\\displaystyle x_{0}} \n \n . The adimensional transmembrane potential  \n \n \n \n u \n \n \n {\\displaystyle u} \n \n  can be rescaled in  mV  by means of the  affine transformation   \n \n \n \n \n V \n \n m \n V \n \n \n = \n 85.7 \n u \n \u2212 \n 84 \n \n \n {\\displaystyle V_{mV}=85.7u-84} \n \n . [ 1 ]   \n \n \n \n v \n \n \n {\\displaystyle v} \n \n ,  \n \n \n \n w \n \n \n {\\displaystyle w} \n \n  and  \n \n \n \n s \n \n \n {\\displaystyle s} \n \n  refer to gating variables, where in particular  \n \n \n \n s \n \n \n {\\displaystyle s} \n \n  can be also used as an indication of  intracellular calcium   \n \n \n \n \n \n \n \n C \n a \n \n \n i \n \n \n \n \n 2 \n + \n \n \n \n \n {\\displaystyle {{Ca}_{i}}^{2+}} \n \n  concentration (given in the adimensional range [0, 1] instead of  molar concentration ). [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2567", "text": "All the above-mentioned ionic  density currents  are partially adimensional and are expressed in  \n \n \n \n \n \n \n 1 \n seconds \n \n \n \n \n \n {\\displaystyle {\\dfrac {1}{\\text{seconds}}}} \n \n . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2568", "text": "Different parameters sets, as shown in Table 1, can be used to reproduce the action potential development of epicardial, endocardial and mid-myocardial human ventricular cells. There are some constants of the model, which are not located in Table 1, that can be deduced with the following formulas: [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2569", "text": "where the temporal constants, i.e.  \n \n \n \n \n \u03c4 \n \n v \n \n \n \u2212 \n \n \n , \n \n \u03c4 \n \n w \n \n \n \u2212 \n \n \n , \n \n \u03c4 \n \n s \n o \n \n \n , \n \n \u03c4 \n \n s \n \n \n , \n \n \u03c4 \n \n o \n \n \n \n \n {\\displaystyle \\tau _{v}^{-},\\tau _{w}^{-},\\tau _{so},\\tau _{s},\\tau _{o}} \n \n  are expressed in seconds, whereas  \n \n \n \n \n v \n \n \u221e \n \n \n \n \n {\\displaystyle v_{\\infty }} \n \n  and  \n \n \n \n \n w \n \n \u221e \n \n \n \n \n {\\displaystyle w_{\\infty }} \n \n  are adimensional. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2570", "text": "The diffusion coefficient  \n \n \n \n D \n \n \n {\\displaystyle D} \n \n  results in a value of  \n \n \n \n 1.171 \n \u00b1 \n 0.221 \n \n \n \n \n \n cm \n \n \n 2 \n \n \n seconds \n \n \n \n \n \n {\\displaystyle 1.171\\pm 0.221{\\dfrac {{\\text{cm}}^{2}}{\\text{seconds}}}} \n \n , which comes from experimental tests on human ventricular tissues. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2571", "text": "In order to trigger the action potential development in a certain position of the domain  \n \n \n \n \u03a9 \n \n \n {\\displaystyle \\Omega } \n \n , a forcing term  \n \n \n \n \n J \n \n app \n \n \n ( \n \n x \n \n , \n t \n ) \n \n \n {\\displaystyle J_{\\text{app}}({\\boldsymbol {x}},t)} \n \n , which represents an externally applied density current, is usually added at the right hand side of the PDE and acts for a short time interval only. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2572", "text": "Assume that  \n \n \n \n \n z \n \n \n \n {\\displaystyle {\\boldsymbol {z}}} \n \n  refers to the vector containing all the gating variables, i.e.  \n \n \n \n \n z \n \n = \n [ \n v \n , \n w \n , \n s \n \n ] \n \n T \n \n \n \n \n {\\displaystyle {\\boldsymbol {z}}=[v,w,s]^{T}} \n \n , and  \n \n \n \n \n F \n \n : \n \n \n R \n \n \n 4 \n \n \n \u2192 \n \n \n R \n \n \n 3 \n \n \n \n \n {\\displaystyle {\\boldsymbol {F}}:\\mathbb {R} ^{4}\\rightarrow \\mathbb {R} ^{3}} \n \n  contains the corresponding three right hand sides of the ionic model. The Bueno-Orovio\u2013Cherry\u2013Fenton model can be rewritten in the compact form: [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2573", "text": "Let  \n \n \n \n p \n \u2208 \n U \n = \n \n H \n \n 1 \n \n \n ( \n \u03a9 \n ) \n \n \n {\\displaystyle p\\in U=H^{1}(\\Omega )} \n \n  and  \n \n \n \n \n q \n \n \u2208 \n \n W \n \n = \n [ \n \n L \n \n 2 \n \n \n ( \n \u03a9 \n ) \n \n ] \n \n 3 \n \n \n \n \n {\\displaystyle {\\boldsymbol {q}}\\in {\\boldsymbol {W}}=[L^{2}(\\Omega )]^{3}} \n \n  be two generic test functions. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2574", "text": "To obtain the  weak formulation : [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2575", "text": "Finally the weak formulation reads:"}
{"_id": "WikiPedia_Cardio$$$corpus_2576", "text": "There are several methods to discretize in space this system of equations, such as the  finite element method  (FEM) or  isogeometric analysis  (IGA). [ 7 ] [ 8 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2577", "text": "Time discretization  can be performed in several ways as well, such as using a  backward differentiation formula  (BDF) of order  \n \n \n \n \u03c3 \n \n \n {\\displaystyle \\sigma } \n \n  or a  Runge\u2013Kutta method  (RK). [ 7 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2578", "text": "Let  \n \n \n \n \n \n \n T \n \n \n \n h \n \n \n \n \n {\\displaystyle {\\mathcal {T}}_{h}} \n \n  be a  tessellation  of the computational domain  \n \n \n \n \u03a9 \n \n \n {\\displaystyle \\Omega } \n \n  by means of a certain type of elements (such as  tetrahedrons  or  hexahedra ), with  \n \n \n \n h \n \n \n {\\displaystyle h} \n \n  representing a chosen measure of the size of a single element  \n \n \n \n K \n \u2208 \n \n \n \n T \n \n \n \n h \n \n \n \n \n {\\displaystyle K\\in {\\mathcal {T}}_{h}} \n \n . \nConsider the set  \n \n \n \n \n \n P \n \n \n r \n \n \n ( \n K \n ) \n \n \n {\\displaystyle \\mathbb {P} ^{r}(K)} \n \n  of  polynomials  with degree smaller or equal than  \n \n \n \n r \n \n \n {\\displaystyle r} \n \n  over an element  \n \n \n \n K \n \n \n {\\displaystyle K} \n \n . Define  \n \n \n \n \n \n \n X \n \n \n \n h \n \n \n r \n \n \n = \n { \n f \n \u2208 \n \n C \n \n 0 \n \n \n ( \n \n \n \n \u03a9 \n \u00af \n \n \n \n ) \n : \n f \n \n \n | \n \n \n K \n \n \n \u2208 \n \n \n P \n \n \n r \n \n \n ( \n K \n ) \n \n \n \u2200 \n K \n \u2208 \n \n \n \n T \n \n \n \n h \n \n \n } \n \n \n {\\displaystyle {\\mathcal {X}}_{h}^{r}=\\{f\\in C^{0}({\\bar {\\Omega }}):f|_{K}\\in \\mathbb {P} ^{r}(K)\\,\\,\\forall K\\in {\\mathcal {T}}_{h}\\}} \n \n  as the finite dimensional space, whose dimension is  \n \n \n \n \n N \n \n h \n \n \n = \n dim \n \u2061 \n ( \n \n \n \n X \n \n \n \n h \n \n \n r \n \n \n ) \n \n \n {\\displaystyle N_{h}=\\dim({\\mathcal {X}}_{h}^{r})} \n \n . \nThe set of basis functions of  \n \n \n \n \n \n \n X \n \n \n \n h \n \n \n r \n \n \n \n \n {\\displaystyle {\\mathcal {X}}_{h}^{r}} \n \n  is referred to as  \n \n \n \n { \n \n \u03d5 \n \n i \n \n \n \n } \n \n i \n = \n 1 \n \n \n \n N \n \n h \n \n \n \n \n \n \n {\\displaystyle \\{\\phi _{i}\\}_{i=1}^{N_{h}}} \n \n . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2579", "text": "The semidiscretized formulation of the first equation of the model reads: find  \n \n \n \n \n u \n \n h \n \n \n = \n \n u \n \n h \n \n \n ( \n t \n ) \n = \n \n \u2211 \n \n j \n = \n 1 \n \n \n \n N \n \n h \n \n \n \n \n \n \n \n \n u \n \u00af \n \n \n \n \n j \n \n \n ( \n t \n ) \n \n \u03d5 \n \n j \n \n \n \n \n {\\displaystyle u_{h}=u_{h}(t)=\\sum _{j=1}^{N_{h}}{\\bar {u}}_{j}(t)\\phi _{j}} \n \n  projection of the solution  \n \n \n \n u \n ( \n t \n ) \n \n \n {\\displaystyle u(t)} \n \n  on  \n \n \n \n \n \n \n X \n \n \n \n h \n \n \n r \n \n \n \n \n {\\displaystyle {\\mathcal {X}}_{h}^{r}} \n \n ,  \n \n \n \n \u2200 \n t \n \u2208 \n ( \n 0 \n , \n T \n ) \n \n \n {\\displaystyle \\forall t\\in (0,T)} \n \n , such that [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2580", "text": "with  \n \n \n \n \n u \n \n h \n \n \n ( \n 0 \n ) \n = \n \n \u2211 \n \n j \n = \n 1 \n \n \n \n N \n \n h \n \n \n \n \n \n ( \n \n \n \u222b \n \n \u03a9 \n \n \n \n u \n \n 0 \n \n \n \n \u03d5 \n \n j \n \n \n \n d \n \u03a9 \n \n ) \n \n \n \u03d5 \n \n j \n \n \n \n \n {\\displaystyle u_{h}(0)=\\sum _{j=1}^{N_{h}}\\left(\\int _{\\Omega }u_{0}\\phi _{j}\\,d\\Omega \\right)\\phi _{j}} \n \n ,  \n \n \n \n \n \n z \n \n \n h \n \n \n = \n \n \n z \n \n \n h \n \n \n ( \n t \n ) \n = \n [ \n \n v \n \n h \n \n \n ( \n t \n ) \n , \n \n w \n \n h \n \n \n ( \n t \n ) \n , \n \n s \n \n h \n \n \n ( \n t \n ) \n \n ] \n \n T \n \n \n \n \n {\\displaystyle {\\boldsymbol {z}}_{h}={\\boldsymbol {z}}_{h}(t)=[v_{h}(t),w_{h}(t),s_{h}(t)]^{T}} \n \n  semidiscretized version of the three gating variables, and  \n \n \n \n \n J \n \n ion \n \n \n ( \n \n u \n \n h \n \n \n , \n \n \n z \n \n \n h \n \n \n ) \n = \n \n J \n \n f \n i \n \n \n ( \n \n u \n \n h \n \n \n , \n \n \n z \n \n \n h \n \n \n ) \n + \n \n J \n \n s \n o \n \n \n ( \n \n u \n \n h \n \n \n , \n \n \n z \n \n \n h \n \n \n ) \n + \n \n J \n \n s \n i \n \n \n ( \n \n u \n \n h \n \n \n , \n \n \n z \n \n \n h \n \n \n ) \n \n \n {\\displaystyle J_{\\text{ion}}(u_{h},{\\boldsymbol {z}}_{h})=J_{fi}(u_{h},{\\boldsymbol {z}}_{h})+J_{so}(u_{h},{\\boldsymbol {z}}_{h})+J_{si}(u_{h},{\\boldsymbol {z}}_{h})} \n \n  is the total ionic density current. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2581", "text": "The space discretized version of the first equation can be rewritten as a system of non-linear ODEs by setting  \n \n \n \n \n \n U \n \n \n h \n \n \n ( \n t \n ) \n = \n { \n \n \n \n \n u \n \u00af \n \n \n \n \n j \n \n \n ( \n t \n ) \n \n } \n \n j \n = \n 1 \n \n \n \n N \n \n h \n \n \n \n \n \n \n {\\displaystyle {\\boldsymbol {U}}_{h}(t)=\\{{\\bar {u}}_{j}(t)\\}_{j=1}^{N_{h}}} \n \n  and  \n \n \n \n \n \n Z \n \n \n h \n \n \n ( \n t \n ) \n = \n { \n \n \n \n \n z \n \u00af \n \n \n \n \n j \n \n \n ( \n t \n ) \n \n } \n \n j \n = \n 1 \n \n \n \n N \n \n h \n \n \n \n \n \n \n {\\displaystyle {\\boldsymbol {Z}}_{h}(t)=\\{{\\bar {\\boldsymbol {z}}}_{j}(t)\\}_{j=1}^{N_{h}}} \n \n : [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2582", "text": "where  \n \n \n \n \n \n M \n \n \n i \n j \n \n \n = \n \n \u222b \n \n \u03a9 \n \n \n \n \u03d5 \n \n j \n \n \n \n \u03d5 \n \n i \n \n \n \n d \n \u03a9 \n \n \n {\\displaystyle \\mathbb {M} _{ij}=\\int _{\\Omega }\\phi _{j}\\phi _{i}\\,d\\Omega } \n \n ,  \n \n \n \n \n \n K \n \n \n i \n j \n \n \n = \n \n \u222b \n \n \u03a9 \n \n \n D \n \u2207 \n \n \u03d5 \n \n j \n \n \n \u22c5 \n \u2207 \n \n \u03d5 \n \n i \n \n \n \n d \n \u03a9 \n \n \n {\\displaystyle \\mathbb {K} _{ij}=\\int _{\\Omega }D\\nabla \\phi _{j}\\cdot \\nabla \\phi _{i}\\,d\\Omega } \n \n  and\n \n \n \n \n \n \n ( \n \n \n \n J \n \n \n ion \n \n \n ( \n \n \n U \n \n \n h \n \n \n ( \n t \n ) \n , \n \n \n z \n \n \n h \n \n \n ( \n t \n ) \n ) \n \n ) \n \n \n i \n \n \n = \n \n \u222b \n \n \u03a9 \n \n \n \n J \n \n ion \n \n \n ( \n \n u \n \n h \n \n \n , \n \n \n z \n \n \n h \n \n \n ) \n \n \u03d5 \n \n i \n \n \n \n d \n \u03a9 \n \n \n {\\displaystyle \\left({\\boldsymbol {J}}_{\\text{ion}}({\\boldsymbol {U}}_{h}(t),{\\boldsymbol {z}}_{h}(t))\\right)_{i}=\\int _{\\Omega }J_{\\text{ion}}(u_{h},{\\boldsymbol {z}}_{h})\\phi _{i}\\,d\\Omega } \n \n . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2583", "text": "The non-linear term  \n \n \n \n \n \n J \n \n \n ion \n \n \n ( \n \n \n U \n \n \n h \n \n \n ( \n t \n ) \n , \n \n \n Z \n \n \n h \n \n \n ( \n t \n ) \n ) \n \n \n {\\displaystyle {\\boldsymbol {J}}_{\\text{ion}}({\\boldsymbol {U}}_{h}(t),{\\boldsymbol {Z}}_{h}(t))} \n \n  can be treated in different ways, such as using state variable interpolation (SVI) or ionic currents interpolation (ICI). [ 9 ] [ 10 ] \nIn the framework of SVI, by denoting with  \n \n \n \n { \n \n \n x \n \n \n s \n \n \n K \n \n \n \n } \n \n s \n = \n 1 \n \n \n \n N \n \n q \n \n \n \n \n \n \n {\\displaystyle \\{{\\boldsymbol {x}}_{s}^{K}\\}_{s=1}^{N_{q}}} \n \n  and  \n \n \n \n { \n \n \u03c9 \n \n s \n \n \n K \n \n \n \n } \n \n s \n = \n 1 \n \n \n \n N \n \n q \n \n \n \n \n \n \n {\\displaystyle \\{\\omega _{s}^{K}\\}_{s=1}^{N_{q}}} \n \n  the  quadrature  nodes and weights of a generic element of the mesh  \n \n \n \n K \n \u2208 \n \n \n \n T \n \n \n \n h \n \n \n \n \n {\\displaystyle K\\in {\\mathcal {T}}_{h}} \n \n , both  \n \n \n \n \n u \n \n h \n \n \n \n \n {\\displaystyle u_{h}} \n \n  and  \n \n \n \n \n \n z \n \n \n h \n \n \n \n \n {\\displaystyle {\\boldsymbol {z}}_{h}} \n \n  are evaluated at the quadrature nodes: [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2584", "text": "The equations for the three gating variables, which are ODEs, are directly solved in all the  degrees of freedom  (DOF) of the tessellation  \n \n \n \n \n \n \n T \n \n \n \n h \n \n \n \n \n {\\displaystyle {\\mathcal {T}}_{h}} \n \n  separately, leading to the following semidiscrete form: [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2585", "text": "With reference to the time interval  \n \n \n \n ( \n 0 \n , \n T \n ] \n \n \n {\\displaystyle (0,T]} \n \n , let  \n \n \n \n \u0394 \n t \n = \n \n \n \n T \n N \n \n \n \n \n \n {\\displaystyle \\Delta t={\\dfrac {T}{N}}} \n \n  be the chosen time step, with  \n \n \n \n N \n \n \n {\\displaystyle N} \n \n  number of subintervals. A uniform partition in time  \n \n \n \n [ \n \n t \n \n 0 \n \n \n = \n 0 \n , \n \n t \n \n 1 \n \n \n = \n \u0394 \n t \n , \n \u2026 \n , \n \n t \n \n k \n \n \n , \n \u2026 \n , \n \n t \n \n N \n \u2212 \n 1 \n \n \n , \n \n t \n \n N \n \n \n = \n T \n ] \n \n \n {\\displaystyle [t_{0}=0,t_{1}=\\Delta t,\\ldots ,t_{k},\\ldots ,t_{N-1},t_{N}=T]} \n \n  is finally obtained. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2586", "text": "At this stage, the full discretization of the Bueno-Orovio ionic model can be performed both in a monolithic and segregated fashion. [ 11 ] \nWith respect to the first methodology (the monolithic one), at time  \n \n \n \n t \n = \n \n t \n \n k \n \n \n \n \n {\\displaystyle t=t^{k}} \n \n , the full problem is entirely solved in one step in order to get  \n \n \n \n ( \n \n \n U \n \n \n h \n \n \n k \n + \n 1 \n \n \n , \n \n \n Z \n \n \n h \n \n \n k \n + \n 1 \n \n \n ) \n \n \n {\\displaystyle ({\\boldsymbol {U}}_{h}^{k+1},{\\boldsymbol {Z}}_{h}^{k+1})} \n \n  by means of either  Newton method  or  Fixed-point iterations : [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2587", "text": "where  \n \n \n \n \n \n U \n \n \n \n ext \n \n , \n h \n \n \n k \n \n \n \n \n {\\displaystyle {\\boldsymbol {U}}_{{\\text{ext}},h}^{k}} \n \n  and  \n \n \n \n \n \n Z \n \n \n \n ext \n \n , \n h \n \n \n k \n \n \n \n \n {\\displaystyle {\\boldsymbol {Z}}_{{\\text{ext}},h}^{k}} \n \n  are extrapolations of transmembrane potential and gating variables at previous timesteps with respect to  \n \n \n \n \n t \n \n k \n + \n 1 \n \n \n \n \n {\\displaystyle t^{k+1}} \n \n , considering as many time instants as the order  \n \n \n \n \u03c3 \n \n \n {\\displaystyle \\sigma } \n \n  of the BDF scheme.  \n \n \n \n \u03b1 \n \n \n {\\displaystyle \\alpha } \n \n  is a coefficient which depends on the BDF order  \n \n \n \n \u03c3 \n \n \n {\\displaystyle \\sigma } \n \n . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2588", "text": "If a segregated method is employed, the equation for the evolution in time of the transmembrane potential and the ones of the gating variables are numerically solved separately: [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2589", "text": "Another possible segregated scheme would be the one in which  \n \n \n \n \n \n U \n \n \n h \n \n \n k \n + \n 1 \n \n \n \n \n {\\displaystyle {\\boldsymbol {U}}_{h}^{k+1}} \n \n  is calculated first, and then it is used in the equations for  \n \n \n \n \n \n Z \n \n \n h \n \n \n k \n + \n 1 \n \n \n \n \n {\\displaystyle {\\boldsymbol {Z}}_{h}^{k+1}} \n \n . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2590", "text": "A  bundle branch block  is a partial or complete interruption in the flow of electrical impulses in either of the  bundle branches  of the   heart's electrical system . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2591", "text": "The  heart's electrical activity  begins in the  sinoatrial node  (the heart's natural  pacemaker ), which is situated on the upper right  atrium . The impulse travels next through the left and right atria and summates at the  atrioventricular node . From the AV node the electrical impulse travels down the  bundle of His  and divides into the right and left  bundle branches . The right bundle branch contains one  fascicle . The left bundle branch subdivides into two fascicles: the  left anterior fascicle , and the  left posterior fascicle . Other sources divide the left bundle branch into three fascicles: the left anterior, the left posterior, and the left septal fascicle. The thicker left posterior fascicle bifurcates, with one fascicle being in the septal aspect.  Ultimately, the fascicles divide into millions of  Purkinje fibres , which in turn interdigitate with individual cardiac myocytes, allowing for rapid, coordinated, and synchronous physiologic depolarization of the ventricles. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2592", "text": "When a bundle branch or fascicle becomes injured (by underlying  heart disease ,  myocardial infarction , or cardiac surgery), it may cease to conduct electrical impulses appropriately. This results in altered pathways for ventricular depolarization. Since the electrical impulse can no longer use the preferred pathway across the bundle branch, it may move instead through muscle fibers in a way that both slows the electrical movement and changes the directional propagation of the impulses. As a result, there is a loss of ventricular synchrony, ventricular depolarization is prolonged, and there may be a corresponding drop in cardiac output. When  heart failure  is present, a specialized  pacemaker  may be used to resynchronize the ventricles. In theory a pacemaker like this will shorten the  QRS  interval, thus bringing the timing of contraction of the left and right ventricles closer together and slightly increasing the  ejection fraction . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2593", "text": "A bundle branch block can be diagnosed when the duration of the  QRS complex  on the  ECG  exceeds 120 ms. A right bundle branch block typically causes prolongation of the last part of the QRS complex and may shift the heart's electrical axis slightly to the right. The ECG will show a terminal R wave in lead V1 and a slurred S wave in lead I.\nLeft bundle branch block widens the entire QRS, and in most cases shifts the heart's electrical axis to the left. The ECG will show a QS or rS complex in lead V1 and a monophasic R wave in lead I. Another normal finding with bundle branch block is appropriate T wave discordance. In other words, the T wave will be deflected opposite the terminal deflection of the QRS complex.\nBundle branch block, especially left bundle branch block, can lead to cardiac dyssynchrony. The simultaneous occurrence of left and right bundle branch block leads to total AV block."}
{"_id": "WikiPedia_Cardio$$$corpus_2594", "text": "Depending on the anatomical location of the defect which leads to a bundle branch block, the blocks are further classified into:"}
{"_id": "WikiPedia_Cardio$$$corpus_2595", "text": "The left bundle branch block can be further sub classified into:"}
{"_id": "WikiPedia_Cardio$$$corpus_2596", "text": "Other classifications of bundle branch blocks are;"}
{"_id": "WikiPedia_Cardio$$$corpus_2597", "text": "A simple way to quickly differentiate between the two types is to note the deflection of the QRS complex in the V1 lead. A (V1) QRS segment deflected down indicates left bundle branch block, while a deflection up indicates right bundle branch block. In both types, the QRS is wide (> 0.12 seconds)."}
{"_id": "WikiPedia_Cardio$$$corpus_2598", "text": "Some people with bundle branch blocks are born with this condition. Many others acquire it as a consequence of heart disease. People with bundle branch blocks may still be quite active, and may have nothing more remarkable than an abnormal appearance to their ECG.  However, when bundle blocks are complex and diffuse in the bundle systems, or are associated with additional and significant ventricular muscle damage, they may be a sign of serious underlying heart disease. In more severe cases, a  pacemaker  may be required to restore an optimal electrical supply to the heart muscle. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2599", "text": "The  bundle of His  ( BH ) [ 1 ] :\u200a58\u200a  or  His bundle  ( HB ) [ 1 ] :\u200a232\u200a  ( / h \u026a s /  \"hiss\" [ 2 ] ) is a collection of  heart muscle cells  specialized for  electrical conduction . As part of the  electrical conduction system of the heart , it transmits the  electrical impulses  from the  atrioventricular node  (located between the  atria  and the  ventricles ) to the point of the apex of the fascicular branches via the  bundle branches . The fascicular branches then lead to the  Purkinje fibers , which provide electrical conduction to the ventricles, causing the  cardiac muscle  of the ventricles to  contract  at a  paced  interval."}
{"_id": "WikiPedia_Cardio$$$corpus_2600", "text": "The bundle of His is an important part of the  electrical conduction system of the heart , as it transmits  impulses  from the atrioventricular node, located at the anterior-inferior end of the  interatrial septum , to the ventricles of the heart. The bundle of His branches into the left and the right  bundle branches , which run along the  interventricular septum . The left bundle branch further divides into the  left anterior fascicle  and the  left posterior fascicle . These bundles and fascicles give rise to thin filaments known as  Purkinje fibers . These fibers distribute the impulse to the ventricular muscle. The ventricular conduction system comprises the bundle branches and the Purkinje networks. It takes about 0.03\u20130.04 seconds for the impulse to travel from the bundle of His to the  ventricular muscle ."}
{"_id": "WikiPedia_Cardio$$$corpus_2601", "text": "Disorders affecting the  cardiomyocytes  that make up the electrical conduction system of the heart are called  heart blocks . Heart blocks are separated into different categories based on the location of the cellular damage. Damage to any of the conducting cells in or below the bundle of His is collectively referred to as \"infra-Hisian blocks\". To be specific, blocks that occur in the right or left bundle branches are called \" bundle branch blocks \", and those that occur in either the left anterior or the left posterior fascicles are called \"fascicular blocks\", or \"hemiblocks\". The conditions in which both the right bundle branch and either the left anterior fascicle or the left posterior fascicle are blocked are collectively referred to as  bifascicular blocks , and the condition in which the right bundle branch, the left anterior fascicle, and the left posterior fascicle are blocked is called  trifascicular block . Infra-hisian blocks limit the heart's ability to coordinate the activities of the atria and ventricles, which usually results in a decrease in its efficiency in pumping blood."}
{"_id": "WikiPedia_Cardio$$$corpus_2602", "text": "A 2000 study found that direct His bundle pacing is more effective in producing synchronized ventricular contraction\u2014and therefore in improving cardiac function\u2014than  apical  pacing. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2603", "text": "These specialized muscle fibers in the heart were named after the  Swiss   cardiologist   Wilhelm His Jr. , who discovered them in 1893. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2604", "text": "In  neuroscience , classical  cable theory  uses  mathematical models  to calculate the  electric current  (and accompanying  voltage ) along passive [ a ]   neurites , particularly the  dendrites  that receive  synaptic  inputs at different sites and times. Estimates are made by modeling dendrites and  axons  as cylinders composed of segments with  capacitances   \n \n \n \n \n c \n \n m \n \n \n \n \n {\\displaystyle c_{m}} \n \n  and  resistances   \n \n \n \n \n r \n \n m \n \n \n \n \n {\\displaystyle r_{m}} \n \n  combined in parallel (see Fig. 1). The capacitance of a neuronal fiber comes about because  electrostatic  forces are acting through the very thin lipid bilayer (see Figure 2). The resistance in series along the fiber  \n \n \n \n \n r \n \n l \n \n \n \n \n {\\displaystyle r_{l}} \n \n  is due to the  axoplasm 's significant resistance to movement of  electric charge ."}
{"_id": "WikiPedia_Cardio$$$corpus_2605", "text": "Cable theory in computational  neuroscience  has roots leading back to the 1850s, when Professor  William Thomson  (later known as Lord Kelvin) began developing mathematical models of signal decay in submarine (underwater) telegraphic cables. The models resembled the partial differential equations used by  Fourier  to describe heat conduction in a wire."}
{"_id": "WikiPedia_Cardio$$$corpus_2606", "text": "The 1870s saw the first attempts by Hermann to model  neuronal   electrotonic potentials  also by focusing on analogies with heat conduction. However, it was Hoorweg who first discovered the analogies with Kelvin's undersea cables in 1898 and then Hermann and Cremer who independently developed the cable theory for neuronal fibers in the early 20th century. Further mathematical theories of nerve fiber conduction based on cable theory were developed by Cole and  Hodgkin  (1920s\u20131930s), Offner et al. (1940), and Rushton (1951)."}
{"_id": "WikiPedia_Cardio$$$corpus_2607", "text": "Experimental evidence for the importance of cable theory in modelling the behavior of  axons  began surfacing in the 1930s from work done by Cole, Curtis, Hodgkin,  Sir Bernard Katz , Rushton, Tasaki and others. Two key papers from this era are those of Davis and  Lorente de N\u00f3  (1947) and Hodgkin and Rushton (1946)."}
{"_id": "WikiPedia_Cardio$$$corpus_2608", "text": "The 1950s saw improvements in techniques for measuring the electric activity of individual  neurons . Thus cable theory became important for analyzing data collected from intracellular microelectrode recordings and for analyzing the electrical properties of neuronal  dendrites . Scientists like Coombs,  Eccles , Fatt, Frank, Fuortes and others now relied heavily on cable theory to obtain functional insights of neurons and for guiding them in the design of new experiments."}
{"_id": "WikiPedia_Cardio$$$corpus_2609", "text": "Later, cable theory with its mathematical derivatives allowed ever more sophisticated  neuron models  to be explored by workers such as Jack,  Rall , Redman, Rinzel, Idan Segev, Tuckwell, Bell, and Iannella. More recently, cable theory has been applied to model electrical activity in bundled neurons in the white matter of the brain. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2610", "text": "Note, various conventions of  r m  exist.\nHere  r m  and  c m , as introduced above, are measured per membrane-length unit (per meter (m)). Thus  r m  is measured in  ohm \u00b7meters (\u03a9\u00b7m) and  c m  in  farads  per meter (F/m). This is in contrast to  R m  (in \u03a9\u00b7m 2 ) and  C m  (in F/m 2 ), which represent the specific resistance and capacitance respectively of one unit area of membrane (in m 2 ). Thus, if the radius,  a , of the axon is known, [ b ]  then its circumference is 2 \u03c0a , and its  r m , and its  c m  values can be calculated as:"}
{"_id": "WikiPedia_Cardio$$$corpus_2611", "text": "These relationships make sense intuitively, because the greater the circumference of the axon, the greater the area for charge to escape through its membrane, and therefore the lower the membrane resistance (dividing  R m  by 2 \u03c0a ); and the more membrane available to store charge (multiplying  C m  by 2 \u03c0a ).\nThe  specific electrical resistance ,  \u03c1 l , of the axoplasm allows one to calculate the longitudinal intracellular resistance per unit length,  r l , (in \u03a9\u00b7m \u22121 ) by the equation:"}
{"_id": "WikiPedia_Cardio$$$corpus_2612", "text": "The greater the cross sectional area of the axon,  \u03c0a 2 , the greater the number of paths for the charge to flow through its axoplasm, and the lower the axoplasmic resistance."}
{"_id": "WikiPedia_Cardio$$$corpus_2613", "text": "Several important avenues of extending classical cable theory have recently seen the introduction of endogenous structures in order to analyze the effects of protein polarization within dendrites and different synaptic input distributions over the dendritic surface of a neuron."}
{"_id": "WikiPedia_Cardio$$$corpus_2614", "text": "To better understand how the cable equation is derived, first simplify the theoretical neuron even further and pretend it has a perfectly sealed membrane ( r m =\u221e) with no loss of current to the outside, and no capacitance ( c m \u00a0= 0). A current injected into the fiber  [ c ]  at position  x \u00a0= 0 would move along the inside of the fiber unchanged. Moving away from the point of injection and by using  Ohm's law  ( V \u00a0=\u00a0 IR ) we can calculate the voltage change as:"}
{"_id": "WikiPedia_Cardio$$$corpus_2615", "text": "where the negative is because current flows down the potential gradient."}
{"_id": "WikiPedia_Cardio$$$corpus_2616", "text": "Letting \u0394 x  go towards zero and having infinitely small increments of  x , one can write ( 4 ) as:"}
{"_id": "WikiPedia_Cardio$$$corpus_2617", "text": "or"}
{"_id": "WikiPedia_Cardio$$$corpus_2618", "text": "Bringing  r m  back into the picture is like making holes in a garden hose. The more holes, the faster the water will escape from the hose, and the less water will travel all the way from the beginning of the hose to the end. Similarly, in an axon, some of the current traveling longitudinally through the axoplasm will escape through the membrane."}
{"_id": "WikiPedia_Cardio$$$corpus_2619", "text": "If  i m  is the current escaping through the membrane per length unit, m, then the total current escaping along  y  units must be  y\u00b7i m . Thus, the change of current in the axoplasm, \u0394 i l , at distance, \u0394 x , from position  x =0 can be written as:"}
{"_id": "WikiPedia_Cardio$$$corpus_2620", "text": "or, using continuous, infinitesimally small increments:"}
{"_id": "WikiPedia_Cardio$$$corpus_2621", "text": "i \n \n m \n \n \n \n \n {\\displaystyle i_{m}} \n \n  can be expressed with yet another formula, by including the capacitance. The capacitance will cause a flow of charge (a current) towards the membrane on the side of the cytoplasm. This current is usually referred to as displacement current (here denoted  \n \n \n \n \n i \n \n c \n \n \n \n \n {\\displaystyle i_{c}} \n \n .) The flow will only take place as long as the membrane's storage capacity has not been reached.  \n \n \n \n \n i \n \n c \n \n \n \n \n {\\displaystyle i_{c}} \n \n  can then be expressed as:"}
{"_id": "WikiPedia_Cardio$$$corpus_2622", "text": "where  \n \n \n \n \n c \n \n m \n \n \n \n \n {\\displaystyle c_{m}} \n \n  is the membrane's capacitance and  \n \n \n \n \n \u2202 \n V \n \n \n / \n \n \n \u2202 \n t \n \n \n \n {\\displaystyle {\\partial V}/{\\partial t}} \n \n  is the change in voltage over time. \nThe current that passes the membrane ( \n \n \n \n \n i \n \n r \n \n \n \n \n {\\displaystyle i_{r}} \n \n ) can be expressed as:"}
{"_id": "WikiPedia_Cardio$$$corpus_2623", "text": "and because  \n \n \n \n \n i \n \n m \n \n \n = \n \n i \n \n r \n \n \n + \n \n i \n \n c \n \n \n \n \n {\\displaystyle i_{m}=i_{r}+i_{c}} \n \n  the following equation for  \n \n \n \n \n i \n \n m \n \n \n \n \n {\\displaystyle i_{m}} \n \n  can be derived if no additional current is added from an electrode:"}
{"_id": "WikiPedia_Cardio$$$corpus_2624", "text": "where  \n \n \n \n \n \u2202 \n \n i \n \n l \n \n \n \n \n / \n \n \n \u2202 \n x \n \n \n \n {\\displaystyle {\\partial i_{l}}/{\\partial x}} \n \n  represents the change per unit length of the longitudinal current."}
{"_id": "WikiPedia_Cardio$$$corpus_2625", "text": "Combining equations ( 6 ) and ( 11 ) gives a first version of a cable equation:"}
{"_id": "WikiPedia_Cardio$$$corpus_2626", "text": "which is a second-order  partial differential equation  (PDE)."}
{"_id": "WikiPedia_Cardio$$$corpus_2627", "text": "By a simple rearrangement of equation ( 12 ) (see later) it is possible to make two important terms appear, namely the length constant (sometimes referred to as the space constant) denoted  \n \n \n \n \u03bb \n \n \n {\\displaystyle \\lambda } \n \n  and the time constant denoted  \n \n \n \n \u03c4 \n \n \n {\\displaystyle \\tau } \n \n . The following sections focus on these terms."}
{"_id": "WikiPedia_Cardio$$$corpus_2628", "text": "The length constant,  \n \n \n \n \u03bb \n \n \n {\\displaystyle \\lambda } \n \n  (lambda), is a parameter that indicates how far a stationary current will influence the voltage along the cable. The larger the value of  \n \n \n \n \u03bb \n \n \n {\\displaystyle \\lambda } \n \n , the farther the charge will flow. The length constant can be expressed as:"}
{"_id": "WikiPedia_Cardio$$$corpus_2629", "text": "The larger the membrane resistance,  r m , the greater the value of  \n \n \n \n \u03bb \n \n \n {\\displaystyle \\lambda } \n \n , and the more current will remain inside the axoplasm to travel longitudinally through the axon. The higher the axoplasmic resistance,  \n \n \n \n \n r \n \n l \n \n \n \n \n {\\displaystyle r_{l}} \n \n , the smaller the value of  \n \n \n \n \u03bb \n \n \n {\\displaystyle \\lambda } \n \n , the harder it will be for current to travel through the axoplasm, and the shorter the current will be able to travel.\nIt is possible to solve equation ( 12 ) and arrive at the following equation (which is valid in steady-state conditions, i.e. when time approaches infinity):"}
{"_id": "WikiPedia_Cardio$$$corpus_2630", "text": "Where  \n \n \n \n \n V \n \n 0 \n \n \n \n \n {\\displaystyle V_{0}} \n \n  is the depolarization at  \n \n \n \n x \n = \n 0 \n \n \n {\\displaystyle x=0} \n \n  (point of current injection),  e  is the exponential constant (approximate value 2.71828) and  \n \n \n \n \n V \n \n x \n \n \n \n \n {\\displaystyle V_{x}} \n \n  is the voltage at a given distance  x  from  x =0. When  \n \n \n \n x \n = \n \u03bb \n \n \n {\\displaystyle x=\\lambda } \n \n  then"}
{"_id": "WikiPedia_Cardio$$$corpus_2631", "text": "and"}
{"_id": "WikiPedia_Cardio$$$corpus_2632", "text": "which means that when we measure  \n \n \n \n V \n \n \n {\\displaystyle V} \n \n  at distance  \n \n \n \n \u03bb \n \n \n {\\displaystyle \\lambda } \n \n  from  \n \n \n \n x \n = \n 0 \n \n \n {\\displaystyle x=0} \n \n  we get"}
{"_id": "WikiPedia_Cardio$$$corpus_2633", "text": "Thus  \n \n \n \n \n V \n \n \u03bb \n \n \n \n \n {\\displaystyle V_{\\lambda }} \n \n  is always 36.8 percent of  \n \n \n \n \n V \n \n 0 \n \n \n \n \n {\\displaystyle V_{0}} \n \n ."}
{"_id": "WikiPedia_Cardio$$$corpus_2634", "text": "Neuroscientists are often interested in knowing how fast the membrane potential,  \n \n \n \n \n V \n \n m \n \n \n \n \n {\\displaystyle V_{m}} \n \n , of an axon changes in response to changes in the current injected into the axoplasm. The time constant,  \n \n \n \n \u03c4 \n \n \n {\\displaystyle \\tau } \n \n , is an index that provides information about that value.  \n \n \n \n \u03c4 \n \n \n {\\displaystyle \\tau } \n \n  can be calculated as:"}
{"_id": "WikiPedia_Cardio$$$corpus_2635", "text": "The larger the membrane capacitance,  \n \n \n \n \n c \n \n m \n \n \n \n \n {\\displaystyle c_{m}} \n \n , the more current it takes to charge and discharge a patch of membrane and the longer this process will take. The larger the membrane resistance  \n \n \n \n \n r \n \n m \n \n \n \n \n {\\displaystyle r_{m}} \n \n , the harder it is for a current to induce a change in membrane potential. So the higher the  \n \n \n \n \u03c4 \n \n \n {\\displaystyle \\tau } \n \n  the slower the nerve impulse can travel. That means, membrane potential (voltage across the membrane) lags more behind current injections. Response times vary from 1\u20132 milliseconds in neurons that are processing information that needs high temporal precision to 100 milliseconds or longer. A typical response time is around 20 milliseconds."}
{"_id": "WikiPedia_Cardio$$$corpus_2636", "text": "If one multiplies equation ( 12 ) by  \n \n \n \n \n r \n \n m \n \n \n \n \n {\\displaystyle r_{m}} \n \n  on both sides of the equal sign we get:"}
{"_id": "WikiPedia_Cardio$$$corpus_2637", "text": "and recognize  \n \n \n \n \n \u03bb \n \n 2 \n \n \n = \n \n \n r \n \n m \n \n \n \n \n / \n \n \n \n r \n \n l \n \n \n \n \n \n {\\displaystyle \\lambda ^{2}={r_{m}}/{r_{l}}} \n \n  on the left side and  \n \n \n \n \u03c4 \n = \n \n c \n \n m \n \n \n \n r \n \n m \n \n \n \n \n {\\displaystyle \\tau =c_{m}r_{m}} \n \n  on the right side. The cable equation can now be written in its perhaps best known form:"}
{"_id": "WikiPedia_Cardio$$$corpus_2638", "text": "This is a 1D  heat equation  or  diffusion equation  for which many solution methods, such as Green's functions and Fourier methods, have been developed."}
{"_id": "WikiPedia_Cardio$$$corpus_2639", "text": "It is also a special degenerate case of the  Telegrapher's equation , where the inductance  \n \n \n \n L \n \n \n {\\displaystyle L} \n \n  vanishes and the signal propagation speed  \n \n \n \n 1 \n \n / \n \n \n \n L \n C \n \n \n \n \n {\\displaystyle 1/{\\sqrt {LC}}} \n \n  is infinite."}
{"_id": "WikiPedia_Cardio$$$corpus_2640", "text": "Cameron Health  was a  medical device  developer based in  San Clemente, California , US. Cameron Health had its European office, Cameron Health BV, in  Arnhem ,  The Netherlands . The privately held company's focus was on a new generation of minimally invasive  implantable cardioverter-defibrillator  (ICD) which they called a Subcutaneous Implantable Defibrillator (S-ICD). Cameron Health's approach avoided implanting transvenous leads into the  heart , which had been the usual procedure for cardiac devices. Instead, the Cameron ICD was entirely implanted outside the thoracic wall."}
{"_id": "WikiPedia_Cardio$$$corpus_2641", "text": "In June 2012,  Boston Scientific  acquired Cameron Health for a total sum of $1.3 Billion, paid out incrementally as various revenue milestones were achieved. [ 1 ]  As of February 2016 [update] , Boston Scientific still markets the S-ICD system. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2642", "text": "Every ICD is designed to detect heart rhythms consistent with a catastrophic failure of the body's natural regulation of the heartbeat, which, untreated, could result in death. When an ICD detects a serious  arrhythmia , it issues an electrical impulse to the heart muscle, of a magnitude sufficient to cause the heart to revert to a normal rhythm.  ICDs with transvenous leads administer this shock to the interior of the heart muscle; the Cameron Health device generated a more powerful shock which can be effective from outside the heart.  In the view of Cameron Health, transvenous leads into the heart needlessly complicated the process of implanting a device, and raised other issues and risks which their less invasive approach avoids. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2643", "text": "The Cameron Health subcutaneous ICD sat outside the ribcage and has no connection to the interior of the heart.  The surgical procedure for implantation was minimally invasive as opposed to the traditional procedure of threading leads into the subclavian venous system, through the  superior vena cava  and into one or more endocardial areas of the heart, a procedure often requiring a  cardiologist  with specialized training in  electrophysiology . [ 4 ]  In addition to the risks inherent in cardiac surgery, the leads have themselves proved to be a weakness in some ICD designs. [ 5 ]  According to one estimate, patients with ICDs have a 20 percent chance of lead failure within 10 years, and replacing the leads carries a risk of death of between two and five percent. [ 6 ]  Some device manufacturers have had to replace defective leads which exposed implanted individuals to unnecessary shocks or other malfunctions, in some cases possibly resulting in fatalities. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2644", "text": "The Cameron Health S-ICD had the disadvantage of being somewhat bulkier than existing ICDs. [ 6 ]  Also, this kind of ICD did not include a pacemaker, which narrowed the range of patients for whom it would be appropriate; it was estimated that a majority of patients receiving combination pacemaker/ICD implants would qualify for a pure ICD. These patients tended to have genetic or other conditions predisposing them to sudden cardiac death due to a failure of the heart of maintain a normal rhythm. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2645", "text": "A trial involving 53 patients, who were temporarily implanted with S-ICDs, was reported in 2005 at the  European Society of Cardiology  Congress. [ 10 ]  \nA second series of 55 trial patients was conducted in 2008 and 2009 in 10 centers in  Europe  and  New Zealand .  Of the 55 patients, 53 had two instances of  fibrillation  and in 52 these were successfully converted.  These findings were reported to European Union authorities in 2009, and resulted in approval for marketing the device.  A study of 300 patients is in progress for US approvals. [ 6 ] [ 11 ]   Small nonrandomized early-phase studies primarily intended to show the feasibility of an entirely subcutaneous ICD were updated, combined and published in May 2010.  In this report,  the system successfully and consistently detected and converted episodes of ventricular fibrillation that were induced during electrophysiological testing. In the European trial of 55 patients, after 46 patient-years of follow-up, 54 of 55 patients were alive, and the single death was due to renal failure. In this trial the system successfully detected and treated 12 episodes (100%)of spontaneous, sustained ventricular tachyarrhythmia in three patients,  prior to the onset of syncope, and with no adverse events. One of the three patients was successfully treated for seven successive episodes of  ventricular tachycardia , a condition known as a  \"VT storm\"."}
{"_id": "WikiPedia_Cardio$$$corpus_2646", "text": "Boston Scientific acquired an exclusive option to purchase Cameron Health in 2004, and made an undisclosed equity investment in the company at that time. [ 12 ]  \nIn 2008, several additional investors organized by the investment company  Piper Jaffray [ 13 ]  \nand including PTV Healthcare Capital, Delphi Ventures, Sorrento Ventures, Three Arch Partners and  Versant Ventures  provided just over $50 million to finance the continuing operation of the company. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2647", "text": "In June 2012, Boston Scientific officially acquired Cameron Health for a total sum of $1.3 Billion, paid out incrementally as various revenue milestones were achieved. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2648", "text": "Cardiac aberrancy  is a type of disruption in the shape of the  electrocardiogram  signal, representing abnormal activation of the ventricular heart muscle via the  electrical conduction system of the heart .\nNormal activation utilizes the  bundle of His  and  Purkinje fibers  to produce a narrow (QRS) electrical signal.\nAberration occurs when the electrical activation of the heart, which is caused by a series of  action potentials , is conducting improperly which can result in temporary changes in the morphology that looks like:"}
{"_id": "WikiPedia_Cardio$$$corpus_2649", "text": "This is in contrast to a permanent dysfunction of the electrical pathways that produces wide QRS complexes in one of the above patterns or combinations of patterns (ie,  bifascicular block )."}
{"_id": "WikiPedia_Cardio$$$corpus_2650", "text": "In the context of  atrial fibrillation , the  Ashman phenomenon  is a form of aberrancy."}
{"_id": "WikiPedia_Cardio$$$corpus_2651", "text": "Aberrancy is due to prematurity in which part of the conduction system is still  refractory  and cannot conduct the premature depolarization. This effect can sometimes be seen in the setting of a faster heart rate ( tachycardia ) and so is termed \"rate-related aberrancy.\" After the first aberrant complex, subsequent complexes may be wide due to  concealed conduction  rather than aberrancy."}
{"_id": "WikiPedia_Cardio$$$corpus_2652", "text": "Unlike the  action potential  in  skeletal muscle cells , the cardiac action potential is not initiated by nervous activity. Instead, it arises from a group of specialized cells known as  pacemaker cells , that have automatic action potential generation capability. In healthy hearts, these cells form the  cardiac pacemaker  and are found in the  sinoatrial node  in the right  atrium . They produce roughly 60\u2013100 action potentials every minute. The action potential passes along the cell membrane causing the cell to contract, therefore the activity of the sinoatrial node results in a resting heart rate of roughly 60\u2013100 beats per minute. All cardiac muscle cells are electrically linked to one another, by  intercalated discs  which allow the action potential to pass from one cell to the next. [ 1 ] [ 2 ]  This means that all atrial cells can contract together, and then all ventricular cells."}
{"_id": "WikiPedia_Cardio$$$corpus_2653", "text": "Rate dependence of the action potential is a fundamental property of cardiac cells and alterations can lead to severe cardiac diseases including  cardiac arrhythmia  and sometimes sudden death. [ 3 ] \nAction potential activity within the heart can be recorded to produce an  electrocardiogram  (ECG). This is a series of upward and downward spikes (labelled P, Q, R, S and T) that represent the depolarization (voltage becoming more positive) and repolarization (voltage becoming more negative) of the action potential in the  atria  and  ventricles . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2654", "text": "Similar to skeletal muscle, the  resting membrane potential  (voltage when the cell is not electrically excited) of  ventricular cells  is around \u221290\u00a0millivolts (mV; 1\u00a0mV\u00a0=\u00a00.001\u00a0V), i.e. the inside of the membrane is more negative than the outside. The main ions found outside the cell at rest are sodium (Na + ), and chloride (Cl \u2212 ), whereas inside the cell it is mainly potassium (K + ). [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2655", "text": "The action potential begins with the voltage becoming more positive; this is known as  depolarization  and is mainly due to the opening of  sodium channels  that allow  Na +  to flow into the cell. After a delay (known as the  absolute refractory period ), the action potential terminates as potassium channels open, allowing K +  to leave the cell and causing the membrane potential to return to negative, this is known as  repolarization . Another important ion is  calcium (Ca 2+ ) , which can be found inside the cell in the  sarcoplasmic reticulum  (SR) where calcium is stored, and is also found outside of the cell. Release of Ca 2+  from the SR, via a process called  calcium-induced calcium release , is vital for the plateau phase of the action potential (see phase 2, below) and is a fundamental step in  cardiac excitation-contraction coupling . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2656", "text": "There are important physiological differences between the  pacemaker cells  of the  sinoatrial node , that spontaneously generate the cardiac action potential and those non-pacemaker cells that simply conduct it, such as  ventricular myocytes ). The specific differences in the types of  ion channels  expressed and mechanisms by which they are activated results in differences in the configuration of the action potential waveform, as shown in figure 2."}
{"_id": "WikiPedia_Cardio$$$corpus_2657", "text": "Cardiac automaticity  also known as  autorhythmicity , is the property of the specialized  conductive   muscle cells  of the heart to generate spontaneous cardiac action potentials. [ 8 ] [ 9 ]  Automaticity can be normal or abnormal, caused by temporary  ion channel  characteristic changes such as certain medication usage, or in the case of abnormal automaticity the changes are in  electrotonic environment , caused, for example, by  myocardial infarction . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2658", "text": "The standard model used to understand the cardiac action potential is that of the ventricular myocyte. Outlined below are the five phases of the ventricular myocyte action potential, with reference also to the SAN action potential."}
{"_id": "WikiPedia_Cardio$$$corpus_2659", "text": "In the ventricular myocyte, phase 4 occurs when the cell is at rest, in a period known as  diastole . In the standard non-pacemaker cell the voltage during this phase is more or less constant, at roughly -90 mV. [ 11 ]  The  resting membrane potential  results from the flux of ions having flowed into the cell (e.g. sodium and calcium), the flux of ions having flowed out of the cell (e.g. potassium, chloride and bicarbonate), as well as the flux of ions generated by the different membrane pumps, being perfectly balanced."}
{"_id": "WikiPedia_Cardio$$$corpus_2660", "text": "The activity of these  pumps  serve two purposes. The first is to maintain the existence of the resting membrane potential by countering the depolarisation due to the leakage of ions not at the electrochemical equilibrium (e.g. sodium and calcium). These ions not being at the equilibrium is the reason for the existence of an electrical gradient, for they represent a net displacement of charges across the membrane, which are unable to immediately re-enter the cell to restore the electrical equilibrium. Therefore, their slow re-entrance in the cell needs to be counterbalanced or the cell would slowly lose its membrane potential."}
{"_id": "WikiPedia_Cardio$$$corpus_2661", "text": "The second purpose, intricately linked to the first, is to keep the intracellular concentration more or less constant, and in this case to re-establish the original chemical gradients, that is to force the sodium and calcium which previously flowed into the cell out of it, and the potassium which previously flowed out of the cell back into it (though as the potassium is mostly at the electrochemical equilibrium, its chemical gradient will naturally reequilibrate itself opposite to the electrical gradient, without the need for an active transport mechanism)."}
{"_id": "WikiPedia_Cardio$$$corpus_2662", "text": "For example, the  sodium (Na + )  and  potassium (K + )  ions are maintained by the  sodium-potassium pump  which uses energy (in the form of  adenosine triphosphate (ATP) ) to move three Na +  out of the cell and two K +  into the cell. Another example is the  sodium-calcium exchanger  which removes one Ca 2+  from the cell for three Na +  into the cell. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2663", "text": "During this phase the membrane is most permeable to K + , which can travel into or out of cell through leak channels, including the inwardly rectifying potassium channel. [ 13 ]  Therefore, the resting membrane potential is mostly equal to K +   equilibrium potential  and can be calculated using the  Goldman-Hodgkin-Katz voltage equation ."}
{"_id": "WikiPedia_Cardio$$$corpus_2664", "text": "However,  pacemaker cells  are never at rest. In these cells, phase 4 is also known as the  pacemaker potential . During this phase, the membrane potential slowly becomes more positive, until it reaches a set value (around -40 mV; known as the threshold potential) or until it is depolarized by another action potential, coming from a neighboring cell."}
{"_id": "WikiPedia_Cardio$$$corpus_2665", "text": "The pacemaker potential is thought to be due to a group of channels, referred to as  HCN channels (Hyperpolarization-activated cyclic nucleotide-gated) . These channels open at very negative voltages (i.e. immediately after phase 3 of the previous action potential; see below) and allow the passage of both K +  and Na +  into the cell. Due to their unusual property of being activated by very negative membrane potentials, the movement of ions through the HCN channels is referred to as the  funny current  (see below). [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2666", "text": "Another hypothesis regarding the pacemaker potential is the 'calcium clock'. Calcium is released from the  sarcoplasmic reticulum  within the cell. This calcium then increases activation of the  sodium-calcium exchanger  resulting in the increase in membrane potential (as a +3 charge is being brought into the cell (by the 3Na + ) but only a +2 charge is leaving the cell (by the Ca 2+ ) therefore there is a net charge of +1 entering the cell). This calcium is then pumped back into the cell and back into the SR via calcium pumps (including the  SERCA ). [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2667", "text": "This phase consists of a rapid, positive change in voltage across the cell membrane ( depolarization ) lasting less than 2\u00a0ms in ventricular cells and 10\u201320\u00a0ms in  SAN  cells. [ 16 ]  This occurs due to a net flow of positive charge into the cell."}
{"_id": "WikiPedia_Cardio$$$corpus_2668", "text": "In non-pacemaker cells (i.e. ventricular cells), this is produced predominantly by the activation of  Na +  channels , which increases the membrane conductance (flow) of Na +  (g Na ). These channels are activated when an action potential arrives from a neighbouring cell, through  gap junctions . When this happens, the voltage within the cell increases slightly. If this increased voltage reaches the  threshold potential  (approximately \u221270\u00a0mV) it causes the Na +  channels to open. This produces a larger influx of sodium into the cell, rapidly increasing the voltage further to around +50\u00a0mV, [ 6 ]  i.e. towards the Na +  equilibrium potential. However, if the initial stimulus is not strong enough, and the threshold potential is not reached, the rapid sodium channels will not be activated and an action potential will not be produced; this is known as the  all-or-none law . [ 17 ] [ 18 ]  The influx of  calcium ions  (Ca 2+ ) through  L-type calcium channels  also constitutes a minor part of the depolarisation effect. [ 19 ]  The slope of phase 0 on the action potential waveform (see figure 2) represents the maximum rate of voltage change of the cardiac action potential and is known as dV/dt max ."}
{"_id": "WikiPedia_Cardio$$$corpus_2669", "text": "In pacemaker cells (e.g.  sinoatrial node cells ), however, the increase in membrane voltage is mainly due to activation of L-type calcium channels. These channels are also activated by an increase in voltage, however this time it is either due to the  pacemaker potential  (phase 4) or an oncoming action potential. The L-type calcium channels are activated more slowly than the sodium channels, therefore, the depolarization slope in the pacemaker action potential waveform is less steep than that in the non-pacemaker action potential waveform. [ 11 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2670", "text": "This phase begins with the rapid inactivation of the Na +  channels by the inner gate (inactivation gate), reducing the movement of sodium into the cell. At the same time potassium channels (called I to1 ) open and close rapidly, allowing for a brief flow of potassium ions out of the cell, making the membrane potential slightly more negative. This is referred to as a 'notch' on the action potential waveform. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2671", "text": "There is no obvious phase 1 present in pacemaker cells."}
{"_id": "WikiPedia_Cardio$$$corpus_2672", "text": "This phase is also known as the \"plateau\" phase due to the  membrane potential  remaining almost constant, as the membrane slowly begins to repolarize. This is due to the near balance of charge moving into and out of the cell. During this phase  delayed rectifier potassium channels  (I ks ) allow potassium to leave the cell while L-type calcium channels (activated by the influx of sodium during phase 0) allow the movement of calcium ions into the cell. These calcium ions bind to and open more calcium channels (called ryanodine receptors) located on the sarcoplasmic reticulum within the cell, allowing the flow of calcium out of the SR. These calcium ions are responsible for the contraction of the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_2673", "text": "Calcium also activates chloride channels called I to2 , which allow Cl \u2212  to enter the cell. Increased calcium concentration in the cell also increases activity of the sodium-calcium exchangers, while increased sodium concentration (from the depolarisation of phase 0) increases activity of the sodium-potassium pumps. The movement of all these ions results in the membrane potential remaining relatively constant, with K +  outflux, Cl \u2212  influx as well as Na + /K +  pumps contributing to repolarisation and Ca 2+  influx as well as Na + /Ca 2+  exchangers contributing to depolarisation. [ 21 ] [ 11 ]  This phase is responsible for the large duration of the action potential and is important in preventing irregular heartbeat (cardiac arrhythmia)."}
{"_id": "WikiPedia_Cardio$$$corpus_2674", "text": "There is no plateau phase present in pacemaker action potentials."}
{"_id": "WikiPedia_Cardio$$$corpus_2675", "text": "During phase 3 (the \"rapid repolarization\" phase) of the action potential, the L-type  Ca 2+  channels  close, while the  slow delayed rectifier  (I Ks )  K +  channels  remain open as more potassium leak channels open. This ensures a net outward positive current, corresponding to negative change in  membrane potential , thus allowing more types of K +  channels to open. These are primarily the  rapid delayed rectifier  K +  channels (I Kr ) and the  inwardly rectifying  K +  current, I K1 .\nThis net outward, positive current (equal to loss of positive charge from the cell) causes the cell to repolarize. The delayed rectifier K +  channels close when the membrane potential is restored to about -85 to -90 mV, while I K1  remains conducting throughout phase 4, which helps to set the resting membrane potential [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2676", "text": "Ionic pumps as discussed above, like the  sodium-calcium exchanger  and the  sodium-potassium pump  restore ion concentrations back to balanced states pre-action potential. This means that the intracellular calcium is pumped out, which was responsible for cardiac myocyte contraction. Once this is lost, the contraction stops and the heart muscles relax."}
{"_id": "WikiPedia_Cardio$$$corpus_2677", "text": "In the sinoatrial node, this phase is also due to the closure of the L-type calcium channels, preventing inward flux of Ca 2+  and the opening of the rapid delayed rectifier potassium channels (I Kr ). [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2678", "text": "Cardiac cells have two  refractory periods , the first from the beginning of phase 0 until part way through phase 3; this is known as the absolute refractory period during which it is impossible for the cell to produce another action potential. This is immediately followed, until the end of phase 3, by a relative refractory period, during which a stronger-than-usual stimulus is required to produce another action potential. [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2679", "text": "These two refractory periods are caused by changes in the states of  sodium  and  potassium channels . The rapid  depolarization  of the cell, during phase 0, causes the membrane potential to approach sodium's  equilibrium potential  (i.e. the membrane potential at which sodium is no longer drawn into or out of the cell). As the membrane potential becomes more positive, the sodium channels then close and lock, this is known as the \"inactivated\" state. During this state the channels cannot be opened regardless of the strength of the excitatory stimulus\u2014this gives rise to the absolute refractory period. The relative refractory period is due to the leaking of potassium ions, which makes the membrane potential more negative (i.e. it is hyperpolarised), this resets the sodium channels; opening the inactivation gate, but still leaving the channel closed. Because some of the voltage-gated sodium ion channels have recovered and the voltage-gated potassium ion channels remain open, it is possible to initiate another action potential if the stimulus is stronger than a stimulus which can fire an action potential when the membrane is at rest. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2680", "text": "Gap junctions  allow the action potential to be transferred from one cell to the next (they are said to  electrically couple  neighbouring  cardiac cells ). They are made from the  connexin family  of proteins, that form a pore through which ions (including Na + , Ca 2+  and K + ) can pass. As potassium is highest within the cell, it is mainly potassium that passes through. This increased potassium in the neighbour cell causes the membrane potential to increase slightly, activating the sodium channels and initiating an action potential in this cell. (A brief chemical gradient driven efflux of Na+ through the  connexon  at peak depolarization causes the conduction of cell to cell depolarization, not potassium.) [ 27 ]  These connections allow for the rapid conduction of the action potential throughout the heart and are responsible for allowing all of the cells in the atria to contract together as well as all of the cells in the ventricles. [ 28 ]  Uncoordinated contraction of heart muscles is the basis for arrhythmia and heart failure. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2681", "text": "Ion channels are proteins that change shape in response to different stimuli to either allow or prevent the movement of specific ions across a membrane. They are said to be selectively permeable. Stimuli, which can either come from outside the cell or from within the cell, can include the binding of a specific  molecule  to a receptor on the channel (also known as  ligand-gated ion channels ) or a change in membrane potential around the channel, detected by a sensor (also known as  voltage-gated ion channels ) and can act to open or close the channel. The pore formed by an ion channel is aqueous (water-filled) and allows the ion to rapidly travel across the membrane. [ 33 ]  Ion channels can be selective for specific ions, so there are  Na + ,  K + ,  Ca 2+ , and  Cl \u2212  specific channels. They can also be specific for a certain charge of ions (i.e. positive or negative). [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2682", "text": "Each channel is coded by a set of DNA instructions that tell the cell how to make it. These instructions are known as a  gene . Figure 3 shows the important ion channels involved in the cardiac action potential, the current (ions) that flows through the channels, their main protein subunits (building blocks of the channel), some of their controlling genes that code for their structure, and the phases that are active during the cardiac action potential. Some of the most important ion channels involved in the cardiac action potential are described briefly below."}
{"_id": "WikiPedia_Cardio$$$corpus_2683", "text": "Hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels)  are located mainly in pacemaker cells, these channels become active at very negative membrane potentials and allow for the passage of both Na +  and K +  into the cell (which is a movement known as a funny current, I f ). These poorly selective, cation (positively charged ions) channels conduct more current as the membrane potential becomes more negative (hyperpolarised). The activity of these channels in the SAN cells causes the membrane potential to depolarise slowly and so they are thought to be responsible for the pacemaker potential. Sympathetic nerves directly affect these channels, resulting in an increased heart rate (see below). [ 35 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2684", "text": "These  sodium channels  are voltage-dependent, opening rapidly due to depolarization of the membrane, which usually occurs from neighboring cells, through gap junctions. They allow for a rapid flow of sodium into the cell, depolarizing the membrane completely and initiating an action potential. As the membrane potential increases, these channels then close and lock (become inactive). Due to the rapid influx sodium ions (steep phase 0 in action potential waveform) activation and inactivation of these channels happens almost at exactly the same time. During the inactivation state, Na +  cannot pass through (absolute refractory period). However they begin to recover from inactivation as the membrane potential becomes more negative (relative refractory period)."}
{"_id": "WikiPedia_Cardio$$$corpus_2685", "text": "The two main types of potassium channels in cardiac cells are inward rectifiers and voltage-gated potassium channels. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2686", "text": "Inwardly rectifying potassium channels  (K ir)  favour the flow of K +  into the cell. This influx of potassium, however, is larger when the membrane potential is more negative than the  equilibrium potential  for K +  (~-90 mV). As the membrane potential becomes more positive (i.e. during cell stimulation from a neighbouring cell), the flow of potassium into the cell via the K ir  decreases. Therefore, K ir  is responsible for maintaining the resting membrane potential and initiating the depolarization phase. However, as the membrane potential continues to become more positive, the channel begins to allow the passage of K +   out  of the cell. This outward flow of potassium ions at the more positive membrane potentials means that the K ir  can also aid the final stages of repolarisation. [ 36 ] [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2687", "text": "The  voltage-gated potassium channels  (K v ) are activated by depolarization. The currents produced by these channels include the transient out potassium current  I to1 . This current has two components. Both components activate rapidly, but  I to,fast  inactivates more rapidly than  I to, slow . These currents contribute to the early repolarization phase (phase 1) of the action potential. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2688", "text": "Another form of voltage-gated potassium channels are the delayed rectifier potassium channels. These channels carry potassium currents which are responsible for the plateau phase of the action potential, and are named based on the speed at which they activate: slowly activating  I Ks , rapidly activating  I Kr  and ultra-rapidly activating  I Kur . [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2689", "text": "There are two  voltage-gated calcium channels  within cardiac muscle:  L-type calcium channels  ('L' for Long-lasting) and  T-type calcium channels  ('T' for Transient, i.e. short). L-type channels are more common and are most densely populated within the  T-tubule  membrane of ventricular cells, whereas the T-type channels are found mainly within  atrial  and  pacemaker cells , but still to a lesser degree than L-type channels. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2690", "text": "These channels respond to voltage changes across the membrane differently: L-type channels are activated by more positive membrane potentials, take longer to open and remain open longer than T-type channels. This means that the T-type channels contribute more to depolarization (phase 0) whereas L-type channels contribute to the plateau (phase 2). [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2691", "text": "In the  heart's conduction system  electrical activity that originates from the  sinoatrial node  (SAN) is propagated via the  His - Purkinje  network, the fastest conduction pathway within the heart. The electrical signal travels from the sinoatrial node, which stimulates the  atria  to contract, to the  atrioventricular node (AVN) , which slows down conduction of the action potential from the atria to the  ventricles . This delay allows the ventricles to fully fill with blood before contraction. The signal then passes down through a bundle of fibres called the  bundle of His , located between the ventricles, and then to the  Purkinje fibers  at the bottom (apex) of the heart, causing ventricular contraction. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2692", "text": "In addition to the SAN, the AVN and Purkinje fibres also have pacemaker activity and can therefore spontaneously generate an action potential. However, these cells usually do not depolarize spontaneously, simply because action potential production in the SAN is faster. This means that before the AVN or Purkinje fibres reach the threshold potential for an action potential, they are depolarized by the oncoming impulse from the SAN [ 40 ]  This is called \"overdrive suppression\". [ 41 ]  Pacemaker activity of these cells is vital, as it means that if the SAN were to fail, then the heart could continue to beat, albeit at a lower rate (AVN= 40-60 beats per minute,\nPurkinje fibres = 20-40 beats per minute). These pacemakers will keep a patient alive until the emergency team arrives. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2693", "text": "An example of premature ventricular contraction is the classic  athletic heart syndrome . Sustained training of athletes causes a cardiac adaptation where the resting SAN rate is lower (sometimes around 40 beats per minute). This can lead to  atrioventricular block , where the signal from the SAN is impaired in its path to the ventricles. This leads to uncoordinated contractions between the atria and ventricles, without the correct delay in between and in severe cases can result in sudden death. [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2694", "text": "The speed of action potential production in pacemaker cells is affected, but not controlled by the  autonomic nervous system ."}
{"_id": "WikiPedia_Cardio$$$corpus_2695", "text": "The  sympathetic nervous system  (nerves dominant during the body's  fight-or-flight response ) increase heart rate (positive  chronotropy ), by decreasing the time to produce an action potential in the SAN. Nerves from the  spinal cord  release a molecule called  noradrenaline , which binds to and activates receptors on the pacemaker cell membrane called  \u03b21 adrenoceptors . This activates a protein, called a G s -protein (s for stimulatory). Activation of this G-protein leads to increased levels of  cAMP  in the cell (via the  cAMP pathway ). cAMP binds to the HCN channels (see above), increasing the funny current and therefore increasing the rate of depolarization, during the pacemaker potential. The increased cAMP also increases the opening time of L -type calcium channels, increasing the Ca 2+  current through the channel, speeding up phase 0. [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2696", "text": "The  parasympathetic nervous system  ( nerves  dominant while the body is resting and digesting) decreases heart rate (negative  chronotropy ), by increasing the time taken to produce an action potential in the SAN. A nerve called the  vagus nerve , that begins in the brain and travels to the sinoatrial node, releases a  molecule  called  acetylcholine (ACh)  which binds to a receptor located on the outside of the pacemaker cell, called an  M2 muscarinic receptor . This activates a  G i -protein  (I for inhibitory), which is made up of 3 subunits (\u03b1, \u03b2 and \u03b3) which, when activated, separate from the receptor. The \u03b2 and \u03b3 subunits activate a special set of potassium channels, increasing potassium flow out of the cell and decreasing membrane potential, meaning that the pacemaker cells take longer to reach their threshold value. [ 44 ]  The G i -protein also inhibits the cAMP pathway therefore reducing the sympathetic effects caused by the spinal nerves. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2697", "text": "Antiarrhythmic drugs  are used to regulate  heart rhythms  that are too fast. Other drugs used to influence the cardiac action potential include  sodium channel blockers ,  beta blockers ,  potassium channel blockers , and  calcium channel blockers ."}
{"_id": "WikiPedia_Cardio$$$corpus_2698", "text": "The  cardiac conduction system  ( CCS , also called the  electrical  conduction system of the heart ) [ 1 ]  transmits the  signals  generated by the  sinoatrial node  \u2013 the  heart 's  pacemaker , to cause the  heart muscle  to  contract , and pump blood through the body's  circulatory system . The  pacemaking  signal travels through the  right atrium  to the  atrioventricular node , along the  bundle of His , and through the  bundle branches  to  Purkinje fibers  in the  walls of the ventricles . The Purkinje fibers transmit the signals more rapidly to stimulate contraction of the ventricles. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2699", "text": "The conduction system consists of specialized  heart muscle cells , situated within the  myocardium . [ 3 ]  There is a  skeleton of fibrous tissue  that surrounds the conduction system which can be seen on an  ECG . Dysfunction of the conduction system can cause  irregular heart rhythms  including rhythms that are  too fast  or  too slow ."}
{"_id": "WikiPedia_Cardio$$$corpus_2700", "text": "Electrical signals arising in the  SA node  (located in the right  atrium ) stimulate the atria to contract. Then the signals travel to the  atrioventricular node  (AV node), which is located in the  interatrial septum . After a  short delay that gives the ventricles time to fill with blood,  the electrical signal diverges and is conducted through the left and right  bundle branches  of  His  to the respective  Purkinje fibers  for each side of the heart, as well as to the  endocardium  at the apex of the heart, then finally to the ventricular epicardium; causing the ventricles to  contract. [ 2 ]  These signals are generated rhythmically, which results in the coordinated rhythmic contraction and relaxation of the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_2701", "text": "On the microscopic level, the wave of  depolarization  propagates to adjacent cells via  gap junctions  located on the  intercalated disc . The heart is a  functional syncytium  as opposed to a skeletal muscle  syncytium . In a functional syncytium, electrical impulses propagate freely between cells in every direction, so that the myocardium functions as a single contractile unit. This property allows rapid, synchronous depolarization of the myocardium. While advantageous under normal circumstances, this property can be detrimental, as it has potential to allow the propagation of incorrect electrical signals. These gap junctions can close to isolate damaged or dying tissue, as in a  myocardial infarction  (heart attack)."}
{"_id": "WikiPedia_Cardio$$$corpus_2702", "text": "Embryologic evidence of generation of the cardiac conduction system illuminates the respective roles of this specialized set of cells. Innervation of the heart begins with a brain only centered  parasympathetic   cholinergic  first order. It is then followed by rapid growth of a second order  sympathetic   adrenergic  system arising from the formation of the  thoracic   spinal ganglia . The third order of electrical influence of the heart is derived from the  vagus nerve  as the other peripheral organs form. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2703", "text": "Cardiac muscle has some similarities to neurons and skeletal muscle, as well as important unique properties. Like a neuron, a given myocardial cell has a negative  membrane potential  when at rest. Stimulation above a threshold value induces the opening of  voltage-gated ion channels  and a flood of  cations  into the cell. The positively charged ions entering the cell cause the  depolarization  characteristic of an action potential. Like skeletal muscle, depolarization causes the opening of  voltage-gated calcium channels   and release of Ca 2+  from the  t-tubules . This influx of calcium causes  calcium-induced calcium release  from the  sarcoplasmic reticulum , and free Ca 2+  causes  muscle contraction . After a delay,  potassium channels  reopen, and the resulting flow of K +  out of the cell causes  repolarization  to the resting state. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2704", "text": "There are important physiological differences between nodal cells and ventricular cells; the specific differences in ion channels and mechanisms of polarization give rise to unique properties of SA node cells, most importantly the spontaneous depolarizations necessary for the SA node's pacemaker activity."}
{"_id": "WikiPedia_Cardio$$$corpus_2705", "text": "In order to maximize efficiency of contractions and  cardiac output , the conduction system of the heart has:"}
{"_id": "WikiPedia_Cardio$$$corpus_2706", "text": "An  electrocardiogram  is a recording of the electrical activity of the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_2707", "text": "Under normal conditions, electrical activity is spontaneously generated by the  SA node , the cardiac pacemaker.  This electrical impulse is propagated throughout the right  atrium , and through  Bachmann's bundle  to the left  atrium , stimulating the  myocardium  of the atria to contract.  The conduction of the electrical impulses throughout the atria is seen on the  ECG  as the  P wave . [ 5 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2708", "text": "As the electrical activity is spreading throughout the atria, it travels via specialized pathways, known as  internodal tracts , from the SA node to the  AV node ."}
{"_id": "WikiPedia_Cardio$$$corpus_2709", "text": "The AV node functions as a critical delay in the conduction system.  Without this delay, the  atria  and  ventricles  would contract at the same time, and blood wouldn't flow effectively from the atria to the ventricles. The delay in the AV node forms much of the  PR segment  on the ECG, and part of atrial repolarization can be represented by the PR segment."}
{"_id": "WikiPedia_Cardio$$$corpus_2710", "text": "The distal portion of the AV node is known as the  bundle of His . [ 8 ]  The bundle of His splits into two branches in the interventricular septum: the left bundle branch and the right bundle branch. The left bundle branch activates the  left ventricle , while the right bundle branch activates the  right ventricle ."}
{"_id": "WikiPedia_Cardio$$$corpus_2711", "text": "The left bundle branch is short, splitting into the left anterior fascicle and the left posterior fascicle. The left posterior fascicle is relatively short and broad, with dual blood supply, making it particularly resistant to ischemic damage. The left posterior fascicle transmits impulses to the papillary muscles, leading to  mitral valve  closure. As the left posterior fascicle is shorter and broader than the right, impulses reach the papillary muscles just prior to depolarization, and therefore contraction, of the left ventricle myocardium. This allows pre-tensioning of the chordae tendinae, increasing the resistance to flow through the mitral valve during left ventricular contraction. [ 5 ]  This mechanism works in the same manner as pre-tensioning of car seatbelts."}
{"_id": "WikiPedia_Cardio$$$corpus_2712", "text": "The two bundle branches taper out to produce numerous  Purkinje fibers , which stimulate individual groups of myocardial cells to contract. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2713", "text": "The spread of electrical activity through the ventricular myocardium produces the  QRS complex  on the ECG."}
{"_id": "WikiPedia_Cardio$$$corpus_2714", "text": "Atrial repolarization occurs and is masked during the  QRS complex   by ventricular depolarization on the ECG."}
{"_id": "WikiPedia_Cardio$$$corpus_2715", "text": "The last event of the cycle is the repolarization of the  ventricles . It is the restoring of the resting state. In the ECG, repolarization includes the J point, ST segment, and T and U waves. [ 9 ] \nThe transthoracically measured PQRS portion of an electrocardiogram is chiefly influenced by the  sympathetic nervous system . The T (and occasionally U) waves are chiefly influenced by the  parasympathetic nervous system  guided by integrated  brainstem  control from the  vagus nerve  and the thoracic  spinal accessory ganglia ."}
{"_id": "WikiPedia_Cardio$$$corpus_2716", "text": "An impulse ( action potential ) that originates from the SA node at a relative rate of 60\u2013100\u00a0bpm is known as a normal  sinus rhythm . If SA nodal impulses occur at a rate less than 60\u00a0bpm, the heart rhythm is known as  sinus bradycardia . If SA nodal impulses occur at a rate exceeding 100 bpm, the consequent rapid heart rate is  sinus tachycardia . These conditions are not necessarily bad symptoms, however. Trained athletes, for example, usually show heart rates slower than 60 bpm when not exercising. If the SA node fails to initialize, the AV junction can take over as the main pacemaker of the heart. The AV junction consists of the AV node, the bundle of His, and the surrounding area; it has a regular rate of 40 to 60 bpm. These \"junctional\" rhythms are characterized by a missing or inverted P wave. If both the SA node and the AV junction fail to initialize the electrical impulse, the ventricles can fire the electrical impulses themselves at a rate of 20 to 40\u00a0bpm and will have a QRS complex of greater than 120\u00a0ms. This is necessary for the heart to be in good function."}
{"_id": "WikiPedia_Cardio$$$corpus_2717", "text": "An  arrhythmia  is an abnormal rhythm or speed of rhythm of the heartbeat. A slow  heart rate  of 60 or less beats per minute is defined as  bradycardia . A fast heart rate of more than 100 beats per minute is defined as  tachycardia .\nAn arrhythmia is defined as one that is not  physiological  such as the lowered heart rate that a trained athlete may naturally have developed; the resting heart rates may be less than 60 bpm."}
{"_id": "WikiPedia_Cardio$$$corpus_2718", "text": "When an arrhythmia cannot be treated by  medication  (or other standard  cardioversion  measures), an  artificial pacemaker  may be  implanted  to control the conduction system."}
{"_id": "WikiPedia_Cardio$$$corpus_2719", "text": "Cardiac monitoring  generally refers to continuous or intermittent  monitoring  of  heart  activity to assess a patient's condition relative to their  cardiac rhythm . Cardiac monitoring is usually carried out using  electrocardiography , which is a  noninvasive  process that records the heart's electrical activity and displays it in an electrocardiogram. [ 1 ]  It is different from  hemodynamic  monitoring, which monitors the  pressure  and  flow  of blood within the  cardiovascular system . The two may be performed simultaneously on  critical  heart patients. Cardiac monitoring for ambulatory patients (those well enough to walk around) is known as ambulatory electrocardiography and uses a small, wearable device, such as a  Holter monitor ,  wireless ambulatory ECG , or an  implantable loop recorder . Data from a cardiac monitor can be transmitted to a distant monitoring station in a process known as  telemetry  or  biotelemetry ."}
{"_id": "WikiPedia_Cardio$$$corpus_2720", "text": "Cardiac monitoring in an  emergency department  setting focuses primarily on the monitoring of  arrhythmia ,  myocardial infarction , and  QT interval  monitoring. [ 2 ]  It is categorized into one of three classes using a rating system developed by the American College of Cardiology Emergency Cardiac Care Committee:"}
{"_id": "WikiPedia_Cardio$$$corpus_2721", "text": "Class I: Cardiac monitoring is indicated in all or most patients."}
{"_id": "WikiPedia_Cardio$$$corpus_2722", "text": "Class II: Cardiac monitoring may be beneficial, but it is not essential."}
{"_id": "WikiPedia_Cardio$$$corpus_2723", "text": "Class III: Cardiac monitoring is not indicated because the patient's serious event risk is low. Monitoring will not have therapeutic benefit. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2724", "text": "In the setting of out-of-hospital  acute medical care , ambulance services and other  emergency medical services  providers utilize heart monitors to assess the patient's cardiac rhythm. Providers licensed or certified at the  Paramedic  level are qualified to interpret ECGs. Information obtained from ECGs can then be used to direct the patient's treatment at a care facility, particularly in catheterization labs. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2725", "text": "In the  emergency department , cardiac monitoring is a part of the monitoring of  vital signs  in  emergency medicine , and generally includes  electrocardiography . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2726", "text": "Some digital patient monitors, especially those used by EMS services, often incorporate a defibrillator into the patient monitor itself. These monitor/defibrillators usually have the normal capabilities of an ICU monitor, but have manual (and usually semi-automatic AED) defibrillation capabilities. This is particularly good for EMS services, who need a compact, easy to use monitor and defibrillator, as well as for patient transport.  Most monitor defibrillators also have transcutaneous pacing capability via large AED like adhesive pads (which often can be used for monitoring, defibrillation and pacing) that are applied to the patient in an anterior-posterior configuration. The monitor defibrillator units often have specialized monitoring parameters such as waveform capnography, invasive BP, and, in some monitors, Masimo Rainbow SET pulse oximetry, which can also monitor  carbon monoxide  and  methemoglobin  levels. Most modern monitors also allow for transmission of an ECG sample to an emergency department for interpretation; this process may be used to speed up patient care in certain situations, such as bypassing the ED and proceeding to a  cath lab ."}
{"_id": "WikiPedia_Cardio$$$corpus_2727", "text": "Examples of monitor defibrillators are the Lifepak 12, 15 and 20 made by Physio Control, the Philips Heartstart MRx, and the E, R, and X Series by ZOLL Medical."}
{"_id": "WikiPedia_Cardio$$$corpus_2728", "text": "There are two broad classifications for cardiac event monitors: manual (or dumb) and automatic. Automatic ECG event monitors have the ability to monitor the patient's ECG and make recordings of abnormal events without requiring patient intervention. Manual ECG event recorders require the patient to be symptomatic and to activate the device to record an event; this makes these devices useless whilst, for example, the patient is sleeping. A third classification, the  implantable loop recorder , provides both automatic and manual abilities."}
{"_id": "WikiPedia_Cardio$$$corpus_2729", "text": "An example of automatic monitoring is the transtelephonic cardiac event monitor. This monitor contacts ECG technicians, via telephone, on a regular basis, transmitting  ECG  rhythms for ongoing monitoring. The transtelephonic cardiac event monitor can normally store approximately five \"cardiac events\" usually lasting 30\u201360 seconds."}
{"_id": "WikiPedia_Cardio$$$corpus_2730", "text": "Monitoring of the  heart rate  can be performed as part of  electrocardiography , but it can also be measured conveniently with specific  heart rate monitors . Such heart rate monitors are largely used by performers of various types of  physical exercise ."}
{"_id": "WikiPedia_Cardio$$$corpus_2731", "text": "A generic cardiac monitor has the following functions:"}
{"_id": "WikiPedia_Cardio$$$corpus_2732", "text": "There are many different types of cardiac monitors. In personal use, the  Holter monitor  is an external monitor which uses wires with patches that attach to the skin to continuously measure and record heart activity for 1\u20132 days. [ 5 ]  An Event Recorder can be worn on the body for up to 30 days. [ 6 ]  A Mobile Cardiac Telemetry unit is a wearable monitor that detects, records, and transmits heart rhythms for up to 30 days. For long term use, an  Insertable Cardiac Monitor  is placed under the skin and automatically detects and records abnormal heart rhythms for up to 5 years. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2733", "text": "Monitoring the fetal heart rate is becoming increasingly prevalent in the standard care of antepartum pregnant patients. [ 8 ]  As of 2002, 85% of pregnancies in the United States were monitored using electronic fetal monitoring. Electronic fetal monitoring generally uses Doppler ultrasound technology to provide real-time feedback on the fetus's cardiac activity during both gestation and labor, [ 9 ]  however other technologies such as analyzing the voltage generated by the contracting uterine muscle measured at the skin surface or recording both the fetal ECG and mother's ECG and filtering out the mother's ECG are emerging. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2734", "text": "The new wearable heart rate monitors indirectly measure the heart rate with reflectance photoplethysmography. The monitor illuminates the skin tissue with light emitting diode (LED) and detects the intensity of light reflected with the photodetector. [ 11 ]  Wearable optical heart rate monitors are less reliable than electrode-based heart rate monitors. The accuracy of the wearable optical heart rate monitors varies with the type of exercise. Skin tone and motion artifacts contributes to this error. [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2735", "text": "Cardiac muscle  (also called  heart muscle  or  myocardium ) is one of three types of  vertebrate   muscle tissues , the others being  skeletal muscle  and  smooth muscle . It is an involuntary,  striated muscle  that constitutes the main tissue of the  wall of the heart . The cardiac muscle (myocardium) forms a thick middle layer between the outer layer of the heart wall (the  pericardium ) and the inner layer (the  endocardium ), with blood supplied via the  coronary circulation .  It is composed of individual cardiac muscle cells joined by  intercalated discs , and encased by  collagen fibers  and other substances that form the  extracellular matrix ."}
{"_id": "WikiPedia_Cardio$$$corpus_2736", "text": "Cardiac muscle  contracts  in a similar manner to  skeletal muscle , although with some important differences.  Electrical stimulation in the form of a  cardiac action potential   triggers the release of calcium from the cell's internal calcium store, the  sarcoplasmic reticulum .  The rise in calcium causes the cell's  myofilaments  to slide past each other in a process called  excitation-contraction coupling .\nDiseases of the heart muscle known as  cardiomyopathies  are of major importance.  These include  ischemic  conditions caused by a restricted blood supply to the muscle such as  angina , and  myocardial infarction ."}
{"_id": "WikiPedia_Cardio$$$corpus_2737", "text": "Cardiac muscle tissue or myocardium forms the bulk of the heart. The heart wall is a three-layered structure with a thick layer of myocardium sandwiched between the inner  endocardium  and the outer  epicardium  (also known as the visceral pericardium). The inner endocardium lines the cardiac chambers, covers the  cardiac valves , and joins with the  endothelium  that lines the blood vessels that connect to the heart. On the outer aspect of the myocardium is the  epicardium  which forms part of the  pericardial sac  that surrounds, protects, and lubricates the heart. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2738", "text": "Within the myocardium, there are several sheets of cardiac muscle cells or cardiomyocytes.  The sheets of muscle that wrap around the left ventricle closest to the endocardium are oriented perpendicularly to those closest to the epicardium.  When these sheets contract in a coordinated manner they allow the ventricle to squeeze in several directions simultaneously \u2013 longitudinally (becoming shorter from apex to base), radially (becoming narrower from side to side), and with a twisting motion (similar to wringing out a damp cloth) to squeeze the maximum possible amount of blood out of the heart with each heartbeat. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2739", "text": "Contracting heart muscle uses a lot of energy, and therefore requires a constant flow of blood to provide  oxygen  and nutrients.   Blood  is brought to the myocardium by the  coronary arteries .  These originate from the  aortic root  and lie on the outer or epicardial surface of the heart.  Blood is then drained away by the  coronary veins  into the  right atrium . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2740", "text": "Cardiac muscle cells  (also called  cardiomyocytes ) are the contractile  myocytes  of the cardiac muscle. The cells are surrounded by an  extracellular matrix  produced by supporting  fibroblast  cells. Specialised modified cardiomyocytes known as  pacemaker cells , set the rhythm of the heart contractions. The pacemaker cells are only weakly contractile without sarcomeres, and are connected to neighboring contractile cells via  gap junctions . [ 3 ]  They are located in the  sinoatrial node  (the primary pacemaker) positioned on the wall of the  right atrium , near the entrance of the  superior vena cava . [ 4 ]  Other pacemaker cells are found in the atrioventricular node (secondary pacemaker)."}
{"_id": "WikiPedia_Cardio$$$corpus_2741", "text": "Pacemaker cells carry the impulses that are responsible for the beating of the heart.  They are distributed throughout the heart and are responsible for several functions.  First, they are responsible for being able to  spontaneously generate  and send out  electrical impulses .  They also must be able to receive and respond to electrical impulses from the brain.  Lastly, they must be able to transfer electrical impulses from cell to cell. [ 5 ]  Pacemaker cells in the sinoatrial node, and atrioventricular node are smaller and conduct at a relatively slow rate between the cells. Specialized conductive cells in the  bundle of His , and the  Purkinje fibers  are larger in diameter and conduct signals at a fast rate. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2742", "text": "The Purkinje fibers rapidly conduct electrical signals;  coronary arteries  to bring nutrients to the muscle cells, and  veins  and a  capillary  network to take away waste products. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2743", "text": "Cardiac muscle cells are the contracting cells that allow the heart to pump.  Each cardiomyocyte needs to contract in coordination with its neighboring cells - known as a  functional syncytium  - working to efficiently pump blood from the heart, and if this coordination breaks down then \u2013 despite individual cells contracting \u2013 the heart may not pump at all, such as may occur during  abnormal heart rhythms  such as  ventricular fibrillation . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2744", "text": "Viewed through a microscope, cardiac muscle cells are roughly rectangular, measuring 100\u2013150\u03bcm by 30\u201340\u03bcm. [ 9 ]  Individual cardiac muscle cells are joined at their ends by  intercalated discs  to form long fibers.  Each cell contains  myofibrils , specialized protein contractile fibers of  actin  and  myosin  that slide past each other.  These are organized into  sarcomeres , the fundamental contractile units of muscle cells.  The regular organization of myofibrils into sarcomeres gives cardiac muscle cells a striped or  striated  appearance when looked at through a microscope, similar to skeletal muscle. These striations are caused by lighter  I bands  composed mainly of actin, and darker  A bands  composed mainly of myosin. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2745", "text": "Cardiomyocytes contain  T-tubules , pouches of  cell membrane  that run from the cell surface to the cell's interior which help to improve the efficiency of contraction.  The majority of these cells contain only one  nucleus  (some may have two central nuclei), unlike skeletal muscle cells which contain  many nuclei . Cardiac muscle cells contain many  mitochondria  which provide the energy needed for the cell in the form of  adenosine triphosphate  (ATP), making them highly resistant to fatigue. [ 9 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2746", "text": "T-tubules  are microscopic tubes that run from the cell surface to deep within the cell.  They are continuous with the cell membrane, are composed of the same  phospholipid bilayer , and are open at the cell surface to the  extracellular fluid  that surrounds the cell. T-tubules in cardiac muscle are bigger and wider than those in  skeletal muscle , but fewer in number. [ 9 ]  In the centre of the cell they join, running into and along the cell as a transverse-axial network.  Inside the cell they lie close to the cell's internal calcium store, the  sarcoplasmic reticulum .  Here, a single tubule pairs with part of the sarcoplasmic reticulum called a terminal cisterna in a combination known as a  diad . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2747", "text": "The functions of T-tubules include rapidly transmitting electrical impulses known as  action potentials  from the cell surface to the cell's core, and helping to regulate the concentration of calcium within the cell in a process known as  excitation-contraction coupling . [ 9 ]  They are also involved in mechano-electric feedback, [ 11 ]  as evident from cell contraction induced T-tubular content exchange (advection-assisted diffusion), [ 12 ]  which was confirmed by confocal and 3D electron tomography observations. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2748", "text": "The  cardiac syncytium  is a network of cardiomyocytes connected by  intercalated discs  that enable the rapid transmission of electrical impulses through the network, enabling the syncytium to act in a coordinated contraction of the myocardium. There is an  atrial syncytium  and a  ventricular syncytium  that are connected by cardiac connection fibres. [ 14 ]  Electrical resistance through intercalated discs is very low, thus allowing free diffusion of ions. The ease of ion movement along cardiac muscle fibers axes is such that action potentials are able to travel from one cardiac muscle cell to the next, facing only slight resistance. Each syncytium obeys the  all or none law . [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2749", "text": "Intercalated discs are complex adhering structures that connect the single cardiomyocytes to an electrochemical  syncytium  (in contrast to the skeletal muscle, which becomes a multicellular syncytium during  embryonic development ). The discs are responsible mainly for force transmission during muscle contraction.  Intercalated discs consist of three different types of cell-cell junctions: the actin filament anchoring  fascia adherens junctions , the intermediate filament anchoring  desmosomes , and  gap junctions . [ 16 ]  They allow action potentials to spread between cardiac cells by permitting the passage of ions between cells, producing depolarization of the heart muscle. The three types of junction act together as a single  area composita . [ 16 ] [ 17 ] [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2750", "text": "Under  light microscopy , intercalated discs appear as thin, typically dark-staining lines dividing adjacent cardiac muscle cells. The intercalated discs run perpendicular to the direction of muscle fibers. Under electron microscopy, an intercalated disc's path appears more complex. At low magnification, this may appear as a convoluted electron dense structure overlying the location of the obscured Z-line. At high magnification, the intercalated disc's path appears even more convoluted, with both longitudinal and transverse areas appearing in longitudinal section. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2751", "text": "Cardiac fibroblasts are vital supporting cells within cardiac muscle.  They are unable to provide forceful contractions like  cardiomyocytes , but instead are largely responsible for creating and maintaining the extracellular matrix which surrounds the cardiomyocytes. [ 7 ]   Fibroblasts play a crucial role in responding to injury, such as a  myocardial infarction .  Following injury, fibroblasts can become activated and turn into  myofibroblasts  \u2013 cells which exhibit behaviour somewhere between a fibroblast (generating extracellular matrix) and a  smooth muscle cell  (ability to contract).  In this capacity, fibroblasts can repair an injury by creating collagen while gently contracting to pull the edges of the injured area together. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2752", "text": "Fibroblasts are smaller but more numerous than cardiomyocytes, and several fibroblasts can be attached to a cardiomyocyte at once.  When attached to a cardiomyocyte they can influence the electrical currents passing across the muscle cell's surface membrane, and in the context are referred to as being electrically coupled, [ 22 ]  as originally shown in vitro in the 1960s, [ 23 ]  and ultimately confirmed in native cardiac tissue with the help of optogenetic techniques. [ 24 ]  Other potential roles for fibroblasts include electrical insulation of the  cardiac conduction system , and the ability to transform into other cell types including cardiomyocytes  and  adipocytes . [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2753", "text": "The  extracellular matrix  (ECM) surrounds the cardiomyocyte and fibroblasts.  The ECM is composed of proteins including  collagen  and  elastin  along with  polysaccharides  (sugar chains) known as  glycosaminoglycans . [ 7 ]  Together, these substances give support and strength to the muscle cells, create elasticity in cardiac muscle, and keep the muscle cells hydrated by binding water molecules."}
{"_id": "WikiPedia_Cardio$$$corpus_2754", "text": "The matrix in immediate contact with the muscle cells is referred to as the  basement membrane , mainly composed of  type IV collagen  and  laminin .  Cardiomyocytes are linked to the basement membrane via specialised  glycoproteins  called  integrins . [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2755", "text": "Humans are born with a set number of heart muscle cells, or cardiomyocytes, which increase in size as the heart grows larger during childhood development. Evidence suggests that cardiomyocytes are slowly turned over during aging, but less than 50% of the cardiomyocytes present at birth are replaced during a normal life span. [ 26 ]  The growth of individual cardiomyocytes not only occurs during normal heart development, it also occurs in response to extensive exercise ( athletic heart syndrome ), heart disease, or heart muscle injury such as after a myocardial infarction. A healthy adult cardiomyocyte has a cylindrical shape that is approximately 100\u03bcm long and 10\u201325\u03bcm in diameter.  Cardiomyocyte hypertrophy occurs through sarcomerogenesis, the creation of new sarcomere units in the cell.  During heart volume overload, cardiomyocytes grow through eccentric hypertrophy. [ 27 ]  The cardiomyocytes extend lengthwise but have the same diameter, resulting in ventricular dilation.  During heart pressure overload, cardiomyocytes grow through concentric hypertrophy. [ 27 ]  The cardiomyocytes grow larger in diameter but have the same length, resulting in heart wall thickening."}
{"_id": "WikiPedia_Cardio$$$corpus_2756", "text": "The physiology of cardiac muscle shares many similarities with that of  skeletal muscle .  The primary function of both muscle types is to contract, and in both cases, a contraction begins with a characteristic flow of  ions  across the  cell membrane  known as an  action potential .  The  cardiac action potential  subsequently triggers muscle contraction by increasing the concentration of  calcium  within the cytosol."}
{"_id": "WikiPedia_Cardio$$$corpus_2757", "text": "The  cardiac cycle  is the performance of the human heart from the beginning of one heartbeat to the beginning of the next. It consists of two periods: one during which the heart muscle relaxes and refills with blood, called  diastole , following a period of robust contraction and pumping of blood, dubbed  systole . After emptying, the heart immediately relaxes and expands to receive another influx of blood returning from the lungs and other systems of the body, before again contracting to pump blood to the lungs and those systems. A normally performing heart must be fully expanded before it can efficiently pump again."}
{"_id": "WikiPedia_Cardio$$$corpus_2758", "text": "The rest phase is considered polarized. The  resting potential  during this phase of the beat separates the ions such as sodium, potassium, and calcium. Myocardial cells possess the property of automaticity or spontaneous  depolarization . This is the direct result of a membrane which allows sodium ions to slowly enter the cell until the threshold is reached for depolarization. Calcium ions follow and extend the depolarization even further. Once calcium stops moving inward, potassium ions move out slowly to produce repolarization. The very slow repolarization of the CMC membrane is responsible for the long refractory period. [ 28 ] [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2759", "text": "However, the mechanism by which calcium concentrations within the cytosol rise differ between skeletal and cardiac muscle.  In cardiac muscle, the action potential comprises an inward flow of both sodium and calcium ions.  The flow of sodium ions is rapid but very short-lived, while the flow of calcium is sustained and gives the plateau phase characteristic of cardiac muscle action potentials.  The comparatively small flow of calcium through the  L-type calcium channels  triggers a much larger release of calcium from the sarcoplasmic reticulum in a phenomenon known as   calcium-induced calcium release .  In contrast, in skeletal muscle, minimal calcium flows into the cell during action potential and instead the sarcoplasmic reticulum in these cells is directly coupled to the surface membrane.  This difference can be illustrated by the observation that cardiac muscle fibers require calcium to be present in the solution surrounding the cell to contract, while skeletal muscle fibers will contract without extracellular calcium."}
{"_id": "WikiPedia_Cardio$$$corpus_2760", "text": "During contraction of a cardiac muscle cell, the long protein  myofilaments  oriented along the length of the cell slide over each other in what is known as the  sliding filament theory .  There are two kinds of myofilaments, thick filaments composed of the protein  myosin , and thin filaments composed of the proteins  actin ,  troponin  and  tropomyosin .  As the thick and thin filaments slide past each other the cell becomes shorter and fatter.  In a mechanism known as  cross-bridge cycling , calcium ions bind to the protein troponin, which along with tropomyosin then uncover key binding sites on actin.  Myosin, in the thick filament, can then bind to actin, pulling the thick filaments along the thin filaments.  When the concentration of calcium within the cell falls, troponin and tropomyosin once again cover the binding sites on actin, causing the cell to relax."}
{"_id": "WikiPedia_Cardio$$$corpus_2761", "text": "It was commonly believed that cardiac muscle cells could not be regenerated. However, this was contradicted by a report published in 2009. [ 30 ]  Olaf Bergmann and his colleagues at the  Karolinska Institute  in  Stockholm  tested samples of heart muscle from people born before 1955 who had very little cardiac muscle around their heart, many showing with disabilities from this abnormality.  By using DNA samples from many hearts, the researchers estimated that a 4-year-old renews about 20% of heart muscle cells per year, and about 69% of the heart muscle cells of a 50-year-old were generated after they were born. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2762", "text": "One way that cardiomyocyte regeneration occurs is through the division of pre-existing cardiomyocytes during the normal aging process. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2763", "text": "In the 2000s, the discovery of adult endogenous cardiac stem cells was reported, and studies were published that claimed that various stem cell lineages, including  bone marrow stem cells  were able to differentiate into cardiomyocytes, and could be used to treat  heart failure . [ 32 ] [ 33 ] \nHowever, other teams were unable to replicate these findings, and many of the original studies were later  retracted  for scientific fraud. [ 34 ] [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2764", "text": "Cardiac muscle forms both the atria and the ventricles of the heart.  Although this muscle tissue is very similar between cardiac chambers, some differences exist.  The myocardium found in the ventricles is thick to allow forceful contractions, while the myocardium in the atria is much thinner. The individual myocytes that make up the myocardium also differ between cardiac chambers.  Ventricular cardiomyocytes are longer and wider, with a denser  T-tubule  network.  Although the fundamental mechanisms of calcium handling are similar between ventricular and atrial cardiomyocytes, the calcium transient is smaller and decays more rapidly in atrial myocytes, with a corresponding increase in  calcium buffering  capacity. [ 36 ]  The complement of ion channels differs between chambers, leading to longer action potential durations and effective refractory periods in the ventricles. Certain ion currents such as  I K(UR)  are highly specific to atrial cardiomyocytes, making them a potential target for treatments for  atrial fibrillation . [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2765", "text": "Diseases affecting cardiac muscle, known as  cardiomyopathies , are the leading cause of death in  developed countries . [ 38 ]  The most common condition is  coronary artery disease , in which the  blood supply to the heart is reduced . The  coronary arteries  become narrowed by  the formation of atherosclerotic plaques . [ 39 ]  If these narrowings become severe enough to partially restrict blood flow, the syndrome of  angina  pectoris may occur. [ 39 ]  This typically causes chest pain during exertion that is relieved by rest. If a coronary artery suddenly becomes very narrowed or completely blocked, interrupting or severely reducing blood flow through the vessel, a  myocardial infarction  or heart attack occurs. [ 40 ]  If the blockage is not relieved promptly by  medication ,  percutaneous coronary intervention , or  surgery , then a heart muscle region may become permanently scarred and damaged. [ 41 ]  Specific cardiomyopathies include: increased  left ventricular mass  ( hypertrophic cardiomyopathy ), [ 42 ]  abnormally large ( dilated cardiomyopathy ), [ 43 ]  or abnormally stiff ( restrictive cardiomyopathy ). [ 44 ]  Some of these conditions are caused by genetic mutations and can be inherited. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2766", "text": "Heart muscle can also become damaged despite a normal blood supply. The heart muscle may become inflamed in a condition called  myocarditis , [ 46 ]  most commonly caused by a viral infection [ 47 ]  but sometimes caused by the body's own  immune system . [ 48 ]  Heart muscle can also be damaged by drugs such as alcohol, long standing high blood pressure or  hypertension , or persistent abnormal  heart racing . [ 49 ] \nMany of these conditions, if severe enough, can damage the heart so much that the pumping function of the heart is reduced. If the heart is no longer able to pump enough blood to meet the body's needs, this is described as  heart failure . [ 49 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2767", "text": "Significant damage to cardiac muscle cells is referred to as  myocytolysis  which is considered a type of cellular  necrosis  defined as either coagulative or colliquative. [ 50 ] [ 51 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2768", "text": "The  cardiac pacemaker  is the  heart 's natural rhythm generator. It employs pacemaker  cells  that produce electrical impulses, known as  cardiac action potentials , which control the rate of contraction of the  cardiac muscle , that is, the  heart rate . In most humans, these cells are concentrated in the  sinoatrial (SA) node , the primary pacemaker, which regulates the heart\u2019s  sinus rhythm ."}
{"_id": "WikiPedia_Cardio$$$corpus_2769", "text": "Sometimes a secondary pacemaker sets the pace, if the SA node is damaged or if the  electrical conduction system of the heart  has problems.  Cardiac arrhythmias  can cause  heart block , in which the contractions lose their rhythm. In humans, and sometimes in other animals, a mechanical device called an  artificial pacemaker  (or simply \"pacemaker\") may be used after damage to the body's intrinsic conduction system to produce these impulses synthetically."}
{"_id": "WikiPedia_Cardio$$$corpus_2770", "text": "The  sinoatrial node  (SA node) is the primary pacemaker of the heart. It is a region of cardiac muscle on the wall of the upper  right atrium  near to the  superior vena cava  entrance. The cells that make up the SA node are specialized  cardiomyocytes  known as  pacemaker cells  that can spontaneously generate  cardiac action potentials . These signals are propagated through the heart's  electrical conduction system . [ 1 ] [ 2 ]  Only one percent of the heart muscle cells are conductive, the rest of the cardiomyocytes are  contractile ."}
{"_id": "WikiPedia_Cardio$$$corpus_2771", "text": "The pacemaker cells are connected to neighboring contractile cells via  gap junctions , which enable them to locally depolarize adjacent cells. Gap junctions allow the passage of positive cations from the depolarization of the pacemaker cell to adjacent contractile cells. This starts the depolarization and eventual action potential in contractile cells. Having cardiomyocytes connected via gap junctions allow all contractile cells of the heart to act in a coordinated fashion and contract as a unit. All the while being in sync with the pacemaker cells; this is the property that allows the pacemaker cells to control contraction in all other cardiomyocytes."}
{"_id": "WikiPedia_Cardio$$$corpus_2772", "text": "Cells in the SA node spontaneously  depolarize , ultimately resulting in contraction, approximately 100 times per minute. This native rate is constantly modified by the activity of  sympathetic  and  parasympathetic  nerve fibers via the  autonomic nervous system , so that the average resting  heart rate  in adult humans is about 70 beats per minute."}
{"_id": "WikiPedia_Cardio$$$corpus_2773", "text": "Impulses from the sinus node reach the  atrioventricular node  which acts as the secondary pacemaker. The cells of the AV node normally discharge at about 40\u201360 beats per minute, and are called the  secondary pacemaker ."}
{"_id": "WikiPedia_Cardio$$$corpus_2774", "text": "Further down the electrical conducting system of the heart is the  Bundle of His . The  left  and  right bundle branches , and the  Purkinje fibers , will also produce a spontaneous action potential at a rate of 30\u201340 beats per minute, so if the SA and AV node both fail to function, these cells can become pacemakers. These cells will be initiating action potentials and contraction at a much lower rate than the primary or secondary pacemaker cells."}
{"_id": "WikiPedia_Cardio$$$corpus_2775", "text": "The SA node controls the rate of contraction for the entire heart muscle because its cells have the quickest rate of spontaneous depolarization, thus they initiate action potentials the quickest. The action potential generated by the SA node passes down the  electrical conduction system of the heart , and depolarizes the other potential pacemaker cells (AV node) to initiate action potentials before these other cells have had a chance to generate their own spontaneous action potential, thus they contract and propagate electrical impulses to the pace set by the cells of the SA node. This is the normal conduction of electrical activity in the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_2776", "text": "There are three main stages in the generation of an action potential in a pacemaker cell. Since the stages are analogous to contraction of  cardiac muscle cells , they have the same naming system. This can lead to some confusion as phases one and two are absent, leaving only phases zero, three, and four."}
{"_id": "WikiPedia_Cardio$$$corpus_2777", "text": "The key to the rhythmic firing of pacemaker cells is that, unlike  neurons , these cardiomyocytes will slowly depolarize by themselves and do not need any outside innervation from the autonomic nervous system to fire action potentials."}
{"_id": "WikiPedia_Cardio$$$corpus_2778", "text": "In all other cells, the  resting potential  (-60mV to -70mV) is caused by a continuous outflow or \"leak\" of  potassium  ions through  ion channel   proteins  in the  membrane  that surrounds the cells. However, in pacemaker cells, this potassium permeability (efflux) decreases as time goes on, causing a slow depolarization. In addition, there is a slow, continuous inward flow of  sodium , called the \"funny\" or  pacemaker current . These two relative ion concentration changes slowly depolarize (make more positive) the inside membrane potential (voltage) of the cell, giving these cells their pacemaker potential. When the membrane potential gets depolarized to about -40mV it has reached threshold (cells enter phase 0), allowing an action potential to be generated."}
{"_id": "WikiPedia_Cardio$$$corpus_2779", "text": "Though much faster than the depolarization of phase 4, the upstroke in a pacemaker cell is slow compared to that in an  axon ."}
{"_id": "WikiPedia_Cardio$$$corpus_2780", "text": "The SA and AV node do not have fast sodium channels like neurons, and the depolarization is mainly caused by a slow influx of calcium ions. (The funny current also increases). Calcium enters the cell via voltage-sensitive calcium channels that open when the threshold is reached. This calcium influx produces the rising phase of the action potential, which results in the reversal of membrane potential to a peak of about +10mV. It is important to note that intracellular calcium causes muscular contraction in contractile cells, and is the effector ion. In heart pacemaker cells, phase 0 depends on the activation of  L-type calcium channels  instead of the activation of voltage-gated fast sodium channels, which are responsible for initiating action potentials in contractile (non-pacemaker) cells. For this reason, the pacemaker action potential rising phase slope is more gradual than that of the contractile cell (image 2)."}
{"_id": "WikiPedia_Cardio$$$corpus_2781", "text": "The reversal of membrane potential triggers the opening of potassium leak channels, resulting in the rapid loss of potassium ions from the inside of the cell, causing repolarization (V m  gets more negative). The calcium channels are also inactivated soon after they open. In addition, as sodium channels become inactivated, sodium permeability into the cell is decreased. These ion concentration changes slowly repolarize the cell to resting membrane potential (-60mV). Another important note at this phase is that ionic pumps restore ion concentrations to pre-action potential status. The  sodium-calcium exchanger  ionic pump works to pump calcium out of the  intracellular space , thus effectively relaxing the cell. The  sodium/potassium pump  restores ion concentrations of sodium and potassium ions by pumping sodium out of the cell and pumping (exchanging) potassium into the cell. Restoring these ion concentrations is vital because it enables the cell to reset itself and enables it to repeat the process of spontaneous depolarization leading to activation of an action potential."}
{"_id": "WikiPedia_Cardio$$$corpus_2782", "text": "If the SA node does not function, or the impulse generated in the  SA node is blocked  before it travels down the electrical conduction system, a group of cells further down the heart will become its pacemaker. [ 3 ]  This center is typically represented by cells inside the  atrioventricular node  (AV node), which is an area between the  atria  and  ventricles , within the  atrial septum .  If the AV node also fails,  Purkinje fibers  are occasionally capable of acting as the default or \"escape\" pacemaker."}
{"_id": "WikiPedia_Cardio$$$corpus_2783", "text": "An  ectopic pacemaker  also known as an ectopic focus or ectopic foci, is an excitable group of cells that causes a premature heart beat outside the normally functioning SA node of the heart. It is thus a cardiac pacemaker that is ectopic, producing an ectopic beat. If chronic this can result in  arhythmias  such as  tachycardia ,  bradycardia , or  ventricular fibrillation . An  artificial pacemaker  may be used to counter this."}
{"_id": "WikiPedia_Cardio$$$corpus_2784", "text": "An artificial cardiac pacemaker (or artificial pacemaker, so as not to be confused with the natural cardiac pacemaker) or just pacemaker is an  implanted medical device  that generates electrical impulses delivered by electrodes to the chambers of the heart either the upper atria, or lower ventricles to cause the targeted chambers to contract and pump blood. By doing so, the artificial pacemaker takes over from the primary SA node pacemaker to regulate the function of the heart's electrical conduction system."}
{"_id": "WikiPedia_Cardio$$$corpus_2785", "text": "Cardiac Pacemakers, Inc.  ( CPI ),  doing business as   Guidant Cardiac Rhythm Management , manufactured implantable cardiac rhythm management devices, such as  pacemakers  and  defibrillators . It sold microprocessor-controlled insulin pumps and equipment to regulate heart rhythm. It developed therapies to treat irregular heartbeat. The company was founded in 1971 and is based in  Saint Paul, Minnesota , and is presently a subsidiary of  Boston Scientific . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2786", "text": "CPI was founded in February 1972 in  Saint Paul, Minnesota . The first $50,000 capitalization for CPI was raised from a phone booth on the  Minneapolis  skyway system. [ 2 ]  They began designing and testing their implantable cardiac pacemaker powered with a new longer-life lithium battery in 1971. The first heart patient to receive a CPI pacemaker emerged from surgery in June 1973. Within two years, the upstart company that challenged Medtronic had sold approximately 8,500 pacemakers. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2787", "text": "Medtronic  at the time had 65% of the artificial pacemaker market. CPI was the first spin-off from Medtronic. It competition using the world's first lithium-powered pacemaker. Medtronic's market share plummeted to 35%. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2788", "text": "Founding partners  Anthony Adducci ,  Manny Villafa\u00f1a , Jim Baustert, and Art Schwalm, were former Medtronic employees. Lawsuits ensued, all of which were settled out of court. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2789", "text": "The company sold 8,500 pacemakers, increasing sales from zero in 1972 to over $47 million."}
{"_id": "WikiPedia_Cardio$$$corpus_2790", "text": "In early 1978, CPI was concerned about a friendly takeover attempt. Despite impressive sales, the company's stock price had fluctuated wildly the year before, dropping from $33 to $11 per share. Some speculated that the stock was being sold short, while others attributed the price to the natural volatility of high-tech stock. As a one-product company, CPI was susceptible to changing market conditions, and its founders knew they needed to diversify. They considered two options: acquiring other medical device companies or being acquired themselves. They chose the latter."}
{"_id": "WikiPedia_Cardio$$$corpus_2791", "text": "Several companies expressed interest in acquiring CPI, including  3M , American Hospital Supply,  Pfizer , and  Johnson & Johnson . However,  Eli Lilly and Company , one of the premier pharmaceutical companies in the United States, was the most enthusiastic suitor. \"Lilly had the research expertise, highly compatible interests, and similar values,\" Anthony Adducci recalls. \"At CPI, we haven't been able to dedicate the dollars and time necessary to develop new products beyond our staple lithium-powered pacemaker. Lilly was a $2 billion company. We knew they had tremendous resources, especially in research and development.\" [ 6 ]  Additionally, Eli Lilly and CPI were already interested in developing  insulin  pumps, and Lilly was working with cardiovascular drugs, a natural link to CPI's heart pacemaker business."}
{"_id": "WikiPedia_Cardio$$$corpus_2792", "text": "Before the final negotiations in late 1978, there were numerous flights between Minneapolis and  Indianapolis  for CPI principals and representatives of  Piper, Jaffray & Hopwood's  corporate finance department. Lilly, a pharmaceutical giant, and CPI, the upstart pacemaker company, sat down at a bargaining table at a motel in suburban  Bloomington, Minnesota . CPI's negotiation team included Anthony Adducci, Art Schwalm, Tom King, and Hunt Greene."}
{"_id": "WikiPedia_Cardio$$$corpus_2793", "text": "In December 1978, the company was acquired by Eli Lilly and Company for $127 million. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2794", "text": "CPI designed and manufactured the world's first pacemaker with a lithium anode and a  lithium-iodide  electrolyte solid-state battery. The pacemaker structure is enclosed in a hermetically sealed metallic enclosure, allowing electrode leads to pass in a sealed relationship. The surface of the casing is polished metal, with a zone through which the external electrode leads pass. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2795", "text": "The Lithium-iodide or lithium anode cells revolutionized the medical industry by increasing the pacemaker life from 1 year up to 11 years. It became the standard for pacemaker designs."}
{"_id": "WikiPedia_Cardio$$$corpus_2796", "text": "Cardiac resynchronisation therapy  ( CRT  or  CRT-P ) is the insertion of  electrodes  in the left and right  ventricles  of the heart, as well as on occasion the right  atrium , to treat  heart failure  by coordinating the function of the left and right ventricles via a  pacemaker , a small device inserted into the anterior chest wall. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2797", "text": "CRT is indicated in patients with a low  ejection fraction  (typically <35%) indicating  heart failure , where electrical activity has been compromised, with prolonged  QRS  duration to >120  ms . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2798", "text": "The insertion of electrodes into the ventricles is done under  local anesthetic , with access to the ventricles most commonly via the  subclavian vein , although access may be conferred from the  axillary  or  cephalic veins . Right ventricular access is direct, while left ventricular access is conferred via the  coronary sinus  (CS)."}
{"_id": "WikiPedia_Cardio$$$corpus_2799", "text": "CRT defibrillators ( CRT-D ) also incorporate the additional function of an  implantable cardioverter-defibrillator  (ICD), to quickly terminate an abnormally fast, life-threatening heart rhythm. CRT and CRT-D have become increasingly important therapeutic options for patients with moderate and severe heart failure. [ 3 ]  CRT with pacemaker only is often termed \"CRT-P\" to help distinguish it from CRT with defibrillator (CRT-D)."}
{"_id": "WikiPedia_Cardio$$$corpus_2800", "text": "The key indication for CRT is  left bundle branch block  (LBBB) of the heart, a cardiac abnormality leading to delayed left ventricular contraction. LBBB causes a  QRS  prolongation of \u2265120  ms  on the  electrocardiogram , contributing to poor left ventricular coordination and reduced systolic function, thereby reduced ejection fraction (<35%). This reduction in ejection fraction is considered heart failure. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2801", "text": "Heart failure patients are generally considered if in  New York Heart Association  (NYHA) class II or III heart failure. Current  National Institute for Health and Care Excellence  (NICE) guidelines state that CRT-D device placement is inappropriate for class IV heart failure, but placement of CRT-P devices may be appropriate in certain circumstances. [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2802", "text": "CRT requires the placement of an electrical device for biventricular pacing, along with placement of (at least) two pacing leads, to facilitate stable left ventricular and right ventricular pacing. For all elements, the first stage of the process is local anaesthetic followed by incision to allow for approach from the appropriate vein. From here, the leads and device can be inserted. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2803", "text": "A  venipuncture   is made, and a guide wire inserted into the vein, where it is guided, with use of  real time X-ray imaging , through to the right ventricle. The guide wire is then used to assist in the placement of the electrode lead, which travels through the venous system into the right ventricle where the electrode is embedded. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2804", "text": "This is generally performed subsequent to RV lead placement, with the RV lead providing a backup in case of accidental damage to the  electric fibers of the heart , causing an  asystolic event . As with the RV lead, a guide wire is first inserted, allowing for the insertion of a  multi-delivery catheter . The catheter is subsequently maneuvered to the opening of the coronary sinus in the right atrium. From here a  contrast media  is injected, allowing the surgical team to obtain a coronary sinus  phlebogram  to direct the placement of the lead into the most suitable  coronary vein . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2805", "text": "Once the phlebogram has been obtained, the multi-delivery catheter is used to guide in the lead, from the chosen vein of entry, into the right atrium, through the coronary sinus and into the relevant cardiac vein. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2806", "text": "Left ventricular lead placement is the most complicated and potentially hazardous element of the operation, due to the significant variability of coronary venous structure. Alterations in heart structure, fatty deposits, valves and natural variations all cause additional complications in the process of cannulation. [ 1 ]  However, this risk can be reduced using AI-based [ 8 ]  preoperative visualization of LV venous anatomy using computer tomography (CT) imaging."}
{"_id": "WikiPedia_Cardio$$$corpus_2807", "text": "The device is inserted in a subcutaneous pocket created by the surgeon, the choice of left or right side of the chest wall is determined mainly by the patient's preference or location of preexisting device. The device, similar to that of a traditional  pacemaker , is generally no larger than a pocket watch and has inserts for the electrode leads. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2808", "text": "Several studies have also shown that CRT can decrease mortality, reverse  left ventricular remodeling , and improve quality of life, walking distance, and peak oxygen uptake ( VO 2  max ). [ 9 ]  A 2013 study showed that CRT improved the left ventricular ejection fraction (LVEF) by an average of 10.6% 12 months after placement. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2809", "text": "Key complications include: [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2810", "text": "Several research papers [ 12 ] [ 13 ]  have proposed software platforms for planning and guiding the implantation of CRT devices. This research proposes using pre-operative images to characterize tissue and left ventricle activation to identify potential target regions for deploying the CRT leads."}
{"_id": "WikiPedia_Cardio$$$corpus_2811", "text": "Cardiac rhythmicity  is the spontaneous  depolarization  and  repolarization  event that occurs in a repetitive and stable manner within the cardiac muscle. Rhythmicity is often abnormal or lost in cases of cardiac dysfunction or  cardiac failure . It is the ability of the heart to maintain a relatively stable relation between its  systole  and  diastole . Not increasing one on the expense of the other. However, external factors may lead to the disruption of the heart's rhythmicity."}
{"_id": "WikiPedia_Cardio$$$corpus_2812", "text": "The  cardiac transient outward potassium current  (referred to as  I to1  or  I to [ 1 ]   ) is one of the  ion currents  across the cell membrane of  heart muscle cells . It is the main contributing current during the  repolarizing   phase 1 of the cardiac action potential . It is a result of the movement of positively charged  potassium  (K + ) ions from the  intracellular  to the  extracellular space . I to1  is complemented with I to2  resulting from Cl \u2212  ions to form the transient outward current I to ."}
{"_id": "WikiPedia_Cardio$$$corpus_2813", "text": "I to1  is rapidly activated and deactivated. [ 2 ]  It is activated after the fast increase of the membrane potential following the  phase 0 of the cardiac action potential . Once activated, (K + ) ions from inside the cells flow to the extracellular space. This outward flow of positively charged ions constitutes the I to1  and causes the  transmembrane voltage  to decrease. This decrease of the transmembrane potential is known as  repolarization . I to1  is then quickly deactivated, stopping the repolarization and ending the  phase 1  of the action potential."}
{"_id": "WikiPedia_Cardio$$$corpus_2814", "text": "I to1  is  Ca 2+ -independent [ 3 ]  and has been clearly demonstrated in myocytes from different cardiac regions and species. [ 3 ]  There are two kinetic variants of cardiac I to1 : fast I to1 , called I to1,f , and slow Ito, called I to1,s . The channel responsible for I to1,f  is formed by assembly of  Kv4.2  (KCND2) subunits,  Kv4.3  (KCND3) subunits or a combination of the two, while the channel responsible for I to1,s  is composed of  Kv1.4  (KCNA4) subunits. [ 2 ]  In addition, several regulatory subunits and pathways modulating the level and biophysical properties of cardiac I to  have been identified. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2815", "text": "I to1  affects the opening of Ca 2+  channels during Phase 2 of the Action Potential. As a result, changes in I to1  modulate changes in the action potential duration. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2816", "text": "Clinical cardiac electrophysiology  (also referred to as  cardiac electrophysiology  or simply  EP ), is a branch of the medical specialty of  cardiology   concerned with the study and treatment of  rhythm disorders  of the  heart . [ 1 ]  Cardiologists with expertise in this area are usually referred to as electrophysiologists.  Electrophysiologists are trained in the mechanism, function, and performance of the electrical activities of the  heart .  Electrophysiologists work closely with other cardiologists and cardiac surgeons to assist or guide therapy for heart rhythm disturbances ( arrhythmias ). They are trained to perform interventional and surgical procedures to treat cardiac arrhythmia."}
{"_id": "WikiPedia_Cardio$$$corpus_2817", "text": "The training required to become an electrophysiologist is lengthy and requires eight years after medical school (in the U.S.), entailing three years of  internal medicine   residency , three years of clinical  cardiology   fellowship , and two years of clinical cardiac electrophysiology. This is necessary due to the significant complexity of patients that electrophysiologists usually treat, the constant advances in methods and equipment used in their daily practice, making the field of electrophysiology one of the most demanding subspecialties of modern medicine."}
{"_id": "WikiPedia_Cardio$$$corpus_2818", "text": "An electrophysiology study is any of a number of invasive (intracardiac) and non-invasive recording of spontaneous electrical activity, as well as of cardiac responses to  programmed electrical stimulation . These studies are performed to assess  arrhythmias , elucidate symptoms, evaluate abnormal  electrocardiograms , assess risk of developing arrhythmias in the future, and design treatment."}
{"_id": "WikiPedia_Cardio$$$corpus_2819", "text": "In addition to diagnostic testing of the electrical properties of the heart, electrophysiologists are trained in therapeutic and surgical methods to treat many of the rhythm disturbances of the heart.  Therapeutic modalities employed in this field include  antiarrhythmic drug  therapy and surgical implantation of  pacemakers  and  implantable cardioverter-defibrillators ."}
{"_id": "WikiPedia_Cardio$$$corpus_2820", "text": "Common rhythms dealt with include  atrial fibrillation ,  ventricular tachycardia , and the  supraventricular tachycardias . Abnormal rhythms have multiple ways they can be treated and choosing is often individualized based on symptoms and patient preference."}
{"_id": "WikiPedia_Cardio$$$corpus_2821", "text": "Electrophysiologists will commonly employ the following diagnostic tests and may be performed or interpreted exclusively by the electrophysiologist. Other tests such as  cardiac stress testing  may be included in an evaluation but are not exclusive to electrophysiology."}
{"_id": "WikiPedia_Cardio$$$corpus_2822", "text": "Initial administration and monitoring of the effect of drugs for treatment of heart rhythm disorders. Electrophysiologists are often involved when severe or life-threatening  arrhythmias  are being treated, or when multiple drugs must be used to treat an arrhythmia.\n Antiarrhythmic agents  such as  flecainide ,  dofetilide , and  amiodarone  are commonly used to try to control rhythms."}
{"_id": "WikiPedia_Cardio$$$corpus_2823", "text": "Ablation therapy is a catheter based ablation of lesions in the heart (with radiofrequency energy, cryotherapy (destructive freezing), microwave, or ultrasound energy) to cure or control arrhythmias (see  radiofrequency ablation ). Ablation is usually performed during the same procedure as the electrophysiology study during which arrhythmias are attempted to be induced as well as elucidating the mechanism of the arrhythmia for which ablation therapy is sought."}
{"_id": "WikiPedia_Cardio$$$corpus_2824", "text": "Implantation of devices include"}
{"_id": "WikiPedia_Cardio$$$corpus_2825", "text": "Additionally, there are, at times, indications to remove these devices and extraction (ie, removal) of these devices can also be performed by electrophysiologists."}
{"_id": "WikiPedia_Cardio$$$corpus_2826", "text": "Once implanted, long-term clinical follow up and reprogramming of implanted devices also falls to the electrophysiologist."}
{"_id": "WikiPedia_Cardio$$$corpus_2827", "text": "Concealed conduction  is tissue stimulation without direct effect, but leading to a change in conduction characteristics. [ 1 ]  The term \"concealed\" is in reference to that the conduction is not observable by electrocardiogram."}
{"_id": "WikiPedia_Cardio$$$corpus_2828", "text": "A common example would be an  interpolated PVC  (a type of  premature ventricular contraction ) during  normal sinus rhythm ; the PVC does not cause an atrial contraction, because the retrograde impulse from the PVC does not completely penetrate the AV node. However, this AV node stimulation can cause a delay in subsequent AV conduction by modifying the AV node's subsequent conduction characteristics. Hence, the P-R interval after the PVC is longer than the baseline P-R interval. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2829", "text": "Concealed conduction can be seen in  cardiac aberrancy  when a bundle branch temporarily blocks due to being refractory, and conduction from the other bundle branch conceals into the blocked branch retrograde thus perpetuation the bundle branch block morphology in subsequent beats. For example, if a  Premature atrial contraction  reaches the right bundle branch while refractory the PAC will conduct with RBBB morphology. As this PAC conducts down the left bundle, it will depolarize the septum then proceed retrograde up the right bundle. Eventually, this will reach refractory conduction tissue and stop. The subsequent beat \u2014 if early enough \u2014 will find the right bundle still refractory and the process will repeat yielding a continued RBBB morphology."}
{"_id": "WikiPedia_Cardio$$$corpus_2830", "text": "Another variation on this concept is seen in  atrial flutter . As a result of the rapid atrial rate, some of the atrial activity fails to get through the AV node in an antegrade direction but can alter the rate at which a subsequent atrial impulse is conducted. In this circumstance, an alteration in the F-wave to QRS relationship is seen. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2831", "text": "Ross Cowie  (born 13 February 1960) is a charity-worker and former  shinty  player and manager,  from  Portree ,  Isle of Skye ,  Scotland .  He is affectionately known as  The Colonel ."}
{"_id": "WikiPedia_Cardio$$$corpus_2832", "text": "Throughout his career, Cowie was involved with  Skye Camanachd  and was most notably manager when they won the   Camanachd Cup  in 1990 [ 1 ]  He was also captain of the Skye second team that had won the Sutherland Cup in 1988."}
{"_id": "WikiPedia_Cardio$$$corpus_2833", "text": "In all he has been manager of Skye Camanachd 3 times, covering an aggregate of 8 years.  [1]  His father, Willie played for Skye Camanachd also, as well as  Lovat Shinty Club .  His uncle Dave Cowie played for Aberdeen FC in 1939."}
{"_id": "WikiPedia_Cardio$$$corpus_2834", "text": "Because of a serious heart condition,  cardiomyopathy , Cowie retired from involvement in the playing side of the sport but retained a position as  president  of Skye Camanachd. \nIn December 2010, Cowie made a dramatic return to top-level shinty with his re-appointment as assistant manager of Skye.  He assisted manager Aonghas MacDonald and was supported by his two star players from the 1990 victory, his brother Willie and  Albert Smith Medal  winner, Willie MacRae. [2]"}
{"_id": "WikiPedia_Cardio$$$corpus_2835", "text": "He spoke to the press in January 2010 about the need for his club to improve performances at all levels, but in particular at second team level. [3]  He became the Skye Camanachd \"Director of Shinty\" in late 2012."}
{"_id": "WikiPedia_Cardio$$$corpus_2836", "text": "Cowie stepped down from the Skye Camanachd committee in December 2018.  [4]  along with fellow club stalwart, Donnie Martin. [5]"}
{"_id": "WikiPedia_Cardio$$$corpus_2837", "text": "Cowie was also an important player and coach for the now defunct Portree United FC, a football club which shared many players in common with Skye Camanachd."}
{"_id": "WikiPedia_Cardio$$$corpus_2838", "text": "After a cardiac arrest in December 2006, which saw him die for several minutes, he became involved in fundraising and raising awareness of cardiac conditions throughout the Highlands of Scotland thorough his charity,  Lucky2BHere . [6]   Lucky2BHere  focuses on making acute care available in remote areas of the Highlands. [7]  Lucky2BHere"}
{"_id": "WikiPedia_Cardio$$$corpus_2839", "text": "The trustees of Lucky2BHere are Professor Steve Leslie, Angus MacDonald, Phil Cunningham and Malcolm Jones."}
{"_id": "WikiPedia_Cardio$$$corpus_2840", "text": "By 2019, Lucky2BHere had raised over \u00a31,000,000 and had distributed over 600 defibrillators. These defibrillators had been instrumental in saving several lives.  [8]"}
{"_id": "WikiPedia_Cardio$$$corpus_2841", "text": "Through 2021, and the aftermath of the  Christian Eriksen  incident at  Euro 2020 , Cowie made a call for the Scottish Government to have emergency life support training in every school in Scotland.  [9]"}
{"_id": "WikiPedia_Cardio$$$corpus_2842", "text": "In 2022, Cowie talked about  Inverness  BID securing 5 new defibs for Inverness City Centre and Lucky2BHere is the biggest purchaser of defibs in Scotland and Northern Ireland. [10]"}
{"_id": "WikiPedia_Cardio$$$corpus_2843", "text": "In May 2024, Cowie was recognised with a  Point of Light Award  and was recognised with an  early day motion  in the  UK Parliament . [11]"}
{"_id": "WikiPedia_Cardio$$$corpus_2844", "text": "Defibrillation  is a treatment for life-threatening  cardiac arrhythmias , specifically  ventricular fibrillation  (V-Fib) and  non-perfusing ventricular tachycardia  (V-Tach). [ 1 ] [ 2 ]  A defibrillator delivers a dose of  electric current  (often called a  counter-shock ) to the  heart . Although not fully understood, this process  depolarizes  a large amount of the  heart muscle , ending the arrhythmia. Subsequently, the body's  natural pacemaker  in the  sinoatrial node  of the heart is able to re-establish normal  sinus rhythm . [ 3 ]  A heart which is in  asystole  (flatline) cannot be restarted by a defibrillator; it would be treated only by  cardiopulmonary resuscitation  (CPR) and medication, and then by cardioversion or defibrillation if it converts into a shockable rhythm."}
{"_id": "WikiPedia_Cardio$$$corpus_2845", "text": "In contrast to defibrillation, synchronized electrical  cardioversion  is an electrical shock delivered in synchrony to the  cardiac cycle . [ 4 ]  Although the person may still be  critically ill , cardioversion normally aims to end poorly perfusing  cardiac arrhythmias , such as  supraventricular tachycardia . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2846", "text": "Defibrillators can be external, transvenous, or  implanted  ( implantable cardioverter-defibrillator ), depending on the type of device used or needed. [ 5 ]  Some external units, known as  automated external defibrillators  (AEDs), automate the diagnosis of treatable rhythms, meaning that lay responders or bystanders are able to use them successfully with little or no training. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2847", "text": "Defibrillation is often an important step in  cardiopulmonary resuscitation  (CPR). [ 6 ] [ 7 ]  CPR is an algorithm-based intervention aimed to restore cardiac and pulmonary function. [ 6 ]  Defibrillation is indicated only in certain types of  cardiac dysrhythmias , specifically  ventricular fibrillation  (VF) and  pulseless ventricular tachycardia . [ 1 ] [ 2 ]  If the heart has completely stopped, as in  asystole  or  pulseless electrical activity (PEA) , defibrillation is not indicated. Defibrillation is also not indicated if the patient is conscious or has a pulse. Improperly given electrical shocks can cause dangerous dysrhythmias, such as ventricular fibrillation. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2848", "text": "A defibrillation device that is often available outside of medical centers is the automated external defibrillator (AED), [ 8 ]  a portable machine that can be used with no previous training. That is possible because the machine produces pre-recorded voice instructions that guide the user. The device automatically checks the patient's condition and applies the correct electric shocks. There also exist written instructions that explain the procedure step-by-step. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2849", "text": "Survival rates for out-of-hospital  cardiac arrests  in North America are poor, often less than 10%. [ 10 ]  Outcome for in-hospital cardiac arrests are higher at 20%. [ 10 ]  Within the group of people presenting with cardiac arrest, the specific cardiac rhythm can significantly impact survival rates. Compared to people presenting with a non-shockable rhythm (such as asystole or PEA), people with a shockable rhythm (such as VF or pulseless ventricular tachycardia) have improved survival rates, ranging between 21 and 50%. [ 6 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2850", "text": "Manual external defibrillators require the expertise of a healthcare professional. [ 13 ] [ 14 ]  They are used in conjunction with an  electrocardiogram , which can be separate or built-in. A healthcare provider first diagnoses the cardiac rhythm and then manually determine the voltage and timing for the electrical shock. These units are primarily found in  hospitals  and on some  ambulances .  For instance, every  NHS  ambulance in the  United Kingdom  is equipped with a manual defibrillator for use by the attending paramedics and technicians.  [ citation needed ]  In the  United States , many advanced  EMTs  and all  paramedics  are trained to recognize lethal arrhythmias and deliver appropriate electrical therapy with a manual defibrillator when appropriate.  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2851", "text": "An internal defibrillator is often used to defibrillate the heart during or after cardiac surgery such as a  heart bypass . The electrodes consist of round metal plates that come in direct contact with the myocardium. Manual internal defibrillators deliver the shock through paddles placed directly on the heart. [ 1 ]  They are mostly used in the  operating room  and, in rare circumstances, in the emergency room during an  open heart procedure ."}
{"_id": "WikiPedia_Cardio$$$corpus_2852", "text": "Automated external defibrillators (AEDs) are designed for use by untrained or briefly trained laypersons. [ 15 ] [ 16 ] [ 17 ]  AEDs contain technology for analysis of heart rhythms. As a result, it does not require a trained health provider to determine whether or not a rhythm is shockable. By making these units publicly available, AEDs have improved outcomes for sudden out-of-hospital cardiac arrests. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2853", "text": "Trained health professionals have more limited use for AEDs than manual external defibrillators. [ 18 ]  Recent studies show that AEDs does not improve outcome in patients with in-hospital cardiac arrests. [ 18 ] [ 19 ]  AEDs have set voltages and does not allow the operator to vary voltage according to need. AEDs may also delay delivery of effective CPR. For diagnosis of rhythm, AEDs often require the stopping of chest compressions and rescue breathing. For these reasons, certain bodies, such as the European Resuscitation Council, recommend using manual external defibrillators over AEDs if manual external defibrillators are readily available. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2854", "text": "As early defibrillation can significantly improve VF outcomes, AEDs have become publicly available in many easily accessible areas. [ 18 ] [ 19 ]  AEDs have been incorporated into the algorithm for  basic life support  (BLS). Many  first responders , such as firefighters, police officers, and security guards, are equipped with them."}
{"_id": "WikiPedia_Cardio$$$corpus_2855", "text": "AEDs can be fully automatic or semi-automatic. [ 20 ]  A semi-automatic AED automatically diagnoses heart rhythms and determines if a shock is necessary. If a shock is advised, the user must then push a button to administer the shock. A fully automated AED automatically diagnoses the heart rhythm and advises the user to stand back while the shock is automatically given. Some types of AEDs come with advanced features, such as a manual override or an  ECG  display."}
{"_id": "WikiPedia_Cardio$$$corpus_2856", "text": "Implantable cardioverter-defibrillators , also known as automatic internal cardiac defibrillator (AICD), are implants similar to  pacemakers  (and many can also perform the pacemaking function). They constantly monitor the patient's heart rhythm, and automatically administer shocks for various life-threatening arrhythmias, according to the device's programming. Many modern devices can distinguish between  ventricular fibrillation ,  ventricular tachycardia , and more benign arrhythmias like  supraventricular tachycardia  and  atrial fibrillation . Some devices may attempt overdrive pacing prior to synchronised cardioversion. When the life-threatening arrhythmia is ventricular fibrillation, the device is programmed to proceed immediately to an unsynchronized shock."}
{"_id": "WikiPedia_Cardio$$$corpus_2857", "text": "There are cases where the patient's ICD may fire constantly or inappropriately. This is considered a  medical emergency , as it depletes the device's battery life, causes significant discomfort and anxiety to the patient, and in some cases may actually trigger life-threatening arrhythmias. Some  emergency medical services  personnel are now equipped with a ring  magnet  to place over the device, which effectively disables the shock function of the device while still allowing the pacemaker to function (if the device is so equipped). If the device is shocking frequently, but appropriately, EMS personnel may administer sedation."}
{"_id": "WikiPedia_Cardio$$$corpus_2858", "text": "A  wearable cardioverter defibrillator  is a portable external defibrillator that can be worn by at-risk patients. [ 21 ]  The unit monitors the patient 24 hours a day and can automatically deliver a biphasic shock if VF or VT is detected. This device is mainly indicated in patients who are not immediate candidates for ICDs. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2859", "text": "The connection between the defibrillator and the patient consists of a pair of electrodes, each provided with  electrically conductive  gel in order to ensure a good connection and to minimize  electrical resistance , also called chest impedance (despite the DC discharge) which would burn the patient.  Gel may be either wet (similar in consistency to  surgical lubricant ) or solid (similar to  gummi candy ).  Solid-gel is more convenient, because there is no need to clean the used gel off the person's skin after defibrillation. However, the use of solid-gel presents a higher risk of burns during defibrillation, since wet-gel electrodes more evenly conduct electricity into the body.  Paddle electrodes, which were the first type developed, come without gel, and must have the gel applied in a separate step.  Self-adhesive electrodes come prefitted with gel.  There is a general division of opinion over which type of electrode is superior in hospital settings; the American Heart Association favors neither, and all modern manual defibrillators used in hospitals allow for swift switching between self-adhesive pads and traditional paddles.  Each type of electrode has its merits and demerits."}
{"_id": "WikiPedia_Cardio$$$corpus_2860", "text": "The most well-known type of electrode (widely depicted in films and television) is the traditional metal \"hard\" paddle with an insulated (usually plastic) handle. This type must be held in place on the patient's skin with approximately 25\u00a0lbs (11.3\u00a0kg) of force while a shock or a series of shocks is delivered. Paddles offer a few advantages over self-adhesive pads.  Many hospitals in the United States continue the use of paddles, with disposable gel pads attached in most cases, due to the inherent speed with which these electrodes can be placed and used. This is critical during cardiac arrest, as each second of  nonperfusion  means tissue loss.  Modern paddles allow for monitoring ( electrocardiography ), though in hospital situations, separate monitoring leads are often already in place."}
{"_id": "WikiPedia_Cardio$$$corpus_2861", "text": "Paddles are reusable, being cleaned after use and stored for the next patient.  Gel is therefore not preapplied, and must be added before these paddles are used on the patient.  Paddles are generally only found on manual external units."}
{"_id": "WikiPedia_Cardio$$$corpus_2862", "text": "Newer types of resuscitation electrodes are designed as an adhesive pad, which includes either solid or wet gel.  These are peeled off their backing and applied to the patient's chest when deemed necessary, much the same as any other sticker. The electrodes are then connected to a defibrillator, much as the paddles would be. If defibrillation is required, the machine is charged, and the shock is delivered, without any need to apply any additional gel or to retrieve and place any paddles.  Most adhesive electrodes are designed to be used not only for defibrillation, but also for  transcutaneous pacing  and synchronized electrical  cardioversion .  These adhesive pads are found on most automated and semi-automated units and are replacing paddles entirely in non-hospital settings.  In hospital, for cases where cardiac arrest is likely to occur (but has not yet), self-adhesive pads may be placed prophylactically."}
{"_id": "WikiPedia_Cardio$$$corpus_2863", "text": "Pads also offer an advantage to the untrained user, and to medics working in the sub-optimal conditions of the field.  Pads do not require extra leads to be attached for monitoring, and they do not require any force to be applied as the shock is delivered.  Thus, adhesive electrodes minimize the risk of the operator coming into physical (and thus electrical) contact with the patient as the shock is delivered by allowing the operator to be up to several feet away.  (The risk of electrical shock to others remains unchanged, as does that of shock due to operator misuse.)  Self-adhesive electrodes are single-use only.  They may be used for multiple shocks in a single course of treatment, but are replaced if (or in case) the patient recovers then reenters cardiac arrest."}
{"_id": "WikiPedia_Cardio$$$corpus_2864", "text": "Special pads are used for children under the age of 8 or those under 55\u00a0lbs. (22\u00a0kg). [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2865", "text": "Resuscitation electrodes are placed according to one of two schemes. The anterior-posterior scheme is the preferred scheme for long-term electrode placement. One electrode is placed over the left precordium (the lower part of the chest, in front of the heart). The other electrode is placed on the back, behind the heart in the region between the scapula. This placement is preferred because it is best for non-invasive pacing."}
{"_id": "WikiPedia_Cardio$$$corpus_2866", "text": "The anterior-apex scheme (anterior-lateral position) can be used when the anterior-posterior scheme is inconvenient or unnecessary. In this scheme, the anterior electrode is placed on the right, below the clavicle. The apex electrode is applied to the left side of the patient, just below and to the left of the pectoral muscle. This scheme works well for defibrillation and cardioversion, as well as for monitoring an ECG."}
{"_id": "WikiPedia_Cardio$$$corpus_2867", "text": "Researchers have created a software modeling system capable of mapping an individual's  chest  and determining the best position for an external or internal cardiac defibrillator. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2868", "text": "Defibrillation halts chaotic cardiac activity by forcibly depolarizing heart cells, disrupting re-entrant circuits, and allowing for the heart's natural pacemaker to take over. [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2869", "text": "Cardiac cells require a strong electrical stimulus to raise their transmembrane potential to the activation threshold. [ 25 ] [ 26 ]  Only a small amount of electrical current enters the cell due to high membrane impedance. [ 25 ] The intracellular voltage of the cell remains uniform, while the extracellular voltage rapidly increases or decreases depending on proximity to the electrodes. [ 25 ] This creates a voltage gradient that alters the transmembrane potential of cells, potentially resetting irregular electrical activity to restore normal cardiac rhythm. [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2870", "text": "Irregular rhythms often result from re-entrant circuits, where electrical impulses circle within the heart tissue due to areas of slow conduction or unidirectional block. [ 27 ]  The widespread depolarization from the shock interrupts these circuits, stopping the erratic propagation of electrical signals. [ 25 ] [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2871", "text": "After the cells depolarize, they enter a refractory period, during which they cannot be re-excited. [ 28 ] [ 29 ]  This allows the heart's natural pacemaker, the sinoatrial node, to resume control of the rhythm. During this period, ion pumps actively restore the normal distribution of ions, re-establishing the resting membrane potential. [ 28 ] [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2872", "text": "Defibrillators were first demonstrated in 1899 by  Jean-Louis Pr\u00e9vost  and Fr\u00e9d\u00e9ric Batelli, two  physiologists  from the  University of Geneva , Switzerland. They discovered that small electrical shocks could induce ventricular fibrillation in dogs, and that larger charges would reverse the condition. [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2873", "text": "In 1933, Dr. Albert Hyman, heart specialist at the Beth Davis Hospital of New York City and C. Henry Hyman, an electrical engineer, looking for an alternative to injecting powerful drugs directly into the heart, came up with an invention that used an electrical shock in place of drug injection. This invention was called the  Hyman Otor  where a hollow needle is used to pass an insulated wire to the heart area to deliver the electrical shock.  The hollow steel needle acted as one end of the circuit and the tip of the insulated wire the other end.  Whether the  Hyman Otor  was a success is unknown. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2874", "text": "The external defibrillator, as it is known today, was invented by electrical engineer  William Kouwenhoven  in 1930. Kouwenhoven studied the relationship between electric shocks and their effects on the human heart when he was a student at Johns Hopkins University School of Engineering. His studies helped him invent a device to externally jump start the heart. He invented the defibrillator and tested it on a dog, like Pr\u00e9vost and Batelli. The first use on a human was in 1947 by  Claude Beck , [ 33 ]  professor of surgery at  Case Western Reserve University ."}
{"_id": "WikiPedia_Cardio$$$corpus_2875", "text": "Beck's theory was that ventricular fibrillation often occurred in hearts that were fundamentally healthy, in his terms \"Hearts that are too good to die\", and that there must be a way of saving them.  Beck first used the technique successfully on a 14-year-old boy who was having his  breastbone  separated from his  ribs  because of a congenital growth disorder, causing breathing problems. The boy's chest was surgically opened, and manual cardiac massage was undertaken for 45 minutes until the arrival of the defibrillator.  Beck used internal paddles on either side of the heart, along with  procainamide , an  antiarrhythmic  drug, and achieved return of a perfusing cardiac rhythm. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2876", "text": "These early defibrillators used the alternating current from a power socket, transformed from the 110\u2013240 volts available in the line, up to between 300 and 1000 volts, to the exposed heart by way of \"paddle\" type electrodes.  The technique was often ineffective in reverting VF while morphological studies showed damage to the cells of the heart muscle post-mortem.  The nature of the AC machine with a large transformer also made these units very hard to transport, and they tended to be large units on wheels. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2877", "text": "Until the early 1950s, defibrillation of the heart was possible only when the chest cavity was open during surgery. The technique used an alternating voltage from a 300 or greater  volt  source derived from standard AC power, delivered to the sides of the exposed heart by \"paddle\" electrodes where each electrode was a flat or slightly concave metal plate of about 40\u00a0mm diameter. The closed-chest defibrillator device which applied an alternating voltage of greater than 1000 volts, conducted by means of externally applied electrodes through the chest cage to the heart, was pioneered by Dr V. Eskin with assistance by A. Klimov in Frunze, USSR (today known as  Bishkek ,  Kyrgyzstan ) in the mid-1950s. [ 34 ]  The duration of AC shocks was typically in the range of 100\u2013150 milliseconds. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2878", "text": "Early successful experiments of successful defibrillation by the discharge of a capacitor performed on animals were reported by  N. L. Gurvich  and G. S. Yunyev in 1939. [ 36 ]  In 1947 their works were reported in western medical journals. [ 37 ]  Serial production of Gurvich's pulse defibrillator started in 1952 at the electromechanical plant of the institute, and was designated model \u0418\u0414-1-\u0412\u042d\u0418 ( \u0418\u043c\u043f\u0443\u043b\u044c\u0441\u043d\u044b\u0439 \u0414\u0435\u0444\u0438\u0431\u0440\u0438\u043b\u043b\u044f\u0442\u043e\u0440 1, \u0412\u0441\u0435\u0441\u043e\u044e\u0437\u043d\u044b\u0439 \u042d\u043b\u0435\u043a\u0442\u0440\u043e\u0442\u0435\u0445\u043d\u0438\u0447\u0435\u0441\u043a\u0438\u0439 \u0418\u043d\u0441\u0442\u0438\u0442\u0443\u0442 , or in English,  Pulse Defibrillator 1, All-Union Electrotechnical Institute ). It is described in detail in Gurvich's 1957 book,  Heart Fibrillation and Defibrillation . [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2879", "text": "The first Czechoslovak  \"universal defibrillator Prema\" was manufactured in 1957 by the company Prema, designed by Dr. Bohumil Pele\u0161ka. In 1958 his device was awarded Grand Prix at  Expo 58 . [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2880", "text": "In 1958, US senator  Hubert H. Humphrey  visited  Nikita Khrushchev  and among other things he visited the Moscow Institute of Reanimatology, where, among others, he met with Gurvich. [ 40 ]   Humphrey immediately recognized importance of reanimation research and after that a number of American doctors visited Gurvich. At the same time, Humphrey worked on establishing a federal program in the  National Institute of Health   in physiology and medicine, telling Congress: \"Let's compete with U.S.S.R. in research on reversibility of death\". [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2881", "text": "In 1959  Bernard Lown  commenced research in his animal laboratory in collaboration with engineer  Barouh Berkovits  into a technique which involved charging of a bank of  capacitors  to approximately 1000 volts with an  energy  content of 100\u2013200  joules  then delivering the charge through an inductance such as to produce a heavily damped sinusoidal wave of finite duration (~5  milliseconds ) to the heart by way of paddle electrodes.  This team further developed an understanding of the optimal timing of shock delivery in the cardiac cycle, enabling the application of the device to  arrhythmias  such as  atrial fibrillation ,  atrial flutter , and supraventricular  tachycardias  in the technique known as \" cardioversion \"."}
{"_id": "WikiPedia_Cardio$$$corpus_2882", "text": "The Lown-Berkovits waveform, as it was known, was the standard for defibrillation until the late 1980s. Earlier in the 1980s, the \"MU lab\" at the University of Missouri had pioneered numerous studies introducing a new waveform called a biphasic truncated waveform (BTE). In this waveform an exponentially decaying DC voltage is reversed in polarity about halfway through the shock time, then continues to decay for some time after which the voltage is cut off, or truncated. The studies showed that the biphasic truncated waveform could be more efficacious while requiring the delivery of lower levels of energy to produce defibrillation. [ 35 ]  An added benefit was a significant reduction in weight of the machine. The BTE waveform, combined with automatic measurement of transthoracic impedance, is the basis for modern defibrillators. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2883", "text": "A major breakthrough was the introduction of portable defibrillators used out of the hospital. Already Pele\u0161ka's Prema defibrillator was designed to be more portable than original Gurvich's model. In Soviet Union, a portable version of Gurvich's defibrillator, model \u0414\u041f\u0410-3 (DPA-3), was reported in 1959. [ 42 ]   In the west this was pioneered in the early 1960s by Prof.  Frank Pantridge  in  Belfast .  Today portable defibrillators are among the many very important tools carried by ambulances.  They are the only proven way to resuscitate a person who has had a  cardiac arrest unwitnessed by Emergency Medical Services (EMS) who is still in  persistent ventricular fibrillation or ventricular  tachycardia  at the arrival of pre-hospital providers."}
{"_id": "WikiPedia_Cardio$$$corpus_2884", "text": "Gradual improvements in the design of defibrillators, partly based on the work developing implanted versions (see below), have led to the availability of Automated External Defibrillators. These devices can analyse the heart rhythm by themselves, diagnose the shockable rhythms, and charge to treat.  This means that no clinical skill is required in their use, allowing lay people to respond to emergencies effectively."}
{"_id": "WikiPedia_Cardio$$$corpus_2885", "text": "Until the mid 1990s, external defibrillators delivered a Lown type waveform (see  Bernard Lown ), a heavily damped  sinusoidal  impulse having a mainly uniphasic characteristic. Biphasic defibrillation alternates the direction of the pulses, completing one cycle in approximately 12 milliseconds. Biphasic defibrillation was originally developed and used for implantable cardioverter-defibrillators. When applied to external defibrillators, biphasic defibrillation significantly decreases the energy level necessary for successful defibrillation, decreasing the risk of burns and  myocardial  damage."}
{"_id": "WikiPedia_Cardio$$$corpus_2886", "text": "Ventricular fibrillation (VF) could be returned to  sinus rhythm  in 60% of cardiac arrest patients treated with a single shock from a monophasic defibrillator. Most biphasic defibrillators have a first shock success rate of greater than 90%. [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2887", "text": "A further development in defibrillation came with the invention of the implantable device, known as an  implantable cardioverter-defibrillator  (or ICD).  This was pioneered at  Sinai Hospital  in  Baltimore  by a team that included Stephen Heilman, Alois Langer, Jack Lattuca,  Morton Mower ,  Michel Mirowski , and  Mir Imran , with the help of industrial collaborator Intec Systems of Pittsburgh. [ 44 ]  Mirowski teamed up with Mower and Staewen, and together they commenced their research in 1969. However, it was 11 years before they treated their first patient. Similar developmental work was carried out by Schuder and colleagues at the  University of Missouri ."}
{"_id": "WikiPedia_Cardio$$$corpus_2888", "text": "The work was commenced, despite doubts amongst leading experts in the field of arrhythmias and sudden death. There was doubt that their ideas would ever become a clinical reality. In 1962  Bernard Lown  introduced the external  DC  defibrillator. This device applied a direct current from a discharging capacitor through the chest wall into the heart to stop heart  fibrillation . [ 45 ]  In 1972, Lown stated in the journal  Circulation  \u2013 \"The very rare patient who has frequent bouts of ventricular fibrillation is best treated in a coronary care unit and is better served by an effective antiarrhythmic program or surgical correction of inadequate coronary blood flow or ventricular malfunction. In fact, the implanted defibrillator system represents an imperfect solution in search of a plausible and practical application.\" [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2889", "text": "The problems to be overcome were the design of a system which would allow detection of ventricular fibrillation or ventricular tachycardia. Despite the lack of financial backing and grants, they persisted and the first device was implanted in February 1980 at  Johns Hopkins Hospital  by Dr.  Levi Watkins  Jr. assisted by  Vivien Thomas . Modern ICDs do not require a  thoracotomy  and possess  pacing , cardioversion, and defibrillation capabilities."}
{"_id": "WikiPedia_Cardio$$$corpus_2890", "text": "The invention of implantable units is invaluable to some people with regular heart problems, although they are generally only given to those people who have already had a cardiac episode."}
{"_id": "WikiPedia_Cardio$$$corpus_2891", "text": "People can live long normal lives with the devices.  Many patients have multiple implants.  A patient in Houston, Texas had an implant at the age of 18 in 1994 by the recent Dr. Antonio Pacifico. He was awarded \"Youngest Patient with Defibrillator\" in 1996. Today these devices are implanted into small babies shortly after birth."}
{"_id": "WikiPedia_Cardio$$$corpus_2892", "text": "As devices that can quickly produce dramatic improvements in patient health, defibrillators are often depicted in movies, television, video games and other fictional media. Their function, however, is often exaggerated with the defibrillator inducing a sudden, violent jerk or convulsion by the patient. The pad placement is also shown wrong, along with sudden rising of patient to large height when shock is given. In reality, while the muscles may contract, such dramatic patient presentation is rare. Similarly, medical providers are often depicted defibrillating patients with a \"flat-line\" ECG rhythm (also known as  asystole ). This is not normal medical practice, as the heart cannot be restarted by the defibrillator itself. Only the cardiac arrest rhythms  ventricular fibrillation  and pulseless  ventricular tachycardia  are normally defibrillated. The purpose of defibrillation is to depolarize the entire heart all at once so that it is synchronized, effectively inducing temporary asystole, in the hope that in the absence of the previous abnormal electrical activity, the heart will spontaneously resume beating normally. Someone who is already in asystole cannot be helped by electrical means, and usually needs urgent  CPR  and  intravenous  medication (and even these are rarely successful in cases of asystole). A useful analogy to remember is to think of defibrillators as power-cycling, rather than jump-starting, the heart. There are also several heart rhythms that can be \"shocked\" when the patient is not in cardiac arrest, such as  supraventricular tachycardia  and ventricular tachycardia that produces a  pulse ; this more-complicated procedure is known as  cardioversion , not defibrillation."}
{"_id": "WikiPedia_Cardio$$$corpus_2893", "text": "In  Australia  up until the 1990s it was relatively rare for ambulances to carry defibrillators. This changed in 1990 after Australian  media mogul   Kerry Packer  had a cardiac arrest due to a heart attack and, purely by chance, the ambulance that responded to the call carried a defibrillator. After recovering, Kerry Packer donated a large sum to the  Ambulance Service of New South Wales  in order that all ambulances in  New South Wales  should be fitted with a personal defibrillator, which is why defibrillators in Australia are sometimes  colloquially  called \"Packer Whackers\". [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2894", "text": "Defibrillation threshold  indicates the minimum amount of energy needed to return normal rhythm to a heart that is beating in a  cardiac dysrhythmia . Typical examples are the minimum amount of energy, expressed in  joules , delivered by external defibrillator paddles or pads, required to break  atrial fibrillation  and restore normal  sinus rhythm . Other common scenarios are restoring normal rhythm from  atrial flutter ,  ventricular tachycardia  or  ventricular fibrillation . The defibrillation threshold ranking in these settings, from lowest to highest, would be, in order, ventricular tachycardia, atrial flutter, atrial fibrillation, ventricular fibrillation. The highest amount of energy that an  external defibrillator  can deliver at the present time is 360 joules biphasic. In clinical practice, the real threshold can be approximated but not exactly established, since the defibrillating shock can be delivered only once. Aside from that, energy isn't directly related to stimulus strength and efficiency, which is primarily determined by the delivered charge over time in  mC  and not power over time or energy, which are still used due to historical reasons. Charge based thresholds are more realistic parameters for shock efficacy. Usual values delivered by biphasic defibrillators lay between 50 and 300 mC. The amount of charge needed is influenced by certain medications, in particular  sotalol , tend to lower such threshold, while others, such as  amiodarone , may increase it. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2895", "text": "Defibrillation threshold is a concept also applicable to internal or  implantable cardiac defibrillators . [ 2 ]  The test needed to establish the defibrillation threshold is often referred to as DFT."}
{"_id": "WikiPedia_Cardio$$$corpus_2896", "text": "In  mammals , cardiac electrical activity originates from specialized  myocytes  of the  sinoatrial node  (SAN) which generate spontaneous and rhythmic  action potentials  (AP). The unique functional aspect of this type of myocyte is the absence of a stable  resting potential  during diastole.  Electrical discharge from this  cardiomyocyte  may be characterized by a slow smooth transition from the Maximum Diastolic Potential (MDP, -70 mV) to the threshold (-40 mV) for the initiation of a new AP event. The voltage region encompassed by this transition is commonly known as pacemaker phase, or slow diastolic depolarization or phase 4."}
{"_id": "WikiPedia_Cardio$$$corpus_2897", "text": "The duration of this slow diastolic depolarization (pacemaker phase) thus governs the cardiac chronotropism. It is also important to point out that the modulation of the cardiac rate by the  autonomic nervous system  also acts on this phase. Sympathetic stimuli induce the acceleration of rate by increasing the slope of the pacemaker phase, while parasympathetic activation exerts the opposite action."}
{"_id": "WikiPedia_Cardio$$$corpus_2898", "text": "The amount of net inward current required to move the cell membrane potential during the pacemaker phase is extremely small, in the order of few pAs, but this net flux arises from the time to time changing contribution of several currents that flow with different voltage and time dependence. Evidence in support of the active presence of K + , Ca 2+  , Na +   channels and Na + /K +  exchanger during the pacemaker phase have been variously reported in the literature, but several indications point to the  funny current  (I f ) as one of the most important. [ 1 ] [ 2 ]  There is now substantial evidence that also sarcoplasmic reticulum (SR) Ca 2+  -transients participate in the generation of the diastolic depolarization via a process involving the Na\u2013Ca exchanger."}
{"_id": "WikiPedia_Cardio$$$corpus_2899", "text": "In  electrocardiography , during a  cardiac cycle , once an action potential is initiated, there is a period of time that a new action potential cannot be initiated. This is termed the  effective refractory period  (ERP) of the tissue. This period is approximately equal to the  absolute refractory period  (ARP), it occurs because the fast  sodium channels  remain closed until the cell fully repolarizes. [ 1 ] \nDuring this period, depolarization on adjacent cardiac muscles does not produce a new depolarization in the current cell as it has to refract back to phase 4 of the action potential before a new action potential can activate it. ERP acts as a protective mechanism and keeps the heart rate in check and prevents  arrhythmias , and it helps coordinates muscle contraction.  Anti-arrhythmic agents  used for arrhythmias usually prolong the ERP. For the treatment of  atrial fibrillation , it is a problem that the prolongation of the ERP by these agents also affects the ventricles, which can induce other types of arrhythmias. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2900", "text": "Einthoven's triangle  is an imaginary formation of three limb leads in a triangle used in the  electrocardiography , formed by the two shoulders and the pubis. [ 1 ]  The shape forms an inverted equilateral triangle with the heart at the center. It is named after  Willem Einthoven , who theorized its existence. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2901", "text": "Einthoven used these measuring points, by immersing the hands and feet in pails of salt water, as the contacts for his  string galvanometer , the first practical ECG machine. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2902", "text": "Electrodes may be placed  distally  or  proximally  on the limb without affecting the recording. [ 5 ]  The right leg electrode acts to reduce interference, and can be placed anywhere without an effect on the ECG results. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2903", "text": "Each lead measures the electric field created by the heart during the  depolarization  and  repolarization  of  myocytes . The electric field can be represented as a vector that changes continuously and can be measured by recording the voltage difference between electrodes. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2904", "text": "Einthoven's triangle can be helpful in the identification in incorrect placement of leads. Incorrect placement of leads can lead to error in the recording, which can ultimately lead to misdiagnosis."}
{"_id": "WikiPedia_Cardio$$$corpus_2905", "text": "If the arm electrodes are reversed, lead I changes polarity, causing lead II and lead III to switch. If the right arm electrode is reversed with the leg's electrode, lead II changes polarity, causing lead I to become lead III, and vice versa. Reversal of the left arm and leg causes a change in polarity of lead III and switching of leads I and II. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2906", "text": "Electroanatomic mapping  is a method of creating a three dimensional model of the  human heart  during  clinical cardiac electrophysiology  procedures."}
{"_id": "WikiPedia_Cardio$$$corpus_2907", "text": "The fundamental concept of electroanatomic mapping systems is to localize catheters within the heart in three dimensional space (a sort of \" GPS \" within the heart). Building a 3-D model of the heart with real-time visualization permits reduction in  fluoroscopy  use. In addition to 3-D structure, the voltage and timing of signals at each point of the heart is recorded to generate different maps to understand and treat different rhythm disturbances."}
{"_id": "WikiPedia_Cardio$$$corpus_2908", "text": "Each of the three systems utilizes different techniques to localize catheters:  [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2909", "text": "There are three electroanatomic mapping systems commercially available."}
{"_id": "WikiPedia_Cardio$$$corpus_2910", "text": "Biosense-Webster, a subsidiary of  Johnson & Johnson , produces a cardiac electrophysiology system called CARTO. [ 2 ]  The system is designed to visualise the real-time calculated position and orientation of a specialised  RF ablation   catheter  within the patient's heart in order to minimise  radiation exposure  during  fluoroscopy , increase the accuracy of targeted RF ablation and reacquisition of  pacing  sites for re- ablation . [ 3 ]   Its navigation system calculates the position and orientation of the catheter tip, using three known magnetic sources as references. The system uses  static magnetic fields  that are calibrated and computer controlled. Due to the nature of magnetic fields, the orientation may also be calculated while the tip is stationary. By calculating the strength and orientation of the magnetic fields at a given location, the x,y,z position may be calculated along with the  roll, pitch, yaw  orientation. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2911", "text": "St. Jude Medical , now a part of  Abbott , manufactures EnSite family of cardiac mapping systems, the latest edition being EnSite Precision, which allows speedy heart mapping during catheter ablation with better accuracy to be able to treat cardiac rhythm disturbances.  [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2912", "text": "Mapping system developed by  Boston Scientific ."}
{"_id": "WikiPedia_Cardio$$$corpus_2913", "text": "Mapping systems generate three kinds of data:"}
{"_id": "WikiPedia_Cardio$$$corpus_2914", "text": "Electrocardiography  is the process of producing an  electrocardiogram  ( ECG  or  EKG [ a ] ), a recording of the heart's electrical activity through repeated  cardiac cycles . [ 4 ]  It is an  electrogram  of the  heart  which is a graph of  voltage  versus time of the electrical activity of the heart [ 5 ]  using  electrodes  placed on the skin. These electrodes detect the small electrical changes that are a consequence of  cardiac muscle   depolarization  followed by  repolarization  during each  cardiac cycle  (heartbeat). Changes in the normal ECG pattern occur in numerous cardiac abnormalities, including:"}
{"_id": "WikiPedia_Cardio$$$corpus_2915", "text": "Traditionally, \"ECG\" usually means a  12-lead ECG  taken while lying down as discussed below.\nHowever, other devices can record the electrical activity of the heart such as a  Holter monitor  but also some models of  smartwatch  are capable of recording an ECG.\nECG signals can be recorded in other contexts with other devices."}
{"_id": "WikiPedia_Cardio$$$corpus_2916", "text": "In a conventional 12-lead ECG, ten electrodes are placed on the patient's limbs and on the surface of the chest. The overall  magnitude  of the heart's  electrical potential  is then measured from twelve different angles (\"leads\") and is recorded over a period of time (usually ten seconds). In this way, the overall magnitude and direction of the heart's electrical depolarization is captured at each moment throughout the  cardiac cycle . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2917", "text": "There are three main components to an ECG: [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2918", "text": "During each heartbeat, a healthy heart has an orderly progression of depolarization that starts with  pacemaker cells  in the  sinoatrial node , spreads throughout the  atrium , and passes through the  atrioventricular node  down into the  bundle of His  and into the  Purkinje fibers , spreading down and to the left throughout the  ventricles . [ 12 ]  This orderly pattern of depolarization gives rise to the characteristic ECG tracing. To the trained  clinician , an ECG conveys a large amount of information about the structure of the heart and the function of its electrical conduction system. [ 13 ]  Among other things, an ECG can be used to measure the rate and rhythm of heartbeats, the size and position of the  heart chambers , the presence of any damage to the heart's muscle cells or conduction system, the effects of heart drugs, and the function of implanted  pacemakers . [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2919", "text": "The overall goal of performing an ECG is to obtain information about the electrical functioning of the heart. Medical uses for this information are varied and often need to be combined with knowledge of the structure of the heart and physical examination signs to be interpreted. Some  indications  for performing an ECG include the following:"}
{"_id": "WikiPedia_Cardio$$$corpus_2920", "text": "ECGs can be recorded as short intermittent tracings or  continuous  ECG monitoring. Continuous monitoring is used for critically ill patients, patients undergoing general anesthesia, [ 18 ] [ 17 ]  and patients who have an infrequently occurring cardiac arrhythmia that would unlikely be seen on a conventional ten-second ECG. Continuous monitoring can be conducted by using  Holter monitors , internal and external  defibrillators  and  pacemakers , and/or  biotelemetry . [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2921", "text": "For adults, evidence does not support the use of ECGs among those without symptoms or at low risk of  cardiovascular disease  as an effort for prevention. [ 20 ] [ 21 ] [ 22 ]  This is because an ECG may falsely indicate the existence of a problem, leading to  misdiagnosis , the recommendation of invasive procedures, and  overtreatment . However, persons employed in certain critical occupations, such as aircraft pilots, [ 23 ]  may be required to have an ECG as part of their routine health evaluations.  Hypertrophic cardiomyopathy  screening may also be considered in adolescents as part of a  sports physical  out of concern for  sudden cardiac death . [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2922", "text": "Electrocardiograms are recorded by machines that consist of a set of electrodes connected to a central unit. [ 25 ]  Early ECG machines were constructed with  analog electronics , where the signal drove a motor to print out the signal onto paper. Today, electrocardiographs use  analog-to-digital converters  to convert the electrical activity of the heart to a  digital signal . Many ECG machines are now portable and commonly include a screen, keyboard, and printer on a small wheeled cart. Recent advancements in electrocardiography include developing even smaller devices for inclusion in fitness trackers and  smart watches . [ 26 ]  These smaller devices often rely on only two electrodes to deliver a single lead I. [ 27 ]  Portable twelve-lead devices powered by batteries are also available."}
{"_id": "WikiPedia_Cardio$$$corpus_2923", "text": "Recording an ECG is a safe and painless procedure. [ 28 ]  The machines are powered by  mains power  but they are designed with several safety features including an earthed (ground) lead.\nOther features include:"}
{"_id": "WikiPedia_Cardio$$$corpus_2924", "text": "Most modern ECG machines include  automated interpretation   algorithms . This analysis calculates features such as the  PR interval ,  QT interval ,  corrected QT (QTc) interval , PR axis, QRS axis, rhythm and more. The results from these automated algorithms are considered \"preliminary\" until verified and/or modified by expert interpretation. Despite recent advances, computer misinterpretation remains a significant problem and can result in clinical mismanagement. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2925", "text": "Besides the standard electrocardiograph machine, there are other devices capable of recording ECG signals. Portable devices have existed since the  Holter monitor  was introduced in 1962.\nTraditionally, these monitors have used electrodes with patches on the skin to record the ECG, but new devices can stick to the chest as a single patch without need for wires, developed by Zio (Zio XT), TZ Medical (Trident),  Philips  (BioTel) and BardyDx (CAM) among many others.\nImplantable devices such as the  artificial cardiac pacemaker  and  implantable cardioverter-defibrillator  are capable of measuring a \"far field\" signal between the leads in the heart and the implanted battery/generator that resembles an ECG signal (technically, the signal recorded in the heart is called an  electrogram , which is interpreted differently).\nAdvancement of the Holter monitor became the  implantable loop recorder  that performs the same function but in an implantable device with batteries that last on the order of years."}
{"_id": "WikiPedia_Cardio$$$corpus_2926", "text": "Additionally, there are available various  Arduino  kits with ECG sensor modules and  smartwatch  devices that are capable of recording an ECG signal as well, such as with the 4th generation  Apple Watch ,  Samsung Galaxy Watch 4  and newer devices."}
{"_id": "WikiPedia_Cardio$$$corpus_2927", "text": "Electrodes are the actual conductive pads attached to the body surface. [ 31 ]  Any pair of electrodes can measure the  electrical potential difference  between the two corresponding locations of attachment. Such a pair forms  a lead . However, \"leads\" can also be formed between a physical electrode and a  virtual electrode,  known as  Wilson's central terminal  ( WCT ), whose potential is defined as the average potential measured by three limb electrodes that are attached to the right arm, the left arm, and the left foot, respectively. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2928", "text": "Commonly, 10 electrodes attached to the body are used to form 12 ECG leads, with each lead measuring a specific electrical potential difference (as listed in the table below). [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2929", "text": "Leads are broken down into three types: limb; augmented limb; and precordial or chest. The 12-lead ECG has a total of three  limb leads  and three  augmented limb leads  arranged like spokes of a wheel in the  coronal plane  (vertical), and six  precordial leads  or  chest leads  that lie on the perpendicular  transverse plane  (horizontal). [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2930", "text": "Leads should be placed in standard positions. Exceptions due to emergency or other issues should be recorded to avoid erroneous analysis. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2931", "text": "The 12 standard ECG leads are listed below. All leads are effectively bipolar, with one positive and one negative electrode; the term \"unipolar\" is not useful. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2932", "text": "Two types of electrodes in common use are a flat paper-thin sticker and a self-adhesive circular pad.\nThe former are typically used in a single ECG recording while the latter are for continuous recordings as they stick longer.\nEach electrode consists of an  electrically conductive  electrolyte gel and a  silver/silver chloride  conductor. [ 36 ] \nThe gel typically contains  potassium chloride  \u2013 sometimes  silver chloride  as well \u2013 to permit  electron  conduction from the skin to the wire and to the electrocardiogram. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2933", "text": "The common virtual electrode, known as Wilson's central terminal (V W ), is produced by averaging the measurements from the electrodes RA, LA, and LL to give an average potential of the body:"}
{"_id": "WikiPedia_Cardio$$$corpus_2934", "text": "In a 12-lead ECG, all leads except the limb leads are assumed to be unipolar (aVR, aVL, aVF, V 1 , V 2 , V 3 , V 4 , V 5 , and V 6 ).\nThe measurement of a voltage requires two contacts and so, electrically, the unipolar leads are measured from the common lead (negative) and the unipolar lead (positive).\nThis averaging for the common lead and the abstract unipolar lead concept makes for a more challenging understanding and is complicated by sloppy usage of \"lead\" and \"electrode\".\nIn fact, instead of being a constant reference, V W  has a value that fluctuates throughout the heart cycle. It also does not truly represent the center-of-heart potential due to the body parts the signals travel through. [ 38 ]   Because voltage is by definition a bipolar measurement between two points, describing an electrocardiographic lead as \"unipolar\" makes little sense electrically and should be avoided.  The American Heart Association states \"All leads are effectively 'bipolar,' and the term 'unipolar' in description of the augmented limb leads and the precordial leads lacks precision.\" [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2935", "text": "Leads I, II and III are called the  limb leads . The electrodes that form these signals are located on the limbs \u2013 one on each arm and one on the left leg. [ 40 ] [ 41 ]  The limb leads form the points of what is known as  Einthoven's triangle . [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2936", "text": "Leads aVR, aVL, and aVF are the  augmented limb leads . They are derived from the same three electrodes as leads I, II, and III, but they use Goldberger's central terminal as their negative pole. Goldberger's central terminal is a combination of inputs from two limb electrodes, with a different combination for each augmented lead. It is referred to immediately below as \"the negative pole\"."}
{"_id": "WikiPedia_Cardio$$$corpus_2937", "text": "Together with leads I, II, and III, augmented limb leads aVR, aVL, and aVF form the basis of the  hexaxial reference system , which is used to calculate the heart's electrical axis in the frontal plane. [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2938", "text": "Older versions of the nodes (VR, VL, VF) use Wilson's central terminal as the negative pole, but the amplitude is too small for the thick lines of old ECG machines. The Goldberger terminals scale up (augments) the Wilson results by 50%, at the cost of sacrificing physical correctness by not having the same negative pole for all three. [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2939", "text": "The  precordial leads  lie in the transverse (horizontal) plane, perpendicular to the other six leads. The six precordial electrodes act as the positive poles for the six corresponding precordial leads: (V 1 , V 2 , V 3 , V 4 , V 5 , and V 6 ). Wilson's central terminal is used as the negative pole. Recently, unipolar precordial leads have been used to create bipolar precordial leads that explore the right to left axis in the horizontal plane. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2940", "text": "Additional electrodes may rarely be placed to generate other leads for specific diagnostic purposes.  Right-sided  precordial leads may be used to better study pathology of the right ventricle or for  dextrocardia  (and are denoted with an R (e.g., V 5R ).  Posterior leads  (V 7  to V 9 ) may be used to demonstrate the presence of a posterior myocardial infarction. The  Lewis lead  or S5-lead (requiring an electrode at the right sternal border in the second intercostal space) can be used to better detect atrial activity in relation to that of the ventricles. [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2941", "text": "An  esophageal lead  can be inserted to a part of the  esophagus  where the distance to the posterior wall of the  left atrium  is only approximately 5\u20136\u00a0mm (remaining constant in people of different age and weight). [ 47 ]  An esophageal lead avails for a more accurate differentiation between certain cardiac arrhythmias, particularly  atrial flutter ,  AV nodal reentrant tachycardia  and orthodromic  atrioventricular reentrant tachycardia . [ 48 ]  It can also evaluate the risk in people with  Wolff-Parkinson-White syndrome , as well as terminate  supraventricular tachycardia  caused by  re-entry . [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2942", "text": "An intracardiac electrogram (ICEG) is essentially an ECG with some added  intracardiac leads  (that is, inside the heart). The standard ECG leads (external leads) are I, II, III, aVL, V 1 , and V 6 . Two to four intracardiac leads are added via cardiac catheterization. The word \"electrogram\" (EGM) without further specification usually means an intracardiac electrogram. [ 49 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2943", "text": "A standard 12-lead ECG report (an electrocardiograph) shows a 2.5 second tracing of each of the twelve leads. The tracings are most commonly arranged in a grid of four columns and three rows. The first column is the limb leads (I, II, and III), the second column is the augmented limb leads (aVR, aVL, and aVF), and the last two columns are the precordial leads (V 1  to V 6 ).\nAdditionally, a rhythm strip may be included as a fourth or fifth row. [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2944", "text": "The timing across the page is continuous and notes tracings of the 12 leads for the same time period.\nIn other words, if the output were traced by needles on paper, each row would switch which leads as the paper is pulled under the needle.\nFor example, the top row would first trace lead I, then switch to lead aVR, then switch to V 1 , and then switch to V 4 , and so none of these four tracings of the leads are from the same time period as they are traced in sequence through time. [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2945", "text": "Each of the 12 ECG leads records the electrical activity of the heart from a different angle, and therefore align with different anatomical areas of the heart. Two leads that look at neighboring anatomical areas are said to be  contiguous . [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2946", "text": "In addition, any two precordial leads next to one another are considered to be contiguous. For example, though V 4  is an anterior lead and V 5  is a lateral lead, they are contiguous because they are next to one another."}
{"_id": "WikiPedia_Cardio$$$corpus_2947", "text": "The study of the conduction system of the heart is called  cardiac electrophysiology  (EP). An EP study is performed via a right-sided  cardiac catheterization : a wire with an electrode at its tip is inserted into the right heart chambers from a peripheral vein, and placed in various positions in close proximity to the conduction system so that the electrical activity of that system can be recorded. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2948", "text": "Standard catheter positions for an EP study include \"high right atrium\" or hRA near the  sinus node , a \"His\" across the septal wall of the tricuspid valve to measure  bundle of His , a \"coronary sinus\" into the  coronary sinus , and a \"right ventricle\" in the apex of the right ventricle. [ 51 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2949", "text": "Interpretation of the ECG is fundamentally about understanding the  electrical conduction system of the heart .\nNormal conduction starts and propagates in a predictable pattern, and deviation from this pattern can be a normal variation or be  pathological .\nAn ECG does not equate with mechanical pumping activity of the heart; for example,  pulseless electrical activity  produces an ECG that should pump blood but no pulses are felt (and constitutes a  medical emergency  and  CPR  should be performed).\n Ventricular fibrillation  produces an ECG but is too dysfunctional to produce a life-sustaining cardiac output. Certain rhythms are known to have good cardiac output and some are known to have bad cardiac output.\nUltimately, an  echocardiogram  or other anatomical imaging modality is useful in assessing the mechanical function of the heart. [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2950", "text": "Like all medical tests, what constitutes \"normal\" is based on  population studies . The heartrate range of between 60 and 100 beats per minute (bpm) is considered normal since data shows this to be the usual resting heart rate. [ 53 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2951", "text": "Interpretation of the ECG is ultimately that of pattern recognition.\nIn order to understand the patterns found, it is helpful to understand the theory of what ECGs represent.\nThe theory is rooted in  electromagnetics  and boils down to the four following points: [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2952", "text": "Thus, the overall direction of depolarization and repolarization produces positive or negative deflection on each lead's trace.\nFor example, depolarizing from right to left would produce a positive deflection in lead I because the two vectors point in the same direction.\nIn contrast, that same depolarization would produce minimal deflection in V 1  and V 2  because the vectors are perpendicular, and this phenomenon is called isoelectric."}
{"_id": "WikiPedia_Cardio$$$corpus_2953", "text": "Normal rhythm produces four entities \u2013 a  P wave , a  QRS complex , a  T wave , and a  U wave  \u2013 that each have a fairly unique pattern."}
{"_id": "WikiPedia_Cardio$$$corpus_2954", "text": "Changes in the structure of the heart and its surroundings (including blood composition) change the patterns of these four entities."}
{"_id": "WikiPedia_Cardio$$$corpus_2955", "text": "The U wave is not typically seen and its absence is generally ignored. Atrial repolarization is typically hidden in the much more prominent QRS complex and normally cannot be seen without additional, specialized electrodes."}
{"_id": "WikiPedia_Cardio$$$corpus_2956", "text": "ECGs are normally printed on a grid.\nThe horizontal axis represents time and the vertical axis represents voltage.\nThe standard values on this grid are shown in the adjacent image at 25mm/sec: [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2957", "text": "The \"large\" box is represented by a heavier  line weight  than the small boxes."}
{"_id": "WikiPedia_Cardio$$$corpus_2958", "text": "The standard printing speed in the United States is 25\u00a0mm per sec (5 big boxes per second), but in other countries it can be 50\u00a0mm per sec.\nFaster speeds such as 100 and 200\u00a0mm per sec are used during electrophysiology studies."}
{"_id": "WikiPedia_Cardio$$$corpus_2959", "text": "Not all aspects of an ECG rely on precise recordings or having a known scaling of amplitude or time.\nFor example, determining if the tracing is a sinus rhythm only requires feature recognition and matching, and not measurement of amplitudes or times (i.e., the scale of the grids are irrelevant).\nAn example to the contrary, the voltage requirements of  left ventricular hypertrophy  require knowing the grid scale."}
{"_id": "WikiPedia_Cardio$$$corpus_2960", "text": "In a normal heart, the heart rate is the rate at which the  sinoatrial node  depolarizes since it is the source of depolarization of the heart.\nHeart rate, like other  vital signs  such as blood pressure and respiratory rate, change with age.\nIn adults, a normal heart rate is between 60 and 100 bpm (normocardic), whereas it is higher in children. [ 56 ] \nA heart rate below normal is called \" bradycardia \" (<60 in adults) and above normal is called \" tachycardia \" (>100 in adults).\nA complication of this is when the atria and ventricles are not in synchrony and the \"heart rate\" must be specified as atrial or ventricular (e.g., the ventricular rate in  ventricular fibrillation  is 300\u2013600 bpm, whereas the atrial rate can be normal [60\u2013100] or faster [100\u2013150]). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2961", "text": "In normal resting hearts, the physiologic rhythm of the heart is  normal sinus rhythm  (NSR).\nNormal sinus rhythm produces the prototypical pattern of P wave, QRS complex, and T wave.\nGenerally, deviation from normal sinus rhythm is considered a  cardiac arrhythmia .\nThus, the first question in interpreting an ECG is whether or not there is a sinus rhythm.\nA criterion for sinus rhythm is that P waves and QRS complexes appear 1-to-1, thus implying that the P wave causes the QRS complex. [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2962", "text": "Once sinus rhythm is established, or not, the second question is the rate.\nFor a sinus rhythm, this is either the rate of P waves or QRS complexes since they are 1-to-1.\nIf the rate is too fast, then it is  sinus tachycardia , and if it is too slow, then it is  sinus bradycardia ."}
{"_id": "WikiPedia_Cardio$$$corpus_2963", "text": "If it is not a sinus rhythm, then determining the rhythm is necessary before proceeding with further interpretation.\nSome arrhythmias with characteristic findings:"}
{"_id": "WikiPedia_Cardio$$$corpus_2964", "text": "Determination of rate and rhythm is necessary in order to make sense of further interpretation."}
{"_id": "WikiPedia_Cardio$$$corpus_2965", "text": "The heart has several axes, but the most common by far is the axis of the QRS complex (references to \"the axis\" imply the QRS axis).\nEach axis can be computationally determined to result in a number representing degrees of deviation from zero, or it can be categorized into a few types. [ 57 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2966", "text": "The QRS axis is the general direction of the ventricular depolarization wavefront (or mean electrical vector) in the frontal plane.\nIt is often sufficient to classify the axis as one of three types: normal, left deviated, or right deviated.\nPopulation data shows that a normal QRS axis is from \u221230\u00b0 to 105\u00b0, with 0\u00b0 being along lead I and positive being inferior and negative being superior (best understood graphically as the  hexaxial reference system ). [ 58 ] \nBeyond +105\u00b0 is  right axis deviation  and beyond \u221230\u00b0 is  left axis deviation  (the third quadrant of \u221290\u00b0 to \u2212180\u00b0 is very rare and is an indeterminate axis).\nA shortcut for determining if the QRS axis is normal is if the QRS complex is mostly positive in lead I and lead II (or lead I and aVF if +90\u00b0 is the upper limit of normal). [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2967", "text": "The normal QRS axis is generally  down and to the left , following the anatomical orientation of the heart within the chest. An abnormal axis suggests a change in the physical shape and orientation of the heart or a defect in its conduction system that causes the ventricles to depolarize in an abnormal way. [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2968", "text": "The extent of a normal axis can be +90\u00b0 or 105\u00b0 depending on the source."}
{"_id": "WikiPedia_Cardio$$$corpus_2969", "text": "All of the waves on an ECG tracing and the intervals between them have a predictable time duration, a range of acceptable amplitudes ( voltages ), and a typical morphology. Any deviation from the normal tracing is potentially pathological and therefore of clinical significance. [ 60 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2970", "text": "For ease of measuring the amplitudes and intervals, an ECG is printed on graph paper at a standard scale: each 1\u00a0mm (one small box on the standard 25mm/s ECG paper) represents 40 milliseconds of time on the x-axis, and 0.1 millivolts on the y-axis. [ 61 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2971", "text": "In electrocardiogram (ECG) signal processing, Time-Frequency Analysis (TFA) is an important technique used to reveal how the frequency characteristics of ECG signals change over time, especially in non-stationary signals such as arrhythmias or transient cardiac events."}
{"_id": "WikiPedia_Cardio$$$corpus_2972", "text": "Common Methods for Time-Frequency Analysis"}
{"_id": "WikiPedia_Cardio$$$corpus_2973", "text": "Provides instantaneous frequency distribution."}
{"_id": "WikiPedia_Cardio$$$corpus_2974", "text": "Steps for Time-Frequency Analysis"}
{"_id": "WikiPedia_Cardio$$$corpus_2975", "text": "Step1: Preprocessing"}
{"_id": "WikiPedia_Cardio$$$corpus_2976", "text": "Step2: Select an Appropriate TFA Method"}
{"_id": "WikiPedia_Cardio$$$corpus_2977", "text": "Step3: Compute the Time-Frequency Spectrum"}
{"_id": "WikiPedia_Cardio$$$corpus_2978", "text": "Step4: Feature Extraction"}
{"_id": "WikiPedia_Cardio$$$corpus_2979", "text": "Step5: Pattern Recognition or Diagnosis"}
{"_id": "WikiPedia_Cardio$$$corpus_2980", "text": "Application Scenarios"}
{"_id": "WikiPedia_Cardio$$$corpus_2981", "text": "Heart Rate Variability Analysis (HRV):"}
{"_id": "WikiPedia_Cardio$$$corpus_2982", "text": "Atrial Fibrillation Detection:"}
{"_id": "WikiPedia_Cardio$$$corpus_2983", "text": "Ventricular Fibrillation Analysis:"}
{"_id": "WikiPedia_Cardio$$$corpus_2984", "text": "The animation shown to the right illustrates how the path of electrical conduction gives rise to the ECG waves in the limb leads. \nWhat is green zone\u00a0?\nRecall that a positive current (as created by depolarization of cardiac cells) traveling towards the positive electrode and away from the negative electrode creates a positive deflection on the ECG. Likewise, a positive current traveling away from the positive electrode and towards the negative electrode creates a negative deflection on the ECG. [ 64 ] [ 65 ]  The red arrow represents the overall direction of travel of the depolarization. The magnitude of the red arrow is proportional to the amount of tissue being depolarized at that instance. The red arrow is simultaneously shown on the axis of each of the 3 limb leads. Both the direction and the magnitude of the red arrow's projection onto the axis of each limb lead is shown with blue arrows. Then, the direction and magnitude of the blue arrows are what theoretically determine the deflections on the ECG. For example, as a blue arrow on the axis for Lead I moves from the negative electrode, to the right, towards the positive electrode, the ECG line rises, creating an upward wave. As the blue arrow on the axis for Lead I moves to the left, a downward wave is created. The greater the magnitude of the blue arrow, the greater the deflection on the ECG for that particular limb lead. [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2985", "text": "Frames 1\u20133 depict the depolarization being generated in and spreading through the  sinoatrial node . The SA node is too small for its depolarization to be detected on most ECGs. Frames 4\u201310 depict the depolarization traveling through the atria, towards the  atrioventricular node . During frame 7, the depolarization is traveling through the largest amount of tissue in the atria, which creates the highest point in the P wave. Frames 11\u201312 depict the depolarization traveling through the AV node. Like the SA node, the AV node is too small for the depolarization of its tissue to be detected on most ECGs. This creates the flat PR segment. [ 67 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2986", "text": "Frame 13 depicts an interesting phenomenon in an over-simplified fashion. It depicts the depolarization as it starts to travel down the interventricular septum, through the  bundle of His  and  bundle branches . After the Bundle of His, the conduction system splits into the left bundle branch and the right bundle branch. Both branches conduct action potentials at about 1\u00a0m/s. However, the action potential starts traveling down the left bundle branch about 5 milliseconds before it starts traveling down the right bundle branch, as depicted by frame 13. This causes the depolarization of the interventricular septum tissue to spread from left to right, as depicted by the red arrow in frame 14. In some cases, this gives rise to a negative deflection after the PR interval, creating a Q wave such as the one seen in lead I in the animation to the right. Depending on the mean electrical axis of the heart, this phenomenon can result in a Q wave in lead II as well. [ 68 ] [ 69 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2987", "text": "Following depolarization of the interventricular septum, the depolarization travels towards the apex of the heart. This is depicted by frames 15\u201317 and results in a positive deflection on all three limb leads, which creates the R wave. Frames 18\u201321 then depict the depolarization as it travels throughout both ventricles from the apex of the heart, following the action potential in the  Purkinje fibers . This phenomenon creates a negative deflection in all three limb leads, forming the S wave on the ECG. Repolarization of the atria occurs at the same time as the generation of the QRS complex, but it is not detected by the ECG since the tissue mass of the ventricles is so much larger than that of the atria. Ventricular contraction occurs between ventricular depolarization and repolarization. During this time, there is no movement of charge, so no deflection is created on the ECG. This results in the flat ST segment after the S wave. [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2988", "text": "Frames 24\u201328 in the animation depict repolarization of the ventricles. The epicardium is the first layer of the ventricles to repolarize, followed by the myocardium. The endocardium is the last layer to repolarize. The plateau phase of depolarization has been shown to last longer in endocardial cells than in epicardial cells. This causes repolarization to start from the apex of the heart and move upwards. Since repolarization is the spread of negative current as membrane potentials decrease back down to the resting membrane potential, the red arrow in the animation is pointing in the direction opposite of the repolarization. This therefore creates a positive deflection in the ECG, and creates the T wave. [ 71 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2989", "text": "Ischemia or  non-ST elevation myocardial infarctions  (non-STEMIs) may manifest as  ST depression  or inversion of  T waves . It may also affect the  high frequency band of the QRS ."}
{"_id": "WikiPedia_Cardio$$$corpus_2990", "text": "ST elevation myocardial infarctions  (STEMIs) have different characteristic ECG findings based on the amount of time elapsed since the MI first occurred. The earliest sign is  hyperacute T waves,  peaked T waves due to local  hyperkalemia  in ischemic myocardium. This then progresses over a period of minutes to elevations of the  ST segment  by at least 1\u00a0mm. Over a period of hours, a pathologic  Q wave  may appear and the T wave will invert. Over a period of days the ST elevation will resolve. Pathologic Q waves generally will remain permanently. [ 72 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2991", "text": "The  coronary artery  that has been occluded can be identified in an STEMI based on the location of ST elevation. The  left anterior descending  (LAD) artery supplies the anterior wall of the heart, and therefore causes ST elevations in anterior leads (V 1  and V 2 ). The  LCx  supplies the lateral aspect of the heart and therefore causes ST elevations in lateral leads (I, aVL and V 6 ). The  right coronary artery  (RCA) usually supplies the inferior aspect of the heart, and therefore causes ST elevations in inferior leads (II, III and aVF). [ 73 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2992", "text": "An ECG tracing is affected by patient motion. Some rhythmic motions (such as shivering or  tremors ) can create the illusion of cardiac arrhythmia. [ 74 ]  Artifacts are distorted signals caused by a secondary internal or external sources, such as muscle movement or interference from an electrical device. [ 75 ] [ 76 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2993", "text": "Distortion poses significant challenges to healthcare providers, [ 75 ]  who employ various techniques [ 77 ]  and strategies to safely recognize [ 78 ]  these false signals. [ medical citation needed ]  Accurately separating the ECG artifact from the true ECG signal can have a significant impact on patient outcomes and  legal liabilities . [ 79 ] [ unreliable medical source? ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2994", "text": "Improper lead placement (for example, reversing two of the limb leads) has been estimated to occur in 0.4% to 4% of all ECG recordings, [ 80 ]  and has resulted in improper diagnosis and treatment including unnecessary use of  thrombolytic  therapy. [ 81 ] [ 82 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2995", "text": "Whitbread, consultant nurse and paramedic, suggests ten rules of the normal ECG, deviation from which is likely to indicate pathology. [ 83 ]  These have been added to, creating the 15 rules for 12-lead (and 15- or 18-lead) interpretation. [ 84 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_2996", "text": "Rule 1: All waves in aVR are negative."}
{"_id": "WikiPedia_Cardio$$$corpus_2997", "text": "Rule 2: The ST segment (J point) starts on the isoelectric line (except in V1 & V2 where it may be elevated by not greater than 1\u00a0mm)."}
{"_id": "WikiPedia_Cardio$$$corpus_2998", "text": "Rule 3: The PR interval should be 0.12\u20130.2 seconds long."}
{"_id": "WikiPedia_Cardio$$$corpus_2999", "text": "Rule 4: The QRS complex should not exceed 0.11\u20130.12 seconds."}
{"_id": "WikiPedia_Cardio$$$corpus_3000", "text": "Rule 5: The QRS and T waves tend to have the same general direction in the limb leads."}
{"_id": "WikiPedia_Cardio$$$corpus_3001", "text": "Rule 6: The R wave in the precordial (chest) leads grows from V1 to at least V4 where it may or may not decline again."}
{"_id": "WikiPedia_Cardio$$$corpus_3002", "text": "Rule 7: The QRS is mainly upright in I and II."}
{"_id": "WikiPedia_Cardio$$$corpus_3003", "text": "Rule 8: The P wave is upright in I II and V2 to V6."}
{"_id": "WikiPedia_Cardio$$$corpus_3004", "text": "Rule 9: There is no Q wave or only a small q (<0.04 seconds in width) in I, II and V2 to V6."}
{"_id": "WikiPedia_Cardio$$$corpus_3005", "text": "Rule 10: The T wave is upright in I II and V2 to V6. The end of the T wave should not drop below the isoelectric baseline."}
{"_id": "WikiPedia_Cardio$$$corpus_3006", "text": "Rule 11: Does the deepest S wave in V1 plus the tallest R wave in V5 or V6 equal >35\u00a0mm?"}
{"_id": "WikiPedia_Cardio$$$corpus_3007", "text": "Rule 12: Is there an  Epsilon wave ?"}
{"_id": "WikiPedia_Cardio$$$corpus_3008", "text": "Rule 13: Is there an J wave?"}
{"_id": "WikiPedia_Cardio$$$corpus_3009", "text": "Rule 14: Is there a  Delta wave ?"}
{"_id": "WikiPedia_Cardio$$$corpus_3010", "text": "Rule 15: Are there any patterns representing an  occlusive myocardial infarction  (OMI)?"}
{"_id": "WikiPedia_Cardio$$$corpus_3011", "text": "Numerous diagnoses and findings can be made based upon electrocardiography, and many are discussed above. Overall, the diagnoses are made based on the patterns. For example, an \"irregularly irregular\" QRS complex without P waves is the hallmark of  atrial fibrillation ; however, other findings can be present as well, such as a  bundle branch block  that alters the shape of the QRS complexes. ECGs can be interpreted in isolation but should be applied \u2013 like all  diagnostic tests  \u2013 in the context of the patient. For example, an observation of peaked T waves is not sufficient to diagnose hyperkalemia; such a diagnosis should be verified by measuring the blood potassium level. Conversely, a discovery of hyperkalemia should be followed by an ECG for manifestations such as peaked T waves, widened QRS complexes, and loss of P waves. The following is an organized list of possible ECG-based diagnoses. [ 85 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3012", "text": "Rhythm disturbances or arrhythmias: [ 86 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3013", "text": "Heart block  and conduction problems:"}
{"_id": "WikiPedia_Cardio$$$corpus_3014", "text": "Electrolytes disturbances and intoxication:"}
{"_id": "WikiPedia_Cardio$$$corpus_3015", "text": "Ischemia and infarction:"}
{"_id": "WikiPedia_Cardio$$$corpus_3016", "text": "Structural:"}
{"_id": "WikiPedia_Cardio$$$corpus_3017", "text": "Other phenomena:"}
{"_id": "WikiPedia_Cardio$$$corpus_3018", "text": "The word is derived from the  Greek   electro , meaning related to electrical activity;  kardia , meaning heart; and  graph , meaning \"to write\". [ 99 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3019", "text": "Electrocardiography  in suspected  myocardial infarction  has the main purpose of detecting  ischemia  or acute coronary injury in  emergency department  populations coming for symptoms of myocardial infarction (MI). Also, it can distinguish clinically different types of myocardial infarction."}
{"_id": "WikiPedia_Cardio$$$corpus_3020", "text": "The standard 12 lead  electrocardiogram  (ECG) has several limitations. An ECG represents a brief sample in time. Because unstable ischemic syndromes have rapidly changing supply versus demand characteristics, a single ECG may not accurately represent the entire picture. [ 1 ]  It is therefore desirable to obtain  serial  12 lead ECGs, particularly if the first ECG is obtained during a pain-free episode. Alternatively, many  emergency departments  and  chest pain centers  use computers capable of continuous ST segment monitoring. [ 2 ]  The standard 12 lead ECG also does not directly examine the  right ventricle , and is relatively poor at examining the posterior basal and lateral walls of the  left ventricle . In particular, acute myocardial infarction in the distribution of the circumflex artery is likely to produce a nondiagnostic ECG. [ 1 ]  The use of additional ECG leads like right-sided leads V3R and V4R and posterior leads V7, V8, and V9 may improve sensitivity for right ventricular and posterior myocardial infarction. In spite of these limitations, the 12 lead ECG stands at the center of risk stratification for the patient with suspected acute myocardial infarction. Mistakes in interpretation are relatively common, and the failure to identify high risk features has a negative effect on the quality of patient care. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3021", "text": "The 12 lead ECG is used to classify MI patients into one of three groups: [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3022", "text": "The 2018 European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Health Federation Universal Definition of Myocardial Infarction for the ECG diagnosis of the ST segment elevation type of acute myocardial infarction require new ST elevation at J point of at least 1mm (0.1 mV) in two contiguous leads with the cut-points: \u22651 mm in all leads other than leads V2-V3. For leads V2-V3: \u22652 mm in men \u226540 years, \u22652.5 mm in men <40 years, or \u22651.5 mm in women regardless of age. This assumes usual calibration of 1mV/10mm. [ 5 ]  These elevations must be present in anatomically contiguous leads. [ 4 ]  (I, aVL, V5, V6 correspond to the lateral wall; V3-V4 correspond to the anterior wall\u00a0; V1-V2 correspond to the septal wall; II, III, aVF correspond to the inferior wall.) This criterion is problematic, however, as acute myocardial infarction is not the most common cause of ST segment elevation in  chest pain  patients. [ 6 ]  Over 90% of healthy men have at least 1\u00a0mm (0.1 mV) of ST segment elevation in at least one precordial lead. [ 7 ]  The clinician must therefore be well versed in recognizing the so-called ECG mimics of acute myocardial infarction, which include  left ventricular hypertrophy ,  left bundle branch block ,  paced rhythm ,  early repolarization ,  pericarditis ,  hyperkalemia , and  ventricular aneurysm . [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3023", "text": "There are heavily researched clinical decision tools such as the TIMI Scores which help prognose and diagnose STEMI based on clinical data. For example, TIMI scores are frequently used to take advantage of EKG findings to prognose patients with MI symptoms. [ 10 ]  Based on symptoms and electrocardiographic findings, practitioners can differentiate between unstable angina, NSTEMI and STEMI, normally in the emergency room setting. [ 11 ]  Other calculators such as the GRACE [ 12 ]  and HEART  [ 13 ]  scores, assess other major cardiac events using electrocardiogram findings, both predicting mortality rates for 6 months and 6 weeks, respectively. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3024", "text": "Sometimes the earliest presentation of acute myocardial infarction is the hyperacute T wave, which is treated the same as ST segment elevation. [ 14 ]  In practice this is rarely seen, because it only exists for 2\u201330 minutes after the onset of infarction. [ 15 ]  Hyperacute T waves need to be distinguished from the peaked T waves associated with  hyperkalemia . [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3025", "text": "In the first few hours the ST segments usually begin to rise. [ 17 ]  Pathological  Q waves  may appear within hours or may take greater than 24 hr. [ 17 ]  The  T wave  will generally become inverted in the first 24 hours, as the ST elevation begins to resolve. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3026", "text": "Long term changes of ECG include persistent Q waves (in 90% of cases) and persistent inverted T waves. [ 17 ]  Persistent ST elevation is rare except in the presence of a  ventricular aneurysm . [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3027", "text": "A  cardiac electrophysiology  study ( EP test  or  EP study ) is a  minimally invasive procedure  using  catheters  introduced through a  vein  or  artery  to record electrical activity from within the  heart . [ 1 ]  This electrical activity is recorded when the heart is in a normal rhythm ( sinus rhythm ) to assess the conduction system of the heart and to look for additional electrical connections ( accessory pathways ), and during any  abnormal heart rhythms  that can be induced. [ 2 ]  EP studies are used to investigate the cause, location of origin, and best treatment for various abnormal heart rhythms, and are often followed by a  catheter ablation  during the same procedure. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3028", "text": "It is important for patients not to eat or drink for up to 12 hours before the procedure. This is to prevent vomiting, which can result in aspiration, and also cause severe bleeding from the insertion site of the catheter. Failure to follow this simple preparation may result in dangerous consequences. In general, small amounts of water can be consumed up to 2 hours before the exam. Patients should try to schedule the exam at a time when they will be having symptoms and will not need to drive for 2 to 3 days."}
{"_id": "WikiPedia_Cardio$$$corpus_3029", "text": "An EP study is typically performed in an EP lab or  cath lab . These are specially equipped operating rooms that usually contain an X-ray machine capable of acquiring live X-ray video images (a  fluoroscope ), equipment to record electrical signals from the heart, a stimulator to electrically excite the heart and control the heart rate, and  ablation equipment  to destroy abnormal tissue. [ 3 ]  A 3D navigation system that tracks and records the catheter position and associated electrical signals may also be used. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3030", "text": "The procedure may be performed awake under  local anaesthetic , or under  general anaesthetic . Monitoring equipment is attached including an automated  blood pressure cuff  and a  pulse oximeter  to measure the oxygen saturation of the blood. A peripheral  venous cannula  is generally inserted to allow medication to be given such as  sedatives ,  anesthesia , or drugs. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3031", "text": "An access site that will allow catheters to be passed to the heart via an artery or vein is shaved and cleaned, usually in the  groin . The blood vessels used to reach the heart (the  femoral  or  subclavian veins , and sometimes the  femoral artery ) are punctured before a guidewire and plastic sheath are inserted into the vessel using the  Seldinger technique . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3032", "text": "Once the catheter is in and all preparations are complete elsewhere in the lab, the EP study begins. The X-ray machine will give the doctor a live view of the heart and the position of the electrodes. He will guide the (steerable) electrodes to the correct position inside the heart. The electrophysiologist begins by moving the electrodes along the conduction pathways and along the inner walls of the heart, measuring the electrical activity along the way."}
{"_id": "WikiPedia_Cardio$$$corpus_3033", "text": "The next step is pacing the heart, this means he/she will speed up or slow down the heart by placing the electrode at certain points along the conductive pathways of the heart and control the depolarization rate of the heart. The doctor will pace each chamber of the heart one by one, looking for any abnormalities. Then the electrophysiologist tries to provoke arrhythmias and reproduce any conditions that have resulted in the patient's placement in the study. This is done by injecting electric current into the conductive pathways and into the  endocardium  at various places. Last, the electrophysiologist may administer various drugs ( proarrhythmic agents ) to induce arrhythmia (inducibility of VT/VF [ 4 ] ). If the arrhythmia is reproduced by the drugs (inducible), the electrophysiologist will search out the source of the abnormal electrical activity. The entire procedure can take several hours."}
{"_id": "WikiPedia_Cardio$$$corpus_3034", "text": "If at any step during the EP study the electrophysiologist finds the source of the abnormal electrical activity, they may try to  ablate  the cells that are misfiring. This is done using high-energy  radio frequencies  (similar to  microwaves ) to effectively heat up the abnormal cells, to form scar tissue.\nThis can be painful with pain felt in the heart itself, the neck and shoulder areas. A more recent method of ablation is  cryoablation , which is considered less risky and less painful. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3035", "text": "When the necessary procedures are complete, the catheter is removed. Firm pressure is applied to the site to prevent bleeding. This may be done by hand or with a mechanical device. Other closure techniques include an internal suture and plug. If the femoral artery was used, the patient will probably be asked to lie flat for several hours (3 to 6) to prevent bleeding or the development of a  hematoma . Trying to sit up or even lift the head is strongly discouraged until an adequate  clot  has formed. The patient will be moved to a recovery area where he/she will be monitored."}
{"_id": "WikiPedia_Cardio$$$corpus_3036", "text": "For patients who had a catheterization at the femoral artery or vein (and even some of those with a radial insertion site), in general recovery is fairly quick, as the only damage is at the insertion site. The patient will probably feel fine within 8 to 12 hours after the procedure, but may feel a small pinch at the insertion site. After a short period of general rest, the patient may resume some minor activity such as gentle, short, slow walks after the first 24 hours. If stairs must be climbed, they should be taken one step at a time and very slowly. All vigorous activity must be postponed until approved by a physician."}
{"_id": "WikiPedia_Cardio$$$corpus_3037", "text": "It is also important to note that unless directed by a doctor, some patients should avoid taking blood thinners and foods that contain salicylates, such as cranberry-containing products until the clot has healed (1\u20132 weeks)."}
{"_id": "WikiPedia_Cardio$$$corpus_3038", "text": "As with any surgical procedure, cardiac catheterizations come with a generic list of possible complications. One of the complications that are sometimes reported involves some temporary nerve involvement. Sometimes a small amount of swelling occurs that can put pressure on nerves in the area of the incision.  Venous thrombosis  is the most common complication with an incidence ranging between 0.5 and 2.5%. [ 6 ]  There have been reports of patients feeling like they have hot fluid like blood or urine running down their leg for up to a month or two after the incision has healed. This usually passes with time, but patients should tell their doctor if they have these symptoms and if they last."}
{"_id": "WikiPedia_Cardio$$$corpus_3039", "text": "More severe but relatively rare complications include: damage or trauma to a blood vessel, which could require repair; infection from the skin puncture or from the catheter itself; cardiac perforation, causing blood to leak into the sac around the heart and compromising the heart's pumping action, requiring removal using a needle under the breast bone (pericardiocentesis); hematoma at the site(s) of the puncture(s); induction of a dangerous cardiac rhythm requiring an external shock(s); a clot may be dislodged, which may travel to a distant organ and impede blood flow or cause a stroke; myocardial infarction; unanticipated reactions to the medications used during the procedure; damage to the conduction system, requiring a permanent pacemaker; death."}
{"_id": "WikiPedia_Cardio$$$corpus_3040", "text": "A  flatline  is an electrical time sequence measurement that shows no activity and therefore, when represented, shows a flat line instead of a moving one. It almost always refers to either a flatlined  electrocardiogram , where the heart shows no electrical activity [ 1 ]  ( asystole ), or to a flat  electroencephalogram , in which the  brain  shows no electrical activity ( brain death ). Both of these specific cases are involved in various definitions of  death ."}
{"_id": "WikiPedia_Cardio$$$corpus_3041", "text": "A cardiac flatline is also called  asystole . It can possibly be generated by malfunction of the  electrocardiography  device, but it is recommended to first rule out true asystole because of the emergence of such condition."}
{"_id": "WikiPedia_Cardio$$$corpus_3042", "text": "Definition:"}
{"_id": "WikiPedia_Cardio$$$corpus_3043", "text": "A cardiac flatline is referred to as asystole. It can be identified by using an ECG/EKG (electrocardiogram) test.  Asystole  occurs when the electrical and mechanical activities of the heart stop. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3044", "text": "Causes:"}
{"_id": "WikiPedia_Cardio$$$corpus_3045", "text": "ECG/EKG flatline or asystole occurs when the heart's electrical and mechanical activities stop. It also results from other causes such as  hypoxia ,  acidosis ,  hypokalemia ,  hyperkalemia ,  hypovolemia , toxins,  pulmonary thrombosis , and  coronary thrombosis . Additional causes could also include  tension pneumothorax  and  cardiac tamponade . These conditions should be treated immediately when identified. [ 3 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3046", "text": "ECG flat line also occurs when the electrocardiographic (ECG/EKG) leads or recording electrodes are placed incorrectly. It can be caused by malfunction of the electrocardiogram (ECG/EKG) machine. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3047", "text": "Diagnosis:"}
{"_id": "WikiPedia_Cardio$$$corpus_3048", "text": "ECG flatline or asystole is diagnosed when a person, who is in  cardiac arrest  (the heart stops beating), is experiencing the following conditions:"}
{"_id": "WikiPedia_Cardio$$$corpus_3049", "text": "The eclectrocardiogram (ECG) test records the heart's electrical activity and will show a flat line if the heart stops beating. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3050", "text": "A neurological flatline is referred to as  brain death . It can be identified by using an EEG ( electroencephalogram ) test. Brain death is the loss of function of the brain, the  cerebrum , that is responsible for thinking and the deep brain or the  brain stem  that is responsible for the breathing and reflexes such as  pupillary light reflex  (the constriction of the pupil of the eye in response to light) and  gag reflex  or pharyngeal reflex (contraction of pharyngeal muscle). [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3051", "text": "EEG flat line or brain death can result from a head injury that leads to brain damage and bleeding. Brain death also results from a lack of blood flow to the brain because the heart stops beating (cardiac arrest), which is when the ECG imaging shows a cardiac flat line (asystole). [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3052", "text": "Brain death is diagnosed if a person is experiencing all of the following three conditions:"}
{"_id": "WikiPedia_Cardio$$$corpus_3053", "text": "The electroencephalogram (EEG) records the brain's electrical activity and will show a flat line if the brain is dead. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3054", "text": "In a study published in the New England Journal of Medicine, 631 subjects' end of life was observed. Of the 631 subjects, 480 subjects were analyzed using a computer program that recorded each subject's vitals in order to monitor for return of pulse or heart activity after at least 1 minute of flatlining. The study found that 14% of subjects had a return of heart activity but none regained consciousness. [ 5 ]  Neuro flatline or brain death happens after cardiac arrest or cardiac flatline. It can take 2 to 20 seconds after cardiac flatline for the brain to show no activity. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3055", "text": "The definition of death has changed over time, but the loss of cardiac and neurological function have been the main criteria for centuries. The concept of flatlining begins to take form with the invention of technologies for death determination."}
{"_id": "WikiPedia_Cardio$$$corpus_3056", "text": "It began in 1837 when Professor Manni at the University of Rome offered a cash prize to the doctor who could offer a true test of death. The winner, Dr.  Eugene Bouchut  used new technology\u2013 the stethoscope\u2013 to determine death when heart sounds were absent for over two minutes. In 1883 he updated his criteria to require five minutes without heart sounds to qualify cardiac death. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3057", "text": "Then, the standard for viewing cardiac activity changed in 1887 when Augustus Waller recorded the first ECG from the human heart with a mercury capillary electrometer. [ 8 ]  This sparked research into modern ECG technology, which was developed from the mercury capillary electrometer by Willem Einthoven. In 1901 to 1905, Einthoven developed the  string galvanometer , which could measure and record the heart's electrical activity. Electrodes were place on three points, the \u201cEinthoven leads\u201d, the right and left arms and on the left foot same as today and provided precise recordings of the heart. [ 9 ]  This led to Einthoven's Nobel Prize in 1924. [ 10 ] [ 8 ]  With the ECG, the characteristics of a dying heart were identified, creating the leading tool for diagnosing death\u2013 even to this day. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3058", "text": "However, in the mid 19th century with the invention of the defibrillator and cardioversion, it was realized that the flatline on the ECG did not always mean death. [ 7 ]  This instigated research into other ways to determine death, which eventually lead to the idea of brain death."}
{"_id": "WikiPedia_Cardio$$$corpus_3059", "text": "In 1924, a German physiologist and psychiatrist  Hans Berger  recorded the first EEG on a human brain. [ 11 ]  The machine consisted of steel electrodes that get mounted on the scalp with an EEG cap to visualize and interpret signals. [ 12 ]  He noted that the human brain has a specific pattern, called alpha oscillations, and went on to publish this in 1929. [ 13 ]   The presence of this technology along with resuscitation technology saw the use of the EEG to determine a time in which the person had reached total death. In 1959, this concept\u2013 brain death\u2013 was first coined as: \"le coma d\u00e9pass\u00e9 by Mollaret and Goulon. [ 12 ]  They determined that a person reached this state when they were apneic, comatose, without brainstem reflexes, and showed no electroencephalographic (EEG) activity. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3060", "text": "When an individual experiences asystole or cardiac flatline, there is no electrical activity in their heart which is evidenced by the flatline recorded by an ECG. [ 2 ]  The lack of electrical activity also means that the individual's heart will stop pumping. Following a cardiac flatline a fast intervention is a priority and can affect individual outcomes and recovery."}
{"_id": "WikiPedia_Cardio$$$corpus_3061", "text": "Treatment [ 14 ]  for cardiac flatline or asystole can involve:"}
{"_id": "WikiPedia_Cardio$$$corpus_3062", "text": "Treatment decisions will depend on where an individual is when they go into asystole. When an individual goes into cardiac arrest providers will start CPR immediately and then try to determine whether the rhythm is shockable. While defibrillation is often portrayed as a common treatment option in popular media, since asystole is an unshockable rhythm  defibrillation  is not a recommended course of treatment. Successful resuscitation is generally unlikely and is inversely related to the length of time spent attempting resuscitation."}
{"_id": "WikiPedia_Cardio$$$corpus_3063", "text": "Following a treatment intervention, the individuals who survive may still suffer long-term consequences of their cardiac flatline. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3064", "text": "An individual's cardiac flatline can progress to neurological flatline, which is also referred to as brain death. After an individual's heart stops beating, if providers are unable to successfully intervene within the window, the individual's brain cells will die from this lack of blood and oxygen and this damage is irreversible and permanent. The criteria to diagnose brain death has been outlined in the above sections of this article. While brain death cannot be treated, individuals and their families have several options  [ 4 ]  available to them:"}
{"_id": "WikiPedia_Cardio$$$corpus_3065", "text": "The  forward problem of electrocardiology  is a computational and mathematical approach to study the  electrical activity  of the  heart  through the body surface. [ 1 ]  The principal aim of this study is to computationally reproduce an  electrocardiogram  (ECG), which has important clinical relevance to define  cardiac pathologies  such as  ischemia  and  infarction , or to test  pharmaceutical intervention . Given their important functionalities and the relative small invasiveness, the  electrocardiography  techniques are used quite often as clinical  diagnostic tests . Thus, it is natural to proceed to computationally reproduce an ECG, which means to mathematically model the cardiac behaviour inside the body. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3066", "text": "The three main parts of a forward model for the ECG are:"}
{"_id": "WikiPedia_Cardio$$$corpus_3067", "text": "Thus, to obtain an ECG, a mathematical electrical cardiac model must be considered, coupled with a diffusive model in a  passive conductor  that describes the electrical propagation inside the  torso . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3068", "text": "The coupled model is usually a  three-dimensional model  expressed in terms of  partial differential equations . Such model is typically solved by means of  finite element method  for the solution's space evolution and  semi-implicit numerical schemes  involving  finite differences  for the solution's time evolution. However, the computational costs of such techniques, especially with three dimensional simulations, are quite high. Thus, simplified models are often considered, solving for example the heart electrical activity independently from the problem on the torso. To provide realistic results, three dimensional anatomically realistic models of the heart and the torso must be used. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3069", "text": "Another possible simplification is a  dynamical model  made of three  ordinary differential equations . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3070", "text": "The electrical activity of the heart is caused by the flow of  ions  across the  cell membrane , between the intracellular and extracellular spaces, which determines a wave of excitation along the  heart muscle  that coordinates the cardiac contraction and, thus, the pumping action of the heart that enables it to push  blood  through the  circulatory system . The modeling of cardiac electrical activity is thus related to the modelling of the flow of ions on a  microscopic  level, and on the propagation of the excitation wave along the muscle  fibers  on a  macroscopic  level. [ 1 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3071", "text": "Between the mathematical model on the macroscopic level,  Willem Einthoven  and  Augustus Waller  defined the ECG through the conceptual model of a dipole rotating around a fixed point, whose projection on the  lead  axis determined the lead recordings. Then, a  two-dimensional  reconstruction of the heart activity in the frontal plane was possible using the  Einthoven's limbs leads  I, II and III as theoretical basis. [ 5 ] \nLater on, the rotating cardiac dipole was considered inadequate and was substituted by  multipolar  sources moving inside a bounded torso domain. The main shortcoming of the methods used to quantify these sources is their lack of details, which are however very relevant to realistically simulate cardiac phenomena. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3072", "text": "On the other hand, microscopic models try to represent the behaviour of single cells and to connect them considering their electrical properties. [ 6 ] [ 7 ] [ 8 ]  These models present some challenges related to the different scales that need to be captured, in particular considering that, especially for large scale phenomena such as re-entry or  body surface potential , the collective behaviour of the cells is more important than that of every single cell. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3073", "text": "The third option to model the electrical activity of the heart is to consider a so-called \"middle-out approach\", where the model incorporates both lower and higher level of details. This option considers the behaviour of a block of cells, called a continuum cell, thus avoiding scale and detail problems. The model obtained is called  bidomain model , which is often replaced by its simplification, the  monodomain model . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3074", "text": "The basic assumption of the bidomain model is that the heart tissue can be divided in two ohmic conducting continuous media, connected but separated through the cell membrane. This media are called intracellular and extracellular regions, the former representing the cellular tissues, and the latter representing the space between cells. [ 2 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3075", "text": "The standard formulation of the bidomain model, including a dynamical model for the ionic current, is the following [ 2 ] \n \n \n \n \n \n \n { \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n V \n \n m \n \n \n ) \n + \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n u \n \n e \n \n \n ) \n = \n \n A \n \n m \n \n \n \n ( \n \n \n C \n \n m \n \n \n \n \n \n \n \u2202 \n \n V \n \n m \n \n \n \n \n \u2202 \n t \n \n \n \n \n + \n \n I \n \n ion \n \n \n ( \n \n V \n \n m \n \n \n , \n w \n ) \n \n ) \n \n + \n \n I \n \n app \n \n \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n H \n \n \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n ( \n \n \n \u03c3 \n \n \n i \n \n \n + \n \n \n \u03c3 \n \n \n e \n \n \n ) \n \u2207 \n \n u \n \n e \n \n \n \n ) \n \n + \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n V \n \n m \n \n \n ) \n = \n 0 \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n H \n \n \n \n \n \n \n \n \n \n \u2202 \n w \n \n \n \u2202 \n \n t \n \n \n \n \n + \n g \n ( \n \n V \n \n m \n \n \n , \n w \n ) \n = \n 0 \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n H \n \n \n \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{cases}\\nabla \\cdot ({\\boldsymbol {\\sigma }}_{i}\\nabla V_{m})+\\nabla \\cdot ({\\boldsymbol {\\sigma }}_{i}\\nabla u_{e})=A_{m}\\left(C_{m}{\\dfrac {\\partial V_{m}}{\\partial t}}+I_{\\text{ion}}(V_{m},w)\\right)+I_{\\text{app}}&{\\text{in }}\\Omega _{H}\\\\\\nabla \\cdot \\left(({\\boldsymbol {\\sigma }}_{i}+{\\boldsymbol {\\sigma }}_{e})\\nabla u_{e}\\right)+\\nabla \\cdot ({\\boldsymbol {\\sigma }}_{i}\\nabla V_{m})=0&{\\text{in }}\\Omega _{H}\\\\{\\frac {\\partial w}{\\partial {t}}}+g(V_{m},w)=0&{\\text{in }}\\Omega _{H}\\end{cases}}} \n \n \nwhere  \n \n \n \n \n V \n \n m \n \n \n \n \n {\\displaystyle V_{m}} \n \n  and  \n \n \n \n \n u \n \n e \n \n \n \n \n {\\displaystyle u_{e}} \n \n  are the transmembrane and extracellular potentials respectively,   \n \n \n \n \n I \n \n ion \n \n \n \n \n {\\displaystyle I_{\\text{ion}}} \n \n  is the ionic current, which depends also from a so-called gating variable  \n \n \n \n w \n \n \n {\\displaystyle w} \n \n  (accounting for cellular-level ionic behavior), and  \n \n \n \n \n I \n \n app \n \n \n \n \n {\\displaystyle I_{\\text{app}}} \n \n  is an external current applied to the domain. Moreover,  \n \n \n \n \n \n \u03c3 \n \n \n i \n \n \n \n \n {\\displaystyle {\\boldsymbol {\\sigma }}_{i}} \n \n  and  \n \n \n \n \n \n \u03c3 \n \n \n e \n \n \n \n \n {\\displaystyle {\\boldsymbol {\\sigma }}_{e}} \n \n  are the intracellular and extracellular conductivity tensors,  \n \n \n \n \n A \n \n m \n \n \n \n \n {\\displaystyle A_{m}} \n \n  is the  surface to volume ratio of the cell membrane and  \n \n \n \n \n C \n \n m \n \n \n \n \n {\\displaystyle C_{m}} \n \n  is the membrane capacitance per unit area. Here the domain  \n \n \n \n \n \u03a9 \n \n H \n \n \n \n \n {\\displaystyle \\Omega _{H}} \n \n  represents the heart muscle. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3076", "text": "The boundary conditions for this version of the bidomain model are obtained through the assumption that there is no flow of intracellular potential outside of the heart, which means that\n \n \n \n \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n V \n \n m \n \n \n \u22c5 \n \n n \n \n + \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n u \n \n e \n \n \n \u22c5 \n \n n \n \n = \n 0 \n \n \n \n on\u00a0 \n \n \u03a3 \n \n \n {\\displaystyle {\\boldsymbol {\\sigma }}_{i}\\nabla V_{m}\\cdot \\mathbf {n} +{\\boldsymbol {\\sigma }}_{i}\\nabla u_{e}\\cdot \\mathbf {n} =0\\quad \\quad {\\text{on }}\\Sigma } \n \n \nwhere  \n \n \n \n \u03a3 \n = \n \u2202 \n \n \u03a9 \n \n H \n \n \n \n \n {\\displaystyle \\Sigma =\\partial \\Omega _{H}} \n \n  denotes the boundary of the heart domain and  \n \n \n \n \n n \n \n \n \n {\\displaystyle \\mathbf {n} } \n \n  is the outward unit normal to  \n \n \n \n \u03a3 \n \n \n {\\displaystyle \\Sigma } \n \n . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3077", "text": "The monodomain model is a simplification of the bidomain model that, in spite of some unphysiological assumptions, is able to represent realistic electrophysiological phenomena at least for what concerns the transmembrane potential  \n \n \n \n \n V \n \n m \n \n \n \n \n {\\displaystyle V_{m}} \n \n . [ 2 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3078", "text": "The standard formulation is the following partial differential equation, whose only unknown  \n \n \n \n \n V \n \n m \n \n \n \n \n {\\displaystyle V_{m}} \n \n  is the transmembrane potential:\n \n \n \n \n \u03c7 \n \n C \n \n m \n \n \n \n \n \n \u2202 \n \n V \n \n m \n \n \n \n \n \u2202 \n t \n \n \n \n \u2212 \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03c3 \n \n \n i \n \n \n \n \n \u03bb \n \n 1 \n + \n \u03bb \n \n \n \n \u2207 \n \n V \n \n m \n \n \n \n ) \n \n + \n \u03c7 \n \n I \n \n ion \n \n \n = \n \n I \n \n app \n \n \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n H \n \n \n \n \n {\\displaystyle \\chi C_{m}{\\frac {\\partial V_{m}}{\\partial t}}-\\nabla \\cdot \\left({\\boldsymbol {\\sigma }}_{i}{\\frac {\\lambda }{1+\\lambda }}\\nabla V_{m}\\right)+\\chi I_{\\text{ion}}=I_{\\text{app}}\\quad \\quad {\\text{in }}\\Omega _{H}} \n \n \nwhere  \n \n \n \n \u03bb \n \n \n {\\displaystyle \\lambda } \n \n  is a parameter that relates the intracellular and extracellular conductivity tensors. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3079", "text": "The boundary condition used for this model is [ 9 ] \n \n \n \n \n \n ( \n \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n V \n \n m \n \n \n \n ) \n \n \u22c5 \n \n n \n \n = \n 0 \n \n \n \n on\u00a0 \n \n \u2202 \n \n \u03a9 \n \n H \n \n \n . \n \n \n {\\displaystyle \\left({\\boldsymbol {\\sigma }}_{i}\\nabla V_{m}\\right)\\cdot \\mathbf {n} =0\\quad \\quad {\\text{on }}\\partial \\Omega _{H}.}"}
{"_id": "WikiPedia_Cardio$$$corpus_3080", "text": "In the forward problem of electrocardiography, the torso is seen as a passive conductor and its model can be derived starting from the  Maxwell's equations  under quasi-static assumption. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3081", "text": "The standard formulation consists of a partial differential equation with one unknown scalar field, the torso potential  \n \n \n \n \n u \n \n T \n \n \n \n \n {\\displaystyle u_{T}} \n \n . Basically, the torso model is the following generalized  Laplace equation \n \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n T \n \n \n \u2207 \n \n u \n \n T \n \n \n ) \n = \n 0 \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n T \n \n \n , \n \n \n {\\displaystyle \\nabla \\cdot ({\\boldsymbol {\\sigma }}_{T}\\nabla u_{T})=0\\quad \\quad {\\text{in }}\\Omega _{T},} \n \n \nwhere  \n \n \n \n \n \n \u03c3 \n \n \n T \n \n \n \n \n {\\displaystyle {\\boldsymbol {\\sigma }}_{T}} \n \n  is the conductivity tensor and  \n \n \n \n \n \u03a9 \n \n T \n \n \n \n \n {\\displaystyle \\Omega _{T}} \n \n  is the domain surrounding the heart,  i.e.  the human torso. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3082", "text": "As for the bidomain model, the torso model can be derived from the Maxwell's equations and the  continuity equation  after some assumptions. First of all, since the electrical and magnetic activity inside the body is generated at low level, a quasi-static assumption can be considered. Thus, the body can be viewed as a passive conductor, which means that its capacitive, inductive and propagative effect can be ignored. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3083", "text": "Under quasi-static assumption, the Maxwell's equations are [ 1 ] \n \n \n \n \n \n \n { \n \n \n \n \u2207 \n \u22c5 \n \n E \n \n \n \n = \n \n \n \u03c1 \n \n \u03f5 \n \n 0 \n \n \n \n \n \n \n \n \n \u2207 \n \u00d7 \n \n E \n \n \n \n = \n 0 \n \n \n \n \n \u2207 \n \u22c5 \n \n B \n \n \n \n = \n 0 \n \n \n \n \n \u2207 \n \u00d7 \n \n B \n \n \n \n = \n \n \u03bc \n \n 0 \n \n \n \n J \n \n \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{cases}\\nabla \\cdot \\mathbf {E} &={\\frac {\\rho }{\\epsilon _{0}}}\\\\\\nabla \\times \\mathbf {E} &=0\\\\\\nabla \\cdot \\mathbf {B} &=0\\\\\\nabla \\times \\mathbf {B} &=\\mu _{0}\\mathbf {J} \\end{cases}}} \n \n \nand the continuity equation is [ 1 ] \n \n \n \n \n \u2207 \n \u22c5 \n \n J \n \n = \n 0. \n \n \n {\\displaystyle \\nabla \\cdot \\mathbf {J} =0.}"}
{"_id": "WikiPedia_Cardio$$$corpus_3084", "text": "Since its curl is zero, the electrical field can be represented by the gradient of a scalar potential field, the torso potential"}
{"_id": "WikiPedia_Cardio$$$corpus_3085", "text": "where the negative sign means that the current flows from higher to lower potential regions. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3086", "text": "Then, the total current density can be expressed in terms of the conduction current and other different applied currents so that, from continuity equation, [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3087", "text": "Then, substituting ( 1 ) in ( 2 )\n \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n T \n \n \n \u2207 \n \n u \n \n T \n \n \n ) \n = \n \u2207 \n \u22c5 \n \n \n J \n \n \n app \n \n \n = \n \n I \n \n v \n \n \n \n \n {\\displaystyle \\nabla \\cdot ({\\boldsymbol {\\sigma }}_{T}\\nabla u_{T})=\\nabla \\cdot \\mathbf {J} _{\\text{app}}=I_{v}}"}
{"_id": "WikiPedia_Cardio$$$corpus_3088", "text": "in which  \n \n \n \n \n I \n \n v \n \n \n \n \n {\\displaystyle I_{v}} \n \n  is the current per unit volume. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3089", "text": "Finally, since aside from the heart there is no current source inside the torso, the current per unit volume can be set to zero, giving the generalized Laplace equation, which represents the standard formulation of the diffusive problem inside the torso [ 1 ] \n \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n T \n \n \n \u2207 \n \n u \n \n T \n \n \n ) \n = \n 0 \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n T \n \n \n . \n \n \n {\\displaystyle \\nabla \\cdot ({\\boldsymbol {\\sigma }}_{T}\\nabla u_{T})=0\\quad \\quad {\\text{in }}\\Omega _{T}.}"}
{"_id": "WikiPedia_Cardio$$$corpus_3090", "text": "The boundary conditions accounts for the properties of the media surrounding the torso, i.e. of the air around the body. Generally, air has null conductivity which means that the current cannot flow outside the torso. This is translated in the following equation [ 1 ] \n \n \n \n \n \n \n \u03c3 \n \n \n T \n \n \n \u2207 \n \n u \n \n T \n \n \n \u22c5 \n \n \n n \n \n \n T \n \n \n = \n 0 \n \n \n \n on\u00a0 \n \n \n \u0393 \n \n T \n \n \n \n \n {\\displaystyle {\\boldsymbol {\\sigma }}_{T}\\nabla u_{T}\\cdot \\mathbf {n} _{T}=0\\quad \\quad {\\text{on }}\\Gamma _{T}}"}
{"_id": "WikiPedia_Cardio$$$corpus_3091", "text": "where  \n \n \n \n \n \n n \n \n \n T \n \n \n \n \n {\\displaystyle \\mathbf {n} _{T}} \n \n  is the unit outward normal to the torso and  \n \n \n \n \n \u0393 \n \n T \n \n \n \n \n {\\displaystyle \\Gamma _{T}} \n \n  is the torso boundary, which means the torso surface. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3092", "text": "Usually, the torso is considered to have isotropic conductivity, which means that the current flows in the same way in all directions. However, the torso is not an empty or homogeneous envelope, but contains different organs characterized by different conductivity coefficients, which can be experimentally obtained. A simple example of conductivity parameters in a torso that considers the bones and the lungs is reported in the following table. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3093", "text": "The coupling between the electrical activity model and the torso model is achieved by means of suitable boundary conditions at the epicardium, i.e. at the interface surface between the heart and the torso. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3094", "text": "The heart-torso model can be fully coupled, if a perfect electrical transmission between the two domains is considered, or can be uncoupled, if the heart electrical model and the torso model are solved separately with a limited or imperfect exchange of information between them. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3095", "text": "The complete coupling between the heart and the torso is obtained imposing a perfect electrical transmission condition between the heart and the torso. This is done considering the following two equations, that establish a relationship between the extracellular potential and the torso potential [ 2 ] \n \n \n \n \n \n \n \n \n \n u \n \n e \n \n \n \n \n \n = \n \n u \n \n T \n \n \n \n \n \n on\u00a0 \n \n \u03a3 \n \n \n \n \n ( \n \n \n \u03c3 \n \n \n e \n \n \n \u2207 \n \n u \n \n e \n \n \n ) \n \u22c5 \n \n \n n \n \n \n e \n \n \n \n \n \n = \n \u2212 \n ( \n \n \n \u03c3 \n \n \n T \n \n \n \u2207 \n \n u \n \n T \n \n \n ) \n \u22c5 \n \n \n n \n \n \n T \n \n \n \n \n \n \n on\u00a0 \n \n \u03a3 \n . \n \n \n \n \n \n \n {\\displaystyle {\\begin{aligned}u_{e}&=u_{T}&{\\text{on }}\\Sigma \\\\({\\boldsymbol {\\sigma }}_{e}\\nabla u_{e})\\cdot \\mathbf {n} _{e}&=-({\\boldsymbol {\\sigma }}_{T}\\nabla u_{T})\\cdot \\mathbf {n} _{T}\\quad &{\\text{on }}\\Sigma .\\end{aligned}}} \n \n \nThis equations ensure the continuity of both the potential and the current across the epicardium. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3096", "text": "Using these boundary conditions, it is possible to obtain two different fully coupled heart-torso models, considering either the bidomain or the monodomain model for the heart electrical activity. From the numerical viewpoint, the two models are computationally very expensive and have similar computational costs. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3097", "text": "Boundary conditions that represent a perfect electrical coupling between the heart and the torso are the most used and the classical ones. However, between the heart and the torso there is the  pericardium , a sac with a double wall that contains a serous fluid which has a specific effect on the electrical transmission. Considering the  capacitance   \n \n \n \n \n C \n \n p \n \n \n \n \n {\\displaystyle C_{p}} \n \n  and the  resistive \n \n \n \n \n R \n \n p \n \n \n \n \n {\\displaystyle R_{p}} \n \n  effect that the pericardium has, alternative boundary conditions that take into account this effect can be formulated as follows [ 10 ] \n \n \n \n \n \n \n \n \n \n R \n \n p \n \n \n \n \n \u03c3 \n \n \n e \n \n \n \u2207 \n \n u \n \n e \n \n \n \u22c5 \n \n n \n \n \n \n \n = \n \n R \n \n p \n \n \n \n C \n \n p \n \n \n \n \n \n \u2202 \n ( \n \n u \n \n T \n \n \n \u2212 \n \n u \n \n e \n \n \n ) \n \n \n \u2202 \n t \n \n \n \n + \n ( \n \n u \n \n T \n \n \n \u2212 \n \n u \n \n e \n \n \n ) \n \n \n \n \n \n on\u00a0 \n \n \u03a3 \n \n \n \n \n \n \n \u03c3 \n \n \n e \n \n \n \u2207 \n \n u \n \n e \n \n \n \u22c5 \n \n n \n \n \n \n \n = \n \n \n \u03c3 \n \n \n T \n \n \n \u2207 \n \n u \n \n T \n \n \n \u22c5 \n \n n \n \n \n \n \n \n \n on\u00a0 \n \n \u03a3 \n \n \n \n \n \n \n {\\displaystyle {\\begin{aligned}R_{p}{\\boldsymbol {\\sigma }}_{e}\\nabla u_{e}\\cdot \\mathbf {n} &=R_{p}C_{p}{\\frac {\\partial (u_{T}-u_{e})}{\\partial t}}+(u_{T}-u_{e})\\quad \\quad &{\\text{on }}\\Sigma \\\\{\\boldsymbol {\\sigma }}_{e}\\nabla u_{e}\\cdot \\mathbf {n} &={\\boldsymbol {\\sigma }}_{T}\\nabla u_{T}\\cdot \\mathbf {n} \\quad \\quad &{\\text{on }}\\Sigma \\end{aligned}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_3098", "text": "The fully coupled heart-torso model, considering the  bidomain model  for the heart electrical activity, in its complete form is [ 2 ] \n \n \n \n \n \n \n { \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n V \n \n m \n \n \n ) \n + \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n u \n \n e \n \n \n ) \n = \n \n A \n \n m \n \n \n \n ( \n \n \n C \n \n m \n \n \n \n \n \n \n \u2202 \n \n V \n \n m \n \n \n \n \n \u2202 \n t \n \n \n \n \n + \n \n I \n \n ion \n \n \n ( \n \n V \n \n m \n \n \n , \n w \n ) \n \n ) \n \n + \n \n I \n \n app \n \n \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n H \n \n \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n ( \n \n \n \u03c3 \n \n \n i \n \n \n + \n \n \n \u03c3 \n \n \n e \n \n \n ) \n \u2207 \n \n u \n \n e \n \n \n \n ) \n \n + \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n V \n \n m \n \n \n ) \n = \n 0 \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n H \n \n \n \n \n \n \n \n \n \n \n \u2202 \n w \n \n \n \u2202 \n \n t \n \n \n \n \n \n + \n g \n ( \n \n V \n \n m \n \n \n , \n w \n ) \n = \n 0 \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n H \n \n \n \n \n \n \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n T \n \n \n \u2207 \n \n u \n \n T \n \n \n ) \n = \n 0 \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n T \n \n \n \n \n \n \n ( \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n V \n \n m \n \n \n ) \n \u22c5 \n \n n \n \n + \n ( \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n u \n \n e \n \n \n ) \n \u22c5 \n \n n \n \n = \n 0 \n \n \n \n on\u00a0 \n \n \u03a3 \n \n \n \n \n \n u \n \n e \n \n \n = \n \n u \n \n T \n \n \n \n \n \n on\u00a0 \n \n \u03a3 \n \n \n \n \n ( \n \n \n \u03c3 \n \n \n e \n \n \n \u2207 \n \n u \n \n e \n \n \n ) \n \u22c5 \n \n n \n \n = \n ( \n \n \n \u03c3 \n \n \n T \n \n \n \u2207 \n \n u \n \n T \n \n \n ) \n \u22c5 \n \n n \n \n \n \n \n on\u00a0 \n \n \u03a3 \n \n \n \n \n ( \n \n \n \u03c3 \n \n \n T \n \n \n \u2207 \n \n u \n \n T \n \n \n ) \n \u22c5 \n \n n \n \n = \n 0 \n \n \n \n on\u00a0 \n \n \n \u0393 \n \n T \n \n \n \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{cases}\\nabla \\cdot ({\\boldsymbol {\\sigma }}_{i}\\nabla V_{m})+\\nabla \\cdot ({\\boldsymbol {\\sigma }}_{i}\\nabla u_{e})=A_{m}\\left(C_{m}{\\dfrac {\\partial V_{m}}{\\partial t}}+I_{\\text{ion}}(V_{m},w)\\right)+I_{\\text{app}}&{\\text{in }}\\Omega _{H}\\\\[1ex]\\nabla \\cdot \\left(({\\boldsymbol {\\sigma }}_{i}+{\\boldsymbol {\\sigma }}_{e})\\nabla u_{e}\\right)+\\nabla \\cdot ({\\boldsymbol {\\sigma }}_{i}\\nabla V_{m})=0&{\\text{in }}\\Omega _{H}\\\\[1ex]{\\dfrac {\\partial w}{\\partial {t}}}+g(V_{m},w)=0&{\\text{in }}\\Omega _{H}\\\\[1ex]\\nabla \\cdot ({\\boldsymbol {\\sigma }}_{T}\\nabla u_{T})=0&{\\text{in }}\\Omega _{T}\\\\[1ex]({\\boldsymbol {\\sigma }}_{i}\\nabla V_{m})\\cdot \\mathbf {n} +({\\boldsymbol {\\sigma }}_{i}\\nabla u_{e})\\cdot \\mathbf {n} =0&{\\text{on }}\\Sigma \\\\[1ex]u_{e}=u_{T}&{\\text{on }}\\Sigma \\\\[1ex]({\\boldsymbol {\\sigma }}_{e}\\nabla u_{e})\\cdot \\mathbf {n} =({\\boldsymbol {\\sigma }}_{T}\\nabla u_{T})\\cdot \\mathbf {n} &{\\text{on }}\\Sigma \\\\[1ex]({\\boldsymbol {\\sigma }}_{T}\\nabla u_{T})\\cdot \\mathbf {n} =0&{\\text{on }}\\Gamma _{T}\\end{cases}}} \n \n \nwhere the first four equations are the  partial differential equations  representing the bidomain model, the ionic model and the torso model, while the remaining ones represent the boundary conditions for the bidomain and torso models and the coupling conditions between them. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3099", "text": "The fully coupled heart-torso model considering the  monodomain model  for the electrical activity of the heart is more complicated that the bidomain problem. Indeed, the coupling conditions relate the torso potential with the extracellular potential, which is not computed by the monodomain model. Thus, it is necessary to use also the second equation of the  bidomain model  (under the same assumptions under which the monodomain model is derived), yielding: [ 2 ] \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n ( \n \n \n \u03c3 \n \n \n i \n \n \n + \n \n \n \u03c3 \n \n \n e \n \n \n ) \n \u2207 \n \n u \n \n e \n \n \n \n ) \n \n + \n \u2207 \n \u22c5 \n ( \n \n \n \u03c3 \n \n \n i \n \n \n \u2207 \n \n V \n \n m \n \n \n ) \n = \n 0 \n \n \n \n in\u00a0 \n \n \n \u03a9 \n \n H \n \n \n . \n \n \n {\\displaystyle \\nabla \\cdot \\left(({\\boldsymbol {\\sigma }}_{i}+{\\boldsymbol {\\sigma }}_{e})\\nabla u_{e}\\right)+\\nabla \\cdot ({\\boldsymbol {\\sigma }}_{i}\\nabla V_{m})=0\\quad \\quad {\\text{in }}\\Omega _{H}.}"}
{"_id": "WikiPedia_Cardio$$$corpus_3100", "text": "This way, the coupling conditions do not need to be changed, and the complete heart-torso model is composed of two different blocks: [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3101", "text": "The fully coupled heart-torso models are very detailed models but they are also computationally expensive to solve. [ 2 ]  A possible simplification is provided by the so-called  uncoupled assumption  in which the heart is considered completely electrically isolated from the heart. [ 2 ]  Mathematically, this is done imposing that the current cannot flow across the epicardium, from the heart to the torso, namely [ 2 ] \n \n \n \n \n \n \n \u03c3 \n \n \n e \n \n \n \u2207 \n \n u \n \n e \n \n \n \u22c5 \n \n n \n \n = \n 0 \n \n \n \n on\u00a0 \n \n \u03a3 \n . \n \n \n {\\displaystyle {\\boldsymbol {\\sigma }}_{e}\\nabla u_{e}\\cdot \\mathbf {n} =0\\quad \\quad {\\text{on }}\\Sigma .}"}
{"_id": "WikiPedia_Cardio$$$corpus_3102", "text": "Applying this equation to the boundary conditions of the fully coupled models, it is possible to obtained two uncoupled heart-torso models, in which the electrical models can be solved separately from the torso model reducing the computational costs. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3103", "text": "The uncoupled version of the fully coupled heart-torso model that uses the bidomain to represent the electrical activity of the heart is composed of two separated parts: [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3104", "text": "As in the case of the fully coupled heart-torso model which uses the monodomain model, also in the corresponding uncoupled model extracellular potential needs to be computed. In this case, three different and independent problems must be solved: [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3105", "text": "Solving the fully coupled or the uncoupled heart-torso models allows to obtain the electrical potential generated by the heart in every point of the human torso, and in particular on the whole surface of the torso. Defining the electrodes positions on the torso, it is possible to find the time evolution of the potential on such points. Then, the  electrocardiograms  can be computed, for example according to the 12 standard leads, considering the following formulas [ 2 ] \n \n \n \n \n \n \n { \n \n \n \n \n I \n \n \n \n = \n \n u \n \n T \n \n \n ( \n L \n ) \n \u2212 \n \n u \n \n T \n \n \n ( \n R \n ) \n \n \n \n \n \n I \n I \n \n \n \n = \n \n u \n \n T \n \n \n ( \n F \n ) \n \u2212 \n \n u \n \n T \n \n \n ( \n R \n ) \n \n \n \n \n \n I \n I \n I \n \n \n \n = \n \n u \n \n T \n \n \n ( \n F \n ) \n \u2212 \n \n u \n \n T \n \n \n ( \n L \n ) \n \n \n \n \n \n a \n V \n R \n \n \n \n = \n \n \n 3 \n 2 \n \n \n ( \n \n u \n \n T \n \n \n ( \n R \n ) \n \u2212 \n \n u \n \n w \n \n \n ) \n \n \n \n \n \n a \n V \n L \n \n \n \n = \n \n \n 3 \n 2 \n \n \n ( \n \n u \n \n T \n \n \n ( \n L \n ) \n \u2212 \n \n u \n \n w \n \n \n ) \n \n \n \n \n \n a \n V \n F \n \n \n \n = \n \n \n 3 \n 2 \n \n \n ( \n \n u \n \n T \n \n \n ( \n F \n ) \n \u2212 \n \n u \n \n w \n \n \n ) \n \n \n \n \n \n \n V \n \n \n i \n \n \n \n \n = \n \n u \n \n T \n \n \n ( \n \n V \n \n i \n \n \n ) \n \u2212 \n \n u \n \n w \n \n \n \n i \n = \n 1 \n , \n \u2026 \n , \n 6 \n \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{cases}\\mathrm {I} &=u_{T}(L)-u_{T}(R)\\\\\\mathrm {II} &=u_{T}(F)-u_{T}(R)\\\\\\mathrm {III} &=u_{T}(F)-u_{T}(L)\\\\\\mathrm {aVR} &={\\frac {3}{2}}(u_{T}(R)-u_{w})\\\\\\mathrm {aVL} &={\\frac {3}{2}}(u_{T}(L)-u_{w})\\\\\\mathrm {aVF} &={\\frac {3}{2}}(u_{T}(F)-u_{w})\\\\\\mathrm {V} _{i}&=u_{T}(V_{i})-u_{w}\\quad i=1,\\dots ,6\\end{cases}}} \n \n \nwhere  \n \n \n \n \n u \n \n W \n \n \n = \n ( \n \n u \n \n T \n \n \n ( \n L \n ) \n + \n \n u \n \n T \n \n \n ( \n R \n ) \n + \n \n u \n \n T \n \n \n ( \n F \n ) \n ) \n \n / \n \n 3 \n \n \n {\\displaystyle u_{W}=(u_{T}(L)+u_{T}(R)+u_{T}(F))/3} \n \n  and  \n \n \n \n L \n , \n R \n , \n F \n , \n { \n \n V \n \n i \n \n \n \n } \n \n i \n = \n 1 \n \n \n 6 \n \n \n \n \n {\\displaystyle L,R,F,\\{V_{i}\\}_{i=1}^{6}} \n \n  are the standard locations of the electrodes. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3106", "text": "The heart-torso models are expressed in terms of  partial differential equations  whose unknowns are function of both space and time. They are in turn coupled with an ionic model which is usually expressed in terms of a system of  ordinary differential equations . A variety of numerical schemes can be used for the solution of those problems. Usually, the  finite element method  is applied for the space discretization and semi-implicit finite-difference schemes are used for the time discretization. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3107", "text": "Uncoupled heart-torso model are the simplest to treat numerically because the heart electrical model can be solved separately from the torso one, so that classic numerical methods to solve each of them can be applied. This means that the bidomain and monodomain models can be solved for example with a  backward differentiation formula  for the time discretization, while the problems to compute the extracellular potential and torso potential can be easily solved by applying only the finite element method because they are time independent. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3108", "text": "The fully coupled heart-torso models, instead, are more complex and need more sophisticated numerical models. For example, the fully heart-torso model that uses the bidomain model for the electrical simulation of the cardiac behaviour can be solved considering  domain decomposition  techniques, such as a Dirichlet-Neumann domain decomposition. [ 2 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3109", "text": "To simulate and  electrocardiogram  using the fully coupled or uncoupled models, a three-dimensional reconstruction of the human torso is needed. Today, diagnostic imaging techniques such as  MRI  and  CT  can provide a sufficiently accurate images that allow to reconstruct in detail anatomical human parts and, thus, obtain a suitable torso geometry.\nFor example, the Visible Human Data [ 13 ]  is a useful dataset to create a three-dimensional torso model detailed with internal organs including the skeletal structure and muscles. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3110", "text": "Even if the results are quite detailed, solving a three-dimensional model is usually quite expensive. A possible simplification is a dynamical model based on three coupled ordinary differential equations. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3111", "text": "The quasi-periodicity of the heart beat is reproduced by a three-dimensional trajectory around an attracting limit cycle in the  \n \n \n \n ( \n x \n , \n y \n ) \n \n \n {\\displaystyle (x,y)} \n \n  plane. The principal peaks of the ECG, which are the P,Q,R,S and T, are described at fixed angles  \n \n \n \n \n \u03b8 \n \n P \n \n \n , \n \n \u03b8 \n \n Q \n \n \n , \n \n \u03b8 \n \n R \n \n \n , \n \n \u03b8 \n \n S \n \n \n \n \u00a0and\u00a0 \n \n \n \u03b8 \n \n T \n \n \n \n \n {\\displaystyle \\theta _{P},\\theta _{Q},\\theta _{R},\\theta _{S}{\\text{ and }}\\theta _{T}} \n \n , which give the following three ODEs [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3112", "text": "x \n \u2032 \n \n \n \n \n = \n \u03b1 \n z \n \u2212 \n \u03c9 \n y \n \n \n \n \n \n y \n \u2032 \n \n \n \n \n = \n \u03b1 \n y \n + \n \u03c9 \n x \n \n \n \n \n \n z \n \u2032 \n \n \n \n \n = \n \n \u2212 \n \n \u2211 \n \n i \n \u2208 \n { \n P \n , \n Q \n , \n R \n , \n S \n , \n T \n } \n \n \n \n a \n \n i \n \n \n \u0394 \n \n \u03b8 \n \n i \n \n \n \n exp \n \n \n ( \n \n \u2212 \n \n \u0394 \n \n \u03b8 \n \n i \n \n \n 2 \n \n \n \n \n / \n \n \n 2 \n \n b \n \n i \n \n \n 2 \n \n \n \n \n ) \n \n \u2212 \n ( \n z \n \u2212 \n \n z \n \n 0 \n \n \n ) \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{aligned}x'&=\\alpha z-\\omega y\\\\[1ex]y'&=\\alpha y+\\omega x\\\\[1ex]z'&=\\textstyle -\\sum _{i\\in \\{P,Q,R,S,T\\}}a_{i}\\Delta \\theta _{i}{\\text{exp}}\\left(-{\\Delta \\theta _{i}^{2}}/{2b_{i}^{2}}\\right)-(z-z_{0})\\end{aligned}}} \n \n \nwith  \n \n \n \n \u03b1 \n = \n 1 \n \u2212 \n \n \n \n x \n \n 2 \n \n \n + \n \n y \n \n 2 \n \n \n \n \n \n \n {\\textstyle \\alpha =1-{\\sqrt {x^{2}+y^{2}}}} \n \n ,  \n \n \n \n \u0394 \n \n \u03b8 \n \n i \n \n \n = \n ( \n \u03b8 \n \u2212 \n \n \u03b8 \n \n i \n \n \n ) \n \n mod \n \n ( \n \n \n 2 \n \u03c0 \n ) \n \n \n {\\displaystyle \\Delta \\theta _{i}=(\\theta -\\theta _{i}){\\bmod {(}}2\\pi )} \n \n ,  \n \n \n \n \u03b8 \n = \n \n atan \n \n 2 \n ( \n y \n , \n x \n ) \n \n \n {\\displaystyle \\theta ={\\text{atan}}2(y,x)}"}
{"_id": "WikiPedia_Cardio$$$corpus_3113", "text": "The equations can be easily solved with classical numerical algorithms like  Runge-Kutta methods  for ODEs. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3114", "text": "The  pacemaker current  ( I f , or  I K f , also called  funny current ) is an  electric current  in the  heart  that flows through the  HCN channel  or pacemaker channel. Such channels are important parts of the  electrical conduction system of the heart  and form a component of the  natural pacemaker ."}
{"_id": "WikiPedia_Cardio$$$corpus_3115", "text": "First described in the late 1970s in  Purkinje fibers  and  sinoatrial   myocytes , the cardiac pacemaker \"funny\" (I f ) current has been extensively characterized and its role in cardiac pacemaking has been investigated. [ 1 ] [ 2 ] [ 3 ]  Among the unusual features which justified the name \"funny\" are mixed Na +  and K +  permeability, activation on  hyperpolarization , and very slow kinetics. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3116", "text": "The funny current is highly expressed in spontaneously active cardiac regions, such as the  sinoatrial node  (SAN, the natural pacemaker region), the  atrioventricular node  (AVN) and the Purkinje fibres of conduction tissue. The funny current is a mixed sodium\u2013potassium current that activates upon hyperpolarization at voltages in the diastolic range (normally from \u221260/\u221270 mV to \u221240 mV). When, at the end of a sinoatrial action potential, the membrane repolarizes below the I f  threshold (about \u221240/\u221250 mV), the funny current is activated and supplies inward current, which is responsible for starting the  diastolic depolarization  phase (DD); by this mechanism, the funny current controls the rate of spontaneous activity of sinoatrial myocytes, and thus the cardiac rate. The reversal potential of the funny current lies between -20 and -10 mV.  [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3117", "text": "Another unusual feature of I f  is its dual activation by voltage and by cyclic nucleotides.  Cyclic adenosine monophosphate  (cAMP) molecules bind directly to f-channels and increase their open probability. [ 5 ]  cAMP dependence is a particularly relevant physiological property, since it underlies the I f -dependent autonomic regulation of heart rate. Sympathetic stimulation raises the level of cAMP-molecules which bind to f-channels and shift the I f  activation range to more positive voltages; this mechanism leads to an increase of the current at diastolic voltages and therefore to an increase of the steepness of DD and heart rate acceleration."}
{"_id": "WikiPedia_Cardio$$$corpus_3118", "text": "Parasympathetic stimulation (which acts to increase probability of potassium channels opening but decreases the probability of calcium channel opening) decreases the heart rate by the opposite action, that is by shifting the I f  activation curve towards more negative voltages. When vagally-released acetylcholine (ACh) binds to  muscarinic M2 receptors , this promotes dissociation of \u03b2\u03b3 subunit complexes, leading to direct opening of the G-protein\u2013gated inwardly rectifying K+ channel (Girk/Kir)  IKACh. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3119", "text": "A similar current, termed I h  (hyperpolarization-activated), has also been described in different types of neurons, where it has a variety of functions, including the contribution to control of rhythmic firing, regulation of neuronal excitability, sensory transduction, synaptic plasticity and more. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3120", "text": "The molecular determinants of the pacemaker current belong to the  HCN channel  ( hyperpolarization -activated  cyclic nucleotide \u2013gated channel), of which 4  isoforms  (HCN1 to HCN4) are known. Based on their sequence, HCN channels are classified as members of the superfamily of voltage-gated K +  (Kv) and CNG channels. [ 3 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3121", "text": "Because of their relevance to generation of pacemaker activity and modulation of spontaneous frequency, f-channels are natural targets of drugs aimed to pharmacologically control heart rate. Several agents called \"heart rate reducing agents\" act by specifically inhibiting f-channel function. [ 3 ]   Ivabradine  is the most specific and selective I f  inhibitor and the only member of this family that is now marketed for pharmacological treatment of chronic stable angina in patients with normal sinus rhythm who have a contraindication or intolerance to beta-blockers. Recent studies have also indicated that funny channel inhibition can be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients with heart rate \u226570 bpm. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3122", "text": "Cardiovascular diseases represent a major cause of worldwide mortality, and the relevance of the genetic component in these diseases has recently become more apparent. Genetic alterations of HCN4 channels (the molecular correlate of sinoatrial f-channels) coupled to rhythm disturbances have been reported in humans. For example, an inherited mutation of a highly conserved residue in the CNBD of the HCN4 protein (S672R) is associated with inherited  sinus bradycardia . [ 10 ]   In vitro  studies indicate that the S672R mutation causes a hyperpolarizing shift of the HCN4 channel open probability curve of about 5 mV in heterozygosis, an effect similar to the hyperpolarizing shift caused by parasympathetic stimulation and able to explain a reduction of inward current during diastole and the resulting slower spontaneous rate. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3123", "text": "Biological pacemakers, generally intended as cell substrates able to induce spontaneous activity in silent tissue, represent a potential tool to overcome the limitations of  electronic pacemakers . One of the strategies used to generate biological pacemakers involves the use of cells inherently expressing or engineered to express funny channels. Different types of stem cells can be used for this purpose. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3124", "text": "The  Heart Rhythm Society  is an international  non-profit organization  that promotes education and advocacy for cardiac arrhythmia professionals and patients. The society was founded in 1979 and counted over 7,500 members from over 90 countries as of January 2023. [ 1 ] [ third-party source needed ]  The official journal of the Heart Rhythm Society is  Heart   Rhythm , which provides readers scientific developments devoted to  arrhythmias , devices, and cardiovascular  electrophysiology . The Heart Rhythm Society is headquartered in  Washington, DC , US. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3125", "text": "The Heart Rhythm Society, through its efforts during Atrial Fibrillation Awareness Month in September and throughout the year, is working to increase public knowledge about atrial fibrillation, including its symptoms, warning signs, and treatments. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3126", "text": "Sudden Cardiac Arrest Awareness Month represents an initiative by the Heart Rhythm Society to raise awareness and help the public become more familiar with sudden cardiac arrest, how it affects people, and what can be done to help save lives. [ 5 ]  The society's award-winning \"Apples and Oranges\" campaign uses a simple analogy to educate people about the difference between a heart attack and sudden cardiac arrest. The campaign targets heart attack survivors, who are at the highest risk for sudden cardiac arrest, and stresses the importance of maintaining a healthy heart lifestyle and learning critical risk markers, especially their ejection fraction, which is the percentage of blood pumped out of the left ventricle with each heartbeat. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3127", "text": "In October 2012, the Heart Rhythm Society launched a multi-year, national awareness campaign, \"Arrest the Risk\", in an effort to elevate the issue of preventing sudden cardiac arrest, early intervention, and appropriate treatment among the African-American and Hispanic populations; increase awareness of disparities at the point of care; and reduce mortality and re-hospitalization rates from sudden cardiac arrest in the US. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3128", "text": "The Heart Rhythm Society's government advocacy efforts center on operating as an intermediary between regulatory agencies and its members. The society promotes programs to take action regarding legislation, creates and endorses clinical guidelines, and helps its members find funding opportunities from government agencies such as the National Institutes of Health. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3129", "text": "The society also provides several educational initiatives including courses held throughout the year, certification and  continuing medical education  programs and an annual conference, called Scientific Sessions. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3130", "text": "Presidents of the Heart Rhythm Society from inception are listed below.  The leadership cycle is five years, with service as president being in the fourth year.  This allows the society to project presidents three years in advance.   Anne M. Gillis , whose election to the presidency for the 2012\u201313 term was revealed at the May 2009 meeting of the society, was the second non-American to serve in that capacity.  The first non-American president was Bernard S. Goldman in 1982; the second was Anne M. Gillis (both are Canadian). [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3131", "text": "An  implantable cardioverter-defibrillator  ( ICD ) or  automated implantable cardioverter defibrillator  ( AICD ) is a device  implantable  inside the body, able to perform  defibrillation , and depending on the type,  cardioversion  and  pacing  of the heart. The ICD is the first-line treatment and prophylactic therapy for patients at risk for  sudden cardiac death  due to  ventricular fibrillation  and  ventricular tachycardia . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3132", "text": "\"AICD\" was trademarked by the Boston Scientific corporation, so the more generic \"ICD\" is preferred terminology."}
{"_id": "WikiPedia_Cardio$$$corpus_3133", "text": "On average ICD  batteries  last about six to ten years. [ 2 ]  Advances in technology, such as batteries with more capacity or rechargeable batteries, [ 3 ]  may allow batteries to last over ten years. The leads (electrical cable wires connecting the device to the heart) have much longer average longevity, but can malfunction in various ways, specifically  insulation  failure or fracture of the  conductor ; thus, ICDs and leads generally require replacement after every 5 to 10 years. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3134", "text": "The process of implantation of an ICD system is similar to implantation of an  artificial pacemaker . In fact, ICDs are composed of an ICD generator and of wires. The first component or generator contains a computer chip or circuitry with  RAM  (memory), programmable software, a  capacitor  and a battery; this is implanted typically under the skin in the left upper chest. The second part of the system is an  electrode  wire or wires that, similar to pacemakers, are connected to the generator and passed through a vein to the right chambers of the heart. The lead usually lodges in the apex or septum of the  right ventricle . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3135", "text": "Just like pacemakers, ICDs can have a single wire or lead in the heart (in the right ventricle, single chamber ICD), two leads (in the right atrium and right ventricle, dual chamber ICD) or three leads (biventricular ICD, one in the right atrium, one in the right ventricle and one on the outer wall of the  left ventricle ). The difference between pacemakers and ICDs is that pacemakers are also available as temporary units and are generally designed to correct slow heart rates, i.e.  bradycardia , while ICDs are often permanent safeguards against sudden life-threatening arrhythmias."}
{"_id": "WikiPedia_Cardio$$$corpus_3136", "text": "Recent developments include the  subcutaneous ICD  (S-ICD) which is placed entirely under the skin, leaving the vessels and heart untouched.  [ 7 ]  Implantation with an S-ICD is regarded as a procedure with even less risks, it is currently suggested for patients with previous history of infection or increased risk of infection. It is also recommended for very active patients, younger patients with will likely outlive their transvenous ICD (TV-ICD) leads and those with complicated anatomy/arterial access. S-ICDs are not able to be used in patients with  ventricular tachycardia  or  bradycardia .  [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3137", "text": "People who have an implanted cardioverter-defibrillator can live full lives. Patients overall have either a sustained or improved quality of life after ICD implantation when compared to before ICD implantation. [ 9 ]  It may provide a strong degree of reassurance. As with a pacemaker, however, living with an ICD does impose some restrictions on the person's lifestyle."}
{"_id": "WikiPedia_Cardio$$$corpus_3138", "text": "Almost all forms of physical activities can be performed by patients with an ICD with moderation. [ 10 ]  All forms of sports that do not pose a risk of damaging the ICD or because of the underlying cardiomyopathy can be undertaken by the patient. Special care should be taken not to put excessive strain on the shoulder, arm and torso area where the ICD is implanted. Doing so may damage the ICD or the leads going from the ICD generator to the patient's heart. Particularly to be avoided are exercises that cause the  clavicle  to be pulled down towards the ribs, such as lifting weights with the arm, on the ICD site, while standing."}
{"_id": "WikiPedia_Cardio$$$corpus_3139", "text": "ICD patients in the United States are prohibited from professional or commercial driving per the Cardiovascular Advisory Panel Guidelines for the Medical Examination of Commercial Motor Vehicle Drivers. [ 11 ]  A driving abstinence for private drivers is recommended following ICD implantation, but the timeframe is variable depending on the country (between 3 and 6 months for secondary prevention and 1\u20134 weeks for primary prevention). Following an appropriate ICD-therapy, a driving ban is recommended for 3\u20136 months depending on the country. After inappropriate ICD-therapy delivered for non-ventricular arrhythmias or due to the device malfunction, driving restrictions usually apply until the cause of the inappropriate therapy has been eliminated. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3140", "text": "Equipment using magnets or generating magnetic fields, or any similar environment, must be avoided by patients with an ICD. As with other metallic objects, an ICD is normally a  contraindication  to the use of  magnetic resonance imaging  (MRI).  However, several ICD manufacturers [ who? ]  have recently [ when? ]  introduced  MR-Conditional  ICDs, which allow the use of MRI under specified safe operating conditions. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3141", "text": "Implantable cardioverter defibrillators have demonstrated clear life-saving benefits, while concerns about patient acceptance and  psychological  adjustment to the ICD have been the focus of much research. [ 13 ]   Researchers, including those from the field of  cardiac psychology , have concluded that the quality of life (QoL) of ICD patients is at least equal to, or better than, that of those taking  anti-arrhythmic medications . [ 14 ]   The largest study of examined 2,521 patients with stable heart failure in the SCD-HeFT trial. [ 15 ]   Results indicated that there were no differences between ICD-treated and medication-treated groups at 30 months in patient-reported QoL. [ 16 ]  Psychological adjustment following ICD implantation has also been well studied. In rare cases, the ICD can become infected and is usually bacterial in origin but other organisms such as certain fungi have occasionally been implicated. [ 17 ]  This is more likely to occur in people with  diabetes ,  heart failure ,  kidney failure , or  a suppressed immune system . [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3142", "text": "Anxiety  is a common psychological  side effect , with approximately 13\u201338% of ICD patients reporting clinically significant anxiety. [ 18 ] [ 19 ]  The primary etiological factors contributing to anxiety in ICD patients have not been determined, however.  Depressive  symptoms are also common, but the incidence of these problems has been shown to be similar to those observed in other cardiac patient groups, with approximately 24\u201341% of patients with ICDs experiencing depressive symptoms. [ 19 ]  Problems in psychosocial adjustment to ICDs, including the experience of anxiety, among spouses or other romantic partners are also prevalent. [ 20 ]  This phenomenon may be related, at least in part, to shared shock anxiety and avoidance of physical and sexual contact. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3143", "text": "Patients are generally required to follow up with their electrophysiologist cardiologist at regular intervals, mostly 3 to 6 months. At this time, many device manufactures have some form of home monitoring to allow for device data to be sent in electronically to the physician. [ 22 ]  Recent advances include app integration for home interrogation and remote care has been correlated with some mortality benefit.  [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3144", "text": "Implantation of ICD is meant to prevent  sudden cardiac death  and is indicated under various conditions. Two broad but distinct categories are primary and secondary prevention. Primary prevention refers to patients who have not suffered a life-threatening arrhythmia episode. Secondary prevention has the strongest evidence for benefit and it refers to survivors of cardiac arrest secondary to  ventricular fibrillation  (VF) or hemodynamically unstable sustained  ventricular tachycardia  (VT) after reversible causes are excluded. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3145", "text": "Similarly, ICD use in primary prevention is to prevent cardiac death in patients who are at risk for sustained ventricular tachycardia or ventricular fibrillation. This population accounts for the bulk of all ICD implants. There are a multitude of guideline indications for ICD use in primary preventions with varying degree of supporting evidence. Periodically, both the American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology provide an update to this guideline. Some of the Class I indications are as follows: [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3146", "text": "A number of clinical trials have demonstrated the superiority of the ICD over AAD (antiarrhythmic drugs) in the prevention of death from malignant arrhythmias.\nThe SCD-HeFT trial (published in 2005) [ 25 ]  showed a significant all-cause mortality benefit for patients with ICD.  Congestive heart failure  patients that were implanted with an ICD had an all-cause death risk 23% lower than placebo and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. 1 \nReporting in 1999, the  Antiarrhythmics Versus Implantable Defibrillators  (AVID) trial consisted of 1,016 patients, and deaths in those treated with AAD were more frequent ( n  = 122) compared with deaths in the ICD groups ( n  = 80,  p  < 0.001). [ 26 ]  In 2002 the  MADITII  trial showed benefit of ICD treatment in patients after myocardial infarction with reduced left ventricular function (EF<30)."}
{"_id": "WikiPedia_Cardio$$$corpus_3147", "text": "Initially ICDs were implanted via thoracotomy with defibrillator patches applied to the  epicardium  or  pericardium . The device was attached via subcutaneous and transvenous leads to the device contained in a subcutaneous abdominal wall pocket. The device itself acts as an electrode. Most ICDs nowadays are implanted transvenously with the devices placed in the left pectoral region similar to pacemakers. Intravascular spring or coil electrodes are used to defibrillate.  The devices have become smaller and less invasive as the technology advances.  Current ICDs weigh only 70\u00a0grams and are about 12.9\u00a0mm thick."}
{"_id": "WikiPedia_Cardio$$$corpus_3148", "text": "A recent study by Birnie and colleagues at the University of Ottawa Heart Institute has demonstrated that ICDs are underused in both the United States and Canada. [ 27 ]  An accompanying editorial by Simpson of Queen's University explores some of the economic, geographic, social and political reasons for this. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3149", "text": "The development of the ICD was pioneered at  Sinai Hospital  in  Baltimore  by a team including  Michel Mirowski ,  Morton Mower ,  Alois Langer , William Staewen, and Joseph \"Jack\" Lattuca. Mirowski teamed up with Mower and Staewen and together they commenced their research in 1969 but it was 11 years before they treated their first patient. [ 29 ] [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3150", "text": "The work was commenced against much skepticism even by leading experts in the field of arrhythmias and sudden death. There was doubt that their ideas would ever become a clinical reality. In 1972  Bernard Lown , the inventor of the external  defibrillator , and Paul Axelrod stated in the journal  Circulation  \u2013 \"The very rare patient who has frequent bouts of ventricular fibrillation is best treated in a coronary care unit and is better served by an effective  anti-arrhythmic  program or surgical correction of inadequate coronary blood flow or ventricular malfunction. In fact, the implanted defibrillator system represents an imperfect solution in search of a plausible and practical application.\" [ 29 ] [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3151", "text": "The problems to be overcome were the design of a system which would allow detection of ventricular fibrillation or ventricular tachycardia. Despite the lack of financial backing and grants, they persisted and the first device was implanted in February 1980 at  Johns Hopkins Hospital  by Dr.  Levi Watkins  Jr. [ 29 ] [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3152", "text": "The first devices required  the chest to be cut open  and a mesh electrode sewn onto the heart; the  pulse generator  was placed in the abdomen. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3153", "text": "ICDs constantly monitor the rate and rhythm of the heart and can deliver therapies, by way of an electrical shock, when the heart rate exceeds a preset number.  More modern devices have software designed to attempt a discrimination between  ventricular fibrillation  and  ventricular tachycardia  (VT), and may try to pace the heart faster than its intrinsic rate in the case of VT, to try to break the tachycardia before it progresses to ventricular fibrillation. This is known as overdrive pacing, or anti-tachycardia pacing (ATP).  ATP is only effective if the underlying rhythm is ventricular tachycardia, and is never effective if the rhythm is ventricular fibrillation."}
{"_id": "WikiPedia_Cardio$$$corpus_3154", "text": "Many modern ICDs use a combination of various methods to determine if a fast rhythm is normal,  supraventricular tachycardia , ventricular tachycardia, or ventricular fibrillation."}
{"_id": "WikiPedia_Cardio$$$corpus_3155", "text": "Rate discrimination  evaluates the rate of the lower chambers of the  heart  (the  ventricles ) and compares it to the rate in the upper chambers of the heart (the  atria ). If the rate in the atria is faster than or equal to the rate in the ventricles, then the rhythm is most likely not ventricular in origin, and is usually more benign. If this is the case, the ICD does not provide any therapy, or withholds it for a programmable length of time."}
{"_id": "WikiPedia_Cardio$$$corpus_3156", "text": "Rhythm discrimination  will see how regular a ventricular tachycardia is. Generally, ventricular tachycardia is regular. If the rhythm is irregular, it is usually due to conduction of an irregular rhythm that originates in the atria, such as  atrial fibrillation . In the picture, an example of  torsades de pointes  can be seen; this represents a form of irregular ventricular tachycardia. In this case, the ICD will rely on rate, not regularity, to make the correct diagnosis."}
{"_id": "WikiPedia_Cardio$$$corpus_3157", "text": "Morphology discrimination  checks the morphology of every ventricular beat and compares it to what the ICD knows is the morphology of normally conducted ventricular impulse for the patient.  This normal ventricular impulse is often an average of a multiple of normal beats of the patient acquired in the recent past and known as a template."}
{"_id": "WikiPedia_Cardio$$$corpus_3158", "text": "The integration of these various parameters is very complex, and clinically, the occurrence of inappropriate therapy is still occasionally seen and a challenge for future software advancements."}
{"_id": "WikiPedia_Cardio$$$corpus_3159", "text": "An  implantable loop recorder  ( ILR ), also known as an  insertable cardiac monitor  ( ICM ), is a small device that is implanted under the skin of the chest for  cardiac monitoring , to record the heart's electrical activity for an extended period. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3160", "text": "The ILR  monitors the electrical activity  of the heart, continuously storing information in its  circular memory  (hence the name \"loop\" recorder) as  electrocardiograms  (ECGs). Abnormal electrical activity -  arrhythmia  is recorded by \"freezing\" a segment of the memory for later review. Limited number of episodes of abnormal activity can be stored, [ 2 ]  with the most recent episode replacing the oldest. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3161", "text": "Recording can be activated in two ways. First, recording may be activated automatically according to  heart rate  ranges previously defined and set in the ILR by the physician. If the heart rate drops below, or rises above, the set rates, the ILR will record without the patient's knowledge.  The second way the ILR records is through a hand-held \"patient activator\" whereby the patient triggers a recording by pushing a button when they notice symptoms such as skipped beats, lightheadedness or dizziness. [ 4 ]  The ILR records by \"freezing\" the electrical information preceding, during and after the symptoms in the format of an electrocardiogram. [ 1 ]  The technician or physician can download and review the recorded events during an office visit using a special  programmer [ 4 ]  or via online data transmission. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3162", "text": "The ILR is a useful  diagnostic  tool to investigate patients who experience symptoms such as  syncope  (fainting),  seizures , recurrent  palpitations , lightheadedness, or dizziness not often enough to be captured by a 24-hour or 30-day external monitor. Because of the ILR's long battery life (up to 3 years), the heart can be monitored for an extended period."}
{"_id": "WikiPedia_Cardio$$$corpus_3163", "text": "New devices are able to store a total of 60 minutes of recordings on their memory. Thirty minutes is reserved for automatic storage of arrhythmias according to preprogrammed criteria. The remaining 30 minutes can be divided into a selectable number of slots for storage of manually triggered retrograde recordings as an answer to symptoms (fainting, palpitations etc.) which may be caused by an arrhythmia. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3164", "text": "Recent studies have underscored the diagnostic effectiveness and cost-efficiency of implantable loop recorders (ILRs) in specific patient populations. In patients with unexplained palpitations, especially those with infrequent symptoms, ILRs have shown a significantly higher diagnostic yield compared to conventional methods. One study reported a diagnosis in 73% of subjects using ILRs, against 21% with conventional strategies, while also proving to be more cost-effective despite higher initial costs. [ 6 ]  Another study focused on ILR use for detecting asymptomatic atrial fibrillation in individuals aged 70-90 years with additional stroke risk factors. This trial found that ILR screening led to a threefold increase in atrial fibrillation detection and anticoagulation initiation. However, it did not show a significant reduction in the risk of stroke or systemic arterial embolism, indicating that not all screen-detected atrial fibrillation might warrant anticoagulation treatment. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3165", "text": "The ILR is implanted by an  electrophysiologist  under  local anesthesia . A small incision (about 3\u20134\u00a0cm or 1.5 inches) is made just lateral to the sternum below the nipple line, usually on the patient's left side. [ 8 ]  A pocket is created under the skin, and the ILR is placed in the pocket. Patients can go home the day of the procedure with few restrictions on activities. [ 4 ]  Bruising and discomfort in the implant area may persist for several weeks."}
{"_id": "WikiPedia_Cardio$$$corpus_3166", "text": "Patients are instructed in use of the activator, and advised to schedule an appointment with their physician after using it so that information stored in the ILR can be retrieved for diagnosis."}
{"_id": "WikiPedia_Cardio$$$corpus_3167", "text": "In the  electrocardiogram , the  intrinsicoid deflection  is the downstroke of the  QRS complex , from its highest amplitude until it reaches the baseline or lower. [ 1 ]  Since the  ventricles  normally  depolarize  from inside to outside, this deflection reflects the depolarization vector from the  endocardium  to the  epicardium . The  time of the onset of the intrinsicoid deflection , also referred to as the  ventricular activation time  or  R wave peak time , is measured from the beginning of the QRS complex to the peak of the R wave. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3168", "text": "In the presence of bundle branch block or ventricular hypertrophy, the depolarization impulse takes a longer than normal period of time to reach the recording electrode. This delays the onset of the intrinsicoid deflection.\nThis prolongation or delay is an important criterion for diagnosing bundle branch block or ventricular hypertrophy. Time of onset of intrinsicoid deflection > 0.04 seconds (just over one small box) is used as a non-voltage related criterion to diagnose  left ventricular hypertrophy . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3169", "text": "Leonardo Krys  [1944-2009] was a travel agent whose 1991 heart attack aboard a  Lufthansa  flight prompted U.S.-based airlines to install  Automated External Defibrillators , or AED, on their planes."}
{"_id": "WikiPedia_Cardio$$$corpus_3170", "text": "On November 30, 1991, Krys boarded a Lufthansa 747 in Miami, headed to Frankfurt, Germany. About an hour out, he suffered the symptoms of a cardiac infarction. The crew did not make an unscheduled landing and landed in Germany after a 10 hours flight. Upon landing, the plane was met by an ambulance which transported Krys to a hospital. At the hospital, the doctors concluded that Krys had indeed suffered a heart attack."}
{"_id": "WikiPedia_Cardio$$$corpus_3171", "text": "Krys and his wife argued that Lufthansa's crew acted negligently in responding to the symptoms displayed by Mr. Krys and thus aggravated the damage to his heart. They won a lawsuit against Lufthansa in Miami federal court which the 11th Circuit Court of Appeals upheld. [ 1 ]  Later the  United States Supreme Court  refused to hear the airline's appeal arguing that the incident should have been classified as an accident, per the Warsaw Convention, capping his payout."}
{"_id": "WikiPedia_Cardio$$$corpus_3172", "text": "The result of this suit prompted the airlines to review their safety manuals, including portable defibrillators and training the crew on how to use them."}
{"_id": "WikiPedia_Cardio$$$corpus_3173", "text": "Leo (as he was known by his friend and family) was born in Argentina, and moved with his family to  Miami, USA  in the late 1970s, due to the local economical and political situation."}
{"_id": "WikiPedia_Cardio$$$corpus_3174", "text": "He owned a travel agency at the time of the heart attack, but the health crisis spurred a midlife career switch to acting. He acted in  Telemundo   telenovelas , local theater, an episode of  America's Most Wanted  (as an Israeli searching for his son's killer), several independent films and in Latin pop star  La India 's video, Traicion, as a priest."}
{"_id": "WikiPedia_Cardio$$$corpus_3175", "text": "One of Krys' son,  Sebastian , is a four-time American  Grammy  winner and eight-time  Latin Grammy Awards  producer and mixer (as of 2011)"}
{"_id": "WikiPedia_Cardio$$$corpus_3176", "text": "Leonardo Krys died of a heart attack in Miami, on March 14, 2009."}
{"_id": "WikiPedia_Cardio$$$corpus_3177", "text": "3BJ4 ,  3HFC ,  3HFE ,  4UMO ,  4V0C"}
{"_id": "WikiPedia_Cardio$$$corpus_3178", "text": "3784"}
{"_id": "WikiPedia_Cardio$$$corpus_3179", "text": "16535"}
{"_id": "WikiPedia_Cardio$$$corpus_3180", "text": "ENSG00000282076 ENSG00000053918"}
{"_id": "WikiPedia_Cardio$$$corpus_3181", "text": "ENSMUSG00000009545"}
{"_id": "WikiPedia_Cardio$$$corpus_3182", "text": "P51787"}
{"_id": "WikiPedia_Cardio$$$corpus_3183", "text": "P97414"}
{"_id": "WikiPedia_Cardio$$$corpus_3184", "text": "NM_181798 NM_000218 NM_181797"}
{"_id": "WikiPedia_Cardio$$$corpus_3185", "text": "NM_008434"}
{"_id": "WikiPedia_Cardio$$$corpus_3186", "text": "NP_000209 NP_861463"}
{"_id": "WikiPedia_Cardio$$$corpus_3187", "text": "NP_032460"}
{"_id": "WikiPedia_Cardio$$$corpus_3188", "text": "K v 7.1  ( KvLQT1 ) is a  potassium   channel   protein  whose primary subunit in humans is encoded by the  KCNQ1   gene . [ 5 ]   It's mutation causes  Long QT syndrome , K v 7.1 is a voltage and  lipid-gated  potassium channel present in the  cell membranes  of cardiac tissue and in inner ear  neurons  among other tissues.  In the cardiac  cells , K v 7.1 mediates the I Ks  (or slow delayed rectifying K + ) current that contributes to the  repolarization  of the cell, terminating the cardiac  action potential  and thereby the heart's  contraction . It is a member of the  KCNQ family  of potassium channels."}
{"_id": "WikiPedia_Cardio$$$corpus_3189", "text": "KvLQT1 is made of six membrane-spanning domains S1-S6, two intracellular domains, and a pore loop. [ 6 ]   The KvLQT1 channel is made of four KCNQ1 subunits, which form the actual ion channel."}
{"_id": "WikiPedia_Cardio$$$corpus_3190", "text": "This gene encodes a protein for a voltage-gated potassium channel required for the repolarization phase of the cardiac action potential. The gene product can form heteromultimers with two other potassium channel proteins,  KCNE1  and  KCNE3 . The gene is located in a region of  chromosome 11  that contains a large number of contiguous genes that are abnormally imprinted in cancer and the  Beckwith-Wiedemann syndrome . Two alternative transcripts encoding distinct isoforms have been described. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3191", "text": "Mutations  in the gene can lead to a defective protein and several forms of inherited arrhythmias as  Long QT syndrome [ 8 ]  which is a prolongation of the  QT interval  of heart repolarization,  Short QT syndrome , [ 8 ]  and Familial  Atrial Fibrillation .  KvLQT1 are also expressed in the pancreas, and KvLQT1 Long QT syndrome patients has been shown to have hyperinsulinemic hypoglycaemia following an oral glucose load. [ 9 ]  Currents arising from K v 7.1 in over-expression systems have never been recapitulated in native tissues - K v 7.1 is always found in native tissues with a modulatory subunit.  In cardiac tissue, these subunits comprise KCNE1 and yotiao.  Though  physiologically  irrelevant,  homotetrameric  K v 7.1 channels also display a unique form of C-type inactivation that reaches equilibrium quickly, allowing KvLQT1 currents to plateau.  This is different from the inactivation seen in A-type currents, which causes rapid current decay."}
{"_id": "WikiPedia_Cardio$$$corpus_3192", "text": "KvLQT1 has been shown to  interact  with  PRKACA , [ 11 ]   PPP1CA [ 11 ]  and  AKAP9 . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3193", "text": "KvLQT1 can also associate with any of the five members of the KCNE family of proteins, but interactions with  KCNE1 ,  KCNE2 ,  KCNE3  are the only interactions within this protein family that affect the human heart. KCNE2,  KCNE4 , and  KCNE5  have been shown to have an inhibitory effect on the functionality of KvLQT1, while KCNE1 and KCNE3 are activators of KvLQT1. [ 6 ]   KvLQT1 can associate with KCNE1 and KCNE4 with the activation effects of KCNE1 overriding the inhibitory effects of KCNE4 on the KvLQT1 channel, and KvLQT1 will commonly associate with anywhere from two to four different KCNE proteins in order to be functional. [ 6 ]   However, KvLQT1 most commonly associates with KCNE1 and forms the KvLQT1/KCNE1 complex since it has only been seen to function in vivo when associated with another protein. [ 6 ]   KCNQ1 will form a  heteromer  with KCNE1 in order to slow its activation and enhance the current density at the plasma membrane of the neuron. [ 6 ] [ 12 ]   In addition to associating with KCNE proteins, the  N-terminal  juxtamembranous domain of KvLQT1 can also associate with  SGK1 , which stimulates the slow delayed potassium rectifier current.  Since SGK1 requires structural integrity to stimulate KvLQT1/KCNE1, any mutations present in the KvLQT1 protein can result in reduced stimulation of this channel by SGK1. [ 13 ]   General mutations in KvLQT1 have been known to cause a decrease in this slow delayed potassium rectifier current, longer cardiac action potentials, and a tendency to have tachyarrhythmias. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3194", "text": "KCNE1  (minK), can assemble with KvLQT1 to form a slow delayed potassium rectifier channel.  KCNE1 slows the inactivation of KvLQT1 when the two proteins form a heteromeric complex, and the current amplitude is greatly increased compared to WT-KvLQT1  homotetrameric  channels.  KCNE1 associates with the pore region of KvLQT1, and its  transmembrane  domain contributes to the selectivity filter of this heteromeric channel complex. [ 12 ]  The  alpha helix  of the KCNE1 protein interacts with the pore domain S5/S6 and with the S4 domain of the KvLQT1 channel.  This results in structural modifications of the voltage sensor and the selectivity filter of the KvLQT1 channel. [ 14 ]   Mutations in either the alpha subunit of this complex, KvLQT1 or the beta subunit, KCNE1, can lead to  Long QT Syndrome  or other cardiac rhythmic deformities. [ 13 ]   When associated with KCNE1, the KvLQT1 channel activates much more slowly and at a more positive  membrane potential .  It is believed that two KCNE1 proteins interact with a  tetrameric  KvLQT1 channel, since experimental data suggests that there are 4 alpha subunits and 2 beta subunits in this complex. [ 14 ] \nKVLQT1/KCNE1 channels are taken up from the plasma membrane through a  RAB5  dependent mechanism, but inserted into the membrane by  RAB11 , a  GTPase . [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3195", "text": "51\u00b003\u203255\u2033N   114\u00b008\u203206\u2033W \ufeff / \ufeff 51.0654\u00b0N 114.135\u00b0W \ufeff /  51.0654; -114.135"}
{"_id": "WikiPedia_Cardio$$$corpus_3196", "text": "The  Libin Cardiovascular Institute  is an entity of  Alberta Health Services  and the  University of Calgary .  It connects all cardiovascular research, education and patient care in Southern Alberta, serving a population of about two million. Its more than 1,500 members include physicians, clinicians and other health professionals, researchers and trainees."}
{"_id": "WikiPedia_Cardio$$$corpus_3197", "text": "The Libin Cardiovascular Institute was made possible through the donation of founding donors Mona and  Alvin Libin ."}
{"_id": "WikiPedia_Cardio$$$corpus_3198", "text": "On March 6, 2003, the Alvin and Mona Libin Foundation presented $15 million to Alberta Health Services and the University of Calgary to form the Libin Cardiovascular Institute. It was then the largest one-time donation to the organizations. The institute was formally created on January 27, 2004."}
{"_id": "WikiPedia_Cardio$$$corpus_3199", "text": "The Foundation renewed their commitment to the Institute in May 2022 with a  $7.5 million donation ."}
{"_id": "WikiPedia_Cardio$$$corpus_3200", "text": "Research within the Libin Cardiovascular Institute extends from basic biomedical and clinical research to health outcomes and care delivery research.  Notable successes include:"}
{"_id": "WikiPedia_Cardio$$$corpus_3201", "text": "Programs under the jurisdiction of the Libin Cardiovascular Institute include  Cardiology  and  Cardiovascular Surgery , in addition to contributions to other medical programs as well as graduate studies in the sciences. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3202", "text": "The LCI also offers fellowships and/or advanced training in  interventional cardiology ,  electrophysiology , amyloidosis, heart function and  cardiac MRI . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3203", "text": "The Libin Cardiovascular Institute is a wide-ranging program of cardiovascular integration which houses a growing list of scientists, clinicians, and researchers from various sites working together to advance the cardiovascular health of Albertans."}
{"_id": "WikiPedia_Cardio$$$corpus_3204", "text": "The Alberta Heritage Foundation for Medical Research (AHFMR) Prize for Excellence in Cardiovascular Research was established in honour of Mr. Alvin Libin for his many contributions to the AHFMR (now  Alberta Innovates )."}
{"_id": "WikiPedia_Cardio$$$corpus_3205", "text": "This $25,000 prize is awarded to an outstanding international researcher whose work has had a major impact on the understanding, prevention, recognition, or treatment of cardiovascular disease."}
{"_id": "WikiPedia_Cardio$$$corpus_3206", "text": "Past winners include:"}
{"_id": "WikiPedia_Cardio$$$corpus_3207", "text": "Lifepak  (stylized  LIFEPAK ) is a series of vital signs monitors and external cardiac  defibrillators  produced by medical technology company  Physio-Control . [ 1 ] [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3208", "text": "Lifepak defibrillators are manufactured and distributed from the company headquarters in  Redmond, Washington ."}
{"_id": "WikiPedia_Cardio$$$corpus_3209", "text": "Physio-Control publicly demonstrated its first Lifepak branded defibrillator, Lifepak 33, in November 1968 and began commercial sale of the unit the next year in 1969. [ 5 ] [ 6 ]  The Lifepak 33 was the lightest defibrillator available at launch, weighing 34 pounds. The defibrillator was referred to by media as a \"90-day wonder\" due to the entirety of its development occurring within a 90-day period. Despite being the companies first \"LIFEPAK\" branded defibrillator, it was named the Lifepak 33 due to the companies target weight of 33 pounds for the defibrillator. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3210", "text": "In 1971, the Lifepak 911 was released with 12-lead ECG monitoring capability, with the Lifepak 2 being released the following year. The Lifepak 2 was designed specifically for rapid-response vehicles in emergency services, and was the first to allow transmission of ECGs via telephone to hospitals for prehospital assessment by cardiologists. In 1973, the Lifepak 3 was released with a \"non-fade\" display and the ability to \"freeze\" the cardioscope. The Lifepak 1 was released the same year and was marketed as a more basic, but more compact model, lacking a cardiograph for ECG monitoring. In 1974, the Lifepak 4 was released with an integrated ECG recorder, and was followed by the Physio 260 (for home use) and Physio 1440 cardiac care system defibrillators were released to the public. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3211", "text": "In 1976, the Lifepak 5 was released weighing only 5 pounds and 19 ounces, with a modified Lifepak 5 accompanying the 65-member American Medical Expedition to  Mount Everest  in 1981 and the China-Everest Expedition in 1982. The Lifepak 6 featured a modular design with removable paddles holder and ECG printer, the Lifepak 8 featured the ability to perform transchest  external pacing , and the Lifepak 100 and 200 automatic advisor defibrillators were released with an Incorporated Shock Advisory System able to recognise shockable arrhythmias. in 1989, the Lifepak 9 and 10 both integrated a \"Code Summary\" record for documentation, featuring the ability to record times medication was administered, when shocks were delivered and how many shocks were delivered. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3212", "text": "In 1994, the Lifepak 11 was released, which set standards in prehospital 12-lead acquisition and transmission. In 1997, the Lifepak 500 was released as a  public access defibrillator , and brought AEDs to the mainstream public. The following year, the Lifepak 12 was released, with improved monitoring and diagnostic capabilities, as well as a standardised button layout. Some ambulance services still use the Lifepak 12 due to its reliability and advanced capabilities. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3213", "text": "In 1999, biphasic defibrillation waveforms were made available for the Lifepak 12 and 500 defibrillators and the 'ADAPTIV' biphasic waveform would become the standard waveform used in future models. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3214", "text": "In 2002, the Lifepak 20 defibrillator/monitor was introduced to replace the 9 in the hospital market, while the Lifepak CR Plus was introduced for the public market. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3215", "text": "In 2006, the Lifepak 1000 was introduced to replace the Lifepak 500 in the professional AED market. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3216", "text": "In 2008, the Lifepak 15 was introduced to replace the Lifepak 12 in the prehospital and hospital settings and featured a more refined design, color LCD display, CPR metronome and  Bluetooth  connectivity for wireless transmission of ECGs. The 15 was also the first model to support  Masimo   RainbowSET  pulse oximetry. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3217", "text": "The newest model, Lifepak 35, was introduced in 2024 and features a complete redesign from earlier models including omitting most of the hard button controls and instead using a touchscreen to control most functions of the device. The 35 also features a diagnostic quality LCD display, cprINSIGHT and STJInsight technologies, pediatric AED protocols, and live 12 or 15 lead ECGs. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3218", "text": "Advanced models include the Lifepak 12, 15, 20, and 35 for use by healthcare professionals such as  emergency medical technicians  and  paramedics .  Automatic  units include the Lifepak 500, Lifepak 1000, Lifepak CR Plus and the Lifepak CR2 for use by members of the public who have been trained to operate them. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3219", "text": "Most Lifepak defibrillators are capable of performing more than only defibrillation. Many models allow for  cardiac monitoring  (including heart rate monitoring and 12-Lead  ECG  acquisition and interpretation) and alert the users to sudden changes. The Lifepak 15, 20/20e, 35 and CR2 include a CPR metronome that is also capable of verbally aiding rescuers in providing ventilations. Advanced Lifepak monitor/defibrillators also include options for  synchronized cardioversion ,  external pacing , oxygen saturation monitoring,  End tidal CO2 , and both non-invasive and invasive blood pressure. [ 12 ]  The Lifepak CR2 and 35 include CPRInsight analysis technology which allows for chest compression during analysis of the patient's  ECG . [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3220", "text": "In the 1975 film  Three Days of the Condor , several Lifepak 911 monitors are used in an  ICU . One of them sounds an alarm when a patient is murdered."}
{"_id": "WikiPedia_Cardio$$$corpus_3221", "text": "Macroshock  is a medical term for the effects of body exposed to electrical current, which can lead to severe injury or death by  electrocution . It is used most often in the medical field, but is also commonly used in the fields of electrophysiology and bioengineering. [ 1 ] [ better\u00a0source\u00a0needed ]  Definitions of the term are inconsistent; there are three most commonly accepted definitions. Depending upon the medical text used, a macroshock is either:"}
{"_id": "WikiPedia_Cardio$$$corpus_3222", "text": "Possible sources of macroshock include: poorly designed or malfunctioning  electrophysiology  equipment,  lightning , damaged power cords or other electrical hazards around the household, downed power lines, high-voltage electrical equipment such as transformer stations and other industrial electrical equipment, and malfunctioning electrical or electricity-using mechanical equipment capable of delivering a strong current, or which operates at a high voltage."}
{"_id": "WikiPedia_Cardio$$$corpus_3223", "text": "Microshock  refers to the risk that patients undergoing medical procedures involving externally protruding intracardiac  electrical conductors , such as external  pacemaker   electrodes , or  saline  filled  catheters , could suffer an electric shock causing ventricular fibrillation (VF) due to currents entering the body via these parts. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3224", "text": "It is important to note that microshock (or micro-shock) are not IEV [ 2 ]  defined terms and are not used in any international standard."}
{"_id": "WikiPedia_Cardio$$$corpus_3225", "text": "\"Micro-shock\" is an otherwise imperceptible electric current applied directly, or in very close proximity, to the heart muscle of sufficient strength, frequency, and duration to cause disruption of normal cardiac function."}
{"_id": "WikiPedia_Cardio$$$corpus_3226", "text": "Note: It can be safely assumed (and it usually is) that micro-shock is only possible during certain medical procedures as the electric current needs to be focused directly into the heart by some conductor inserted by invasive means for some desired medical outcome (for example Cardiac Catheterisation)."}
{"_id": "WikiPedia_Cardio$$$corpus_3227", "text": "Micro-shock, if it occurs, is not always lethal. \u201c Micro-electrocution \u201d is the term that should be used whenever a micro-shock causes death."}
{"_id": "WikiPedia_Cardio$$$corpus_3228", "text": "\u201c Macro-shock \u201d is when a much larger current is passed through the body, usually via a skin to skin pathway, but more generally the current is not applied directly through the heart muscle. The current in macro-shock events can vary widely from being imperceptible to being extremely destructive of tissue. (see  Macroshock )"}
{"_id": "WikiPedia_Cardio$$$corpus_3229", "text": "\u201c Electric Shock \u201d is usually referring to macro-shock. (see  Electric Shock )"}
{"_id": "WikiPedia_Cardio$$$corpus_3230", "text": "\u201c Electrocution \u201d is usually referring to a macro-shock that has caused prolonged or severe disruption of normal cardiac function - ultimately leading to death. (see  Electrocution )"}
{"_id": "WikiPedia_Cardio$$$corpus_3231", "text": "Microschock requires direct electrical connection to the heart muscle and is normally illustrated using a diagram such as Figure 1 (from TGE)."}
{"_id": "WikiPedia_Cardio$$$corpus_3232", "text": "(an image is to be uploaded here shortly)"}
{"_id": "WikiPedia_Cardio$$$corpus_3233", "text": "In this scenario the patient has inadvertently contacted both a source of current (it does not have to be AC, as shown) as well as a common return pathway during an invasive cardiac medical procedure. If the current flowing is below the threshold of perception, or the patient is sedated, or anaesthetized, there may be no pain or reflex response of either arm. If the current flow continues for sufficient time, at sufficient strength, the patient may die. Because of the low current and lack of patient response, this death may be unexpected, and without any obvious cause. In practice, however, this has never been proven to have happened. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3234", "text": "To a novice, however, this scenario looks incredibly dangerous, and it is therefore worth examining in some detail."}
{"_id": "WikiPedia_Cardio$$$corpus_3235", "text": "Firstly, let's follow the path of the electric current. There is a generic source of current. This source can be either large or small, as only a small voltage is required to drive the low current for micro-shock. Such sources might be, a wall socket, a faulty item of equipment, an inappropriate item of equipment, a poorly designed item of equipment, or an item of equipment designed to deliver current into the body. Our patient has unfortunately been contacted to one such electrical source and current is dispersing through their right arm and upper torso, to eventually converge on a catheter (as labelled \u2013 but it could be a lead or wire) that is placed into their heart. This concentration of current flow at the heart muscle is the danger from micro-shock.  If the catheter is conductive (from end to end) insulated in its passage through the body, the current may follow the catheter, emerging through the skin into some other energized item of equipment. For the circuit as shown to be complete, the loop needs to also be connected to the same ground/low-potential as the equipment. Finally, the hazardous circuit is complete \u2013 current can flow and if it continues the patient is in mortal danger. Again, while this is theoretically possible this has never been proven to have actually happened. [ 3 ]  Proving this type of event after the fact is difficult in autopsy, as the cause of the fatal  ventricular fibrillation  would be unknown and the death appears to be idiopathic."}
{"_id": "WikiPedia_Cardio$$$corpus_3236", "text": "So, why has this situation not arisen? Generally, electrically conductive connections made in or around a patient's heart will be those of medical-grade electrical equipment. In countries that have a regulatory environment (example: such as much of Europe and North America) micro-shock is contemplated and the surgical equipment is regulated to prevent micro-shock. These medical-grade products are generally constructed to strict standards that limit the allowable currents flowing via such connections (applied parts). This decreases the risk to the patient and increases the margin of safety."}
{"_id": "WikiPedia_Cardio$$$corpus_3237", "text": "There has never been a documented case of microshock. A U.S. Senate inquiry in the early 1970s, sparked by exaggerated reports of thousands of U.S. hospital patients dying of microshock, heard expert testimony about the effect. A review of the evidence in the early 2000s found that not a single case had been reported in the 30 years since the Senate inquiry. [ 4 ]  Regular checks of the FDA's MAUDE database also show no evidence of this risk being manifest, before or since the review."}
{"_id": "WikiPedia_Cardio$$$corpus_3238", "text": "Based on studies with dogs by Prof Leslie Geddes in the middle of last century, it is theorised that a current as low as 10 \u03bcA ( microampere ) directly through the  heart , may send a human patient directly into  ventricular fibrillation . Of course, the exact outcome is dependent on the duration of the current, the exact position of contact, the frequency of current oscillation, and the timing of the shock with the heart's rhythm e.g. R on T phenomenon. It is feared that such a small current may be introduced unwittingly, and unobserved, creating a very perilous situation for the patient. To guard against this slim theoretical possibility then, modern medical devices include a range of protective measures to limit current in cardiac-connected circuits to the assumed safe levels of below 10 \u03bcA ( microampere ). These measures include isolated patient connections, high impedance connections and current limiting circuits. Despite the in-built protections, and lack of observed incidents, microshock continues to be a concern to many practitioners of the fields of Biomedical and Clinical Engineering."}
{"_id": "WikiPedia_Cardio$$$corpus_3239", "text": "Despite the evidence of decades of absence of reports, in any condition where electrical conductors are run into the body in proximity of the heart (i.e. cardiac catheterizations) precautions are still taken to ensure hazardous current is not introduced through these conductors and it is still regarded as a high-risk activity."}
{"_id": "WikiPedia_Cardio$$$corpus_3240", "text": "Microvasculature remodeling  refers to the alterations in a blood vessel network resulting from  arteriogenesis  and  angiogenesis .  Briefly, arteriogenesis is an increase in arterial diameter while angiogenesis is an increase in the number of capillaries either by sprouting from or splitting existing capillaries.  External events stimulate these two types of vessel growth through a combination of mechanical and chemical pathways (Prior et al., 2004)."}
{"_id": "WikiPedia_Cardio$$$corpus_3241", "text": "The  mini-maze procedures  are  cardiac surgery  procedures intended to cure  atrial fibrillation  (AF), a common disturbance of heart rhythm.  They are procedures derived from the original maze procedure developed by  James Cox, MD ."}
{"_id": "WikiPedia_Cardio$$$corpus_3242", "text": "James Cox, MD , and associates developed the \"maze\" or \"Cox maze\" procedure, an \"open-heart\"  cardiac surgery  procedure intended to eliminate  atrial fibrillation , and performed the first one in 1987. [ 1 ]  \"Maze\" refers to the series of incisions arranged in a maze-like pattern in the  atria . The intention was to eliminate AF by using incisional scars to block abnormal electrical circuits (atrial macroreentry) that AF requires. This required an extensive series of  endocardial  (from the inside of the heart) incisions through both atria, a median sternotomy (vertical incision through the breastbone) and  cardiopulmonary bypass  (heart-lung machine;  extracorporeal circulation ). A series of improvements were made, culminating in 1992 in the Cox maze III procedure, originally a cut-and-sew procedure, but later performed with cryosurgical lesions. [ 2 ]  In 2002 Maze\u00a0IV was first used combining  bipolar radiofrequency  clamps with linear cryoprobes. [ 2 ]  Cox-Maze IV is now considered to be the \"gold standard\" for effective surgical cure of AF, but the results are institution dependent. [ 3 ]   It was quite successful in eliminating AF, but had drawbacks as well. [ 4 ]  The Cox maze III is sometimes referred to as the \"Traditional maze\", the \"cut and sew maze\", or simply the \"maze\". [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3243", "text": "Efforts have since been made to equal the success of the Cox maze III while reducing surgical complexity and likelihood of complications. During the late 1990s, operations similar to the Cox maze, but with fewer  atrial  incisions, led to the use of the terms \"minimaze\", \"mini maze\" and \"mini-maze\", [ 5 ]  although these were still major operations."}
{"_id": "WikiPedia_Cardio$$$corpus_3244", "text": "A primary goal has been to perform a curative, \"maze-like\" procedure  epicardially  (from the outside of the heart), so that it could be performed on a normally beating heart, without cardiopulmonary bypass. Until recently this was not thought possible; as recently as 2004, Dr. Cox defined the mini-maze as requiring an  endocardial  approach: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3245", "text": "\"In summary, it would appear that placing the following lesions can cure most patients with  atrial fibrillation  of either type:  pulmonary vein  encircling incision, left atrial isthmus lesion with its attendant coronary sinus lesion, and the right  atrial  isthmus lesion. We call this pattern of  atrial  lesions the \"mini-maze Procedure\" ... None of the present energy sources\u2014including cryotherapy, unipolar radiofrequency, irrigated radiofrequency, bipolar radiofrequency, microwave, and laser energy\u2014are capable of creating the left atrial isthmus lesion from the epicardial surface, because of the necessity of penetrating through the circumflex  coronary artery  to reach the left atrial wall near the posterior  mitral  annulus. Therefore, the mini-maze procedure cannot be performed epicardially by means of any presently available energy source.\" [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3246", "text": "Although Dr. Cox's 2004 definition specifically excludes an epicardial approach to eliminate AF, he and others pursued this important goal, and the meaning of the term changed as successful epicardial procedures were developed. In 2002 Saltman performed a completely  endoscopic  surgical  ablation  of AF [ 7 ]  and subsequently published their results in 14 patients. [ 8 ]  These were performed epicardially, on the beating heart,  without cardiopulmonary bypass or median sternotomy . Their method came to be known as the minimaze or microwave minimaze procedure, because  microwave energy  was used to make the lesions that had previously been performed by the surgeon's scalpel."}
{"_id": "WikiPedia_Cardio$$$corpus_3247", "text": "Shortly thereafter,  Randall K. Wolf , MD and others developed a procedure using  radiofrequency  energy rather than microwave, and different, slightly larger incisions. In 2005, he published his results in the first 27 patients. [ 9 ]   This came to be known as the Wolf minimaze procedure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3248", "text": "Today, the terms \"minimaze\", \"mini-maze\", and \"mini maze\" are still sometimes used to describe open heart procedures requiring cardiopulmonary bypass and median sternotomy, but more commonly they refer to minimally invasive, epicardial procedures not requiring cardiopulmonary bypass, such as those developed by Saltman, Wolf, and others. These procedures are characterized by:"}
{"_id": "WikiPedia_Cardio$$$corpus_3249", "text": "Completely Endoscopic Microwave Ablation of Atrial Fibrillation on the Beating Heart Using Bilateral Thoracoscopy:  The microwave minimaze requires three 5\u00a0mm to 1\u00a0cm incisions on each side of the chest for the surgical tools and the  endoscope . The  pericardium  is entered, and two sterile rubber tubes are threaded behind the heart, in the transverse and oblique sinuses.  These tubes are joined, then used to guide the flexible  microwave  antenna energy source through the sinuses behind the heart, to position it for  ablation . Energy is delivered and the  atrial  tissue heated and destroyed in a series of steps as the  microwave  antenna is withdrawn behind the heart. The lesions form a \"box-like\" pattern around all four  pulmonary veins  behind the heart. The left atrial appendage is usually removed. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3250", "text": "Video-assisted Bilateral Epicardial Bipolar Radiofrequency Pulmonary Vein Isolation and Left Atrial Appendage Excision:  The Wolf minimaze requires one 5\u00a0cm and two 1\u00a0cm incisions on each side of the chest. These incisions allow the surgeon to maneuver the tools, view areas through an  endoscope , and to see the heart directly. The right side of the left  atrium  is exposed first. A clamp-like tool is positioned on the left  atrium  near the right  pulmonary veins , and the  atrial  tissue is heated between the jaws of the clamp, cauterizing the area. The clamp is removed. The  autonomic  nerves ( ganglionated plexi ) that may cause AF [ 10 ]  may be eliminated as well. Subsequently, the left side of the chest is entered. The ligament of Marshall (a vestigial structure with marked  autonomic  activity) is removed. The clamp is subsequently positioned on the left  atrium  near the left  pulmonary veins  for  ablation . Direct testing to demonstrate complete electrical isolation of the  pulmonary veins , and that the ganglionated plexi are no longer active, may be performed. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3251", "text": "Surgical ablation of atrial fibrillation with off-pump, epicardial,  high-intensity focused ultrasound :  Although the HIFU minimaze is performed epicardially, on the normally beating heart, it is also usually performed in conjunction with other  cardiac surgery , and so would not be minimally invasive in those cases. An  ultrasonic  device is positioned epicardially, on the left  atrium , around the  pulmonary veins , and intense acoustic energy is directed at the  atrium  to destroy tissue in the appropriate regions near the  pulmonary veins . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3252", "text": "The mechanism by which AF is eliminated by curative procedures such as the maze, minimaze, or  catheter ablation  is controversial.  All successful methods destroy tissue in the areas of the left  atrium  near the junction of the  pulmonary veins , hence these regions are thought to be important.  A concept gaining support is that paroxysmal AF is mediated in part by the  autonomic nervous system [ 10 ]  and that the intrinsic cardiac nervous system, which is located in these regions, plays an important role. [ 12 ]  Supporting this is the finding that targeting these autonomic sites improves the likelihood of successful elimination of AF by  catheter ablation . [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3253", "text": "The minimaze procedures are alternatives to  catheter ablation  of AF, and the patient selection criteria are similar.  Patients are considered for minimaze procedures if they have moderate or severe symptoms and have failed medical therapy; asymptomatic patients are generally not considered.  Those most likely to have a good outcome have paroxysmal (intermittent) AF, and have a heart that is relatively normal. Those with severely enlarged  atria , [ 15 ]  marked  cardiomyopathy , or severely leaking  heart valves  are less likely to have a successful result; these procedures are generally not recommended for such patients. Previous  cardiac surgery  provides technical challenges due to scarring on the outside of the heart, but does not always preclude minimaze surgery. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3254", "text": "A 2013 review found the results of the minimally-invasive mini-maze procedure to be intermediate between the standard maze procedure and catheter ablation. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3255", "text": "Long-term success of the minimaze procedures awaits a consensus. Attaining a consensus is hindered by several problems; perhaps the most important of these is incomplete or inconsistent post-procedure follow-up to determine if  atrial fibrillation  has recurred, although many reasons have been considered. [ 17 ]  It has been clearly demonstrated that longer or more intensive follow-up identifies much more recurrent  atrial fibrillation , [ 18 ]  hence a procedure with more careful follow-up will appear to be less successful. In addition, procedures continue to evolve rapidly, so long follow-up data do not accurately reflect current procedural methods. For more recent minimaze procedures, only relatively small and preliminary reports are available. With those caveats in mind, it can be said that reported short-term freedom from  atrial fibrillation  following the radiofrequency (\"Wolf\") procedure ranges from 67% to 91%  [ 8 ] [ 9 ] [ 11 ]  with longer-term results in a similar range, but limited primarily to patients with paroxysmal  atrial fibrillation . [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3256", "text": "The  monodomain model  is a reduction of the  bidomain model  of the electrical propagation in myocardial tissue.\nThe reduction comes from assuming that the intra- and extracellular domains have equal anisotropy ratios.\nAlthough not as physiologically accurate as the  bidomain model , it is still adequate in some cases, and has reduced complexity. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3257", "text": "Being  \n \n \n \n \n T \n \n \n \n {\\displaystyle \\mathbb {T} } \n \n  the spatial domain, and  \n \n \n \n T \n \n \n {\\displaystyle T} \n \n  the final time, the monodomain model can be formulated as follows [ 2 ] \n \n \n \n \n \n \n \u03bb \n \n 1 \n + \n \u03bb \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n = \n \u03c7 \n \n ( \n \n \n C \n \n m \n \n \n \n \n \n \u2202 \n v \n \n \n \u2202 \n t \n \n \n \n + \n \n I \n \n ion \n \n \n \n ) \n \n \n \n \n in\u00a0 \n \n \n T \n \n \u00d7 \n ( \n 0 \n , \n T \n ) \n , \n \n \n {\\displaystyle {\\frac {\\lambda }{1+\\lambda }}\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right)=\\chi \\left(C_{m}{\\frac {\\partial v}{\\partial t}}+I_{\\text{ion}}\\right)\\quad \\quad {\\text{in }}\\mathbb {T} \\times (0,T),}"}
{"_id": "WikiPedia_Cardio$$$corpus_3258", "text": "where  \n \n \n \n \n \n \u03a3 \n \n \n i \n \n \n \n \n {\\displaystyle \\mathbf {\\Sigma } _{i}} \n \n  is the intracellular conductivity tensor,  \n \n \n \n v \n \n \n {\\displaystyle v} \n \n  is the transmembrane potential,  \n \n \n \n \n I \n \n ion \n \n \n \n \n {\\displaystyle I_{\\text{ion}}} \n \n  is the transmembrane ionic current per unit area,  \n \n \n \n \n C \n \n m \n \n \n \n \n {\\displaystyle C_{m}} \n \n  is the membrane capacitance per unit area,  \n \n \n \n \u03bb \n \n \n {\\displaystyle \\lambda } \n \n  is the intra- to extracellular conductivity ratio, and  \n \n \n \n \u03c7 \n \n \n {\\displaystyle \\chi } \n \n  is the membrane surface area per unit volume (of tissue). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3259", "text": "The monodomain model can be easily derived from the  bidomain model . This last one can be written as [ 1 ] \n \n \n \n \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n + \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n e \n \n \n \n ) \n \n \n \n \n = \n \u03c7 \n \n ( \n \n \n C \n \n m \n \n \n \n \n \n \u2202 \n v \n \n \n \u2202 \n t \n \n \n \n + \n \n I \n \n ion \n \n \n \n ) \n \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n + \n \u2207 \n \u22c5 \n \n ( \n \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n + \n \n \n \u03a3 \n \n \n e \n \n \n \n ) \n \n \u2207 \n \n v \n \n e \n \n \n \n ) \n \n \n \n \n = \n 0 \n \n \n \n \n \n \n {\\displaystyle {\\begin{aligned}\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right)+\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v_{e}\\right)&=\\chi \\left(C_{m}{\\frac {\\partial v}{\\partial t}}+I_{\\text{ion}}\\right)\\\\\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right)+\\nabla \\cdot \\left(\\left(\\mathbf {\\Sigma } _{i}+\\mathbf {\\Sigma } _{e}\\right)\\nabla v_{e}\\right)&=0\\end{aligned}}}"}
{"_id": "WikiPedia_Cardio$$$corpus_3260", "text": "Assuming equal anisotropy ratios, i.e.  \n \n \n \n \n \n \u03a3 \n \n \n e \n \n \n = \n \u03bb \n \n \n \u03a3 \n \n \n i \n \n \n \n \n {\\displaystyle \\mathbf {\\Sigma } _{e}=\\lambda \\mathbf {\\Sigma } _{i}} \n \n , the second equation can be written as [ 1 ] \n \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n \n v \n \n e \n \n \n \n ) \n \n = \n \u2212 \n \n \n 1 \n \n 1 \n + \n \u03bb \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n . \n \n \n {\\displaystyle \\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v_{e}\\right)=-{\\frac {1}{1+\\lambda }}\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right).}"}
{"_id": "WikiPedia_Cardio$$$corpus_3261", "text": "Then, inserting this into the first bidomain equation gives the unique equation of the monodomain model [ 1 ] \n \n \n \n \n \n \n \u03bb \n \n 1 \n + \n \u03bb \n \n \n \n \u2207 \n \u22c5 \n \n ( \n \n \n \n \u03a3 \n \n \n i \n \n \n \u2207 \n v \n \n ) \n \n = \n \u03c7 \n \n ( \n \n \n C \n \n m \n \n \n \n \n \n \u2202 \n v \n \n \n \u2202 \n t \n \n \n \n + \n \n I \n \n ion \n \n \n \n ) \n \n . \n \n \n {\\displaystyle {\\frac {\\lambda }{1+\\lambda }}\\nabla \\cdot \\left(\\mathbf {\\Sigma } _{i}\\nabla v\\right)=\\chi \\left(C_{m}{\\frac {\\partial v}{\\partial t}}+I_{\\text{ion}}\\right).}"}
{"_id": "WikiPedia_Cardio$$$corpus_3262", "text": "Differently from the bidomain model, the monodomain model is usually equipped with an isolated boundary condition, which means that it is assumed that there is not current that can flow from or to the domain (usually the heart). [ 3 ] [ 4 ]  Mathematically, this is done imposing a zero transmembrane potential flux (homogeneous  Neumann boundary condition ),  i.e. : [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3263", "text": "where  \n \n \n \n \n n \n \n \n \n {\\displaystyle \\mathbf {n} } \n \n  is the unit outward normal of the domain and  \n \n \n \n \u2202 \n \n T \n \n \n \n {\\displaystyle \\partial \\mathbb {T} } \n \n  is the domain boundary."}
{"_id": "WikiPedia_Cardio$$$corpus_3264", "text": "This  applied mathematics \u2013related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3265", "text": "In  cardiology , the  P wave  on an  electrocardiogram  (ECG) represents  atrial depolarization , which results in atrial contraction, or  atrial systole ."}
{"_id": "WikiPedia_Cardio$$$corpus_3266", "text": "The P wave is a summation wave generated by the depolarization front as it transits the atria. Normally the right atrium depolarizes slightly earlier than left atrium since the depolarization wave originates in the  sinoatrial node , in the high right atrium and then travels to and through the left atrium. The depolarization front is carried through the atria along semi-specialized conduction pathways including  Bachmann's bundle  resulting in uniform shaped waves. Depolarization originating elsewhere in the atria (atrial ectopics) result in P waves with a different morphology from normal."}
{"_id": "WikiPedia_Cardio$$$corpus_3267", "text": "Peaked P waves (> 0.25 mV) suggest right atrial enlargement,  cor pulmonale , ( P pulmonale  rhythm), [ 1 ]  but have a low predictive value (~20%). [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3268", "text": "A P wave with increased amplitude can indicate  hypokalemia . [ 3 ]  It can also indicate  right atrial enlargement . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3269", "text": "A P wave with decreased amplitude can indicate  hyperkalemia . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3270", "text": "Bifid P waves (known as  P mitrale ) indicate left-atrial abnormality - e.g. dilatation  [ 6 ]  or hypertrophy. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3271", "text": "If at least three different shaped P waves can be seen in a given ECG lead tracing, this implies that even if one of them arises from the SA node, at least two others are arising elsewhere. This is taken as evidence of multiple (i.e. at least two)  ectopic foci , and is called multifocal (or more correctly, multiform) atrial rhythm if the rate is \u2264100) or  multifocal atrial tachycardia  if the rate is over 100. [ 7 ]  This appears particularly commonly in exacerbations of  chronic obstructive lung disease . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3272", "text": "If the baseline has a totally irregular form, this suggests fibrillatory waves of  atrial fibrillation  or possibly artefact; a saw tooth shaped baseline suggests the flutter waves of  atrial flutter . With either of these rhythms, if the ventricular rate is fast, the fibrillatory or flutter waves can easily be misinterpreted as P waves."}
{"_id": "WikiPedia_Cardio$$$corpus_3273", "text": "Absence of the  P wave  with a flat  baseline  may indicate:"}
{"_id": "WikiPedia_Cardio$$$corpus_3274", "text": "If P waves are not clearly delineated in the surface ECG, a  Lewis lead  may be used to better visualize P waves."}
{"_id": "WikiPedia_Cardio$$$corpus_3275", "text": "This occurs a mean of 320 ms after the end of the P wave, with a duration of 2-3 times that of the P wave and a polarity always opposite to that of the P wave. It is represented on the surface ECG by a so-called Ta wave. The clinical relevance of this is that, although a normal phenomenon, the nadir of the Ta wave can occur just after the QRS complex and cause ST depression similar to (and easily mistaken with) that occurring with disease states such as cardiac ischaemia. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3276", "text": "An  artificial cardiac pacemaker , commonly referred to as simply a  pacemaker , is an  implanted   medical device  that generates  electrical pulses  delivered by  electrodes  to one or more of the  chambers of the heart . Each pulse causes the targeted chamber(s) to  contract  and pump blood, [ 3 ]  thus regulating the function of the  electrical conduction system of the heart ."}
{"_id": "WikiPedia_Cardio$$$corpus_3277", "text": "The primary purpose of a pacemaker is to maintain an even  heart rate , either because the heart's natural  cardiac pacemaker  provides an inadequate or irregular heartbeat, or because there is a  block  in the heart's electrical conduction system. Modern pacemakers are externally programmable and allow a cardiologist to select the optimal pacing modes for individual patients. Most pacemakers are on demand, in which the stimulation of the heart is based on the dynamic demand of the  circulatory system . Others send out a fixed rate of impulses. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3278", "text": "A specific type of pacemaker, called an  implantable cardioverter-defibrillator , combines pacemaker and  defibrillator  functions in a single  implantable device . [ 5 ]  Others, called  biventricular pacemakers , have multiple electrodes stimulating different positions within the ventricles (the lower heart chambers) to improve their synchronization. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3279", "text": "Percussive pacing, also known as transthoracic mechanical pacing, is the use of the closed fist, usually on the left lower edge of the  sternum  over the  right ventricle  in the  vena cava , striking from a distance of 20 \u2013 30\u00a0cm to induce a ventricular beat (the  British Journal of Anaesthesia  suggests this must be done to raise the ventricular pressure to 10\u201315\u00a0mmHg to induce electrical activity). This is an old procedure used only as a life-saving means until an electrical pacemaker is brought to the patient. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3280", "text": "Transcutaneous pacing (TCP), also called external pacing, is recommended for the initial stabilization of hemodynamically significant  bradycardias  of all types. The procedure is performed by placing two pacing pads on the patient's chest, either in the anterior/lateral position or the anterior/posterior position. The rescuer selects the pacing rate, and gradually increases the pacing current (measured in mA) until electrical capture (characterized by a wide  QRS complex  with a tall, broad  T wave  on the  ECG ) is achieved, with a corresponding pulse. Pacing artifact on the ECG and severe muscle twitching may make this determination difficult. External pacing should not be relied upon for an extended period of time. It is an emergency procedure that acts as a bridge until transvenous pacing or other therapies can be applied. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3281", "text": "Temporary epicardial pacing is used during open heart surgery should the surgical procedure create atrio-ventricular block. The electrodes are placed in contact with the outer wall of the ventricle (epicardium) to maintain satisfactory cardiac output until a temporary transvenous electrode has been inserted. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3282", "text": "Transvenous pacing, when used for temporary pacing, is an alternative to transcutaneous pacing. A pacemaker wire is placed into a vein, under sterile conditions, and then passed into either the right atrium or right ventricle. The pacing wire is then connected to an external pacemaker outside the body. Transvenous pacing is often used as a bridge to permanent pacemaker placement. It can be kept in place until a permanent pacemaker is implanted or until there is no longer a need for a pacemaker and then it is removed."}
{"_id": "WikiPedia_Cardio$$$corpus_3283", "text": "Permanent pacing with an implantable pacemaker involves transvenous placement of one or more pacing electrodes within a chamber, or chambers, of the heart, while the pacemaker is implanted under the skin below the clavicle. The procedure is performed by incision of a suitable vein into which the electrode  lead  is inserted and passed along the vein, through the valve of the heart, until positioned in the chamber. The procedure is facilitated by  fluoroscopy  which enables the physician to view the passage of the electrode lead. After satisfactory lodgement of the electrode is confirmed, the opposite end of the electrode lead is connected to the pacemaker generator."}
{"_id": "WikiPedia_Cardio$$$corpus_3284", "text": "There are three basic types of permanent pacemakers, classified according to the number of  chambers  involved and their basic operating mechanism: [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3285", "text": "The pacemaker generator is a  hermetically sealed  device containing a power source, usually a  lithium battery , a sensing amplifier which processes the electrical manifestation of naturally occurring heart beats as sensed by the heart electrodes, the  computer  logic for the pacemaker and the output circuitry which delivers the pacing impulse to the electrodes."}
{"_id": "WikiPedia_Cardio$$$corpus_3286", "text": "Most commonly, the generator is placed below the subcutaneous fat of the chest wall, above the muscles and bones of the chest. However, the placement may vary on a case-by-case basis."}
{"_id": "WikiPedia_Cardio$$$corpus_3287", "text": "The outer casing of pacemakers is so designed that it will rarely be rejected by the body's  immune system . It is usually made of  titanium , which is inert in the body."}
{"_id": "WikiPedia_Cardio$$$corpus_3288", "text": "Leadless pacemakers are devices that are as small as a capsule and are small enough to allow the generator to be placed within the heart, therefore avoiding the need for pacing leads. [ 11 ]     As pacemaker leads can fail over time, a pacing system that avoids these components offers theoretical advantages.  Leadless pacemakers can be implanted into the heart using a steerable catheter fed into the  femoral vein  via an incision in the groin. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3289", "text": "Modern pacemakers usually have multiple functions. The most basic form monitors the heart's native electrical rhythm. When the pacemaker wire or \"lead\" does not detect heart electrical activity in the chamber \u2013 atrium or ventricle \u2013 within a normal beat-to-beat time period \u2013 most commonly one second \u2013 it will stimulate either the atrium or the ventricle with a short low voltage pulse. If it does sense electrical activity, it will hold off stimulating. This sensing and stimulating activity continues on a beat by beat basis and is called \"demand pacing\". In the case of a dual-chamber device, when the upper chambers have a spontaneous or stimulated activation, the device starts a countdown to ensure that in an acceptable \u2013 and programmable \u2013 interval, there is an activation of the ventricle, otherwise again an impulse will be delivered."}
{"_id": "WikiPedia_Cardio$$$corpus_3290", "text": "The more complex forms include the ability to sense and/or stimulate both the atrial and ventricular chambers."}
{"_id": "WikiPedia_Cardio$$$corpus_3291", "text": "From this the basic ventricular \"on demand\" pacing mode is VVI or with automatic rate adjustment for exercise VVIR \u2013 this mode is suitable when no synchronization with the atrial beat is required, as in atrial fibrillation. The equivalent atrial pacing mode is AAI or AAIR which is the mode of choice when atrioventricular conduction is intact but the  sinoatrial node  of the natural pacemaker is unreliable \u2013 sinus node disease (SND) or  sick sinus syndrome . Where the problem is  atrioventricular block  (AVB) the pacemaker is required to detect (sense) the atrial beat and after a normal delay (0.1\u20130.2 seconds) trigger a ventricular beat, unless it has already happened \u2013 this is VDD mode and can be achieved with a single pacing lead with electrodes in the right atrium (to sense) and ventricle (to sense and pace). These modes AAIR and VDD are unusual in the US but widely used in Latin America and Europe. [ 13 ] [ 14 ]  The DDDR mode is most commonly used as it covers all the options though the pacemakers require separate atrial and ventricular leads and are more complex, requiring careful programming of their functions for optimal results."}
{"_id": "WikiPedia_Cardio$$$corpus_3292", "text": "Automatic pacemakers are designed to be over-ridden by the heart's natural rate at any moment that it gets back to a non-pathologic  normal sinus rhythm  and can reinitiate influencing the electric activity in the heart when the pathologic event happens again. [ 15 ]  A \" ventricular -demand pacemaker\" produces a narrow vertical spike on the  ECG , just before a wide  QRS . The spike of an \" atrial -demand pacemaker\" appears just before the  P wave . [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3293", "text": "Comparably, a  Triggered Pacemaker  is activated immediately after an electrical activity is commenced in the heart tissue by itself. A \"ventricular triggered pacemaker\" produces the impulse just after a pulse is created in the ventricular tissue and it appears as a simultaneous spike with QRS. An \"atrial triggered pacemaker\" is the mode in which an impulse is produced immediately after an electrical event in the atrium. It appears as a  discharge  following the p wave but prior to the QRS which is commonly widened. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3294", "text": "Cardiac resynchronization therapy (CRT) is used for people with  heart failure  in whom the left and right ventricles do not contract simultaneously ( ventricular dyssynchrony ), which occurs in approximately 25\u201350% of heart failure patients. To achieve CRT, a biventricular pacemaker (BVP) is used, which can pace both the  septal  and lateral walls of the  left ventricle . By pacing both sides of the left ventricle, the pacemaker can resynchronize the ventricular contractions."}
{"_id": "WikiPedia_Cardio$$$corpus_3295", "text": "CRT devices have at least two leads, one passing through the  vena cava  and the  right atrium  into the  right ventricle  to stimulate the  septum , and another passing through the  vena cava  and the right atrium and inserted through the  coronary sinus  to pace the epicardial wall of the left ventricle. Often, for patients in normal sinus rhythm, there is also a lead in the right atrium to facilitate synchrony with the atrial contraction. Thus, the timing between the atrial and ventricular contractions, as well as between the septal and lateral walls of the left ventricle can be adjusted to achieve optimal cardiac function."}
{"_id": "WikiPedia_Cardio$$$corpus_3296", "text": "CRT devices have been shown to reduce mortality and improve quality of life in patients with heart failure symptoms; a LV ejection fraction less than or equal to 35% and QRS duration on EKG of 120\u00a0ms or greater. [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3297", "text": "Biventricular pacing alone is referred to as CRT-P (for pacing). For selected patients at risk of arrhythmias, CRT can be combined with an  implantable cardioverter-defibrillator  (ICD): such devices, known as CRT-D (for defibrillation), also provide effective protection against life-threatening arrhythmias. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3298", "text": "Conventional placement of ventricular leads in or around the tip or  apex  of the right ventricle, or RV apical pacing, can have negative effects on heart function. It has been associated with increased risk of  atrial fibrillation ,  heart failure , weakening of the heart muscle and potentially shorter life expectancy.  His bundle pacing  (HBP) leads to a more natural or perfectly natural ventricular activation and has generated strong research and clinical interest. By stimulating the  His\u2013Purkinje  fiber network directly with a special lead and placement technique, HBP causes a synchronized and therefore more effective ventricular activation and avoids long-term heart muscle disease. HBP in some cases can also correct  bundle branch block  patterns. [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3299", "text": "A major step forward in pacemaker function has been to attempt to mimic nature by utilizing various inputs to produce a rate-responsive pacemaker using parameters such as the  QT interval , pO 2  \u2013 pCO 2  (dissolved  oxygen  or  carbon dioxide  levels) in the arterial-venous system, physical activity as determined by an  accelerometer ,  body temperature ,  ATP  levels,  adrenaline , etc.\nInstead of producing a static, predetermined heart rate, or intermittent control, such a pacemaker, a 'Dynamic Pacemaker', could compensate for both actual respiratory loading and potentially anticipated respiratory loading. The first dynamic pacemaker was invented by Anthony Rickards of the  National Heart Hospital , London, UK, in 1982. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3300", "text": "Dynamic pacemaking technology could also be applied to future  artificial hearts . Advances in transitional tissue welding would support this and other artificial organ/joint/tissue replacement efforts. Stem cells may be of interest in transitional tissue welding. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3301", "text": "Many advancements have been made to improve the control of the pacemaker once implanted. Many of these have been made possible by the transition to  microprocessor  controlled pacemakers. Pacemakers that control not only the ventricles but the  atria  as well have become common. Pacemakers that control both the atria and ventricles are called dual-chamber pacemakers. Although these dual-chamber models are usually more expensive, timing the contractions of the atria to precede that of the ventricles improves the pumping efficiency of the heart and can be useful in congestive heart failure."}
{"_id": "WikiPedia_Cardio$$$corpus_3302", "text": "Rate responsive pacing allows the device to sense the physical activity of the patient and respond appropriately by increasing or decreasing the base pacing rate via rate response algorithms."}
{"_id": "WikiPedia_Cardio$$$corpus_3303", "text": "The DAVID trials [ 24 ]  have shown that unnecessary pacing of the right ventricle can exacerbate  heart failure  and increases the incidence of atrial fibrillation. The newer dual-chamber devices can keep the amount of right ventricle pacing to a minimum and thus prevent worsening of the heart disease."}
{"_id": "WikiPedia_Cardio$$$corpus_3304", "text": "A pacemaker may be implanted whilst a person is awake using  local anesthetic  to numb the skin with or without  sedation , or asleep using a  general anesthetic . [ 25 ]  An antibiotic is usually given to reduce the risk of infection. [ 25 ]   Pacemakers are generally implanted in the front of the chest in the region of the left or right shoulder.  The skin is prepared by clipping or shaving any hair over the implant site before cleaning the skin with a disinfectant such as  chlorhexidine .  An incision is made below the collar bone and a space or pocket is created under the skin to house the pacemaker generator.  This pocket is usually created just above the  pectoralis major  muscle (prepectoral), but in some cases the device may be inserted beneath the muscle (submuscular). [ 26 ]  The  lead or leads  are fed into the heart through a large vein guided by X-ray imaging ( fluoroscopy ). The tips of the leads may be positioned within the  right ventricle , the  right atrium , or the coronary sinus, depending on the type of pacemaker required. [ 25 ]  Surgery is typically completed within 30 to 90 minutes.  Following implantation, the surgical wound should be kept clean and dry until it has healed.  Some movements of the shoulder within a few weeks of insertion carry a risk of dislodging the pacemaker leads. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3305", "text": "The batteries within a pacemaker generator typically last 5 to 10 years. When the batteries are nearing the end of life, the generator is replaced in a procedure that is usually simpler than a new implant. Replacement involves making an incision to remove the existing device, disconnecting the leads from the old device and reconnecting them to a new generator, reinserting the new device and closing the skin. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3306", "text": "Once the pacemaker is implanted, it is periodically checked to ensure the device is operational and performing appropriately; the device can be checked as often as is deemed necessary. Routine pacemaker checks are typically done in-office every six months, though will vary depending upon patient/device status and remote monitoring availability. Newer pacemaker models can also be interrogated remotely, with the patient transmitting their pacemaker data using a transmitter at home connected to a cellular telephone network."}
{"_id": "WikiPedia_Cardio$$$corpus_3307", "text": "During in-office follow-up, diagnostic tests may include:"}
{"_id": "WikiPedia_Cardio$$$corpus_3308", "text": "A patient's lifestyle is usually not modified to any great degree after the insertion of a pacemaker. There are a few activities that are unwise, such as full-contact sports and exposure of the pacemaker to intense magnetic fields."}
{"_id": "WikiPedia_Cardio$$$corpus_3309", "text": "The pacemaker patient may find that some types of everyday actions need to be modified. For instance, the shoulder harness of a vehicle  seatbelt  may be uncomfortable if it falls across the pacemaker insertion site. Women will not be able to wear bras for a while after the operation, and later might have to wear bras with wide shoulder straps."}
{"_id": "WikiPedia_Cardio$$$corpus_3310", "text": "For some sports and physical activities, special pacemaker protection can be worn to prevent possible injuries, or damage to the pacemaker leads."}
{"_id": "WikiPedia_Cardio$$$corpus_3311", "text": "Pacemakers may be affected by  magnetic  or  electromagnetic fields , and  ionising  and  acoustic radiation . However, a 2013 study found that \"The overall risk of clinically significant adverse events related to EMI (electromagnetic interference) in recipients of CIEDs (cardiovascular implantable electronic devices) is very low. Therefore, no special precautions are needed when household appliances are used. Environmental and industrial sources of EMI are relatively safe when the exposure time is limited and distance from the CIEDs is maximized. The risk of EMI-induced events is highest within the hospital environment.\" [ 27 ]  The study lists and tabulates many sources of interference, and many different potential effects: damage to circuitry, asynchronous pacing, etc. Some sources of hazard in older devices have been eliminated in newer ones."}
{"_id": "WikiPedia_Cardio$$$corpus_3312", "text": "Activities involving strong  magnetic fields  should be avoided. This includes activities such as  arc welding  with certain types of equipment, [ 28 ]  and maintaining heavy equipment that may generate strong magnetic fields. Some medical procedures, particularly  magnetic resonance imaging  (MRI), involve very strong magnetic fields or other conditions that may damage pacemakers."}
{"_id": "WikiPedia_Cardio$$$corpus_3313", "text": "However, many modern pacemakers are specified to be  MR conditional or MRI conditional , safe to use during MRI subject to certain conditions. [ 29 ]  The first to be so specified was the  Medtronic  Revo MRI SureScan, approved by the US FDA in February 2011, [ 30 ]  which was the first to be specified as MR conditional. [ 31 ] [ 32 ]  There are several conditions to use of MR Conditional pacemakers, including certain patients' qualifications and scan settings. An MRI conditional device has to have MRI settings enabled before a scan, and disabled afterwards. [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3314", "text": "As of 2014 [update]  the five most commonly used cardiac pacing device manufacturers (covering more than 99% of the US market) made FDA-approved MR-conditional pacemakers. [ 34 ]  The use of MRI may be ruled out by the patient having an older, non-MRI Conditional pacemaker, or by having old pacing wires inside the heart, no longer connected to a pacemaker."}
{"_id": "WikiPedia_Cardio$$$corpus_3315", "text": "A 2008 US study found [ 35 ]  that the magnetic field created by some headphones used with portable music players or cellphones may cause interference if placed very close to some pacemakers."}
{"_id": "WikiPedia_Cardio$$$corpus_3316", "text": "In addition, according to the  American Heart Association , some home devices have the potential to occasionally inhibit a single beat. Cellphones do not seem to damage pulse generators or affect how the pacemaker works. [ 36 ]  It is recommended that objects containing magnets, or generating a significant magnetic field, should not be in close proximity to a pacemaker. Induction cooktops, in particular, can pose a risk. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3317", "text": "Before medical procedures, the patient should inform all medical personnel that they have a pacemaker. Having a pacemaker does not imply that a patient requires the use of  antibiotics  to be administered before procedures such as dental work. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3318", "text": "A panel of the  Heart Rhythm Society , a US specialist organization based in Washington, DC, deemed that it was legal and ethical to honor requests by patients, or by those with legal authority to make decisions for patients, to deactivate implanted cardiac devices. Lawyers say that the legal situation is similar to removing a feeding tube, though as of 2010 [update]  there was no legal precedent involving pacemakers in the United States. A patient in many jurisdictions (including the US) is deemed to have a right to refuse or discontinue treatment, including a pacemaker that keeps them alive. Physicians have a right to refuse to turn it off, but are advised by the HRS panel that they should refer the patient to a physician who will. [ 39 ] [ 40 ]  Some patients consider that hopeless, debilitating conditions, such as severe strokes or late-stage dementia, can cause so much suffering that they would prefer not to prolong their lives with supportive measures. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3319", "text": "Security and privacy concerns have been raised with pacemakers that allow wireless communication. Unauthorized third parties may be able to read patient records contained in the pacemaker, or reprogram the devices, as has been demonstrated by a team of researchers. [ 42 ]  The demonstration worked at short range; they did not attempt to develop a long range antenna. The proof of concept exploit helps demonstrate the need for better security and patient alerting measures in remotely accessible medical implants. [ 42 ]  In response to this threat, Purdue University and Princeton University researchers have developed a prototype firewall device, called MedMon, which is designed to protect wireless medical devices such as pacemakers and insulin pumps from attackers. [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3320", "text": "Complications from having  surgery  to implant a  pacemaker  are uncommon (each 1-3% approximately), but could include: infection where the pacemaker is implanted or in the bloodstream;  allergic reaction  to the dye or  anesthesia  used during the procedure; swelling, bruising or bleeding at the generator site, or around the heart, especially if the patient is taking  blood thinners , elderly, of thin frame or otherwise on chronic  steroid  use. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3321", "text": "A possible complication of dual-chamber artificial pacemakers is 'pacemaker-mediated tachycardia' (PMT), a form of reentrant tachycardia. In PMT, the artificial pacemaker forms the anterograde (atrium to ventricle) limb of the circuit and the atrioventricular (AV) node forms the retrograde limb (ventricle to atrium) of the circuit. [ 46 ]  Treatment of PMT typically involves reprogramming the pacemaker. [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3322", "text": "Another possible complication is \"pacemaker-tracked tachycardia,\" where a  supraventricular tachycardia  such as  atrial fibrillation  or  atrial flutter  is tracked by the pacemaker and produces beats from a ventricular lead. [ 47 ]  This is becoming exceedingly rare as newer devices are often programmed to recognize supraventricular tachycardias and switch to non-tracking modes. [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3323", "text": "It is important to consider leads as a potential nidus for  thromboembolic  events. The leads are small-diameter wires from the pacemaker to the implantation site in the heart muscle, and are usually placed intravenously through the  subclavian vein  in order to access the right atrium. Placing a foreign object within the venous system in such a manner may disrupt blood-flow and allow for thrombus formation. Therefore, patients with pacemakers may need to be placed on  anti-coagulation therapy to avoid potential life-threatening thrombosis or embolus. [ 49 ] [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3324", "text": "These leads may also damage the  tricuspid valve leaflets , either during placement or through wear and tear over time. This can lead to  tricuspid regurgitation  and  right-sided heart failure , which may require  tricuspid valve replacement . [ 51 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3325", "text": "Sometimes leads will need to be removed. The most common reason for lead removal is infection; however, over time, leads can degrade due to a number of reasons such as lead flexing. [ 52 ]  Changes to the programming of the pacemaker may overcome lead degradation to some extent. However, a patient who has several pacemaker replacements over a decade or two in which the leads were reused may require lead replacement surgery."}
{"_id": "WikiPedia_Cardio$$$corpus_3326", "text": "Lead replacement may be done in one of two ways. Insert a new set of leads without removing the current leads (not recommended as it provides additional obstruction to blood flow and heart valve function) or remove the current leads and then insert replacements. The lead removal technique will vary depending on the surgeon's estimation of the probability that simple traction will suffice to more complex procedures. Leads can normally be disconnected from the pacemaker easily, which is why device replacement usually entails simple surgery to access the device and replace it by simply unhooking the leads from the device to replace and hooking the leads to the new device. The possible complications, such as perforation of the heart wall, come from removing the lead{s} from the patient's body."}
{"_id": "WikiPedia_Cardio$$$corpus_3327", "text": "The free end of a pacemaker lead is actually implanted into the heart muscle with a miniature screw or anchored with small plastic hooks called tines. The longer the leads have been implanted (starting from a year or two), the more likely that they will have additional attachments to the patient's body at various places in the pathway from device to heart muscle, since the body tends to incorporate foreign devices into tissue. In some cases, for a lead that has been inserted for a short amount of time, removal may involve simple traction to pull the lead from the body. Removal in other cases is typically done with a laser or cutting device which threads like a cannula with a cutting edge over the lead and is moved down the lead to remove any organic attachments with tiny cutting lasers or similar device. [ 53 ] [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3328", "text": "Pacemaker lead malposition in various locations has been described in the literature. Treatment varies, depending on the location of the pacer lead and symptoms. [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3329", "text": "Another possible complication called  twiddler's syndrome  occurs when a patient manipulates the pacemaker and causes the leads to be removed from their intended location and causes possible stimulation of other nerves."}
{"_id": "WikiPedia_Cardio$$$corpus_3330", "text": "Overall life expectancy with pacemakers is excellent, and mostly depends upon underlying diseases, presence of atrial fibrillation, age and sex at the time of first implantation. [ 56 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3331", "text": "Sometimes devices resembling pacemakers, called  implantable cardioverter-defibrillators  (ICDs) are implanted. These devices are often used in the treatment of patients at risk from sudden cardiac death. An ICD has the ability to treat many types of heart rhythm disturbances by means of pacing,  cardioversion , or  defibrillation . Some ICD devices can distinguish between ventricular fibrillation and  ventricular tachycardia  (VT), and may try to pace the heart faster than its intrinsic rate in the case of VT, to try to break the tachycardia before it progresses to ventricular fibrillation. This is known as  fast-pacing ,  overdrive pacing , or  anti-tachycardia pacing  (ATP). ATP is only effective if the underlying rhythm is ventricular tachycardia, and is never effective if the rhythm is ventricular fibrillation."}
{"_id": "WikiPedia_Cardio$$$corpus_3332", "text": "In 1889,  John Alexander MacWilliam  reported in the  British Medical Journal  (BMJ) of his experiments in which application of an electrical impulse to the human heart in  asystole  caused a  ventricular  contraction and that a heart rhythm of 60\u201370 beats per minute could be evoked by impulses applied at spacings equal to 60\u201370/minute. [ 58 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3333", "text": "In 1926,  Mark C Lidwill  of the  Royal Prince Alfred Hospital  of Sydney, supported by physicist Edgar H. Booth of the  University of Sydney , devised a portable apparatus which \"plugged into a lighting point\" and in which \"One pole was applied to a skin pad soaked in strong salt solution\" while the other pole \"consisted of a needle insulated except at its point, and was plunged into the appropriate cardiac chamber\". \"The pacemaker rate was variable from about 80 to 120 pulses per minute, and likewise the voltage variable from 1.5 to 120 volts\". [ 59 ]  In 1928, the apparatus was used to revive a  stillborn  infant at  Crown Street Women's Hospital  in Sydney, whose heart continued \"to beat on its own accord\", \"at the end of 10 minutes\" of stimulation. [ 60 ] [ 61 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3334", "text": "In 1932, American physiologist  Albert Hyman , with the help of his brother, described an electro-mechanical instrument of his own, powered by a spring-wound hand-cranked motor. Hyman himself referred to his invention as an \"artificial pacemaker\", the term continuing in use to this day. [ 62 ] [ 63 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3335", "text": "An apparent  hiatus  in the publication of research conducted between the early 1930s and  World War II  may be attributed to the public perception of interfering with nature by \"reviving the dead\". [ 64 ]  For example, \"Hyman did not publish data on the use of his pacemaker in humans because of adverse publicity, both among his fellow physicians, and due to newspaper reporting at the time. Lidwell may have been aware of this and did not proceed with his experiments in humans\". [ 61 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3336", "text": "In 1950, Canadian electrical engineer  John Hopps  designed and built the first external pacemaker based upon observations by cardio-thoracic surgeons  Wilfred Gordon Bigelow  and  John Callaghan  at  Toronto General Hospital . [ 65 ]  The device was first tested on a dog at the  University of Toronto 's Banting Institute. [ 66 ]  A substantial external device using  vacuum tube  technology to provide  transcutaneous pacing , it was somewhat crude and painful to the patient in use and, being powered from an AC wall socket, carried a potential hazard of  electrocution  of the patient and inducing  ventricular fibrillation . [ 67 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3337", "text": "A number of innovators, including  Paul Zoll , made smaller but still bulky transcutaneous pacing devices from 1952 using a large rechargeable battery as the power supply. [ 68 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3338", "text": "In 1957, William L. Weirich published the results of research performed at the  University of Minnesota . These studies demonstrated the restoration of heart rate, cardiac output and mean aortic pressures in animal subjects with complete  heart block  through the use of a  myocardial  electrode. [ 69 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3339", "text": "In 1958 Colombian doctor Alberto Vejarano Laverde and Colombian electrical engineer  Jorge Reynolds Pombo  constructed an external pacemaker, similar to those of Hopps and Zoll, weighing 45\u00a0kg and powered by a 12 volt car  lead\u2013acid battery , but connected to electrodes attached to the heart. This apparatus was successfully used to sustain a 70-year-old priest, Gerardo Florez. [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3340", "text": "The development of the  silicon   transistor  and its first commercial availability in 1956 was the pivotal event that led to the rapid development of practical cardiac pacemaking. [ 71 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3341", "text": "In 1958, engineer  Earl Bakken  of Minneapolis, Minnesota, produced the first wearable external pacemaker for a patient of  C. Walton Lillehei . This transistorized pacemaker, housed in a small plastic box, had controls to permit adjustment of pacing heart rate and output voltage and was connected to electrode  leads  which passed through the skin of the patient to terminate in electrodes attached to the surface of the  myocardium  of the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_3342", "text": "In the UK in the 1960s, Lucas Engineering in  Birmingham  was asked by Mr Abrams of The  Queen Elizabeth Hospital  to produce a prototype for a transistorised replacement for the electro-mechanical product. The team was headed by Roger Nolan, an engineer with the Lucas Group Research Centre. Nolan designed and created the first blocking oscillator and transistor-powered pacemaker. This pacemaker was worn on a belt and powered by a rechargeable sealed battery, enabling users to live a more-normal life."}
{"_id": "WikiPedia_Cardio$$$corpus_3343", "text": "One of the earliest patients to receive this Lucas pacemaker device was a woman in her early 30s. The operation was carried out in 1964 by South African cardiac surgeon Alf Gunning, [ 72 ] [ 73 ]  a student of  Christiaan Barnard . This pioneering operation took place under the guidance of cardiac consultant  Peter Sleight  at the  Radcliffe Infirmary  in Oxford and his cardiac research team at St George's Hospital in London. [ 74 ] [ 75 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3344", "text": "The first clinical implantation into a human of a fully implantable pacemaker was on October 8, 1958, [ 76 ]  at the  Karolinska Institute  in Solna,  Sweden , using a pacemaker designed by inventor  Rune Elmqvist  and surgeon  \u00c5ke Senning  (in collaboration with Elema-Sch\u00f6nander AB, later Siemens-Elema AB), connected to electrodes attached to the  myocardium  of the heart by  thoracotomy . The device failed after three hours. A second device was then implanted which lasted for two days. The world's first implantable pacemaker patient,  Arne Larsson , went on to receive 26 different pacemakers during his lifetime. He died in 2001, at the age of 86, outliving the inventor and the surgeon. [ 77 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3345", "text": "In 1959, temporary  transvenous pacing  was first demonstrated by Seymour Furman and John Schwedel, whereby the  catheter  electrode was inserted via the patient's  basilic vein . [ 78 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3346", "text": "In February 1960, an improved version of the Swedish Elmqvist design was implanted by Doctors  Orestes Fiandra  and Roberto Rubio in the Casmu 1 Hospital of  Montevideo , Uruguay. This pacemaker, the first implanted in the Americas, lasted until the patient died of other ailments, nine months later. The early Swedish-designed devices used batteries recharged by an induction coil from the outside."}
{"_id": "WikiPedia_Cardio$$$corpus_3347", "text": "Implantable pacemakers constructed by engineer  Wilson Greatbatch  entered use in humans from April 1960 following extensive  animal testing . The Greatbatch innovation varied from the earlier Swedish devices in using primary cells (a  mercury battery ) as the energy source. The first patient lived for a further 18 months."}
{"_id": "WikiPedia_Cardio$$$corpus_3348", "text": "The first use of  transvenous pacing  in conjunction with an implanted pacemaker was by  Parsonnet  in the United States, [ 79 ] [ 80 ] [ 81 ]  Lagergren in Sweden [ 82 ] [ 83 ]  and Jean-Jacques Welti in France [ 84 ]  in 1962\u201363.\nThe transvenous, or pervenous, procedure involved incision of a vein into which was inserted the  catheter  electrode lead under  fluoroscopic  guidance, until it was lodged within the  trabeculae  of the right ventricle. This became the method of choice by the mid-1960s."}
{"_id": "WikiPedia_Cardio$$$corpus_3349", "text": "Cardiothoracic surgeon  Leon Abrams  and medical engineer  Ray Lightwood  developed and implanted the first patient-controlled variable-rate heart pacemaker in 1960 at  the University of Birmingham . The first implant took place in March 1960, with two further implants the following month. These three patients made good recoveries and returned to a high quality of life. By 1966, 56 patients had undergone implantation with one surviving for over  5 + 1 \u2044 2  years. [ 85 ] [ 86 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3350", "text": "The preceding implantable devices all suffered from the unreliability and short lifetime of the available primary cell technology, mainly the  mercury battery . In the late 1960s, several companies, including  ARCO  in the US, developed  isotope-powered  pacemakers, but this development was overtaken by the development in 1971 of the  lithium iodide  cell by  Wilson Greatbatch . [ 88 ]  Lithium-iodide or lithium anode cells became the standard for pacemaker designs."}
{"_id": "WikiPedia_Cardio$$$corpus_3351", "text": "A further impediment to the reliability of the early devices was the diffusion of water vapor from body fluids through the  epoxy  resin encapsulation, affecting the electronic circuitry. This phenomenon was overcome by encasing the pacemaker generator in a hermetically sealed metal case, initially by  Telectronics  of Australia in 1969, followed by  Cardiac Pacemakers, Inc.  of  St. Paul, Minnesota  in 1972. This technology, using  titanium  as the encasing metal, became the standard by the mid-1970s."}
{"_id": "WikiPedia_Cardio$$$corpus_3352", "text": "On July 9, 1974,  Manuel A. Villafa\u00f1a  and  Anthony Adducci , the founders of  Cardiac Pacemakers, Inc.  ( Guidant ), manufactured the world's first pacemaker with a lithium anode and a lithium-iodide electrolyte solid-state battery. Lithium-iodide or lithium anode cells increased the life of pacemakers from one year to as long as eleven years, and has become the standard for pacemaker designs. They began designing and testing their implantable cardiac pacemaker powered by a new longer-life lithium battery in 1971. The first patient to receive a CPI pacemaker emerged from surgery in June 1973. [ 87 ] [ 89 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3353", "text": "Liza Morton was fitted with an implantable pacemaker at 11 days old in 1978, at Glasgow\u2019s Yorkhill hospital, Scotland. She was the youngest baby at the time  [ 90 ]   [ 91 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3354", "text": "In 2013, several firms announced devices that could be inserted via a leg catheter rather than invasive surgery. The devices are roughly the size and shape of a pill, much smaller than the size of a traditional pacemaker. Once implanted, the device's prongs contact the muscle and stabilize heartbeats. Development of this type of device was continuing. [ 92 ]  In November 2014, Bill Pike of  Fairbanks, Alaska , received a  Medtronic  Micra pacemaker in Providence St Vincent Hospital in  Portland, Oregon . D. Randolph Jones was the EP doctor. Also in 2014,  St. Jude Medical Inc.  announced the first enrollments in the company's leadless Pacemaker Observational Study evaluating the Nanostim leadless pacing technology. The Nanostim pacemaker received European  CE marking  in 2013. Post-approval implant trials were carried out in Europe. [ 93 ]  The European study was stopped after reports of six perforations that led to two patient deaths. After investigations, St Jude Medical restarted the study. [ 94 ]  In the United States, this therapy had not been approved by the FDA as of 2014 [update] . [ 95 ]  While the St Jude Nanostim and the Medtronic Micra are single-chamber pacemakers, it was anticipated that leadless dual-chamber pacing for patients with atrioventricular block would become possible with further development. [ 96 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3355", "text": "Worldwide each year, in a simple procedure to avoid explosions, thousands of pacemakers are removed from bodies to be cremated. Pacemakers with significant remaining battery life are potentially life-saving devices for people in low- and middle-income countries (LMICs). [ 97 ]  The  Institute of Medicine , a US  non-governmental organization , has reported that inadequate access to advanced cardiovascular technologies is a major contributor to cardiovascular disease morbidity and mortality in LMICs. Ever since the 1970s, multiple studies worldwide have reported on the safety and efficacy of pacemaker reuse. As of 2016 [update] , widely acceptable standards for safe pacemaker and ICD reuse had not been developed, and there continued to be legal and regulatory barriers to widespread adoption of medical device reuse. [ 98 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3356", "text": "Current and prior manufacturers of implantable pacemakers"}
{"_id": "WikiPedia_Cardio$$$corpus_3357", "text": "A  pacemaker action potential  is the kind of  action potential  that provides a reference rhythm for the network. The pacemaker potential is the slow depolarization because of sodium influx, and once threshold has been reached the continued depolarization due to calcium influx. [ 1 ]  Repolarization follows, which is due to the efflux of potassium, which allows for the membrane potential to return to its negative voltage. Additionally, the longer the action potential duration the slower the heart rate will be. [ 2 ]  This means that it takes longer for the threshold to be reached because of the slow influx of sodium and the calcium and potassium channels opening at a later time. This contrasts with  pacemaker potential  or current which drives rhythmic modulation of firing rate."}
{"_id": "WikiPedia_Cardio$$$corpus_3358", "text": "Some pacemaker action generate rhythms for the heart beat ( sino-atrial node ) or the  circadian rhythm  in the  suprachiasmatic nucleus ."}
{"_id": "WikiPedia_Cardio$$$corpus_3359", "text": "In the  pacemaking cells  of the  heart  (e.g., the  sinoatrial node ), the  pacemaker potential  (also called the  pacemaker current ) is the slow, positive increase in voltage across the  cell 's membrane, that occurs between the end of one  action potential  and the beginning of the next. It is responsible for the self-generated rhythmic firing ( automaticity ) of pacemaker cells."}
{"_id": "WikiPedia_Cardio$$$corpus_3360", "text": "The  cardiac pacemaker  is the  heart 's natural rhythm generator. It employs pacemaker  cells  that generate electrical impulses, known as  cardiac action potentials . These potentials cause the  cardiac muscle  to contract, and the rate of which these muscles contract determines the  heart rate ."}
{"_id": "WikiPedia_Cardio$$$corpus_3361", "text": "As with any other cells, pacemaker cells have an electrical charge on their membranes. This electrical charge is called the  membrane potential . After the firing of an action potential, the pacemaking cell's membrane  repolarizes  (decreases in voltage) to its  resting potential  of -60 mV. From here, the membrane gradually  depolarizes  (increases in voltage) to the  threshold potential  of -40 mV, [ 1 ]  upon which the cell would go on to fire the next action potential. The rate of depolarization is the slope: the faster voltage increases, the steeper the slopes are in graphs. The slope determines the time taken to reach the threshold potential, and thus the timing of the next action potential. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3362", "text": "In a healthy sinoatrial node (SAN, a complex tissue within the right atrium containing pacemaker cells that normally determine the intrinsic firing rate for the entire heart [ 3 ] [ 4 ] ), the pacemaker potential is the main determinant of the heart rate. Because the pacemaker potential represents the non-contracting time between heart beats ( diastole ), it is also called the  diastolic depolarization .\nThe amount of net inward current required to move the cell membrane potential during the pacemaker phase is extremely small, in the order of few pAs, but this net flux arises from time to time changing contribution of several currents that flow with different voltage and time dependence. Evidence in support of the active presence of K + , Ca 2+ , Na +  channels and Na + /K +  exchanger during the pacemaker phase have been variously reported in the literature, but several indications point to the \u201cfunny\u201d(I f ) current as one of the most important. [ 5 ] (see  funny current ). There is now substantial evidence that also sarcoplasmic reticulum (SR) Ca 2+ -transients participate to the generation of the diastolic depolarization via a process involving the Na\u2013Ca exchanger."}
{"_id": "WikiPedia_Cardio$$$corpus_3363", "text": "The rhythmic activity of some  neurons  like the  pre-B\u00f6tzinger complex  is modulated by neurotransmitters and neuropeptides, and such modulatory connectivity gives to the neurons the necessary plasticity to generating distinctive, state-dependent rhythmic patterns that depend on pacemaker potentials. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3364", "text": "The heart has several pacemakers, each which fires at its own intrinsic rate:"}
{"_id": "WikiPedia_Cardio$$$corpus_3365", "text": "The potentials will normally travel in order \nSA node \u2192 Atrioventricular node \u2192 Purkinje fibres"}
{"_id": "WikiPedia_Cardio$$$corpus_3366", "text": "Normally, all the foci will end up firing at the SA node rate, not their intrinsic rate in a phenomenon known as overdrive-suppression. Thus, in the normal, healthy heart, only the SA node intrinsic rate is observable."}
{"_id": "WikiPedia_Cardio$$$corpus_3367", "text": "However, in pathological conditions, the intrinsic rate becomes apparent. Consider a heart attack which damages the region of the heart between the SA node and the AV node."}
{"_id": "WikiPedia_Cardio$$$corpus_3368", "text": "SA node \u2192 |block| AV node \u2192 Purkinje fibres"}
{"_id": "WikiPedia_Cardio$$$corpus_3369", "text": "The other foci will not see the SA node firing; however, they will see the atrial foci. The heart will now beat at the intrinsic rate of the AV node."}
{"_id": "WikiPedia_Cardio$$$corpus_3370", "text": "The firing of the pacemaker cells is induced electrically by reaching the threshold potential of the cell membrane. The  threshold potential  is the potential an excitable cell membrane, such as a  myocyte , must reach in order to induce an action potential. [ 7 ]  This  depolarization  is caused by very small net inward currents of calcium ions across the cell membrane, which gives rise to the action potential. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3371", "text": "Bio-pacemakers are the outcome of a rapidly emerging field of research into a replacement for the  electronic pacemaker . The bio-pacemaker turns quiescent myocardial cells (e.g. atrial cells) into pacemaker cells. This is achieved by making the cells express a gene which creates a pacemaker current. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3372", "text": "The  Pan\u2013Tompkins algorithm [ 1 ]  is commonly used to detect  QRS complexes  in electrocardiographic signals ( ECG ). The QRS complex represents the ventricular  depolarization  and the main spike visible in an ECG  signal  (see figure). This feature makes it particularly suitable for measuring  heart rate , the first way to assess the heart health state. In the first derivation of  Einthoven  of a physiological heart, the QRS complex is composed by a downward deflection (Q wave), a high upward deflection (R wave) and a final downward deflection (S wave)."}
{"_id": "WikiPedia_Cardio$$$corpus_3373", "text": "The Pan\u2013Tompkins algorithm applies a series of filters to highlight the frequency content of this rapid heart depolarization and removes the background  noise . Then, it squares the signal to amplify the QRS contribution, which makes identifying the QRS complex more straightforward. Finally, it applies adaptive thresholds to detect the peaks of the filtered signal. The algorithm was proposed by  Jiapu Pan  and  Willis J. Tompkins  in 1985, in the journal IEEE Transactions on Biomedical Engineering. [ 1 ]  The performance of the method was tested on an annotated arrhythmia database ( MIT/BIH [ 2 ] [ 3 ] ) and evaluated also in presence of noise. Pan and Tompkins reported that the 99.3 percent of QRS complexes was correctly detected. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3374", "text": "As a first step, a  band-pass filter  is applied to increase the  signal-to-noise ratio . A filter bandwidth of 5-15  Hz  is suggested to maximize the QRS contribute and reduce muscle noise, baseline wander, powerline interference and the  P wave / T wave  frequency content. [ 1 ]  In the original algorithm proposed in 1985, the band-pass filter was obtained with a  low-pass filter  and a  high-pass filter  in cascade to reduce the computational cost and allow a real-time detection, while ensuring a 3  dB  passband in the 5\u201312\u00a0Hz frequency range, reasonably close to the design goal."}
{"_id": "WikiPedia_Cardio$$$corpus_3375", "text": "For a signal sampled at a frequency of 200\u00a0Hz, Pan and Tompkins suggested the filters with the following  transfer functions   \n \n \n \n H \n ( \n z \n ) \n \n \n {\\displaystyle H(z)} \n \n  in an updated version of their article: [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3376", "text": "As a third step, a derivative filter is applied to provide information about the slope of the QRS. For a signal sampled at 200\u00a0Hz, Pan and Tompkins suggested the following  transfer function : [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3377", "text": "H \n ( \n z \n ) \n = \n 0.1 \n ( \n \u2212 \n \n z \n \n \u2212 \n 2 \n \n \n \u2212 \n 2 \n \n z \n \n \u2212 \n 1 \n \n \n + \n 2 \n \n z \n \n 1 \n \n \n + \n \n z \n \n 2 \n \n \n ) \n \n \n {\\displaystyle H(z)=0.1(-z^{-2}-2z^{-1}+2z^{1}+z^{2})} \n \n for a 5-point derivative filter with gain of 0.1 and a processing delay of 2 samples."}
{"_id": "WikiPedia_Cardio$$$corpus_3378", "text": "The filtered signal is squared to enhance the dominant peaks (QRSs) and reduce the possibility of erroneously recognizing a T wave as an R peak. Then, a moving average filter is applied to provide information about the duration of the QRS complex. The number of samples to average is chosen in order to average on windows of 150 ms. [ 1 ]  The signal so obtained is called integrated signal."}
{"_id": "WikiPedia_Cardio$$$corpus_3379", "text": "In order to detect a QRS complex, the local peaks of the integrated signal are found. A peak is defined as the point in which the signal changes direction (from an increasing direction to a decreasing direction). After each peak, no peak can be detected in the next 200 ms (i.e. the lockout time). This is a physiological constraint due to the  refractory period  during which ventricular depolarization cannot occur even in the presence of a stimulus. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3380", "text": "Each fiducial mark is considered as a potential QRS. To reduce the possibility of wrongly selecting a noise peak as a QRS, each peak amplitude is compared to a threshold  ( Threshold I ) that takes into account the available information about already detected QRS and the noise level:"}
{"_id": "WikiPedia_Cardio$$$corpus_3381", "text": "T \n h \n r \n e \n s \n h \n o \n l \n \n d \n \n I \n \n \n = \n N \n o \n i \n s \n e \n L \n e \n v \n e \n \n l \n \n I \n \n \n + \n 0.25 \n ( \n S \n i \n g \n n \n a \n l \n L \n e \n v \n e \n \n l \n \n I \n \n \n \u2212 \n N \n o \n i \n s \n e \n L \n e \n v \n e \n \n l \n \n I \n \n \n ) \n \n \n {\\displaystyle Threshold_{I}=NoiseLevel_{I}+0.25(SignalLevel_{I}-NoiseLevel_{I})}"}
{"_id": "WikiPedia_Cardio$$$corpus_3382", "text": "where  NoiseLevel I  is the running estimate of the noise level in the integrated signal and  SignalLevel I  is the running estimate of the signal level in the integrated signal."}
{"_id": "WikiPedia_Cardio$$$corpus_3383", "text": "The threshold is automatically updated after detecting a new peak, based on its classification as signal or noise peak:"}
{"_id": "WikiPedia_Cardio$$$corpus_3384", "text": "S \n i \n g \n n \n a \n l \n L \n e \n v \n e \n \n l \n \n I \n \n \n = \n 0.125 \n P \n E \n A \n \n K \n \n I \n \n \n + \n 0.875 \n S \n i \n g \n n \n a \n l \n L \n e \n v \n e \n \n l \n \n I \n \n \n \n \n {\\displaystyle SignalLevel_{I}=0.125PEAK_{I}+0.875SignalLevel_{I}} \n \n (if  PEAK I  is a signal peak)"}
{"_id": "WikiPedia_Cardio$$$corpus_3385", "text": "N \n o \n i \n s \n e \n L \n e \n v \n e \n \n l \n \n I \n \n \n = \n 0.125 \n P \n E \n A \n \n K \n \n I \n \n \n + \n 0.875 \n N \n o \n i \n s \n e \n L \n e \n v \n e \n \n l \n \n I \n \n \n \n \n {\\displaystyle NoiseLevel_{I}=0.125PEAK_{I}+0.875NoiseLevel_{I}} \n \n (if  PEAK I  is a noise peak)"}
{"_id": "WikiPedia_Cardio$$$corpus_3386", "text": "where  PEAK I  is the new peak found in the integrated signal."}
{"_id": "WikiPedia_Cardio$$$corpus_3387", "text": "At the beginning of the QRS detection, a 2 seconds learning phase is needed to initialize  SignalLevel I  and  NoiseLevel I  as a percentage of the maximum and average amplitude of the integrated signal, respectively."}
{"_id": "WikiPedia_Cardio$$$corpus_3388", "text": "If a new  PEAK I  is under the  Threshold I , the noise level is updated. If  PEAK I  is above the  Threshold I , the algorithm implements a further check before confirming the peak as a true QRS, taking into consideration the information provided by the bandpass filtered signal."}
{"_id": "WikiPedia_Cardio$$$corpus_3389", "text": "In the filtered signal the peak corresponding to the one evaluated on the integrated signal is searched and compared with a threshold, calculated in a similar way to the previous step:"}
{"_id": "WikiPedia_Cardio$$$corpus_3390", "text": "T \n h \n r \n e \n s \n h \n o \n l \n \n d \n \n F \n \n \n = \n N \n o \n i \n s \n e \n L \n e \n v \n e \n \n l \n \n F \n \n \n + \n 0.25 \n ( \n S \n i \n g \n n \n a \n l \n L \n e \n v \n e \n \n l \n \n F \n \n \n \u2212 \n N \n o \n i \n s \n e \n L \n e \n v \n e \n \n l \n \n F \n \n \n ) \n \n \n {\\displaystyle Threshold_{F}=NoiseLevel_{F}+0.25(SignalLevel_{F}-NoiseLevel_{F})}"}
{"_id": "WikiPedia_Cardio$$$corpus_3391", "text": "S \n i \n g \n n \n a \n l \n L \n e \n v \n e \n \n l \n \n F \n \n \n = \n 0.125 \n P \n E \n A \n \n K \n \n F \n \n \n + \n 0.875 \n S \n i \n g \n n \n a \n l \n L \n e \n v \n e \n \n l \n \n F \n \n \n \n \n {\\displaystyle SignalLevel_{F}=0.125PEAK_{F}+0.875SignalLevel_{F}} \n \n (if  PEAK F  is a signal peak)"}
{"_id": "WikiPedia_Cardio$$$corpus_3392", "text": "N \n o \n i \n s \n e \n L \n e \n v \n e \n \n l \n \n F \n \n \n = \n 0.125 \n P \n E \n A \n \n K \n \n F \n \n \n + \n 0.875 \n N \n o \n i \n s \n e \n L \n e \n v \n e \n \n l \n \n F \n \n \n \n \n {\\displaystyle NoiseLevel_{F}=0.125PEAK_{F}+0.875NoiseLevel_{F}} \n \n (if  PEAK F  is a noise peak)"}
{"_id": "WikiPedia_Cardio$$$corpus_3393", "text": "where the final F stands for filtered signal."}
{"_id": "WikiPedia_Cardio$$$corpus_3394", "text": "The algorithm takes into account the possibility of setting too high values of  ThresholdI I  and  ThresholdI F.  A check is performed to continuously assess the RR intervals (namely the temporal interval between two consecutively QRS peaks) to overcome this issue. The average RR is computed in two ways to consider both regular and irregular heart rhythm. In the first method  RRaverage1  is computed as the mean of the last RR intervals. In the second method  RRaverage2  is computed as the mean of the last RR intervals that fell between the limits specified as:"}
{"_id": "WikiPedia_Cardio$$$corpus_3395", "text": "R \n R \n l \n o \n w \n = \n 92 \n % \n R \n R \n a \n v \n e \n r \n a \n g \n e \n 2 \n \n \n {\\displaystyle RRlow=92\\%RRaverage2}"}
{"_id": "WikiPedia_Cardio$$$corpus_3396", "text": "R \n R \n h \n i \n g \n h \n = \n 116 \n % \n R \n R \n a \n v \n e \n r \n a \n g \n e \n 2 \n \n \n {\\displaystyle RRhigh=116\\%RRaverage2}"}
{"_id": "WikiPedia_Cardio$$$corpus_3397", "text": "If no QRS is detected in a window of 166% of the average RR ( RRaverage1  or  RRaverage2 , if the heart rhythm is regular or irregular, respectively) ,  the algorithm adds the maximal peak in the window as a potential QRS and classify it considering half the values of the thresholds (both  ThresholdI I  and ThresholdI F ). This check is implemented because the temporal distance between two consecutive beats cannot physiologically change more quickly than this."}
{"_id": "WikiPedia_Cardio$$$corpus_3398", "text": "The algorithm takes particularly into consideration the possibility of a false detection of T waves. If a potential QRS falls up to a 160 ms window after the refractory period from the last correctly detected QRS complex, the algorithm evaluates if it could be a T wave with particular high amplitude. In this case, its slope is compared to that of the precedent QRS complex. If the slope is less than half the previous one, the current QRS is recognized as a T wave and discarded, and it also updates the  NoiseLevel  (both in the filtered signal and the integrated signal)."}
{"_id": "WikiPedia_Cardio$$$corpus_3399", "text": "Once the QRS complex is successfully recognized, the heart rate is computed as a function of the distance in seconds between two consecutive QRS complexes (or R peaks):"}
{"_id": "WikiPedia_Cardio$$$corpus_3400", "text": "H \n R \n \n \n \u00a0 \n ( \n \n bpm \n \n ) \n = \n \n \n 60 \n \n \n \n R \n R \n \n \n \u00a0 \n ( \n \n s \n \n ) \n \n \n \n \n \n {\\displaystyle {\\mathit {HR}}\\ ({\\text{bpm}})={60 \\over {\\mathit {RR}}\\ ({\\text{s}})}}"}
{"_id": "WikiPedia_Cardio$$$corpus_3401", "text": "where bpm stands for beats per minute. The HR is often used to compute the  heart rate variability  (HRV) a measure of the variability of the time interval between heartbeats. HRV is often used in the clinical field [ 6 ]  to diagnose and monitor pathological conditions and their treatment, but also in the  affective computing  research to study new methods to assess the emotional state of people. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3402", "text": "In  electrocardiography , the  PR interval  is the period, measured in milliseconds, that extends from the beginning of the  P wave  (the onset of  atrial   depolarization ) until the beginning of the  QRS complex  (the onset of  ventricular  depolarization); it is normally between 120 and 200 ms in duration.\nThe PR interval is sometimes termed the  PQ interval ."}
{"_id": "WikiPedia_Cardio$$$corpus_3403", "text": "Variations in the PQ interval can be associated with certain medical conditions:"}
{"_id": "WikiPedia_Cardio$$$corpus_3404", "text": "A  Pro-arrhythmic agent  is a chemical, drug, or food that promotes  cardiac arrhythmias ."}
{"_id": "WikiPedia_Cardio$$$corpus_3405", "text": "Omega 3 fatty acids . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3406", "text": "Chocolate ,  Coffee ,  Tea"}
{"_id": "WikiPedia_Cardio$$$corpus_3407", "text": "Caffeine ,  cocaine ,  beta-adrenergic agonists"}
{"_id": "WikiPedia_Cardio$$$corpus_3408", "text": "Encainide ,  Lorcainide"}
{"_id": "WikiPedia_Cardio$$$corpus_3409", "text": "Pulsed field ablation  ( PFA ) is a non-thermal (not using extreme heat or cold) method of biological ablation (removal of structure or functionality) utilizing high-amplitude pulsed (microsecond duration)  electric fields  to create irreversible  electroporation  in tissues. [ 1 ]   [ 2 ]  It is used most widely to treat tumors ( cancer ) or  cardiac arrhythmias . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3410", "text": "Atrial fibrillation  frequently results from bursts of  tachycardia  that originate in muscle bundles extending from the  atrium  to the  pulmonary veins . [ 4 ]   Pulmonary vein isolation  ablation technology  has used thermal methods ( radiofrequency ablation  or, less often,  cryoablation ) to destroy pulmonary vein cells. [ 5 ]  As with thermal methods of ablation, in pulsed field ablation, a thin, flexible tube ( catheter ) is inserted into a blood vessel in the  groin  and threaded up into the heart to  ablate  the areas of the pulmonary vein causing excessively rapid electrical signals. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3411", "text": "A major reason for recurrence of atrial fibrillation after ablation has been the belief of electrical pulmonary vein reconnection, which has not been seen for PFA. [ 7 ]  In one study, atrial fibrillation recurrence in the thermal ablation group was 39% compared to 11% in the PFA group. [ 8 ]  PFA can achieve pulmonary vein isolation faster than other ablation methods. [ 1 ] [ 8 ]   Compared to radiofrequency ablation, PFA produces lesions of greater uniformity. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3412", "text": "Cell death following PFA is usually due to  apoptosis , which is a far less damaging and  inflammatory  form of cell death than  necrosis . [ 1 ] [ 3 ]  In contrast to thermal methods of ablation, PFA specifically kills  cardiomyocytes  (cardiac muscle cells) without injuring surrounding tissues. [ 1 ] [ 2 ]  Thermal ablation methods can damage the  esophagus ,  phrenic nerve , and   coronary vessels  (as high as 5%  [ 8 ] ), which are spared by PFA. [ 1 ]  One study showed an overall complication rate of 0.7% for PFA and no occurrence of phrenic nerve, esophageal, or pulmonary vein injury. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3413", "text": "Because PFA is a relatively newer ablation technique, there is a lack of uniformity in the parameters for its delivery. [ 8 ]  Better standardization could help reduce instances of coronary artery spasm and pulmonary artery hemorrhage, which can occur. [ 8 ]  The equipment cost and lack of specialized training have limited the widespread use of PFA, making it unavailable to many patients. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3414", "text": "Recent (2024) comparisons of PFA with thermal methods have shown reduced time spent in surgery, but no superiority in safety and no better reduction of atrial fibrillation. [ 10 ]  When used in areas other than the pulmonary vein, injuries have been seen. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3415", "text": "The  Purkinje fibers , named for  Jan Evangelista Purkyn\u011b , ( English:  / p \u025c\u02d0r \u02c8 k \u026a n d\u0292 i /   pur- KIN -jee ; [ 1 ]   Czech:   [\u02c8purk\u026a\u0272\u025b]   \u24d8 ;  Purkinje tissue  or  subendocardial branches ) are located in the inner  ventricular  walls of the  heart , [ 2 ]  just beneath the  endocardium  in a space called the subendocardium. The Purkinje fibers are specialized conducting fibers composed of  electrically excitable cells . [ 3 ]  They are larger than  cardiomyocytes  with fewer myofibrils and many  mitochondria . They conduct  cardiac action potentials  more quickly and efficiently than any of the other cells in the heart's  electrical conduction system . [ 4 ]  Purkinje fibers allow the heart's conduction system to create  synchronized contractions  of its ventricles, and are essential for maintaining a consistent  heart rhythm . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3416", "text": "Purkinje fibers are a unique  cardiac  end-organ. Further  histologic  examination reveals that these fibers are split in ventricles walls. The electrical origin of atrial Purkinje fibers arrives from the  sinoatrial node ."}
{"_id": "WikiPedia_Cardio$$$corpus_3417", "text": "Given no aberrant channels, the Purkinje fibers are distinctly shielded from each other by  collagen  or the  cardiac skeleton ."}
{"_id": "WikiPedia_Cardio$$$corpus_3418", "text": "The Purkinje fibers are further specialized to rapidly conduct impulses (having numerous fast  voltage-gated   sodium channels   and  mitochondria , and fewer  myofibrils , than the surrounding muscle tissue). Purkinje fibers take up stain differently from the surrounding muscle cells because of having relatively fewer myofibrils than other cardiac cells.  The presence of glycogen around the nucleus causes Purkinje fibers to appear, on a slide, lighter and larger than their neighbors, being arranged along the longitudinal direction (parallel to the cardiac vector). They are often  binucleated cells . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3419", "text": "Heart rate is governed by many influences from the  autonomic nervous system . The Purkinje fibers do not have any known role in setting heart rate unless the  SA node  is compromised (when they can act as  pacemaker  cells). [ 7 ]  They are influenced by  electrical discharge  from the sinoatrial node."}
{"_id": "WikiPedia_Cardio$$$corpus_3420", "text": "During the  ventricular contraction  portion of the  cardiac cycle , the Purkinje fibers carry the contraction impulse from both the left and right  bundle branch  to the  myocardium  of the ventricles. [ 5 ]  This causes the muscle tissue of the ventricles to contract. This generates  force  to eject  blood  out of the heart, either to the  pulmonary circulation  from the right ventricle, or to the  systemic circulation  from the left ventricle. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3421", "text": "Purkinje fibers also have the ability of firing at a rate of 20\u201340 beats per minute if upstream conduction or pacemaking ability is compromised. [ 9 ]  In contrast, the SA node in normal state can fire at 60-100 beats per minute. [ 9 ]  In short, they generate  action potentials , but at a slower rate than the  sinoatrial node . [ 9 ]  This capability is normally suppressed. Thus, they serve as the last resort when other pacemakers fail. When a Purkinje fiber does fire, it is called a  premature ventricular contraction  or PVC, or in other situations can be a  ventricular escape ."}
{"_id": "WikiPedia_Cardio$$$corpus_3422", "text": "Purkinje fibers are named after the  Czech  scientist  Jan Evangelista Purkyn\u011b , who discovered them in 1839. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3423", "text": "The  QRS complex  is the combination of three of the graphical deflections seen on a typical  electrocardiogram (ECG or EKG) . It is usually the central and most visually obvious part of the tracing. It corresponds to the  depolarization  of the right and left  ventricles  of the heart and contraction of the large ventricular muscles."}
{"_id": "WikiPedia_Cardio$$$corpus_3424", "text": "In adults, the QRS complex normally lasts  80 to 100  ms ; in children it may be shorter. The Q, R, and S waves occur in rapid succession, do not all appear in all leads, and reflect a single event and thus are usually considered together. A  Q wave  is any downward deflection immediately following the  P wave . An  R wave  follows as an upward deflection, and the  S wave  is any downward deflection after the R wave. The  T wave  follows the S wave, and in some cases, an additional  U wave  follows the T wave."}
{"_id": "WikiPedia_Cardio$$$corpus_3425", "text": "To measure the  QRS interval  start at the end of the PR  interval  (or beginning of the Q wave) to the end of the S wave. Normally this  interval  is 0.08 to 0.10 seconds. When the duration is longer it is considered a wide QRS complex."}
{"_id": "WikiPedia_Cardio$$$corpus_3426", "text": "Depolarization of the heart  ventricles  occurs almost simultaneously, via the  bundle of His  and  Purkinje fibers . If they are working efficiently, the QRS complex duration in adults is  80 to 110  ms . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3427", "text": "Any abnormality of conduction takes longer and causes \"widened\" QRS complexes. In  bundle branch block , there can be an abnormal second upward deflection within the QRS complex. In this case, such a second upward deflection is referred to as R\u2032 (pronounced \"R  prime \"). This would be described as an RSR\u2032 pattern."}
{"_id": "WikiPedia_Cardio$$$corpus_3428", "text": "Ventricles contain more muscle mass than the atria. Therefore, the QRS complex is considerably larger than the P wave. The QRS complex is often used to determine the  axis  of the electrocardiogram, although it is also possible to determine a separate P wave axis."}
{"_id": "WikiPedia_Cardio$$$corpus_3429", "text": "The duration, amplitude, and morphology of the QRS complex are useful in diagnosing  cardiac arrhythmias ,  conduction abnormalities ,  ventricular hypertrophy ,  myocardial infarction ,  electrolyte derangements , and other disease states."}
{"_id": "WikiPedia_Cardio$$$corpus_3430", "text": "High frequency analysis  of the QRS complex may be useful for detection of coronary artery disease during an  exercise stress test . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3431", "text": "Duration longer than 45 ms might indicate  left posterior fascicular block , LVH or  LBBB . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3432", "text": "Normal Q waves, when present, represent depolarization of the  interventricular septum . For this reason, they are referred to as septal Q waves and can be appreciated in the lateral leads I, aVL, V5 and V6."}
{"_id": "WikiPedia_Cardio$$$corpus_3433", "text": "Pathologic Q waves occur when the electrical signal passes through stunned or scarred  heart muscle ; as such, they are usually markers of previous  myocardial infarctions , with subsequent fibrosis. A pathologic Q wave is defined as having a deflection amplitude of 25% or more of the subsequent R wave, or being  > 0.04 s  (40\u00a0ms) in width and  > 2 mm  in amplitude. However, diagnosis requires the presence of this pattern in more than one corresponding lead."}
{"_id": "WikiPedia_Cardio$$$corpus_3434", "text": "Looking at the precordial leads, the R wave usually progresses from showing an rS-type complex in V 1  with an increasing R and a decreasing S wave when moving toward the left side. There is usually a qR-type of complex in V 5  and V 6,  with the R-wave amplitude usually taller in V 5  than in V 6 . It is normal to have a narrow QS and rSr' patterns in V 1 , and this is also the case for qRs and R patterns in V 5  and V 6 . The  transition zone  is where the QRS complex changes from predominantly negative to predominantly positive (R/S ratio becoming >1), and this usually occurs at V 3  or V 4 . It is normal to have the transition zone at V 2  (called \"early transition\") and at V 5  (called \"delayed transition\"). [ 11 ]  In biomedical engineering, the maximum amplitude in the R wave is usually called \"R peak amplitude\", or just \"R peak\". [ 12 ] [ 13 ]  Accurate R peak detection is essential in signal processing equipment for  heart rate  measurement and it is the main feature used for  arrhythmia  detection. [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3435", "text": "The definition of  poor R wave progression  (PRWP) varies in the literature. It may be defined, for example, as R wave of less than 2\u20134\u00a0mm in leads V 3  or V 4  and/or presence of a reversed R wave progression, which is defined as R in V 4  < R in V 3  or R in V 3  < R in V 2  or R in V 2  < R in V 1 , or any combination of these. [ 11 ]   Poor R wave progression  is commonly attributed to anterior  myocardial infarction , but it may also be caused by  left bundle branch block ,  Wolff\u2013Parkinson\u2013White syndrome , right and left  ventricular hypertrophy , or a faulty ECG recording technique. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3436", "text": "R wave peak time (RWPT) represents the time from the onset of QRS complex to the peak of R wave, which is usually measured in aVL and V5 or V6 leads. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3437", "text": "R-peak time for right ventricle is measured from leads V1 or V2, where upper range of normal is 35 ms. R wave peak time for left ventricle is measured from lead V5 or V6 and 45 ms is the upper range of normal. [ 7 ]   R wave peak time is considered to be prolonged if it's more than 45 ms."}
{"_id": "WikiPedia_Cardio$$$corpus_3438", "text": "The point where the QRS complex meets the  ST segment  is the J-point. The J-point is easy to identify when the ST segment is horizontal and forms a sharp angle with the last part of the QRS complex. However, when the ST segment is sloped or the QRS complex is wide, the two features do not form a sharp angle and the location of the J-point is less clear. There is no consensus on the precise location of the J-point in these circumstances. [ 17 ]  Two possible definitions are:"}
{"_id": "WikiPedia_Cardio$$$corpus_3439", "text": "Not every QRS complex contains a Q wave, an R wave, and an S wave. By convention, any combination of these waves can be referred to as a QRS complex. However, correct interpretation of difficult ECGs requires exact labeling of the various waves. Some authors use lowercase and capital letters, depending on the relative size of each wave. For example, an Rs complex would be positively deflected, while an rS complex would be negatively deflected. If both complexes were labeled RS, it would be impossible to appreciate this distinction without viewing the actual ECG."}
{"_id": "WikiPedia_Cardio$$$corpus_3440", "text": "Monomorphic refers to all QRS waves in a single lead being similar in shape. Polymorphic means that the QRS change from complex to complex. [ 19 ]  These terms are used in the description of  ventricular tachycardia ."}
{"_id": "WikiPedia_Cardio$$$corpus_3441", "text": "A common algorithm used for QRS complex detection is the  Pan-Tompkins [ 20 ]  algorithm (or method); another is based on the  Hilbert transform . [ 21 ] [ 22 ] [ 23 ] [ 24 ]  Numerous other algorithms have been proposed and investigated. [ 25 ]  In recent research, heart beat detection methods based on  visibility graphs  have been introduced, enabling fast and sample-precise R-peak annotation even in noisy ECG. [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3442", "text": "The  QT interval  is a measurement made on an  electrocardiogram  used to assess some of the electrical properties of the  heart .  It is calculated as the time from the start of the  Q wave  to the end of the  T wave , and approximates to the time taken from when the  cardiac ventricles  start to contract to when they finish relaxing. An abnormally long or abnormally short QT interval is associated with an increased risk of developing  abnormal heart rhythms  and  sudden cardiac death . Abnormalities in the QT interval can be caused by  genetic  conditions such as  long QT syndrome , by certain medications such as  sotalol  or  pitolisant , by disturbances in the concentrations of certain  salts  within the blood such as  hypokalaemia , or by  hormonal imbalances  such as  hypothyroidism ."}
{"_id": "WikiPedia_Cardio$$$corpus_3443", "text": "The QT interval is most commonly measured in  lead  II for evaluation of serial ECGs, with leads I and V5 being comparable alternatives to lead II. Leads III, aVL and V1 are generally avoided for measurement of QT interval. [ 1 ]  The accurate measurement of the QT interval is subjective [ 2 ]  because the end of the T wave is not always clearly defined and usually merges gradually with the baseline. QT interval in an ECG complex can be measured manually by different methods, such as the threshold method, in which the end of the T wave is determined by the point at which the component of the T wave merges with the isoelectric baseline, or the tangent method, in which the end of the T wave is determined by the intersection of a tangent line extrapolated from the T wave at the point of maximum downslope to the isoelectric baseline. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3444", "text": "With the increased availability of digital ECGs with simultaneous 12-channel recording, QT measurement may also be done by the 'superimposed median beat' method. In the superimposed median beat method, a median ECG complex is constructed for each of the 12 leads. The 12 median beats are superimposed on each other and the QT interval is measured either from the earliest onset of the Q wave to the latest offset of the T wave or from the point of maximum convergence for the Q wave onset to the T wave offset. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3445", "text": "The QT interval changes in response to the  heart rate  - as heart rate increase the QT interval shortens.  These changes make it harder to compare QT intervals measured at different heart rates.  To account for this, and thereby improve the reliability of QT measurement, the QT interval can be corrected for heart rate (QTc) using  a variety of mathematical formulae, a process often performed automatically by modern ECG recorders."}
{"_id": "WikiPedia_Cardio$$$corpus_3446", "text": "The most commonly used QT correction formula is the  Bazett's formula , [ 5 ]  named after  physiologist   Henry Cuthbert Bazett  (1885\u20131950), [ 6 ]  calculating the heart rate-corrected QT interval (QTcB)."}
{"_id": "WikiPedia_Cardio$$$corpus_3447", "text": "Bazett's formula is based on observations from a study in 1920. \nBazett's formula is often given in a form that returns QTc in dimensionally suspect units, square root of seconds. The dimensionally correct form of Bazett's formula is:"}
{"_id": "WikiPedia_Cardio$$$corpus_3448", "text": "where QTc B  is the QT interval corrected for heart rate, and RR is the interval from the onset of one  QRS complex  to the onset of the next QRS complex. This dimensionally correct formula returns the QTc in the same units as QT, generally milliseconds. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3449", "text": "In some popular forms of this formula, it is assumed that QT is measured in milliseconds and that RR is measured in seconds, often derived from the heart rate (HR) as 60/HR. Therefore, the result will be given in seconds per square root of milliseconds. [ 8 ]  However, reporting QTc using this formula creates a \"requirement regarding the units in which the original QT and RR are measured.\" [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3450", "text": "In either form, Bazett's non-linear QT correction formula is generally not considered accurate, as it over-corrects at high heart rates and under-corrects at low heart rates. [ 8 ]  Bazett's correction formula is one of the most suitable QT correction formulae for neonates. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3451", "text": "Fridericia [ 10 ]  had proposed an alternative correction formula (QTcF) using the cube-root of RR."}
{"_id": "WikiPedia_Cardio$$$corpus_3452", "text": "The Framingham correction, also called as Sagie's formula based on the  Framingham Heart Study , which used long-term cohort data of over 5,000 subjects, is considered a better [ 11 ]  method. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3453", "text": "Again, here  QT  and  QTlc  are in milliseconds and  RR  is measured in seconds."}
{"_id": "WikiPedia_Cardio$$$corpus_3454", "text": "A  retrospective study  suggests that Fridericia's method and the Framingham method may produce results most useful for stratifying the 30-day and 1-year risks of mortality. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3455", "text": "Definitions of normal QTc vary from being equal to or less than 0.40\u00a0s (\u2264\u00a0400\u00a0ms), [ 13 ]  0.41\u00a0s (\u2264\u00a0410\u00a0ms), [ 15 ]  0.42\u00a0s (\u2264\u00a0420\u00a0ms) [ 14 ]  or 0.44\u00a0s (\u2264\u00a0440\u00a0ms). [ 16 ]  For risk of  sudden cardiac death , \"borderline QTc\" in males is 431\u2013450\u00a0ms; and, in females, 451\u2013470\u00a0ms. An \"abnormal\" QTc in males is a QTc above 450\u00a0ms; and, in females, above 470\u00a0ms. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3456", "text": "If there is not a very high or low heart rate, the upper limits of QT can roughly be estimated by taking QT\u00a0=\u00a0QTc at a heart rate of 60 beats per minute (bpm), and subtracting 0.02\u00a0s from QT for every 10\u00a0bpm increase in heart rate. For example, taking normal QTc\u00a0\u2264\u00a00.42\u00a0s, QT would be expected to be 0.42\u00a0s or less at a heart rate of 60\u00a0bpm. For a heart rate of 70\u00a0bpm, QT would roughly be expected to be equal to or below 0.40\u00a0s. Likewise, for 80\u00a0bpm, QT would roughly be expected to be equal to or below 0.38\u00a0s. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3457", "text": "Prolonged QTc causes premature action potentials during the late phases of depolarization. This increases the risk of developing ventricular arrhythmias, including fatal  ventricular fibrillation . [ 18 ]  Higher rates of prolonged QTc are seen in females, older patients, high systolic blood pressure or heart rate, and short stature. [ 19 ]  Prolonged QTc is also associated with ECG findings called  Torsades de Pointes , which are known to degenerate into ventricular fibrillation, associated with higher mortality rates. There are many causes of prolonged QT intervals, acquired causes being more common than genetic. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3458", "text": "An abnormally prolonged QT interval could be due to  long QT syndrome , whereas an abnormally shortened QT interval could be due to  short QT syndrome ."}
{"_id": "WikiPedia_Cardio$$$corpus_3459", "text": "The QTc length is associated with variations in the  NOS1AP  gene. [ 21 ]  The  autosomal recessive  syndrome of Jervell and Lange-Nielsen is characterized by a prolonged QTc interval in conjunction with  sensorineural hearing loss ."}
{"_id": "WikiPedia_Cardio$$$corpus_3460", "text": "Prolongation of the QT interval may be due to an  adverse drug reaction . [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3461", "text": "Antipsychotics  (especially first generation/\"typical\")"}
{"_id": "WikiPedia_Cardio$$$corpus_3462", "text": "DMARDs and antimalarial drugs"}
{"_id": "WikiPedia_Cardio$$$corpus_3463", "text": "Antibiotics"}
{"_id": "WikiPedia_Cardio$$$corpus_3464", "text": "Other drugs"}
{"_id": "WikiPedia_Cardio$$$corpus_3465", "text": "Some second-generation antihistamines, such as  astemizole , have this effect. The mechanism of action of certain antiarrhythmic drugs, like  amiodarone  or  sotalol , involve intentional pharmacological QT prolongation. In addition, high blood alcohol concentrations prolong the QT interval. [ 30 ]  A possible interaction between  selective serotonin reuptake inhibitors  and  thiazide  diuretics is associated with QT prolongation. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3466", "text": "Hypothyroidism , a condition of low function of the  thyroid  gland, can cause QT prolongation at the  electrocardiogram .  Acute hypocalcemia causes prolongation of the QT interval, which may lead to ventricular dysrhythmias."}
{"_id": "WikiPedia_Cardio$$$corpus_3467", "text": "A shortened QT can be associated with  hypercalcemia . [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3468", "text": "Since 2005, the FDA and European regulators have required that nearly all new molecular entities be evaluated in a Thorough QT (TQT) or similar study to determine a drug's effect on the QT interval. [ 33 ]  The TQT study serves to assess the potential arrhythmia liability of a drug.  Traditionally, the QT interval had been evaluated by having an individual human reader measure approximately nine cardiac beats per clinical timepoint.  However, a substantial portion of drug approvals after 2010 have incorporated a partially automated approach, blending automated software algorithms with expert human readers reviewing a portion of the cardiac beats, to enable the assessment of significantly more beats in order to improve precision and reduce cost. [ 34 ]  In 2014, an industrywide consortium consisting of the FDA,  iCardiac Technologies  and other organizations released the results of a seminal study indicating how waivers from TQT studies can be obtained by the assessment of early phase data. [ 35 ]   As the pharmaceutical industry has gained experience in performing TQT studies, it has also become evident that traditional QT correction formulas such as QTcF, QTcB, and QTcLC may not always be suitable for evaluation of drugs impacting autonomic tone. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3469", "text": "Electrocardiography is a safe and noninvasive tool that can be used to identify those with a higher risk of mortality. In the general population, there has been no consistent evidence that prolonged QTc interval in isolation is associated with an increase in mortality from cardiovascular disease. [ 37 ]  However, several studies [ which? ]  have examined prolonged QT interval as a predictor of mortality for diseased subsets of the population."}
{"_id": "WikiPedia_Cardio$$$corpus_3470", "text": "Rheumatoid arthritis is the most common inflammatory arthritis. [ 38 ]  Studies have linked rheumatoid arthritis with increased death from cardiovascular disease. [ 38 ] \nIn a 2014 study, [ 18 ]  Panoulas et al. found a 50\u00a0ms increase in QTc interval increased the odds of all-cause mortality by 2.17 in patients with rheumatoid arthritis. Patients with the highest QTc interval (>\u00a0424\u00a0ms) had higher mortality than those with a lower QTc interval. The association was lost when calculations were adjusted for C-reactive protein levels. The researchers proposed that inflammation prolonged the QTc interval and created arrhythmias that were associated with higher mortality rates. However, the mechanism by which C-reactive protein is associated with the QTc interval is still not understood."}
{"_id": "WikiPedia_Cardio$$$corpus_3471", "text": "Compared to the general population, type 1 diabetes may increase the risk of mortality, due largely to an increased risk of cardiovascular disease. [ 19 ] [ 39 ]  Almost half of patients with type 1 diabetes have a prolonged QTc interval (>\u00a0440\u00a0ms). [ 19 ]  Diabetes with a prolonged QTc interval was associated with a 29% mortality over 10 years in comparison to 19% with a normal QTc interval. [ 19 ]  Anti-hypertensive drugs increased the QTc interval, but were not an independent predictor of mortality. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3472", "text": "QT interval dispersion (QTd) is the maximum QT interval minus the minimum QT interval, and is linked with ventricular repolarization. [ 40 ]  A QTd over 80\u00a0ms is considered abnormally prolonged. [ 41 ]  Increased QTd is associated with mortality in type 2 diabetes. [ 41 ]  \nQTd is a better predictor of cardiovascular death than QTc, which was unassociated with mortality in type 2 diabetes. [ 41 ]  QTd higher than 80\u00a0ms had a relative risk of 1.26 of dying from cardiovascular disease compared to a normal QTd."}
{"_id": "WikiPedia_Cardio$$$corpus_3473", "text": "QT interval variability  (QTV) refers to the physiological phenomenon of beat-to-beat fluctuations in  QT interval  of  electrocardiograms . Increased QTV appears to be a marker of arrhythmic and cardiovascular death; it may also play a role for noninvasive assessment of sympathetic nervous system activity. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3474", "text": "Other terms used include: \"QT variability\", \"beat-to-beat variability of ventricular repolarization (BRV)\""}
{"_id": "WikiPedia_Cardio$$$corpus_3475", "text": "Under normal resting conditions, beat-to-beat changes in QT interval are very small with a standard deviation typically below 5 ms. Digital high resolution ECG sampled at 300 Hz or higher and dedicated computer algorithms are required for QTV assessment. [ 2 ]  Template-based algorithms that use parts of, or the entire ECG waveform usually deliver good results; [ 3 ]  template stretching or warping techniques [ 4 ]  perform comparably well in the presence of noise."}
{"_id": "WikiPedia_Cardio$$$corpus_3476", "text": "A number of metrics have been proposed for QTV quantification. The QT variability index (QTVi) has been most frequently reported in the literature: \n \n \n \n \n Q \n T \n V \n i \n = \n log \n \u2061 \n \n \n \n S \n D \n Q \n \n T \n \n 2 \n \n \n \n / \n \n ( \n Q \n \n T \n \n m \n e \n a \n n \n \n \n \n ) \n \n 2 \n \n \n \n \n S \n D \n H \n \n R \n \n 2 \n \n \n \n / \n \n ( \n H \n \n R \n \n m \n e \n a \n n \n \n \n \n ) \n \n 2 \n \n \n \n \n \n \n \n {\\displaystyle QTVi=\\log {\\frac {SDQT^{2}/(QT_{mean})^{2}}{SDHR^{2}/(HR_{mean})^{2}}}} \n \n , where  \n \n \n \n S \n D \n Q \n T \n \n \n {\\displaystyle SDQT} \n \n ,  \n \n \n \n S \n D \n H \n R \n \n \n {\\displaystyle SDHR} \n \n ,  \n \n \n \n Q \n \n T \n \n m \n e \n a \n n \n \n \n \n \n {\\displaystyle QT_{mean}} \n \n , and  \n \n \n \n H \n \n R \n \n m \n e \n a \n n \n \n \n \n \n {\\displaystyle HR_{mean}} \n \n  denote standard deviation and mean of QT interval and heart rate time series, respectively. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3477", "text": "More advanced approaches that take into account the relationship between QTV and  heart rate variability  include vector autoregressive process models [ 6 ]  and information domain approaches. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3478", "text": "Refractoriness  is the fundamental property of any object of  autowave  nature (especially  excitable medium ) not responding to stimuli, if the object stays in the specific  refractory state . In common sense,  refractory period  is the characteristic recovery time, a period that is associated with the motion of the image point on the left branch of the isocline  \n \n \n \n \n \n \n u \n \u02d9 \n \n \n \n = \n 0 \n \n \n {\\displaystyle {\\dot {u}}=0} \n \n [ B: 1 ]  (for more details, see also  Reaction\u2013diffusion  and  Parabolic partial differential equation )."}
{"_id": "WikiPedia_Cardio$$$corpus_3479", "text": "In  physiology , [ B: 2 ]  a  refractory period  is a period of time during which an organ or cell is incapable of repeating a particular action, or (more precisely) the amount of time it takes for an  excitable membrane  to be ready for a second  stimulus once it returns to its resting state following an excitation. It most commonly refers to electrically excitable muscle cells or neurons.  Absolute refractory period  corresponds to depolarization and repolarization, whereas  relative refractory period  corresponds to hyperpolarization."}
{"_id": "WikiPedia_Cardio$$$corpus_3480", "text": "After initiation of an action potential, the refractory period is defined two ways:\nThe absolute refractory period coincides with nearly the entire duration of the action potential. In  neurons , it is caused by the  inactivation  of the  voltage-gated sodium channels  that originally opened to depolarize the membrane. These channels remain inactivated until the membrane hyperpolarizes. The channels then close, de-inactivate, and regain their ability to open in response to stimulus."}
{"_id": "WikiPedia_Cardio$$$corpus_3481", "text": "The relative refractory period immediately follows the absolute. As  voltage-gated potassium channels  open to terminate the action potential by repolarizing the membrane, the potassium conductance of the membrane increases dramatically.  K +  ions  moving out of the cell bring the membrane potential closer to the equilibrium potential for potassium. This causes brief hyperpolarization of the membrane, that is, the membrane potential becomes transiently more negative than the normal resting potential. Until the potassium conductance returns to the resting value, a greater stimulus will be required to reach the initiation threshold for a second depolarization. The return to the equilibrium resting potential marks the end of the relative refractory period."}
{"_id": "WikiPedia_Cardio$$$corpus_3482", "text": "The  refractory period  in cardiac physiology is related to the ion currents that, in  cardiac cells  as in nerve cells, flow into and out of the cell freely.  The flow of ions translates into a change in the voltage of the inside of the cell relative to the extracellular space.  As in nerve cells, this characteristic change in voltage is referred to as an action potential.  Unlike that in nerve cells, the cardiac action potential duration is closer to 100 ms (with variations depending on cell type, autonomic tone, etc.).  After an action potential initiates, the cardiac cell is unable to initiate another action potential for some duration of time (which is slightly shorter than the \"true\" action potential duration).  This period of time is referred to as the refractory period, which is 250ms in duration and helps to protect the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_3483", "text": "In the classical sense, the cardiac refractory period is separated into an absolute refractory period and a relative refractory period.  During the absolute refractory period, a new action potential cannot be elicited.  During the relative refractory period, a new action potential can be elicited under the correct circumstances."}
{"_id": "WikiPedia_Cardio$$$corpus_3484", "text": "The cardiac refractory period can result in different forms of  re-entry , which are a cause of  tachycardia . [ 1 ] [ B: 3 ]  Vortices of excitation in the myocardium ( autowave vortices ) are a form of  re-entry . Such vortices can be a mechanism of life-threatening cardiac  arrhythmias . In particular, the  autowave reverberator , more commonly referred to as spiral waves or rotors, can be found within the  atria  and may be a cause of  atrial fibrillation ."}
{"_id": "WikiPedia_Cardio$$$corpus_3485", "text": "The  refractory period in a  neuron  occurs after an  action potential  and generally lasts one millisecond. An action potential consists of three phases."}
{"_id": "WikiPedia_Cardio$$$corpus_3486", "text": "Phase one is depolarization. During depolarization, voltage-gated sodium ion channels open, increasing the neuron's membrane conductance for sodium ions and depolarizing the cell's membrane potential (from typically -70 mV toward a positive potential). In other words, the membrane is made less negative. After the potential reaches the activation threshold (-55 mV), the depolarization is actively driven by the neuron and overshoots the equilibrium potential of an activated membrane (+30 mV)."}
{"_id": "WikiPedia_Cardio$$$corpus_3487", "text": "Phase two is repolarization. During repolarization, voltage-gated sodium ion channels inactivate (different from the closed state) due to the now-depolarized membrane, and voltage-gated potassium channels activate (open). Both the inactivation of the sodium ion channels and the opening of the potassium ion channels act to repolarize the cell's membrane potential back to its resting membrane potential."}
{"_id": "WikiPedia_Cardio$$$corpus_3488", "text": "When the cell's membrane voltage overshoots its resting membrane potential (near -60 mV), the cell enters a phase of hyperpolarization. This is due to a larger-than-resting potassium conductance across the cell membrane. This potassium conductance eventually drops and the cell returns to its resting membrane potential."}
{"_id": "WikiPedia_Cardio$$$corpus_3489", "text": "Recent research has shown that neuronal refractory periods can exceed 20 milliseconds. Furthermore, the relation between hyperpolarization and the neuronal refractory was questioned, as neuronal refractory periods were observed for neurons that do not exhibit hyperpolarization. [ 2 ] [ 3 ]  The neuronal refractory period was shown to be dependent on the origin of the input signal to the neuron, as well as the preceding spiking activity of the neuron. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3490", "text": "The refractory periods are due to the inactivation property of voltage-gated sodium channels and the lag of potassium channels in closing. Voltage-gated sodium channels have two gating mechanisms, the activation mechanism that opens the channel with depolarization and the inactivation mechanism that closes the channel with repolarization.  While the channel is in the inactive state, it will not open in response to depolarization. The period when the majority of sodium channels remain in the inactive state is the absolute refractory period.  After this period, there are enough voltage-activated sodium channels in the closed (active) state to respond to depolarization. However, voltage-gated potassium channels that opened in response to repolarization do not close as quickly as voltage-gated sodium channels; to return to the active closed state. During this time, the extra potassium conductance means that the membrane is at a higher threshold and will require a greater stimulus to cause action potentials to fire. In other words, because the membrane potential inside the axon becomes increasingly negative relative to the outside of the membrane, a stronger stimulus will be required to reach the threshold voltage, and thus, initiate another action potential. This period is the relative refractory period."}
{"_id": "WikiPedia_Cardio$$$corpus_3491", "text": "The muscle action potential lasts roughly 2\u20134\u00a0ms and the absolute refractory period is roughly 1\u20133\u00a0ms, shorter than other cells."}
{"_id": "WikiPedia_Cardio$$$corpus_3492", "text": "In a  biological membrane , the  reversal potential  is the  membrane potential  at which the direction of ionic current reverses. At the reversal potential, there is no net flow of ions from one side of the membrane to the other. For channels that are permeable to only a single type of ion, the reversal potential is identical to the  equilibrium potential  of the ion. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3493", "text": "The equilibrium potential for an ion is the  membrane potential  at which there is no net movement of the ion. [ 1 ] [ 2 ] [ 3 ]  The flow of any inorganic ion, such as  Na +  or  K + ,  through an  ion channel  (since membranes are normally impermeable to ions) is driven by the  electrochemical gradient  for that ion. [ 1 ] [ 2 ] [ 3 ] [ 4 ]  This gradient consists of two parts, the difference in the concentration of that ion across the membrane, and the voltage gradient. [ 4 ]  When these two influences balance each other, the electrochemical gradient for the ion is zero and there is no net flow of the ion through the channel; this also translates to no current across the membrane so long as only one ionic species is involved. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  The voltage gradient at which this equilibrium is reached is the equilibrium potential for the ion and it can be calculated from the  Nernst equation . [ 1 ] [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3494", "text": "We can consider as an example a positively charged ion, such as  K + , and a negatively charged membrane, as it is commonly the case in most organisms. [ 4 ] [ 5 ]  The membrane voltage opposes the flow of the potassium ions out of the cell and the ions can leave the interior of the cell only if they have sufficient thermal energy to overcome the energy barrier produced by the negative membrane voltage. [ 5 ]  However, this biasing effect can be overcome by an opposing concentration gradient if the interior concentration is high enough which favours the potassium ions leaving the cell. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3495", "text": "An important concept related to the equilibrium potential is the  driving force .  Driving force is simply defined as the difference between the actual membrane potential and an ion's equilibrium potential  \n \n \n \n \n V \n \n \n m \n \n \n \n \u2212 \n \n E \n \n \n i \n \n \n \n \u00a0 \n \n \n {\\displaystyle V_{\\mathrm {m} }-E_{\\mathrm {i} }\\ } \n \n where  \n \n \n \n \n E \n \n \n i \n \n \n \n \u00a0 \n \n \n {\\displaystyle E_{\\mathrm {i} }\\ } \n \n refers to the equilibrium potential for a specific ion. [ 5 ]  Relatedly, the membrane current per unit area due to the type  \n \n \n \n i \n \n \n {\\displaystyle i} \n \n  ion channel is given by the following equation:"}
{"_id": "WikiPedia_Cardio$$$corpus_3496", "text": "where  \n \n \n \n \n V \n \n \n m \n \n \n \n \u2212 \n \n E \n \n \n i \n \n \n \n \u00a0 \n \n \n {\\displaystyle V_{\\mathrm {m} }-E_{\\mathrm {i} }\\ } \n \n  is the driving force and  \n \n \n \n \n g \n \n \n i \n \n \n \n \n \n {\\displaystyle g_{\\mathrm {i} }} \n \n  is the  specific conductance , or conductance per unit area. [ 5 ]  Note that the ionic current will be zero if the membrane is impermeable to that ion in question or if the membrane voltage is exactly equal to the equilibrium potential of that ion. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3497", "text": "When V m  is at the reversal potential for an event such as a synaptic potential ( V m  \u2212  E rev  is equal to 0), the identity of the ions that flow during an EPC can be deduced by comparing the reversal potential of the EPC to the equilibrium potential for various ions. For instance several excitatory  ionotropic  ligand-gated  neurotransmitter   receptors  including  glutamate receptors  ( AMPA ,  NMDA , and  kainate ),  nicotinic   acetylcholine  (nACh), and  serotonin  (5-HT 3 ) receptors are nonselective cation channels that pass Na +  and K +  in nearly equal proportions, giving the reversal potential close to zero. The inhibitory ionotropic ligand-gated neurotransmitter receptors that carry  Cl \u2212 , such as  GABA A  and  glycine  receptors, have reversal potentials close to the resting potential (approximately \u201370 mV) in neurons. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3498", "text": "This line of reasoning led to the development of experiments (by Akira Takeuchi and Noriko Takeuchi in 1960) that demonstrated that acetylcholine-activated ion channels are approximately equally permeable to Na +  and K +  ions. The experiment was performed by lowering the external Na +  concentration, which lowers (makes more negative) the Na +  equilibrium potential and produces a negative shift in reversal potential. Conversely, increasing the external K +  concentration raises (makes more positive) the K +  equilibrium potential and produces a positive shift in reversal potential. [ 2 ]   A general expression for reversal potential of synaptic events, including for decreases in conductance, has been derived. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3499", "text": "Signal-averaged electrocardiography  (SAECG) is a special  electrocardiographic  technique, in which multiple electric signals from the  heart  are averaged to remove  interference  and reveal small variations in the  QRS complex , usually the so-called \" late potentials \".  These may represent a predisposition towards potentially dangerous  ventricular tachyarrhythmias ."}
{"_id": "WikiPedia_Cardio$$$corpus_3500", "text": "A resting  electrocardiogram  (ECG) is recorded in the  supine position  using an ECG machine equipped with SAECG software; this can be done by a  physician ,  nurse , or  medical technician .  Unlike standard basal ECG recording, which requires only a few seconds, SAECG recording requires a few minutes (usually about 7-10 minutes), as the machine must record multiple subsequent QRS potentials to remove interference due to  skeletal muscle  and to obtain a  statistically significant  average trace. For this reason, it is important for the patient to lie as still as possible during the recording."}
{"_id": "WikiPedia_Cardio$$$corpus_3501", "text": "SAECG recording yields a single, averaged QRS potential, usually printed in a much larger scale than standard ECGs, upon which the SAECG software performs calculations to reveal small variations (typically 1-25  uV ) in the final portion of the QRS complex (the so-called \" late potentials , or more accurately, \" late ventricular potentials \"). These can be immediately interpreted by comparing results with cut-off values."}
{"_id": "WikiPedia_Cardio$$$corpus_3502", "text": "Late potentials are taken to represent delayed and fragmented  depolarisation  of the  ventricular   myocardium , which may be the substrate for a micro- re-entry  mechanism, implying a higher risk of potentially dangerous ventricular  tachyarrhythmias .  This has been used for the  risk stratification  of  sudden cardiac death  in people who have had a  myocardial infarction , as well as in people with known  coronary heart disease ,  cardiomyopathies , or unexplained  syncope .\nStill, the real predictive value of these findings is questioned. Late potentials may be found in 0-10% of normal volunteers. When used as a prognostic factor for the development of  ventricular tachycardia , they have a  sensitivity  of 72% and a  specificity  of 75%, yielding a  positive predictive value  of 20% and a  negative predictive value  of 20%."}
{"_id": "WikiPedia_Cardio$$$corpus_3503", "text": "Sinoventricular conduction  is a rare form of  cardiac conduction  in which the sinoatrial node generates an impulse that is conducted to the  atrioventricular node  (AV node) in the absence of the right atrium contracting. This is the physiological proof for the presence of the internodal tracts, which have not been clearly demonstrated histologically. On electrocardiogram (ECG), there will be no P wave due to the inactivation of the atrial muscles. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3504", "text": "Hyperkalemia  can lead to sinoventricular conduction, as evidenced on  ECG  by the P waves becoming flatter and flatter and eventually disappearing. The impulse from the sinus node is still conducted via the internodal tracts to the AV node, and thus normal ventricular activation occurs. Sinoventricular conduction has also been demonstrated during acute myocardial ischemia. This has been further elucidated by the absence of P waves in any surface leads despite effective high right atrial pacing. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3505", "text": "Sinus arrhythmia  is a commonly encountered variation of  normal   sinus rhythm . Sinus arrhythmia characteristically presents with an irregular rate in which the variation in the R-R interval is more than 0.12 seconds (120 milliseconds). Additionally, P waves are typically mono-form and in a pattern consistent with atrial activation originating from the  sinus node . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3506", "text": "During respiration, the intermittent  vagus nerve  activation occurs, which results in beat to beat variations in the resting heart rate. During inspiration vagal tone is slowed down and the heart rate goes up (being maximal at the peak of inspiration), while during expiration vagal tone is increased and heart rate decreases, being slowest at end-expiration. [ 2 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3507", "text": "When present, respiratory sinus arrhythmia typically indicates good cardiovascular health and is more commonly seen in young healthy people, especially those with enhanced vagal tone or slower heart rates. [ 3 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3508", "text": "In  electrocardiography , the  ST segment  connects the  QRS complex  and the  T wave  and has a duration of 0.005 to 0.150 sec (5 to 150 ms)."}
{"_id": "WikiPedia_Cardio$$$corpus_3509", "text": "It starts at the J point (junction between the QRS complex and ST segment) and ends at the beginning of the T wave. However, since it is usually difficult to determine exactly where the ST segment ends and the T wave begins, the relationship between the ST segment and T wave should be examined together. The typical ST segment duration is usually around 0.08 sec (80 ms). It should be essentially level with the PR and TP segments."}
{"_id": "WikiPedia_Cardio$$$corpus_3510", "text": "The ST segment represents the isoelectric period when the ventricles are in between depolarization and repolarization."}
{"_id": "WikiPedia_Cardio$$$corpus_3511", "text": "In  fetal electrocardiography , ST waveform analysis (sometimes abbreviated STAN) is used to get an indication of increasing levels of fetal  base deficit . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3512", "text": "In  electrocardiography , the  T wave  represents the  repolarization  of the  ventricles . The interval from the beginning of the  QRS complex  to the apex of the T wave is referred to as the  absolute  refractory period . The last half of the T wave is referred to as the  relative refractory period  or  vulnerable period . The T wave contains more information than the  QT interval . The T wave can be described by its symmetry, skewness, slope of ascending and descending limbs, amplitude and subintervals like the T peak \u2013T end  interval. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3513", "text": "In most  leads , the T wave is positive. This is due to the repolarization of the membrane. During ventricle contraction (QRS complex), the heart depolarizes. Repolarization of the ventricle happens in the opposite direction of depolarization and is negative current, signifying the relaxation of the cardiac muscle of the ventricles. But this negative flow causes a positive T wave; although the cell becomes more negatively charged, the net effect is in the positive direction, and the ECG reports this as a positive spike. [ 2 ]  However, a negative T wave is normal in  lead aVR . Lead V1 generally have a negative T wave. In addition, it is not uncommon to have a negative T wave in lead III, aVL, or aVF. A periodic beat-to-beat variation in the amplitude or shape of the T wave may be termed  T wave alternans ."}
{"_id": "WikiPedia_Cardio$$$corpus_3514", "text": "The  refractory period  of cardiac muscle is distinct from that of skeletal muscle. Nerves that innervate skeletal muscle have an extremely short refractory period after being subjected to an  action potential  (of the order of 1 ms). This can lead to sustained or  tetanic contraction . In the heart, contractions must be spaced to maintain a rhythm. Unlike in muscle, repolarization occurs at a slow rate (100 ms). This prevents the heart from undergoing sustained contractions because it forces the refractory period and  cardiac action potential  firing to be of the same length of time."}
{"_id": "WikiPedia_Cardio$$$corpus_3515", "text": "Repolarization depends on the charges of ions and their flow across membranes. In skeletal muscle cells, repolarization is simple. First,  sodium ions  flow into the cell to depolarize it and cause skeletal muscle contraction. Once the action potential is over,  potassium ions  flow out of the cell due to increased  cell membrane  permeability to those ions. This high permeability contributes to the rapid repolarization of the  membrane potential . This repolarization occurs quickly enough that another action potential can cause depolarization before the last action potential has dissipated. Cardiac muscle differs in that there are more calcium channels that counteract the potassium channels. While potassium quickly flows out of the cell, calcium slowly flows into the cell. This causes the repolarization to occur more slowly, making the refractory period as long as the action potential, preventing sustained contractions."}
{"_id": "WikiPedia_Cardio$$$corpus_3516", "text": "The T wave is representative of the repolarization of the membrane. In an EKG reading, the T wave is notable because it must be present before the next depolarization. An absent or strangely shaped T wave may signify disruption in repolarization or another segment of the heartbeat. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3517", "text": "Normally, T waves are upright in all leads, except aVR and V1 leads. Highest amplitude of T wave is found at V2 and V3 leads. The shape of the T wave is usually asymmetrical with a rounded peak. T wave inversions from V2 to V4 leads are frequently found and normal in children. In normal adults, T wave inversions from V2 to V3 are less commonly found but can be normal. [ 4 ]  The depth of the T wave also becomes progressively shallow from one to the next lead. [ 5 ]  The height of the T wave should not exceed 5\u00a0mm in limb leads and more than 10\u00a0mm in precordial leads. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3518", "text": "Both the abnormalities of the  ST segment  and T wave represents the abnormalities of the ventricular repolarization or secondary to abnormalities in ventricular depolarisation. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3519", "text": "Inverted T wave is considered abnormal if inversion is deeper than 1.0\u00a0mm. Inverted T waves found in leads other than the V1 to V4 leads is associated with increased cardiac deaths. Inverted T waves associated with cardiac signs and symptoms ( chest pain  and  cardiac murmur ) are highly suggestive of  myocardial ischaemia . [ 4 ]  Other ECG changes associate with myocardial ischaemia are:  ST segment  depression with an upright T wave; ST segment depression with biphasic T wave or inverted T wave with negative  QRS complex ; [ 5 ]  T wave symmetrically inverted with a pointed apex, while the ST segment is either bowed upwards or horizontally depressed, or not deviated; and ST segment depression progressing to abnormal T wave during ischaemia free intervals. [ 4 ]  However, ST segment depression is not suggestive of ischaemic location of the heart. ST segment depression in eight or more leads, associated with ST segment elevation in aVR and V1 are associated with left main coronary artery disease or three-vessel disease (blockage of all three major branches of coronary arteries). ST segment depression most prominent from V1 to V3 is suggestive of posterior infarction. Furthermore, tall or wide QRS complex with an upright T wave is further suggestive of the posterior infarction. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3520", "text": "Wellens' syndrome  is caused by the injury or blockage of the  left anterior descending artery , therefore resulting in symmetrical T wave inversions from V2 to V4 with depth more than 5\u00a0mm in 75% of the cases. Meanwhile, the remaining 25% of the cases shows biphasic T wave morphology. ST segments remains neutral in this syndrome. Those who were treated without  angiography  will develop anterior wall myocardial infarction in a mean period of 9 days. [ 4 ]  An episode of chest pain in Wellens' syndrome is associated with ST elevation or depression and later progressed to T wave abnormality after chest pain subsided. T wave inversion less than 5\u00a0mm may still represents myocardial ischaemia, but is less severe than Wellens' syndrome. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3521", "text": "Hypertrophic cardiomyopathy  is the thickening of the  left ventricle , occasionally  right ventricle . It may be associated with left ventricular outflow tract obstruction or may not be associated with it in 75% of the cases. ECG would be abnormal in 75 to 95% of the patients. Characteristic ECG changes would be large  QRS complex  associated with giant T wave inversion [ 4 ]  in lateral leads I, aVL, V5, and V6, together with ST segment depression in left ventricular thickening. For right ventricular thickening, T waves are inverted from V2 to V3 leads. ST and T waves changes may not be apparent in hypertrophic cardiomyopathy, but if there is presence of ST and T waves changes indicates severe hypertrophy or ventricular systolic dysfunction. [ 5 ]  According to Sokolow-Lyon criterion, the height of R wave in V5 or V6 + the height of S wave in V1 more than 35\u00a0mm would be suggestive of left ventricular hypertrophy. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3522", "text": "Both right and left  bundle branch blocks  are associated with similar ST and T wave changes as in hypertrophic cardiomyopathy, but are opposite to the direction of the QRS complex. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3523", "text": "In  pulmonary embolism , T wave can be symmetrically inverted at V2 to V4 leads but  sinus tachycardia  is usually the more common finding. T wave inversion is only present in 19% of mild pulmonary embolism, but the T inversion can be present in 85% of the cases in severe pulmonary embolism. Besides, T inversion can also exists in leads III and aVF. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3524", "text": "Inversion of T waves in most of the ECG leads except aVR indicates many causes most commonly myocardial ischaemia and  intracranial haemorrhage . Others include: hypertrophic cardiomyopathy,  Takotsubo cardiomyopathy  (stress-induced cardiomyopathy),  cocaine  abuse,  pericarditis , pulmonary embolism, and advanced or complete atrioventricular block. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3525", "text": "Numbers from Lepeschkin E in  [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3526", "text": "As the name suggests, Biphasic T waves move in opposite directions. The two main causes of these waves are myocardial ischemia and hypokalemia."}
{"_id": "WikiPedia_Cardio$$$corpus_3527", "text": "Wellens' Syndrome is a pattern of biphasic T waves in V2\u20133. It is generally present in patients with ischemic chest pain."}
{"_id": "WikiPedia_Cardio$$$corpus_3528", "text": "T wave is considered flat when the wave varies from -1.0\u00a0mm to + 1.0\u00a0mm in height.  Hypokalemia  or  digitalis  therapy can cause flattened T wave with a prominent  U wave . As hypokalemia progressively worsens, the T wave becomes more flattened while the U wave becomes more prominent, with progressively deeper ST segment depression. For digitalis toxicity, there will be a sagging QT interval, flattened T wave, and prominent U wave with a shortened QT interval. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3529", "text": "These T waves may be seen in patients displaying  Prinzmetal angina . Additionally, patients exhibiting the early stages of  STEMI  may display these broad and disproportional waves. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3530", "text": "The name of these T waves suggests the shape it exhibits (double peaks). Since these T wave abnormalities may arise from different events, i.e. hypothermia and severe brain damage, they have been deemed as nonspecific, making them much more difficult to interpret. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3531", "text": "High blood  potassium  levels ( hyperkalemia ) can cause \"peaked t-waves.\" [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3532", "text": "Transcutaneous pacing  ( TCP ), also called  external pacing , is a temporary means of pacing a patient's  heart  during a medical emergency. It should not be confused with  defibrillation  (used in more serious cases, in ventricular fibrillation and other shockable rhythms) using a manual or automatic defibrillator, though some newer defibrillators can do both, and pads and an electrical stimulus to the heart are used in transcutaneous pacing and defibrillation. Transcutaneous pacing is accomplished by delivering pulses of electric current through the patient's chest, which stimulates the  heart  to contract. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3533", "text": "The most common  indication  for transcutaneous pacing is an abnormally slow  heart rate . By convention, a heart rate of fewer than 60 beats per minute in the adult patient is called  bradycardia . [ 1 ]  Not all instances of bradycardia require medical treatment. Normal heart rate varies substantially between individuals, and many athletes in particular have a relatively slow resting heart rate. [ 2 ]  In addition, the heart rate is known to naturally slow with age. It is only when bradycardia presents with signs and symptoms of  shock  that it requires  emergency treatment  with transcutaneous pacing."}
{"_id": "WikiPedia_Cardio$$$corpus_3534", "text": "Some common causes of  hemodynamically  significant bradycardia include  myocardial infarction ,  sinus node dysfunction  and  complete heart block . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3535", "text": "Transcutaneous pacing is no longer indicated for the treatment of  asystole  ( cardiac arrest  associated with a \"flat line\" on the  ECG ), with the possible exception of witnessed asystole (as in the case of  bifascicular block  that progresses to  complete heart block  without an  escape rhythm ). [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3536", "text": "During transcutaneous pacing, pads are placed on the patient's chest, either in the anterior/lateral position or the anterior/posterior position. The anterior/posterior position is preferred as it minimizes transthoracic  electrical impedance  by \"sandwiching\" the heart between the two pads [ citation needed ] . The pads are then attached to a monitor/defibrillator, a heart rate is selected, and current (measured in milliamps) is increased until electrical capture (characterized by a wide  QRS complex  with tall, broad T wave on the  ECG ) is obtained, with a corresponding pulse. Pacing artifact on the ECG and severe muscle twitching may make this determination difficult. It is therefore advisable to use another instrument (e.g. SpO2 monitor or bedside doppler) to confirm mechanical capture."}
{"_id": "WikiPedia_Cardio$$$corpus_3537", "text": "Transcutaneous pacing may be uncomfortable for the patient.  [ citation needed ]   Sedation  should therefore be considered. Before pacing the patient in a prehospital setting sedation is recommended by administering an analgesic or an anxiolytic. [ by whom? ]  Prolonged transcutaneous pacing may cause burns on the skin. According to the Zoll M Series Operator's Guide,\" Continuous pacing of neonates can cause skin burns. If it is necessary to pace for more than 30 minutes, periodic inspection of the underlying skin is strongly advised.\"  It is meant to stabilize the patient until a more permanent means of pacing is achieved."}
{"_id": "WikiPedia_Cardio$$$corpus_3538", "text": "Other forms of cardiac pacing are  transvenous pacing , epicardial pacing, [ 5 ]  and permanent pacing with an  implantable pacemaker ."}
{"_id": "WikiPedia_Cardio$$$corpus_3539", "text": "In addition to synchronized transcutaneous pacing offered by newer cardiac monitor/defibrillators, there is also an option for asynchronous pacing. Sometimes in the prehospital setting a situation may arise where ECG electrodes are not available or something interferes with their adhesion to the patient's skin. In these rare situations where the patient must be paced and there are no other alternatives, asynchronous pacing may be used. Again, this setting should only be used as a last resort due to possible adverse cardiac effects it could cause."}
{"_id": "WikiPedia_Cardio$$$corpus_3540", "text": "Transvenous cardiac pacing  ( TVP ), [ 1 ]  also called  endocardial pacing , is a potentially life-saving intervention used primarily to correct profound  bradycardia . It can be used to treat symptomatic bradycardias that do not respond to  transcutaneous pacing  or to drug therapy.  Transvenous pacing is achieved by threading a pacing electrode through a vein into the  right atrium ,  right ventricle , or both."}
{"_id": "WikiPedia_Cardio$$$corpus_3541", "text": "This means of pacing the heart is not as popular as other means of pacing (like transcutaneous pacing,  implanted pacemaker ,  epicardial pacing ) because it is a temporary solution to pace the heart and yet involves a similar level of risk of bleeding as a more permanent solution like placing an implanted pacemaker."}
{"_id": "WikiPedia_Cardio$$$corpus_3542", "text": "For patients who present in an emergency setting with symptomatic bradycardias, usually drugs like  atropine  or  sympathomimetic  drugs ( epinephrine  or  dopamine ) can be used to increase the heart rate to an adequate level until the underlying cause of the bradycardia can be isolated and then, possibly, a permanent pacemaker can be placed."}
{"_id": "WikiPedia_Cardio$$$corpus_3543", "text": "For patients for whom transvenous pacing is chosen, the procedure is done at the bedside with a  local anesthetic  alone or in conjunction with  conscious sedation .  The pacing electrode is advanced through the vein under  fluoroscopic  and  electrocardiographic  guidance.  An  X-ray  after the procedure is always obtained to confirm placement of the pacing electrode."}
{"_id": "WikiPedia_Cardio$$$corpus_3544", "text": "The greater use of atropine and epinephrine or external pacing may make transvenous pacing unnecessary by stabilizing patients early in the process of caring for the patient.  Some debate exists over the efficacity and reliability of transvenous pacing, especially if the need for permanent pacing is anticipated."}
{"_id": "WikiPedia_Cardio$$$corpus_3545", "text": "The  U wave  is a wave on an  electrocardiogram  (ECG). It comes after the  T wave  of ventricular repolarization and may not always be observed as a result of its small size. 'U' waves are thought to represent repolarization of the  Purkinje fibers . [ 1 ] [ 2 ] \nHowever, the exact source of the U wave remains unclear. The most common theories for the origin are:"}
{"_id": "WikiPedia_Cardio$$$corpus_3546", "text": "According to V. Gorshkov-Cantacuzene:"}
{"_id": "WikiPedia_Cardio$$$corpus_3547", "text": "\"The U wave is the momentum carried by the blood in the coronary arteries and blood vessels\". [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3548", "text": "The  resistivity  of stationary blood is expressed as  \n \n \n \n \n ( \n \n Ht \n \n ) \n \n = \n \n | \n \n \n Ht \n \n \u22c5 \n ( \n 1 \n + \n \u03b1 \n \n Ht \n \n ) \n \n \n {\\displaystyle \\left({\\text{Ht}}\\right)=|{\\text{Ht}}\\cdot (1+\\alpha {\\text{Ht}})} \n \n , where  \n \n \n \n \u03b1 \n \n \n {\\displaystyle \\alpha } \n \n  is a coefficient, and  \n \n \n \n \n Ht \n \n \n \n {\\displaystyle {\\text{Ht}}} \n \n  is the  hematocrit ; at that time, as during acceleration of the blood flow occurs a sharp decrease in the longitudinal resistance with small relaxation times."}
{"_id": "WikiPedia_Cardio$$$corpus_3549", "text": "However, multiple factors affect blood resistivity.  Erythrocyte  aggregation occurs at low shear rates and implies that to all vessels (with the exception of large veins) the effect of aggregation is irrelevant. The interior of a blood vessel includes a near-wall layer of plasma (referred to as lubricant), the size of which strictly depends on Reynold's criterion and the  shear rate  of the flowing blood. Given that the thickness of this layer in all blood vessels (except  capillaries ) is less than 5 microns, and the resistivity of the plasma is two times less than in blood, then according to the scheme of parallel insertion, the contribution of this layer to the resistivity is negligible. By reducing the speed of blood flow profiles the dependence of Ht on the radius of the vessel becomes more elongated. However, at normal values of Ht, the effect is also insignificant. With high enough shear rates, the red blood cells become susceptible to deformation. The contribution of this phenomenon is difficult to assess because it is present in the background of all the above effects. However, even the sum of all these factors has little effect on blood resistivity."}
{"_id": "WikiPedia_Cardio$$$corpus_3550", "text": "It follows that at the time of ejection of blood from the left ventricle, part of the pulse is carried away, because there is no electrical resistivity of blood, which gradually increases high up in the  coronary arteries  and  blood vessels . The U wave is the momentum carried by the blood in the coronary arteries and blood vessels. It is possible to take this momentum back to Purkinje fibers along the vessels of the myocardium. This idea is also proved by the fact that  hypertrophy  of the left ventricle,  myocardial ischemia , coronary and insufficiency have momentum there is no possibility to move to the Purkinje fibers, therefore, the ECG recorded a negative U wave."}
{"_id": "WikiPedia_Cardio$$$corpus_3551", "text": "According to many studies [ which? ] , U waves often register in all leads except V6, most frequently in V2 and V3 when the heart rate is greater than 96 beats per minute. Its amplitude is often 0.1\u20130.33  mV.  Particularly difficult is the allocation of the boundaries of the U wave on the background of the T wave and  R wave , which may partial or complete (in the case of T wave) the merger. Higher values of heart rate or  hypocalcemia  U wave are superimposed on the  T wave  and in  tachycardia  \u2014 merges with the R-wave of the next cardiac cycle."}
{"_id": "WikiPedia_Cardio$$$corpus_3552", "text": "Prominent U waves (U waves are described as prominent if they are more than 1-2 mm or 25% of the height of the T wave.) are most often seen in  hypokalemia  but may be present in  hypercalcemia ,  thyrotoxicosis , or exposure to  digitalis ,  epinephrine  and Class 1A and 3  antiarrhythmics , as well as in congenital  long QT syndrome , and in the setting of  intracranial hemorrhage ."}
{"_id": "WikiPedia_Cardio$$$corpus_3553", "text": "An inverted U wave may represent  myocardial ischemia  (and especially appears to have a high positive predictive accuracy for  left anterior descending coronary artery  disease [ 7 ]  ) or left ventricular  volume overload . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3554", "text": "A U-wave can sometimes be seen in normal younger, athletic individuals. [ 9 ]  The U-wave increases in adults that are older and less athletic. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3555", "text": "In  electrocardiography , the ventricular  cardiomyocyte   membrane potential  is about \u221290\u00a0mV at rest, [ 1 ]  which is close to the  potassium   reversal potential . When an  action potential  is generated, the membrane potential rises above this level in five distinct phases. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3556", "text": "The Na +  channel opening is followed by inactivation. Na +  inactivation comes with slowly activating Ca 2+  channels at the same time as a few fast K +  channels open. There is a balance between the outward flow of K +  and the inward flow of Ca 2+  causing a plateau of length in variables. The delayed opening of more Ca 2+ -activated K +  channels, which are activated by build-up of Ca 2+  in the sarcoplasm, while the Ca 2+  channels close, ends the plateau. This leads to repolarization."}
{"_id": "WikiPedia_Cardio$$$corpus_3557", "text": "The depolarization of the membrane allows  calcium  channels to open as well. As sodium channels close calcium provides current to maintain the potential around 20\u00a0mV. The plateau lasts on the order of 100\u00a0ms. At the time that calcium channels are getting activated, channels that mediate the transient outward potassium current open as well. This outward potassium current causes a small dip in membrane potential shortly after  depolarization . This current is observed in human and dog action potentials, but not in guinea pig action potentials."}
{"_id": "WikiPedia_Cardio$$$corpus_3558", "text": "Repolarization  is accomplished by channels that open slowly and are mostly activated at the end of the action potential ( slow delayed-rectifier channels ) and channels that open quickly but are inactivated until the end of the action potential ( rapid delayed rectifier channels ). Fast delayed rectifier channels open quickly but are shut by inactivation at high membrane potentials. As the membrane voltage begins to drop the channels recover from inactivation and carry current."}
{"_id": "WikiPedia_Cardio$$$corpus_3559", "text": "Clara Bonanad  is a clinical  cardiologist  at the University Clinical Hospital,  Valencia  in the department of  Cardiology . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3560", "text": "Bonanada earned her PhD in Medicine at the  University of Valencia  in 2016 and her PhD thesis is \u201cPrognostic impact of Geriatric Syndromes in Acute Coronary Syndromes\u201d. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3561", "text": "Her research on sex differences in the influence of frailty in senior outpatients with heart failure, as well as Bending Oxygen Saturation index (BOSI) and the Risk of Worsening Heart Failure Events in Chronic Heart Failure. [ 5 ] \n [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3562", "text": "This is a list of people notable in the field of  cardiology . Presented along with their year of birth, death, nationality, notability, and reference(s)."}
{"_id": "WikiPedia_Cardio$$$corpus_3563", "text": "Chen Haozhu  ( Chinese :  \u9648\u704f\u73e0 ; 6 November 1924 \u2013 30 October 2020) was a Chinese cardiologist."}
{"_id": "WikiPedia_Cardio$$$corpus_3564", "text": "Chen was born on 6 November 1924 and attended  National Zhongzheng Medical College \u00a0[ zh ] , where he completed a bachelor's degree in 1949. He was responsible for introducing the term \" myocardial infarction \" to Chinese medical professionals, and is credited with pioneering modern cardiology in China by using newer methods of treatment and diagnosis. Chen was the director of the Shanghai Institute of Cardiovascular Diseases and served as vice chair of the Chinese Society of Cardiology, as well as the Chinese Medical Association. [ 1 ]  He taught as a professor at  Zhongshan Hospital , affiliated to  Fudan University , and was elected a member of the  Chinese Academy of Engineering  in 1997. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3565", "text": "Chen died on 30 October 2020, aged 95. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3566", "text": "Bila M. Kapita  is a doctor from  Kinshasa ,  Democratic Republic of the Congo  who aided in initial research efforts investigating  HIV/AIDS  in Africa in the 1980s and 1990s. Kapita is credited as one of the first African scientists to independently identify that AIDS was prevalent in Central Africa. Research work in collaboration with  Project SIDA  helped identify and publicize the heterosexual sexual transmission of HIV. Following his research career, he continued caring for patients with HIV/AIDS and has more recently returned to practicing  cardiology ."}
{"_id": "WikiPedia_Cardio$$$corpus_3567", "text": "Bila M. Kapita was raised in a Swedish mission in the  Bas-Congo  province of the former  Belgian Congo . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3568", "text": "Kapita received medical training in  Brussels, Belgium  at the  Cliniques Universitaires Saint-Luc , where he focused on  cardiology , publishing several research articles on the subject dating back to 1975. [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3569", "text": "Upon return to Zaire, Kapita practiced cardiology and general medicine at the  Mama Yemo Hospital , becoming head of  internal medicine . [ 4 ] [ 5 ] [ 6 ]  Kapita was well established in Kinshasa and served as the head of the Kinshasa Medical Association. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3570", "text": "Kapita noted in retrospect that patients at his hospital displayed an increased amount of  Kaposi's sarcoma  beginning in the mid-1970s. Around the same time, patients were more frequently suffering from  Cryptococcal meningitis . [ 5 ]  Both diseases are  opportunistic infections  which were significant of decreased  immune system  response in patients."}
{"_id": "WikiPedia_Cardio$$$corpus_3571", "text": "Following the initial connection between these opportunistic infections in the United States in 1981, African scientists including Kapita recognized the similar clinical presentation. The prevalence of what would soon become known as  AIDS  in African countries caught the attention of European and American researchers. The United States\u2019  Centers for Disease Control  and  National Institute of Allergy and Infectious Diseases  were alerted to the rising pandemic by former collaborators in Ebola research from Europe such as  Peter Piot . [ 4 ] [ 7 ]  A group of researchers from Belgium, the United States, and France were first introduced to the state of  Africa's AIDS pandemic  in the isolation wards of Kapita's hospital. [ 4 ] [ 5 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3572", "text": "Kapita was welcoming to the international researchers, allowing them to work from his hospital for long periods of time. Due to Kapita's notability in Kinshasa, he was able to protect these scientists from any government discontent involving outside research at the time. [ 4 ]  Peers described Kapita as being true to his ideals and well trained. [ 4 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3573", "text": "Patients in the wards of Mama Yemo were clearly affected by AIDS per the clinical definitions in place at that time. Almost all of the patients confirmed to have AIDS using laboratory based tests were already identified by Kapita without laboratory tests. [ 4 ] [ 7 ] [ 8 ]  Kapita is credited by his collaborators as being one of the first people in Africa to identify the presence of AIDS. [ 8 ]  The visiting researchers would soon realize the extent of AIDS in Africa and began research in Kinshasa. The resulting collaboration between African, American, and European scientists would become known as  Project SIDA . [ 1 ] [ 4 ] [ 5 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3574", "text": "Bila M. Kapita published his own book in 1988 titled  SIDA en Afrique. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3575", "text": "From 1984 to 1991 Kapita collaborated with Project SIDA at Mama Yemo, producing between 20 and 30 research articles on the transmission, history, and future of HIV/AIDS in Africa. Work was conducted in Kapita's hospital early on in the program to increase chances of approval from government authorities. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3576", "text": "Many of Kapita's articles focused on the rate of heterosexual transmission that was largely ignored by the United States in the early 1980s. [ 1 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3577", "text": "Kapita was present at the first  International AIDS Conference  in Atlanta, Georgia in 1985. [ 1 ]  Also in attendance were Project SIDA collaborators Peter Piot and  Nzila Nzilambi \u2014as well as thousands of other scientists. [ 7 ]  During the second International AIDS Conference in  Paris , France, Kapita informed the community of his retrospective discovery of increased cases of Kaposi's sarcoma and  cytomegalovirus , indicators that HIV/AIDS likely existed in Kinshasa as far back as 1975. [ 7 ] [ 11 ]  Prior to public knowledge of HIV prevalence in Zaire at the time, Kapita faced the threat of becoming a political prisoner under  Mobutu Sese Seko \u2019s regime for acknowledging the issue on a global stage without permission from the government. [ 12 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3578", "text": "In 1990, as the civil war was beginning in Zaire, Kapita worked with Peter Piot in arranging an international AIDS conference in Kinshasa. The proceeds of the conference were returned to the region through donations to Mama Yemo Hospital and the establishment of a health clinic in Kapita's village. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3579", "text": "Kapita's work continued for a few years following the 1991 demise of Project SIDA. A notable collaboration featuring Kapita in 1992 was the  World Health Organization  publication:  AIDS in Africa: A Manual for Physicians. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3580", "text": "Following the end of Project SIDA due to civil war in Zaire, Kapita continued to appear on international research articles, the last being published in 1993. [ 14 ]  Kapita continued to work at Mama Yemo, until at least 1997, treating patients with HIV/AIDS. [ 15 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3581", "text": "A hallmark of Project SIDA was the training of Congolese researchers, resulting in many well-trained doctors such as Kapita existing in Kinshasa. American and European collaborators established traditional research procedure in Kinshasa, establishing an  institutional review board  led by Kapita. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3582", "text": "Kapita and the other Zairian collaborators of Project SIDA wished to return to research, but opportunities following the civil war were limited. [ 8 ]  Currently, Kapita practices cardiology at the Centre Medical De Kinshasa in  Gombe, Kinshasa . [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3583", "text": "S\u00edlvia Paula Valentim Lutucuta  (born 14 July 1968) is an Angolan politician and cardiologist, the incumbent Minister of Health."}
{"_id": "WikiPedia_Cardio$$$corpus_3584", "text": "Lutucuta was born in  Huambo  in 1967. She trained in medicine and specialised in cardiology at the  Hospital de Santa Maria  in Lisbon, Portugal. [ 1 ]  In 2000 she moved to Houston in Texas where she undertook post-doctoral research at  Baylor College of Medicine . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3585", "text": "She joined the Angolan Society of Cardiovascular Diseases. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3586", "text": "She is a member of the Member of the MPLA Political Bureau. [ 1 ]  In 2017 she was nominated to be the Minister of Health in Angola. She has created thousands of new jobs, especially in rural layers. Under her leadership vaccines for COVID-19 were rolled out in her country and she organised the funding. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3587", "text": "This Angolan biographical article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3588", "text": "Mrigendra Raj Pandey  is a Nepalese physician from Kathmandu. He is one of the most senior doctors in Nepal and probably the first cardiologist in the country. [ 1 ]  He is the Nepal first Member of the   Royal College of Physicians   and also the   FRCP  from Edinburgh.  He  was also the personal physician to the  King Mahendra . [ 2 ]  He was the founder chief-editor of the  Journal of Nepal Medical Association  from 1963 to 1964. [ 3 ]  He is the founder president of the Nepal Heart Foundation. [ 4 ]  He established the Mrigendra Samjhana Medical  Trust in year 1975. [ 5 ] [ 6 ] [ 7 ]  He is  Patron  of Cardiac Society of Nepal. [ 8 ]  He is involved in various research activities of medical field in Nepal since long time. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3589", "text": "Carlos Enrique Soto Menegazzo  (born August 26, 1951) is a  Guatemalan   cardiologist  and politician who served as  Minister of Public Health and Social Assistance  from 2017 to 2020 under the  government  of  Jimmy Morales . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3590", "text": "On August 29, 2017 he was appointed to replace  Lucrecia Hern\u00e1ndez Mack  as Minister of Public Health. [ 2 ]  Hern\u00e1ndez had announced her resignation the sunday before, in protest over President  Jimmy Morales  ordering the expulsion of  United Nations  anti-corruption investigator  Iv\u00e1n Vel\u00e1squez G\u00f3mez . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3591", "text": "Since February 2014, he had served as director of  Roosevelt Hospital  until that day. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3592", "text": "He is son of Carlos Armando Soto G\u00f3mez y Odilia Perina Menegazzo Vanfrette, his father was Minister of Health too from 1986 to 1990 and deputy of the Guatemalan National Constituent assembly of 1984. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3593", "text": "He married whit Beatriz D\u00edaz in 1969 and they divorced in 1989. He married for the second time with Lucrecia Torcelli in 1989. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3594", "text": "This article about a Guatemalan politician is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3595", "text": "Abiomed, Inc.  is a  medical device  technology company that operates as a stand-alone business within  Johnson & Johnson's  MedTech Segment. [ 2 ]  Abiomed develops and manufactures temporary external and implantable mechanical circulatory support devices. The company is headquartered in  Danvers, Massachusetts  with additional offices in  Woburn ,  Baltimore ,  Berlin ,  Aachen , and  Tokyo ."}
{"_id": "WikiPedia_Cardio$$$corpus_3596", "text": "Andrew Greenfield is President of the company, with Dr. Thorsten Siess as Executive Vice President and Chief Technology Officer and Dr. Chuck Simonton as Executive Vice President and Chief Medical Officer. [ 2 ]  According to Bloomberg, the company \"engages in the research, development, and sale of medical devices to assist or replace the pumping function of the failing heart. It also provides continuum of care to heart failure patients\". [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3597", "text": "As of 2022, the company had secured five FDA approvals and 1,408 patents with 1,416 pending. [ 4 ]  For fiscal year 2022, Abiomed reported $1.032 billion in revenue and reported diluted earnings per share was $2.98 for the year. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3598", "text": "On December 22, 2022,  Johnson & Johnson  completed the acquisition of Abiomed. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3599", "text": "Abiomed was founded in  Danvers, Massachusetts  by  David M. Lederman  in 1981 as Applied Biomedical Corporation. [ 6 ]  That year, the company commenced the development of an  artificial heart . [ 7 ]  Funded by federal research grants, [ 8 ]  Lederman partnered with  The Texas Heart Institute  to develop the  AbioCor , a  grapefruit -sized electromagnetic device with an internal battery that completely replaces the heart without wires or tubes passing through the skin. [ 6 ]   In July 2001, AbioCor became the first artificial heart successfully implanted in a patient, where it pumped more than 20 million times. [ 9 ]  Fourteen of the AbioCor devices were implanted, during  clinical trials  from 2001 to 2004, with the longest-living recipient surviving 512 days. [ 6 ]  The AbioCor won  FDA approval  in 2006 for patients who are near death and do not qualify for a  heart transplant . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3600", "text": "In 2004, Michael R. Minogue became president and CEO of Abiomed. [ 10 ]  In 2005, Abiomed purchased  ventricular assist device  company Impella CardioSystems AG of  Aachen, Germany , [ 11 ]  maker of the  Impella  heart pump, developed by Thorsten Siess, [ 12 ]  who is now the  chief technology officer  at Abiomed. [ 13 ] [ self-published source ]  After Abiomed acquired Impella the company's focus shifted from heart replacement to heart recovery. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3601", "text": "In July 2014, Abiomed acquired German heart pump maker ECP in a deal worth up to $30 million. The deal included a nearly $2.8 million buyout of AIS GmbH Aachen Innovative Solutions, which owns some of the patents licensed to ECP. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3602", "text": "In May 2018, Abiomed was added to the  S&P 500 index . [ 16 ]  During the S&P's rise from 2000 to 3000, Abiomed was the index's top performing stock. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3603", "text": "In 2018, Abiomed built a $17 million Innovation Center to facilitate research and product development at its headquarters in Danvers. [ 18 ]  The 29,800-square-foot facility features laboratories for blood, optical, software, mechanical and electrical research, plus a production line. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3604", "text": "In 2019,  Barron's  ranked Abiomed the fourth best  stock  of the 2010s, with total return of 1,983%. [ 20 ]  while  Fortune  ranked Abiomed 19th on the magazine's list of 100 fastest-growing companies. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3605", "text": "In April 2020, Abiomed acquired medical device company Breethe, a startup that spun out of the University Of Maryland. [ 22 ]  The startup had developed a portable  extracorporeal membrane oxygenation (ECMO)  system that acts like an artificial lung, oxygenating and removing carbon dioxide from the blood of a patient in cardiogenic shock or respiratory failure. [ 23 ]  The technology, now known as the Abiomed Breethe OXY-1 System, received FDA 510(k) clearance later that year. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3606", "text": "In June 2020, Abiomed appointed Charles A. Simonton, MD, as vice president and Chief Medical Officer. [ 25 ]  Also in 2020, the FDA granted Emergency Use Authorization for the Impella heart pump to stabilize COVID-19 patients following the removal of pulmonary blood clots, as well as the use of the Impella in combination with the Breethe extracorporeal membrane oxygenation (ECMO) system, which pumps more oxygen into the bloodstream. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3607", "text": "In February and April 2021, Abiomed appointed neurosurgeon  Myron Rolle  and cardiologist  Paula Johnson  to the board of directors. [ 27 ]  Drs. Rolle and Johnson serve on the Governance and Nominating Committee and Regulatory and Compliance Committee of the board. [ 28 ] [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3608", "text": "In June 2021, Abiomed acquired preCARDIA, a catheter developer whose system allows for a less-invasive option when treating  acute decompensated heart failure  (ADHF) patients. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3609", "text": "In November 2022, Abiomed announced that it would be acquired by Johnson & Johnson in a $16.6 billion deal. [ 31 ]  The deal closed on December 22. [ 32 ]  Following the acquisition, Abiomed continues to operate as a standalone business within Johnson & Johnson's MedTech segment. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3610", "text": "Impella is the world's smallest heart pump. [ 16 ]  It sits in the heart, spinning up to 50,000 revolutions per minute, sending blood throughout the body, allowing the heart to rest and recover. It is inserted through a minimally invasive procedure and guided through an artery to the heart. [ 14 ]  In 2007, the Impella 2.5 heart pump was among 35 healthcare products to receive a 2007 Medical Design Excellence Award. [ 33 ]  As of 2022, the Impella heart pump products include the Impella 2.5, Impella 5.0, Impella CP with SmartAssist, Impella 5.5 with SmartAssist, Impella RP with SmartAssist and Impella Connect, which gives providers 24/7 secure access to Impella status data in the cloud for Impella-supported patients. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3611", "text": "The Abiomed Breethe OXY-1 System is an  extracorporeal membrane oxygenation (ECMO)  system that pumps, oxygenates and removes carbon dioxide from blood of patients suffering from cardiogenic shock or respiratory failure due to ARDS, H1N1, SARS and COVID-19 among other causes. It can be used alone or in conjunction with the Impella heart pump. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3612", "text": "Since 2005 when Abiomed acquired the  Impella  technology, [ 35 ]  the heart devices have received a series of FDA approvals. [ 36 ]  Notably, in 2015, Abiomed received FDA approval to use the Impella 2.5 heart pump during elective and urgent high-risk percutaneous coronary intervention procedures. The FDA approval was based on the PROTECT II randomized controlled trial, which found high-risk percutaneous coronary intervention (PCI) patients who underwent PCI with Impella had fewer major adverse events at 90 days (although statistically non-significant), compared to patients who underwent PCI with the intra-aortic balloon pump (IABP). [ 37 ]  In 2016, the Impella RP system became the first percutaneous single-access heart pump designed for right-heart support to receive FDA approval. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3613", "text": "There is a lack of data from randomized controlled trials for Impella devices in cardiogenic shock, despite calls from the medical community. [ 39 ]  While early studies suggested short term benefits, propensity-matched analyses comparing the Impella device with intra-aortic balloon pump (IABP) showed no benefit for clinically relevant outcomes such as mortality. [ 40 ]  This may be partly due to increased risk of bleeding and peripheral vascular complications with the Impella device. [ 41 ]  Some studies have even suggested an increased risk of mortality with Impella devices, compared to the intra-aortic balloon pump (IABP), with an additional expense of >$50,000 at 30 days. [ 42 ]  There are currently no adequately powered randomized controlled trials of the Impella device for clinically relevant outcomes such as mortality."}
{"_id": "WikiPedia_Cardio$$$corpus_3614", "text": "In 2021, the FDA granted pre-market approval to the Impella RP with SmartAssist, a first single-access, dual-sensor technology device to provide temporary percutaneous ventricular support for patients with acute right heart failure or decompensation after implanting a left ventricular assist device, myocardial infarction, heart transplant or open-heart surgery. [ 43 ]  The FDA also granted breakthrough device designation for its smallest heart pump, the Impella ECP, which measures only 3mm in length. [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3615", "text": "In April 2022, Abiomed's Impella Bridge-to-Recovery (BTR) minimally-invasive heart pump was successfully implanted in the first patient treated with the device as part of an early feasibility study. [ 45 ]  In August 2022, results from the Restore EF study were published in  The Journal of the Society of Cardiovascular Angiography and Interventions . The study demonstrated that Impella-supported high-risk percutaneous coronary intervention (PCI) led to significant improvements in left ventricular ejection fraction (LVEF), angina symptoms, and heart failure symptoms at the 90-day follow-up. [ 46 ]  In October 2022, the FDA granted pre-market approval to the Impella RP Flex with SmartAssist for treatment of acute right heart failure for up to 14 days. [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3616", "text": "Andrew Greenfield is Abiomed's President since the company was acquired by Johnson & Johnson in December 2022. He succeeded Michael R. Minogue who retired after serving as chairman, President and CEO since 2004 when Abiomed's founder, David Lederman, had stepped down. [ 2 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3617", "text": "The  Alliance for Heart Failure  is a coalition of charities, patient groups, professional bodies, public sector organisations and corporate members working together to raise the profile of  heart failure  within the  UK Government , the  National Health Service , and  media .  It was formed in October 2015."}
{"_id": "WikiPedia_Cardio$$$corpus_3618", "text": "The Alliance for Heart Failure's mission is to achieve better outcomes for people with heart failure by ensuring timely diagnosis and access to the right care and support."}
{"_id": "WikiPedia_Cardio$$$corpus_3619", "text": "Current members of the Alliance for Heart Failure are:"}
{"_id": "WikiPedia_Cardio$$$corpus_3620", "text": "The co-chairs are Preeti Minhas from  Health Education for Health  and Richard Corder from  Cardiovascular Care Partnership . They have a 12-month tenure. Day-to-day decisions are made by a steering committee."}
{"_id": "WikiPedia_Cardio$$$corpus_3621", "text": "The Alliance for Heart Failure is supported and funded by  AstraZeneca UK ,  Boehringer Ingelheim Limited ,  Medtronic Limited ,  Novartis Pharmaceuticals UK Ltd , and  Roche Diagnostics Ltd . Funders are not responsible for any of the materials produced by the Alliance for Heart Failure, which are created independently by the Alliance's Secretariat."}
{"_id": "WikiPedia_Cardio$$$corpus_3622", "text": "Heart Failure: A call to action  was published on 22 February 2021. The report evaluates the progress made since the  2016 All Party Parliamentary Group \u2018Focus on Heart Failure\u2019 report  and makes  ten new recommendations  to improve heart failure care and patient outcomes."}
{"_id": "WikiPedia_Cardio$$$corpus_3623", "text": "The report also calls for urgent action to meet the growing demand from a rising number of heart failure cases following the impact of the COVID-19 pandemic  [1]   [2] ."}
{"_id": "WikiPedia_Cardio$$$corpus_3624", "text": "Heart Failure: A call to action was developed with input from heart failure specialists, patient groups, and professional organisations."}
{"_id": "WikiPedia_Cardio$$$corpus_3625", "text": "In 2016, the  All Party Parliamentary Group  on Heart Disease, chaired by  Stuart Andrew MP , held an inquiry into living with  heart failure .  Written and oral evidence was provided by patients, healthcare professionals, and commissioners. The Inquiry's report,  Focus on Heart Failure , was published in September 2016 and made  ten recommendations  for improving heart failure services."}
{"_id": "WikiPedia_Cardio$$$corpus_3626", "text": "Nine members of the Alliance for Heart Failure were co-opted onto an advisory panel for the inquiry.  The panel had ten members in total."}
{"_id": "WikiPedia_Cardio$$$corpus_3627", "text": "The  National Heart Failure Audit  which analysed data from 2020 to 2021, highlighted a serious issue with access to  echocardiography  services, a vital diagnostic tool for heart failure, as well as a problem with follow up specialist care and cardiac rehabilitation for those living long-term with the illness. It also highlighted the chronic challenge of training and developing echocardiographers to ensure sufficient resources to meet demand in the future."}
{"_id": "WikiPedia_Cardio$$$corpus_3628", "text": "The Alliance for Heart Failure  responded to the report  stating that longstanding issues have been exacerbated, rather than caused, by the COVID-19 pandemic."}
{"_id": "WikiPedia_Cardio$$$corpus_3629", "text": "The  National Heart Failure Audit  (2017\u201318), published on 12 September 2019, reported that mortality among patients admitted to hospital remained high overall at 10.1% compared to 9.4% in the previous audit. However, the number of patients seen by heart failure specialists increased to over 82% (from 80% in the last audit), while more than 88% of patients get an echocardiogram. Rates still remain higher for those admitted to Cardiology (92%), however this has decreased since the last report (96%). The rate on General Medical wards remained the same at 84%. The report also recorded an increase in the prescription of key disease-modifying medicines for patients since last year."}
{"_id": "WikiPedia_Cardio$$$corpus_3630", "text": "The Alliance for Heart Failure  responded positively to the report  but called for the regional variation in patient service to be urgently addressed."}
{"_id": "WikiPedia_Cardio$$$corpus_3631", "text": "The  National Confidential Enquiry into Patient Outcome and Death (NCEPOD) , published on 22 November 2018, recommended improvements in the process of care for patients with acute heart failure who died while admitted to hospital as an emergency.  Responding to the report , the Alliance for Heart Failure said that it reinforces the need for urgent action to improve heart failure services, and the important role of heart failure specialist nurses, as part of a full multi-disciplinary heart failure team, in maximising outcomes for patients."}
{"_id": "WikiPedia_Cardio$$$corpus_3632", "text": "The  American Academy of Cardiovascular Perfusion (AACP)  is a professional association located in Fogelsville, PA, that aims to increase knowledge of  cardiovascular   perfusion  by providing educational resources to its members. [ 1 ]  The organization was founded in 1979. [ 1 ]  The AACP was organized in 1979 by Earl Lawrence, who was encouraged to establish the organization by Thomas Wharton. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3633", "text": "This article about a United States health organization is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3634", "text": "The  American College of Cardiology  ( ACC ), based in  Washington, D.C. , is a nonprofit medical association established in 1949. It bestows credentials upon  cardiovascular  specialists who meet its qualifications. Education is a core component of the college, which is also active in the formulation of health policy and the support of cardiovascular research."}
{"_id": "WikiPedia_Cardio$$$corpus_3635", "text": "The American College of Cardiology was chartered and incorporated as a teaching institution in 1949, and established its headquarters, called Heart House, in  Bethesda, Maryland , in 1977. [ citation needed ]  In 2006, the college relocated to  Washington, D.C. 's  West End  neighborhood."}
{"_id": "WikiPedia_Cardio$$$corpus_3636", "text": "Past papers for the institution are held at the National Library of Medicine in Bethesda, Maryland. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3637", "text": "The college is governed by its officers, including the president, president-elect, vice president, secretary, treasurer, chief executive officer and board of trustees (BOT). The current ACC Board of Trustees consists of 14 college members. The president of ACC leads the board of trustees for a one-year term. Members of the board of governors serve as grassroots liaisons between the local chapters and the college's national headquarters. Athena Poppas, MD, FACC, was the president for 2020\u20132021. In July 2023, the college announced that Cathleen Biga, MSN, RN, FACC, would assume the role as president for 2024\u20132025. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3638", "text": "The American College of Cardiology has approximately 54,000 members, including physicians, registered nurses, clinical nurse specialists, nurse practitioners, physician assistants, doctors of pharmacology and practice administrators, specializing in cardiovascular care. Becoming a fellow of the American College of Cardiology, associate fellow or affiliate member is based on training, specialty board certification, scientific and professional accomplishments and duration of active participation in a cardiovascular related field. At least 75 percent of professional activities must be devoted to the field of cardiovascular disease. Those who have long exposure in field of academics, research and patient care are eligible for the fellowship of this college.  The website of ACC has eligibility calculator from which one can find their eligibility score which should be more than 100. Those achieving highest distinction in the field are awarded the title Master of the American College of Cardiology, which is bestowed upon a maximum of three practicing cardiologists each year."}
{"_id": "WikiPedia_Cardio$$$corpus_3639", "text": "The college maintains 48 chapters in the U.S. and Puerto Rico. Chapters are legally distinct entities from national organization and do not share budgets or staffing. Since 2008, national members have automatically become members of a local chapter."}
{"_id": "WikiPedia_Cardio$$$corpus_3640", "text": "As early as the 1980s, the college partnered with the  American Heart Association  to develop the first clinical practice guidelines for cardiovascular practice. In the 1990s, the college used the guidelines to lay the groundwork for studies documenting discrepancies best and actual cardiovascular practices. The college works with national organizations such as the  National Heart, Lung and Blood Institute  to continually develop and update these guidelines."}
{"_id": "WikiPedia_Cardio$$$corpus_3641", "text": "In 2000, the college partnered with the American Heart Association to begin development and publication of national performance measurement standards and data standards for both inpatient and outpatient care based on the guidelines. Measurement sets include:  coronary artery disease ,  hypertension ,  heart failure ,  atrial fibrillation ,  cardiac rehabilitation ,  myocardial infarction ,  primary prevention  and  peripheral arterial disease . In addition, the college has submitted its measures to the  National Quality Forum , with the majority of its measures receiving endorsement as national standards."}
{"_id": "WikiPedia_Cardio$$$corpus_3642", "text": "The college has also collaborated with specialty societies to undertake the task of developing and publishing clinical data standards. Clinical data standards developed include those for acute coronary syndrome, atrial fibrillation, heart failure and  electrophysiology ."}
{"_id": "WikiPedia_Cardio$$$corpus_3643", "text": "The college has published criteria for  single-photon emission computed tomography   myocardial perfusion imaging  (SPECT MPI),  computed tomography  of the heart and  cardiac magnetic resonance imaging , resting  transthoracic  and  transesophageal echocardiography , and coronary revascularization."}
{"_id": "WikiPedia_Cardio$$$corpus_3644", "text": "The college's National Cardiovascular Data Registry is a source for measuring and quantifying outcomes and identifying gaps in the delivery of quality care. Its data are used in select pay-for-reporting and/or performance programs to demonstrate the benefits and challenges of such incentive programs. To date, the college has developed five hospital-based cardiovascular registries. In addition, the PINNACLE Registry is the nation's first and largest practice-based cardiovascular registry. In 2011, the college and The  Society of Thoracic Surgeons  launched the STS/ACC TVT Registry, which tracks transcatheter valve therapy procedures."}
{"_id": "WikiPedia_Cardio$$$corpus_3645", "text": "Currently several key quality initiatives are underway to help translate science into practice and improve outcomes for cardiovascular patients. These projects include the Door to Balloon Alliance, Hospital to Home and Imaging in FOCUS."}
{"_id": "WikiPedia_Cardio$$$corpus_3646", "text": "Launched in November 2006, the Door to Balloon Alliance is focused on helping hospital not only reduce, but successfully sustain the guideline-recommended time of 90 minutes or less from the time a patient with chest pain arrives at an emergency room until they have a balloon dilatation procedure. The alliance provides hospitals with the evidence-based strategies and resources to focus on process improvement, interdisciplinary cooperation and coordination to substantially impact their door-to-balloon times, and thus, improve patient outcomes."}
{"_id": "WikiPedia_Cardio$$$corpus_3647", "text": "The hospital to Home initiative, led by both the American College of Cardiology and the  Institute for Healthcare Improvement , is a national quality improvement campaign to reduce cardiovascular-related hospital rehospitalizations and improve the transition from inpatient to outpatient status for individuals hospitalized with cardiovascular disease. Launched in 2009, it seeks to examine and address readmission problems."}
{"_id": "WikiPedia_Cardio$$$corpus_3648", "text": "Imaging in FOCUS is a community designed to guide implementation of appropriate use criteria and ensure patients are receiving the right care at the right time; the initiative has produced innovations such as pocket cards and mobile applications; access to an online community; and access to webinars, educational programs and performance improvement tools."}
{"_id": "WikiPedia_Cardio$$$corpus_3649", "text": "The American College of Cardiology Foundation offers a variety of educational programs and products tailored to the needs of clinicians in a variety of specialty areas at all stages of their careers."}
{"_id": "WikiPedia_Cardio$$$corpus_3650", "text": "The college also advocates for health policies that allow cardiovascular professionals to provide quality, appropriate and cost-effective care on such issues as Medicare physician payment, medical imaging, health care reform implementation, medical liability reform and funding for prevention and research. The college is also active on policies that address non-communicable diseases."}
{"_id": "WikiPedia_Cardio$$$corpus_3651", "text": "The college also publishes a peer reviewed scientific journal  Journal of the American College of Cardiology  with a high  Impact factor ."}
{"_id": "WikiPedia_Cardio$$$corpus_3652", "text": "The College organizes an annual conference for each year for sharing the latest research in the field of  Cardiology . The college cancelled its flagship conference for the first time since inception of the college for the year 2020 in light of the  COVID-19 pandemic . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3653", "text": "The  American Heart Association  ( AHA ) is a  nonprofit organization  in the United States that funds cardiovascular  medical research , educates consumers on healthy living and fosters appropriate  cardiac  care in an effort to reduce  disability  and deaths caused by  cardiovascular disease  and  stroke . They are known for publishing guidelines on cardiovascular disease and prevention, standards on  basic life support ,  advanced cardiac life support  (ACLS),  pediatric advanced life support  (PALS), and in 2014 issued the first guidelines for preventing strokes in women. [ 1 ]  The American Heart Association is also known for operating a number of highly visible  public service  campaigns starting in the 1970s, and also operates several fundraising events."}
{"_id": "WikiPedia_Cardio$$$corpus_3654", "text": "Originally formed in  Chicago  in 1924, [ 2 ] [ 3 ]  the American Heart Association is currently headquartered in  Dallas , Texas. It was originally headquartered in  New York City . [ 2 ] [ 3 ]  The American Heart Association is a national voluntary health agency. [ 4 ] \nThe mission of the organization, updated in 2018, is \"To be a relentless force for a world of longer, healthier lives.\" [ 5 ]  The organization's work can be divided into five key areas: research; heart and brain health; health equity; advocacy; and professional education and development."}
{"_id": "WikiPedia_Cardio$$$corpus_3655", "text": "In 1924, cardiologists  Paul Dudley White , Hugh D. McCulloch, Joseph Sailer, Robert H. Halsey, James B. Herrick, and, Lewis A. Conner, [ 6 ]  formed the Association for the Prevention and Relief of Heart Disease as a professional society for doctors. In 1948, the organization transitioned into a nationwide voluntary health organization. [ 7 ]  Since 1949, it has funded over $5 billion in cardiovascular, cerebrovascular, and brain health research. [ 8 ]  The organization, now known as the American Heart Association, consists of over 33 million volunteers who are dedicated to improving heart health and reducing deaths from cardiovascular diseases. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3656", "text": "In the 1950s and 1960s, the American Heart Association published several reports and guidelines focused on recommended lifestyles to improve cardiovascular health. This included a 1957 report that said: (1) Diet may play an important role in the pathogenesis of atherosclerosis, (2) The fat content and total calories in the diet are probably important factors, (3) The ratio between saturated and unsaturated fat may be the basic determinant, and (4) A wide variety of other factors besides fat, both dietary and non-dietary, may be important. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3657", "text": "By 1961, these findings had been strengthened, leading to the new 1961 American Heart Association recommendations: (1) Maintain a correct body weight, (2) Engage in moderate exercise, e.g., walking to aid in weight reduction, (3) Reduce intake of total fat, saturated fat, and cholesterol. Increase intake of polyunsaturated fat, (4) Men with a strong family history of atherosclerosis should pay particular attention to diet modification, and (5) Dietary changes should be carried out under medical supervision. These recommendations continued to become more precise from 1957 to 1980, but there maintained \"a general coherence among them\". [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3658", "text": "In 1994, the  Chronicle of Philanthropy , an industry publication, released the results of the largest study of charitable and non-profit organization popularity and credibility. The study showed that the American Heart Association was ranked as the fifth \"most popular charity/non-profit in America\" of over 100 charities researched with 95 percent of Americans over the age of 12 choosing the  Love  and  Like A lot  description categories. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3659", "text": "In 1998, the AHA created the American Stroke Association to help prevent strokes, improve treatments, and maximize recoveries. In 2003, the two organizations created the Get With the Guidelines (GWTG)-Stroke program. [ 11 ]  It is a voluntary registry that hospitals can use to receive the latest scientific treatment guidelines. [ 12 ]  The program also collects data on patient characteristics, hospital adherence to guidelines, and patient outcomes. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3660", "text": "In 2004 the American Heart Association launched the \" Go Red for Women \" campaign [ 13 ]  specifically targeting women, with information about risks and action they can take to protect their health. [ 14 ]  All revenues from the local and national campaigns go to support awareness, research, education and community programs to benefit women. [ 15 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3661", "text": "In 2008, the AHA recommended \u201chands only\u201d CPR as an option for bystanders who want to help keep a cardiac arrest victim alive. [ 16 ] [ 17 ]  This method removes the practice of performing rescue breaths and depends solely on chest compressions. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3662", "text": "On November 30, 2009, The American Heart Association announced a new  cardiac arrest  awareness campaign called Be the Beat. [ 18 ]  The campaign's aim is to teach 12- to 15-year-olds fun ways to learn the basics of  cardiopulmonary resuscitation  and how to use an  automated external defibrillator ."}
{"_id": "WikiPedia_Cardio$$$corpus_3663", "text": "In 2012, the AHA renewed its focus on hands-only CPR by carrying out a national campaign to educate more people on how to perform this method.  Jennifer Coolidge  was a spokesperson for the campaign. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3664", "text": "It also carried out a campaign in 2012 to educate more people on how to carry out hands-only CPR. [ 19 ] [ 20 ] [ 21 ]  The 2012 campaign, which began in  New York City , had  Jennifer Coolidge  as the spokesperson. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3665", "text": "In 2013, the American Heart Association issued a joint guideline recognizing obesity as a disease and recommending its treatment by weight loss. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3666", "text": "In 2014, the American Heart Association issued its first guidelines for preventing strokes in women. [ 1 ]  Just as heart attack systems differ between men and women, men and women also face different stroke risks. For women, the guidelines for preventing strokes focus on factors such as birth control, pregnancy, and depression. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3667", "text": "In 2015, the American Heart Association officially endorsed the  Tobacco 21  campaign, urging local, state and national governments to raise the tobacco and nicotine sales age from 18 to 21. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3668", "text": "In 2016, the American Heart Association, Verily Life Sciences, and AstraZeneca invested $75 million in the One Brave Idea program. The money was awarded to institutions researching new biomarkers, such as genetic and molecular factors, that put individuals at risk for atherosclerosis. [ 25 ] [ 26 ]  It was hoped that the research would help the AHA reach its goals of increasing cardiovascular health by 20% and reducing cardiovascular mortality by 20% by 2020. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3669", "text": "In 2017, the American Heart Association, the American College of Cardiology, and nine other groups redefined high blood pressure for the first time in fourteen years. [ 27 ]  Under the new guidelines, the high blood pressure reading is 130 over 80, a change from the old 140 over 80. The change was made in recognition of the risk of heart disease, disability, and death faced by those with blood pressures at 130 over 80. [ 27 ]  The organization said that they hoped by identifying cardiovascular risks earlier, more people would be able to address the health risks by lifestyle changes instead of medication. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3670", "text": "In 2018, the American Heart Association and American College of Cardiology issued new guidelines for clinicians on the management of  cholesterol  as a way to reduce risk for heart attack and  stroke . Newly included in the guidelines is a recommendation to use coronary artery calcium score if healthcare providers are having difficulty deciding if a patient could benefit from statin medications or should focus solely on lifestyle modifications. The cholesterol guidelines were last updated in 2013. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3671", "text": "In 2020 and 2021, the annual flagship meeting of the organization was held virtually owing to the  COVID-19 pandemic  and resumed as an in-person conference in 2022. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3672", "text": "In June 2024, the American Heart Association celebrated its 100 year anniversary of its founding. [ 30 ]  With the official celebration of its founding, the association was recognized as the nation\u2019s oldest and largest voluntary organization dedicated to fighting heart disease and stroke. [ 31 ]  The association held CPR training, where in many places the first hundred or so people to participate in the 5-minute training were given take-home CPR kits. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3673", "text": "Some of the American Heart Association's research, campaigns, and other work is included here."}
{"_id": "WikiPedia_Cardio$$$corpus_3674", "text": "Since 1949, the association has funded over $5 billion in cardiovascular, cerebrovascular, and brain health research. [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3675", "text": "In 2014, the American Heart Association announced the Strategically Focused Research Network initiative to address \"key strategic issues as determined by the AHA Board of Directors.\" Some of the topics focused on by SFRNs include hypertension, heart failure, heart disease, and health technologies and innovation. [ 34 ] [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3676", "text": "The Go Red for Women campaign started in 2004 to raise awareness that women, and not only men, are vulnerable to heart disease. [ 36 ]  Between 2016 and 2021, the American Heart Association invested $20 million in the Go Red for Women Strategically Focused Research Network. The SFRN also received $52 million from the National Institutes of Health. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3677", "text": "In 2017, the Go Red National Leadership Council was started to engage female executives in the campaign. Additional projects associated with the campaign include Research Goes Red and National Wear Red Day. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3678", "text": "As of 2023, over 900,000 women have joined the campaign and receive updates on what they can do to improve their heart health. The campaign's social media channels had audiences of over 5.3 million in 2022. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3679", "text": "The \"Be the Beat\" challenge encourages people to learn CPR. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3680", "text": "The CEO Roundtable was formed in 2013 and focuses on implementing evidence-based approaches to workplace health. In 2020, the CEOs of CVS Health, Walgreens Boots Alliance, and US Foods joined the association. [ 37 ]  In 2023, there were almost 50 Fortune 100 CEOs in the association. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3681", "text": "In 1998, the association created the American Stroke Association to help prevent strokes, improve treatments, and maximize recoveries. In 2003, the two organizations created the Get With the Guidelines (GWTG)-Stroke program. [ 39 ]  It is a voluntary registry that hospitals can use to receive the latest scientific treatment guidelines. [ 40 ]  The program also collects data on patient characteristics, hospital adherence to guidelines, and patient outcomes. [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3682", "text": "The American Heart Association announced in October of 2024 a grant aimed at improving heart health in rural communities by funding initiatives that address healthcare access and education. This support is expected to enhance resources for prevention and treatment of heart disease in underserved areas. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3683", "text": "This 2023 Spanish-language campaign works to raise awareness among Hispanic Americans about stroke symptoms. The acronym stands for: [ 42 ] [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3684", "text": "The American Stroke Association has launched a new  Spanish-language website,  to educate Hispanic and Latino communities about stroke recognition, prevention, and recovery. [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3685", "text": "This is a joint campaign from the American heart Association and the American Diabetes Association. It works to raise awareness about the connection between diabetes and heart disease. [ 45 ] [ 46 ]  The AHA reports that adults with diabetes are 2-4 times more likely to die from heart disease than adults without diabetes. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3686", "text": "The \"Check. Change. Control.\" program is an evidence-based hypertension management program that encourages blood pressure self-monitoring. In 2019 it was used by more than 315,000 people. [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3687", "text": "This program was started in 2023 to \u201ceducate and prepare teens and adults to be confident to save life in a cardiac emergency.\u201d More than 350,000 people have out-of-hospital cardiac arrests each year, and this program wants to help improve their survival rate. [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3688", "text": "As part of National Wear Red Day, NFL star Damar Hamlin joined the American Heart Association at the Empire State Building to raise awareness about heart health. [ 49 ]  Hamlin, who survived a cardiac arrest on the field during a January 2023 game, shared his experience of how a direct hit caused his heart to stop and emphasized the importance of heart health and emergency response. Cardiologist Dr. Joseph Puma highlighted that timely medical attention, including heart scans, can prevent life-threatening events, urging individuals to seek care if experiencing chest pain, shortness of breath, or other warning signs of heart issues. [ 49 ] [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3689", "text": "Life\u2019s Essential 8 (LE8) are cardiovascular health measurements shared by the AHA. Previously the measurements were known as the LE7, but in 2022, the AHA added sleep health as an additional behavioral metric. The other metrics look at body weight, blood pressure, cholesterol, blood sugar, smoking, physical activity, and diet. [ 51 ] [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3690", "text": "The American Heart Association\u2019s 2024 Impact Goal states, \"Every person deserves the opportunity for a full, healthy life. By 2024, as champions for health equity, the American Heart Association will advance cardiovascular health for all, including identifying and removing barriers to health care access and quality.\" [ 53 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3691", "text": "The AHA partnered with the Deloitte Health Equity Institute and the Society for Human Resource Management Foundation on the Health Equity in the Workforce initiative. The initiative provides tools to help employers improve health equity in the workplace. [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3692", "text": "The AHA's Social Impact Fund is a nationwide fund that provides financial resources for \"evidence-based, community driven entrepreneurial solutions that help remove the social and economic barriers to health equity and drive economic empowerment, healthy food access, affordable housing, access to quality healthcare, transportation, educational opportunities, and reduce recidivism.\" [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3693", "text": "Organizations that have received funding include:"}
{"_id": "WikiPedia_Cardio$$$corpus_3694", "text": "The HSI scholarship program is for students who identify as Hispanic/Latino who are enrolled in public health and healthcare focused programs at 18 Hispanic-serving colleges and universities. [ 58 ] [ 59 ]  The program's goal is to increase representation in health care. [ 60 ]  Students in the program are paired with volunteer mentors. They develop and present a research project that addresses basic, clinical, and educational science, receive a stipend, and participate in professional development workshops. [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3695", "text": "The HBCU Scholars program pairs students with a local American Heart Association researcher and was created to \" support the development of minority scientists and healthcare professionals ,\" and increase the number of minority students who apply and are accepted into biomedical and health science programs. [ 61 ] [ 62 ]   Students and researchers study the impact of cardiovascular disease in their community, learn the factors affecting vulnerable populations, and sample areas of scientific inquiry. [ 62 ]  Students also receive financial stipends. [ 63 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3696", "text": "HeartCorps is the American Heart Association's Public Health AmeriCorps program and is designed to drive health equity in rural America. As of November 2022, twenty-six states participated in the program. [ 64 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3697", "text": "The American Heart Association supports legislation that creates smoke-free workplaces and public spaces. [ 65 ]  Starting in 2014, the AHA called for regulations for e-cigarettes to prevent young people from becoming addicted to nicotine, referencing studies that suggest the e-cigarettes can be a gateway drug. [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3698", "text": "The American Heart Association supports the No Surprises Act, stating it will keep costs and premiums down and encourage more people to seek care from healthcare professionals. [ 67 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3699", "text": "In 2022, the American Heart Association, the Rockefeller Foundation, Kroger, and other partners announced a plan to build a national Food is Medicine Research Initiative to help provide concrete evidence that food-as-medicine programs improve health. [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3700", "text": "In September 2023, the AHA partnered with the National Association of Chain Drug Stores, the American Cancer Society, the American Diabetes Association, and the Food is Medicine Institute at the Friedman School of Nutrition Science and Policy at Tufts University to launch  Nourish My Health . It is a national public education campaign that promotes the protective health benefits of nutritious food. [ 68 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3701", "text": "You're the Cure is the national grassroots network of the American Heart Association. [ 69 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3702", "text": "The American Heart Association publishes healthcare guidelines, statements, and performance measures.A small sample of these professional education and development resources include:"}
{"_id": "WikiPedia_Cardio$$$corpus_3703", "text": "The AHA also holds an annual Scientific Sessions meeting, which covers several days and a number of medical/healthcare topics; and hosts an International Stroke Conference. [ 75 ] [ 76 ] [ 77 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3704", "text": "The Second Century of Science Initiative was announced in 2023 as part of the AHA\u2019s plans to celebrate its first 100 years. Under the Initiative, the AHA awarded $20 million in grants to over 100 scientists in the U.S. The grants were awarded in three categories: the Second Century Implementation Science Award, the Second Century Early Faculty Independence Award, and the Clinical Fellow Research Education Program  [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3705", "text": "In 2003, the AHA and the American Stroke Association created the Get With the Guidelines (GWTG)-Stroke program. [ 78 ]  It is a voluntary registry that hospitals can use to receive the latest scientific treatment guidelines. [ 79 ]  The program also collects data on patient characteristics, hospital adherence to guidelines, and patient outcomes. [ 78 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3706", "text": "Fellowship is open to wide-ranged medical professionals (physicians, scientists, etc.) who demonstrate a major and productive interest in cardiovascular diseases and stroke. The association has 16 different councils. Members (at the Premium Professional or Premium Professional Plus level) of one of these councils can apply for Fellowship. All applicants from all councils will be evaluated against the same criteria. Fellows are entitled to use the post-nominal designation FAmerican Heart Association (Fellow of the American Heart Association), which reflects not only the professional stature of the Fellow but also their record of valuable service to the association and the council. In addition, American Heart Association fellowship offers several benefits; e.g., reduced subscription rates for all American Heart Association print journals and reduced registration fees for American Heart Association Scientific Sessions. [ 80 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3707", "text": "Nancy Brown is the CEO of the American Heart Association. [ 81 ] [ 82 ]  Joseph Wu is the volunteer president and Marsha Jones is the volunteer chairperson. [ 83 ]  Nancy Brown has been the chief executive officer since 2009."}
{"_id": "WikiPedia_Cardio$$$corpus_3708", "text": "The following journals are published by the American Heart Association:"}
{"_id": "WikiPedia_Cardio$$$corpus_3709", "text": "The  Association for Inherited Cardiac Conditions  is the UK national professional body for experts in  genetics  and  cardiology  dealing with inherited diseases of the  heart . [ 1 ]  These include heart muscle diseases such as  hypertrophic cardiomyopathy ,  dilated cardiomyopathy ,  noncompaction cardiomyopathy , and arrhythmogenic cardiomyopathy (also known as  arrhythmogenic right ventricular dysplasia ), as well as inherited arrhythmia disorders such as  long QT syndrome ,  Brugada syndrome , and  catecholaminergic polymorphic ventricular tachycardia  (CPVT). The AICC also represents experts in aortic disease such as  Marfan syndrome  and other systemic diseases which affect the heart or circulation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3710", "text": "Individually, many of these diseases are rare, but in total they affect a large number of people worldwide. They are an important cause of sudden death in young people. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3711", "text": "The AICC was set up in 2009 as part of NHS improvement. [ 3 ] [ 4 ]  The first President was Professor William McKenna. [ 5 ]  It holds an annual conference as well as sessions at the annual meeting of the British Cardiovascular Society [ 6 ]  and the Heart Rhythm Congress. [ 7 ]  Its members are involved in research into the natural history, diagnosis and management of these diseases, including projects such as the 100,000 Genomes Project run by  Genomics England [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3712", "text": "The  AF Association  ( AF\u2013A ) is an international  charity  that provides information and support for patients suspected of having, or diagnosed with  atrial fibrillation  (AF); the most common heart rhythm disorder. [ 1 ]  The AF Association also works to campaign for greater awareness of AF amongst the general public and increase education for  healthcare professionals  and service providers involved in the management of AF. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3713", "text": "In 2007, the AF-A was founded by Mrs Trudie Lobban MBE, Professor A John Camm, Professor Richard Schilling and Consultant Arrhythmia Nurse Mrs Jayne Mudd. The charity was formed after requests from  arrhythmia  patients seeking reliable information and support about this heart rhythm disorder. There are currently over 20,000 members and 30 affiliated groups established worldwide. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3714", "text": "The charity partners with Arrhythmia Alliance (A-A) to facilitate educational meetings and symposia for healthcare professionals, including sessions at the annual Heart Rhythm Congress [ 2 ]   and regional Cardiac Update Meetings held across the UK. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3715", "text": "Know Your Pulse - Since 2009 the AF Association has been campaigning for manual pulse checks to be included in all routine medical checkups carried out by the NHS in England. [ 5 ]  A manual pulse check is one of the easiest ways to detect a cardiac arrhythmia, which otherwise often goes untreated until a stroke or other serious illness occurs."}
{"_id": "WikiPedia_Cardio$$$corpus_3716", "text": "ACT on AF: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3717", "text": "Ask \u2013 are you at risk of AF?;"}
{"_id": "WikiPedia_Cardio$$$corpus_3718", "text": "Check \u2013 your pulse regularly;"}
{"_id": "WikiPedia_Cardio$$$corpus_3719", "text": "Talk \u2013 to your doctor if you have any concern."}
{"_id": "WikiPedia_Cardio$$$corpus_3720", "text": "This includes the annual ACT on AF Friday."}
{"_id": "WikiPedia_Cardio$$$corpus_3721", "text": "Heart Rhythm Week  - in collaboration with Arrhythmia Alliance. Held annually during the first week of June this event involves extensive activities with individuals, groups, medical centres and celebrities focused on raising awareness and greater understanding of AF. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3722", "text": "Sign Against Stroke  - Patient organisations from twenty countries produced the Global Atrial Fibrillation Charter. [ 7 ]  Launched at the World Heart Federation, World Congress of Cardiology Scientific Sessions in Dubai on 18 April 2012. The aim of the charter is to turn the world's attention to atrial fibrillation and AF-related stroke. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3723", "text": "Stop Start Campaign  - supported by the AF Association this initiative seeks to educate healthcare practitioners on the benefits of anticoagulation in AF management, and the inappropriateness of antiplatelet therapy for the prevention of AF-related strokes. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3724", "text": "AF Patient Days - held during the annual Heart Rhythm Congress, Birmingham UK, Europe AF, London UK and at a number of US centres. The AF Association hosts a day of seminars and discussion for those affected by AF. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3725", "text": "Regional Cardiac Update meetings - in association with Arrhythmia Alliance these are designed for healthcare professionals involved in the management of arrhythmias. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3726", "text": "AF Symposium at the Heart Rhythm Congress - held annually in Birmingham, UK. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3727", "text": "GRASP The Initiative (2012) [ 8 ]   - in collaboration with NHS Improvement (NHSI) Heart & Stroke, this report showcases the merits of using the NHS free assessment tool \u2013 GRASP (Guidance on Risk Assessment and Stroke Prevention)."}
{"_id": "WikiPedia_Cardio$$$corpus_3728", "text": "Keeping The Pulse of the NHS (2012) - in collaboration with A-A and Anticoagulation Europe (ACE) this highlights the lottery of quality AF care across England immediately prior to April 2013's NHS changes. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3729", "text": "The AF Report (2011) [ 9 ]   - documents current challenges and options in AF care across England and Wales."}
{"_id": "WikiPedia_Cardio$$$corpus_3730", "text": "Finger on The Pulse (2009 England, 2010 Wales) - evidences the burden of AF for patients and the healthcare services. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3731", "text": "In 2011 an All-Party Parliamentary Group on atrial fibrillation (APGAF) was established in partnership with the AF Association. It is chaired by  Glyn Davies MP , who is himself affected by AF. [ 10 ]  The APGAF has published a number of reports on improving AF care in the NHS. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3732", "text": "The AF-Association receives approximately 60% of its funding from donations, and the remainder from grants. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3733", "text": "The  Baker Heart and Diabetes Institute , commonly known as the  Baker Institute , is an Australian independent  medical research   institute  headquartered in  Melbourne ,  Victoria . Established in 1926, the institute is one of Australia's oldest medical research organisations with a historical focus on  cardiovascular disease . In 2008, it became the country's first medical research institute to target  diabetes ,  heart disease ,  obesity  and their complications at the basic, clinical and population health levels."}
{"_id": "WikiPedia_Cardio$$$corpus_3734", "text": "The Institute is located adjacent to  The Alfred Hospital  within the Alfred Research Alliance Precinct."}
{"_id": "WikiPedia_Cardio$$$corpus_3735", "text": "The Baker Institute's work ranges from cellular and molecular biology research in the laboratory to clinical-based research through to lifestyle and behavioural research that aims to inform prevention strategies."}
{"_id": "WikiPedia_Cardio$$$corpus_3736", "text": "The Institute has identified key areas of strength to enable scientists to channel their talents and energy in answering big-picture questions. Each of these Research Programs is led by senior Institute scientists. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3737", "text": "The Institute's domains provide the management structure for the Institute and bring researchers of kindred skills together."}
{"_id": "WikiPedia_Cardio$$$corpus_3738", "text": "The Baker Medical Research Institute was the creation of Dr. John F. Mackeddie, a clinical doctor and researcher, who had the idea of improving the laboratory facilities at The Alfred Hospital to keep up with advances in research. Mackeddie persuaded his friend, the photography industry pioneer and philanthropist Thomas Baker and his wife, Alice and sister-in-law, Eleanor Shaw, to assume financial responsibility. They decided the Institute should not only provide a better laboratory service for the hospital but should also have facilities for medical research. [ 21 ] :\u200a3\u20137"}
{"_id": "WikiPedia_Cardio$$$corpus_3739", "text": "In 1926, prior to appointing its first director, the Baker Institute hired Australian  bacteriologist  and  biochemist  Phyllis Ashworth as its first biochemist and  electrocardiographer . Ashworth worked with the Institute's newly acquired Cambridge electrocardiograph, alongside her research into  eclampsia . [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3740", "text": "Dr. William J. Penfold, who was internationally renowned in bacteriology and preventative medicine and was prominent in establishing the Australian Medical Research Council, [ 23 ]  was the first director of the Baker from 1926 until 1938. [ 21 ] :\u200a15\u201320\u200a  He was followed by Dr. Arthur B. Corkill, who first came to the Institute as a biochemist. [ 21 ] :\u200a20\u201322\u200a  Corkill described the methods of diagnosis and treatment of diabetes mellitus at The Alfred Hospital in 1927. [ 24 ]  Twenty years later, in 1947, a young biochemist called Joe Bornstein was introduced to Corkill. Their work together resulted in the discovery of the two forms of diabetes\u2014insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM). [ 25 ]  This discovery in 1949 \"... literally changed the concepts, research and treatment of diabetes\". [ 26 ] :\u200a37"}
{"_id": "WikiPedia_Cardio$$$corpus_3741", "text": "From 1949 until 1974, Dr. Thomas E. Lowe was the institute's director. [ 21 ] :\u200a23\u201330\u200a  With a team of notable investigators, Lowe developed the Baker into a major research organisation with world-class facilities. [ 27 ]  The team included:"}
{"_id": "WikiPedia_Cardio$$$corpus_3742", "text": "It was during this time that cardiovascular research became the major focus. Research included the further development of cardiovascular surgery; new techniques of ECG and phonocardiography; treatment of congestive cardiac failure and of arterial hypertension. Sir James Officer Brown researched and tested open heart surgery in pre-clinical trials with the support of the Baker Institute, paving the way for Australia's first successful open heart operation at The Alfred Hospital in 1957 which was undertaken by Kenneth Morris. [ 20 ] :\u200a81\u201383\u200a  Morris went on to make major contributions to cardiac and thoracic surgery, alongside George Stirling (Director of the Cardiothoracic Surgery Unit at The Alfred Hospital from 1971 to 1988), with strong support from the Baker Institute in trialling and developing new cardiothoracic techniques. [ 20 ] :\u200a101\u200a [ 20 ] :\u200a119\u2013126"}
{"_id": "WikiPedia_Cardio$$$corpus_3743", "text": "Professor Paul Korner  AO , a cardiac physiologist noted for his contributions to the understanding of hypertension, took on the role of director in 1975 [ 20 ] :\u200a86\u200a  and by this time, the sole focus of the institute was cardiovascular disease research. Significant advancements during this time included new strategies for hypertension; greater understanding of the role of the autonomic nervous system; insight into the role of cholesterol in atherogenesis and triglycerides as an independent risk factor for coronary atherosclerosis. [ 33 ] :\u200a151\u2013157\u200a   Notable investigators included Paul Nestel (nutrition, CVD, atherosclerosis and lipid metabolism),  Murray Esler  (causes and treatment of high blood pressure and heart failure, and effects of stress on the cardiovascular system) and Garry Jennings (causes, prevention and treatment of CVD, and relationship between exercise, blood pressure, sympathetic nervous system activity and glucose metabolism)."}
{"_id": "WikiPedia_Cardio$$$corpus_3744", "text": "Other notable investigators whose work would come to have a significant bearing on the Institute included Paul Zimmet, who pioneered Australia's first institute dedicated exclusively to diabetes. [ 34 ]  His research in Australian, Pacific, and Indian Ocean populations has highlighted the rise of diabetes worldwide, providing new insights into the genetic and environmental determinants of type 2 diabetes."}
{"_id": "WikiPedia_Cardio$$$corpus_3745", "text": "Professor  John Funder   AC  was appointed Director in 1990 and bought his work on cardiovascular endocrinology, especially aldosterone action to the institute. Funder rewrote the pathophysiology of adrenal steroid action in the cardiovascular system, reshaping what we believe about aldosterone, cortisol and mineralcorticol receptors. [ 35 ]  He was recognised for his contributions to public policy across primary health issues."}
{"_id": "WikiPedia_Cardio$$$corpus_3746", "text": "In 2001, cardiologist-researcher Professor Garry Jennings AO became the institute's sixth director. Under Jennings' leadership, the Institute grew substantially and by 2002, the Institute had its own purpose-built facilities adjacent to The Alfred Hospital. By 2007, a national Aboriginal Health research program was established [ 36 ]  to help address the profound health disadvantage experienced by Aboriginal Australians and Torres Strait Islanders. Jennings also oversaw one of the most significant changes in the institute's history, the merger in 2008 of the Baker Heart Research Institute [ 37 ]  with the International Diabetes Institute, which was founded and led by Zimmet. This created Australia's first multidisciplinary medical research institute dedicated to the prevention and treatment of cardiovascular disease, diabetes, obesity and their complications, such as kidney disease."}
{"_id": "WikiPedia_Cardio$$$corpus_3747", "text": "In January 2016, Professor Thomas Marwick was appointed Director of the Institute. Professor Thomas Marwick FACC FESC FRCP FRACP had been Director of the Menzies Institute for Medical Research at the University of Tasmania and a Cardiologist at the Royal Hobart Hospital. He holds an MBBS from the University of Melbourne, a PhD from the University of Louvain and an MPH from Harvard School of Public Health. He has previously held the role of Head of the Cardiovascular Imaging, Heart and Vascular Institute and Imaging Institute at the Cleveland Clinic."}
{"_id": "WikiPedia_Cardio$$$corpus_3748", "text": "In May 2023, the Baker Institute appointed respected cardiovascular researcher and cardiologist Professor John Greenwood MBChB, PhD as their new Director. Professor Greenwood was the Director of the Cardiovascular Clinical Research Facility at Leeds Teaching Hospitals NHS Trust in the United Kingdom and President of the British Cardiovascular Society."}
{"_id": "WikiPedia_Cardio$$$corpus_3749", "text": "J. F. Mackeddie, a pathologist originally from Scotland, but who practised in Melbourne in the early 20th century, became a close friend of Thomas Baker through being neighbours on land south of the city. Mackeddie was \"concerned with the science of diseases and the need to apply the advancing knowledge of biological science to human illness\u2026\u201d [ citation needed ]  After convincing Baker to donate funds, firstly to the Alfred Hospital and then for research, he went on to become one of the founding Trustees of the Baker Medical Research Institute. Mackeddie recruited A. B. (Basil) Corkill as a biochemist for the new Institute. The salary was paid by Thomas Baker."}
{"_id": "WikiPedia_Cardio$$$corpus_3750", "text": "The only consistent basic research in relation to diabetes and carbohydrate metabolism in the 20 years from 1925 was carried out at the Baker Institute in Melbourne."}
{"_id": "WikiPedia_Cardio$$$corpus_3751", "text": "The initial project dealt with new techniques for diagnosing diseases of the nervous system, in particular, the changes in cell content and chemistry of  cerebro-spinal fluid  in various diseases. [ 21 ] :\u200a66\u200a  Other projects in the early days involved  bacteriology , at the time the institute was started, the advancing edge of scientific medicine, and its application to the management of  infectious disease  in man. In the 1930s microbiology was a focus, with many of those projects reliant upon  blood cultures  and the techniques developed were published in a monograph \u2013 \"Blood Cultures and their Significance\" by H Butler in 1937. The Monograph Series lasted until 1974 \u2013 with 9 published. They covered  anaesthesia ,  tumours , the  cardiovascular system  and  scleroderma ."}
{"_id": "WikiPedia_Cardio$$$corpus_3752", "text": "Basil Corkill described the methods of diagnosis and treatment of diabetes mellitus at the Alfred Hospital in 1927. [ 24 ]  Twenty years later, in 1947, Joe Bornstein a young  biochemist  was introduced to Basil Corkill, who by then was Director of the Baker Institute. Their work together resulted in the discovery of the 2 forms of diabetes \u2013 insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM). [ 25 ]  This discovery in 1949 \u201c..literally changed the concepts, research and treatment of diabetes\". [ 26 ] :\u200a37"}
{"_id": "WikiPedia_Cardio$$$corpus_3753", "text": "In the circumstances of the formation of the Institute it was to be expected that much of the research, at least in the earlier years, would be directed to the application of existing knowledge to the practical problems of clinical medicine."}
{"_id": "WikiPedia_Cardio$$$corpus_3754", "text": "In their collection of memoirs of Baker Medical Research Institute Alumni, Andrew and Barnett describe the work of the Baker Institute to have \u201c..always been in the interface between scientific medicine and the practice of medicine, a field engendered and enhanced by its association with Alfred Hospital\". [ 33 ] :\u200a50\u200a  They remark that from its earliest days, the staff were involved in communicating the outputs of research to the clinical community and the community in general. An example being the statewide tours of Victoria that Basil Corkill and Ewen Downe made to introduce the new insulin treatment of diabetes mellitus. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3755", "text": "In 1940, Paul Fantl became interested in  blood clotting . At the time, synthetic  Vitamin K  was being produced and was often in short supply. Using very simple equipment \u2013 test tubes, water bath, stop watches and a  centrifuge  \u2013 he was \"in the forefront of a revolutionary concept that led to the recognition of Factors V, VII, and X\", and with Miss Nance, internationally credited with the discovery of Factor V. [ 21 ] :\u200a103\u200a  He went on to become a member of the International Committee for the Standardisation of the Nomenclature of Blood Clotting Factors in 1956. In 1963 he was honoured when the Fantl-Koller Schema was declared. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3756", "text": "Other areas of research up to 1949 included  asthma ,  eye disease ,  immunoproteins ,  scleroderma  and surgery. The research on surgery lead to the development of cardiac surgery at the Alfred Hospital."}
{"_id": "WikiPedia_Cardio$$$corpus_3757", "text": "In the 1950s Tom Lowe decided to make a study of congestive heart failure. He concluded \"that the body's fluid system was an 'open system' with an intake and output and divisions of the contents under control of various factors\". [ 20 ] :\u200a272\u200a  He was also interested in  electrocardiography , especially vector cardiography and had machines constructed to show the three-dimensional view."}
{"_id": "WikiPedia_Cardio$$$corpus_3758", "text": "Between 1949 and 1974, staff at the Baker Medical Research Institute also devoted a significant amount of time and energy to equipment construction to meet the needs of their researchers, this included some early, crude versions of  heart-lung machines  to aid in cardiac surgery. [ 20 ] :\u200a122\u200a  Some research on the  alimentary canal  also was undertaken, however this work ceased in 1968. [ 21 ] :\u200a68\u201374"}
{"_id": "WikiPedia_Cardio$$$corpus_3759", "text": "In 1949, cardiovascular research was one of the major growth edges of medicine was cardiology. At the time, it represented two-thirds of the total research in the Baker Medical Research Institute. Cardiology research included:"}
{"_id": "WikiPedia_Cardio$$$corpus_3760", "text": "The International Diabetes Institute was started in Melbourne in 1984 by Professor Paul Zimmet  AO  a number of years after his appointment to the Royal Southern Memorial Hospital. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3761", "text": "\"The research of Paul and his team in Pacific and Indian Ocean populations has provided new insights into the genetic contribution of NIDDM as well as the role of obesity, physical activity, nutrition and sociocultural change in the  aetiology  of this disorder\". [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3762", "text": "In 1980 Zimmet was asked by the Council of the Australian Diabetes Society to prepare a submission, along with colleague Dr Ian Martin, titled 'Diabetes in Australia'. The submission was to the Federal Minister of Health. The submission highlighted the impact of diabetes in the community and what government needed to invest to find a cure or treatment and to support people with diabetes. [ 26 ] :\u200a75\u200a  At the same time, with Drv Matthew Cohen, Zimmet was the first to report their experience with home glucose monitoring and its acceptance in the diabetic population. They found better control, less  hypoglycaemia  and 95% acceptance. [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3763", "text": "One of the most significant contributions of the International Diabetes Institute has been the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). In 2000 it was the first national study to provide estimates of the number of people with diabetes (based on blood tests) and its public health and societal impact. It is now considered an integral component of the National Diabetes Strategy to tackle the mounting problem of diabetes and its complications in Australia. [ 40 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3764", "text": "In addition to research, the IDI operated diabetes clinics in Melbourne from the site of the Caulfield Hospital. The diabetes clinics are the largest in Victoria, with more than 8000 patients per year and continue to be operated by Baker IDI from the organisation's site in Prahran in Melbourne's inner south-east."}
{"_id": "WikiPedia_Cardio$$$corpus_3765", "text": "In 2008 the Baker Heart Research Institute, as it was then known, merged with the International Diabetes Institute which had operated in Melbourne for over 25 years. [ 26 ] :\u200a69"}
{"_id": "WikiPedia_Cardio$$$corpus_3766", "text": "Baker IDI Heart and Diabetes Institute houses  World Health Organization  Collaborating Centres for Research & Training in Cardiovascular Disease [ 41 ]  and Diabetes (WHO Collaborating Centre for the Epidemiology of Diabetes Mellitus and Health Promotion for NCD Control). [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3767", "text": "In 2017 the Baker Institute streamlined their name and became the Baker Heart and Diabetes Institute."}
{"_id": "WikiPedia_Cardio$$$corpus_3768", "text": "Research, education to the public, health professionals, biomedical research students and patient care are located within the Alfred Medical Research and Education Precinct in Melbourne and  Adelaide  and the Baker IDI Centre for Indigenous Vascular and Diabetes Research in Alice Springs. International projects in heart disease and diabetes are currently conducted in  Mauritius ,  South Africa ,  Fiji ,  India  and  Vietnam ."}
{"_id": "WikiPedia_Cardio$$$corpus_3769", "text": "The Baker Heart Research Institute is funded from a diverse range of Government and private sources including the corporate sector, trusts and foundations and individual donors. Financial supporters from the  pharmaceutical industry  since 2016 include  Abbott Laboratories ,  Amgen ,  AstraZeneca ,  Bayer ,  Boehringer Ingelheim ,  Eli Lilly and Company ,  GlaxoSmithKline ,  Merck & Co. ,  Novo Nordisk ,  Pfizer  and  Sanofi . The  United States government  has also provided funding through the  Centers for Disease Control and Prevention  and  National Institutes of Health . [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3770", "text": "In 2007 the Baker IDI Concise Financial Report showed receipts from granting bodies of $32.6 million. A further $7.4 million came from donations and bequests and $20.27 million from commercial income. [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3771", "text": "The institute was a founding partner of the Alfred Medical Research and Education Precinct in 2002, which also includes Alfred Health,  Monash University ,  Burnet Institute ,  La Trobe University  and  Deakin University . [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3772", "text": "The Baker Institute is also a partner of Monash Partners Academic Health Science Centre, an Australian health industry, research and educational collaboration. [ 46 ]  In March 2015, Monash Partners was recognised by the  National Health and Medical Research Council  as one of four Advanced Health Research and Translation Centres in Australia. [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3773", "text": "Baker Institute's longest partnership has been with The Alfred Hospital, which dates back to the institute's inception in 1926 on the hospital site. One of the significant developments of this partnership has been the Alfred Baker Medical Unit, which was established in 1949 and is the hub of joint research and clinical activity between the two institutions. [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3774", "text": "The  Blood Pressure Association  (or BPA) is a British  charitable organisation , established in October 2000, that seeks to provide information and support to people with high blood pressure (also known as  hypertension ) and to educate the general public about the importance of  blood pressure  to health."}
{"_id": "WikiPedia_Cardio$$$corpus_3775", "text": "It is based at  St George's Hospital  in  Tooting ,  London ."}
{"_id": "WikiPedia_Cardio$$$corpus_3776", "text": "Every second week of September the Association runs a Blood Pressure Testing Week as part of its  Know Your Numbers  campaign, where doctors, nurses, pharmacists and trainers offer free blood pressure tests in  hospitals ,  pharmacies , health centres and shopping centres throughout the UK.  Sir David Attenborough  was appointed patron of the Association in May 2005."}
{"_id": "WikiPedia_Cardio$$$corpus_3777", "text": "The  British Cardiovascular Society  (BCS) is a United Kingdom-wide health organisation based in London. It aims to represent all healthcare professionals working in the field of cardiology, set standards for prevention, diagnosis, and clinical care, and communicate those standards to the community and the patients through training, education and public outreach."}
{"_id": "WikiPedia_Cardio$$$corpus_3778", "text": "The first idea for the BCS came in 1910 by the Scottish  cardiologist  Sir  James Mackenzie . At an Association of Physicians meeting in Oxford on 22 April 1922, the Cardiac Club was formed by 5 cardiologists:  Carey F. Coombs ,  T. F. Cotton , John Cowan,  A. G. Gibson  (as chair), and  W. E. Hume . It was founded in 1922 at the Club's first active meeting by 15 founder members \u2014 the original five plus ten others, including  Thomas J. Horder  and  Thomas Lewis  \u2014 and with one honorary member, namely Mackenzie. [ 1 ]  In April 1937 it became the Cardiac Society of Great Britain and Ireland. In 1946 it became the  British Cardiac Society ."}
{"_id": "WikiPedia_Cardio$$$corpus_3779", "text": "It was incorporated (03005604) on 1 January 1995 as the British Cardiac Society. [ 2 ]  It became the British Cardiovascular Society on 8 May 2006. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3780", "text": "It produces the  Heart journal ; this was established in 1939 as the  British Heart Journal . The Editor is  Catherine Otto . Another journal it produces is called  Open Heart ."}
{"_id": "WikiPedia_Cardio$$$corpus_3781", "text": "It is situated in  Fitzrovia  in the  London Borough of Camden . It became a UK Registered Charity in 2002. Its membership (2,500) included doctors and nurses. It is an affiliate of the  European Society of Cardiology . [ 4 ]  The current President of the Society for the 2018\u20132021 term is Simon Ray, Honorary Professor of Cardiology of  Manchester University . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3782", "text": "51\u00b031\u203224.8\u2033N   0\u00b08\u203223.0\u2033W \ufeff / \ufeff 51.523556\u00b0N 0.139722\u00b0W \ufeff /  51.523556; -0.139722"}
{"_id": "WikiPedia_Cardio$$$corpus_3783", "text": "This article about an organisation in the  United Kingdom  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3784", "text": "The  British Heart Foundation  ( BHF ) is a cardiovascular research  charity  in the United Kingdom. [ 5 ]  It funds medical research related to heart and circulatory diseases and their risk factors, and runs influencing work aimed at shaping public policy and raising awareness. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3785", "text": "In 2021, a study conducted by YouGov ranked the British Heart Foundation as the top charity or organisation in the UK by per cent of adults who hold a positive opinion of the organisation. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3786", "text": "The British Heart Foundation was founded in 1961 by a group of  medical professionals  who were concerned about the increasing  death rate  from  cardiovascular disease . They wanted to fund extra research into the causes, diagnosis, treatment, and prevention of heart and circulatory diseases. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3787", "text": "Dr Charmaine Griffiths has been the BHF's Chief Executive since February 2020, succeeding Simon Gillespie OBE.\nProfessor Bryan Williams OBE became the charity's first Chief Scientific and Medical Officer (CSMO) in December 2023, after Professor Sir  Nilesh Samani  stood down as Medical Director after more than 7 years in the role. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3788", "text": "The BHF's Board of Trustees is made up of up to 14 Trustees, and is a mix of medically-qualified and lay members: [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3789", "text": "Karen A. Frank is the Chair of the Board of Trustees."}
{"_id": "WikiPedia_Cardio$$$corpus_3790", "text": "King Charles III  has been the BHF's Patron since May 2024, succeeding  Prince Philip, Duke of Edinburgh . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3791", "text": "The British Heart Foundation's main focus is to fund cardiovascular research, aiming to spend around \u00a3100 million a year funding scientists around the UK. They are currently funding over 1000 research projects. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3792", "text": "Since 2008 the BHF has been investing in Centres of Research Excellence. The six current centres bring together scientists from a number of disciplines to work on research projects to beat heart and circulatory disease. [ 12 ] \nThe current Centres of Research are:"}
{"_id": "WikiPedia_Cardio$$$corpus_3793", "text": "In 2013 the BHF committed to funding three multi-institution Centres of Regenerative Medicine, investing \u00a37.5 million over four years to fund scientists looking for new treatments for  heart failure . [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3794", "text": "The British Heart Foundation Clinical Research Collaborative was launched in 2019, hosted by the  British Cardiovascular Society . [ 14 ]  Designed to support the planning of high-quality national cardiovascular research, it brings together professional societies, research groups and patient and public involvement to better coordinate and prioritise research efforts. [ 14 ]  It also launched a fund to support the development of clinical research in cardiovascular disease, providing grants from \u00a35,000-20,000, and all topic ideas will be considered. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3795", "text": "Other patients and public activities include:"}
{"_id": "WikiPedia_Cardio$$$corpus_3796", "text": "In 2020, The British Heart Foundation had a net income of just over \u00a3107m. [ 17 ]  In the same year, the BHF spent over \u00a393m on funding cardiovascular research. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3797", "text": "The charity announced, in June 2021, that it had joined forces with leading cardiovascular research funders around the world to form the Global Cardiovascular Research Funders Forum (GCRFF). [ 19 ]  In addition to the British Heart Foundation, the Forum's members are:"}
{"_id": "WikiPedia_Cardio$$$corpus_3798", "text": "In 2019, The British Heart Foundation launched the Big Beat Challenge, a global competition with a single award of \u00a330m for the research team who proposed a transformational solution to any cardiovascular disease. [ 21 ]  The Big Beat Challenge was open to applications from any country globally, and accepted proposals in any research area related to cardiovascular disease. Based on a panel of BHF research-funding committee members and an International Advisory panel, a shortlist was finalised in January 2020 to include a robotic heart, a 'Google map' of atherosclerosis, a project harnessing artificial intelligence (AI) and wearables to create a cardiovascular digital twin of a patient, and a genetic cure for inherited heart conditions. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3799", "text": "CureHeart, led by co-PIs Professor  Hugh Christian Watkins  and Professor  Christine Seidman , which aims to find a cure for genetic cardiomyopathies, was announced as the winner of the Big Beat Challenge in July 2022. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3800", "text": "BHF fundraising events accounted for nearly \u00a354m of income in 2019-20. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3801", "text": "The BHF won the bid to be named as the London Marathon charity partner for the 2022 raise, aiming to raise \u00a33m through the partnership to invest in clinical research. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3802", "text": "The annual London to Brighton Bike Ride is a flagship fundraising event, with over 16,000 cyclists and raising over \u00a32.8m. [ 26 ]  The event was cancelled in 2020 and 2021, and was expected to return in 2022 with PureGym as the sponsor. [ 26 ] [ needs update ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3803", "text": "The BHF runs the largest network of charity shops in the UK, and generates income through online sales too. [ 27 ]  As of 2021, they run around 730 shops which include over 160 furniture and electrical shops selling up to 85,000 items daily. [ 28 ]  The BHF Retail division makes roughly \u00a330 million every year. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3804", "text": "In June 2011, the British Heart Foundation was one of several health charities, alongside  Cancer Research UK , the  Alzheimer's Society  and  Parkinson's UK , targeted by animal rights pressure group  Animal Aid , in a series of newspaper advertisements urging the public not to donate to the organizations under the pretence of funding experiments on animals. [ 32 ] [ 33 ]  The pressure group argued that 100 dogs had died since 1988 during the experiments. [ 34 ] [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3805", "text": "The BHF has responded to these criticisms by saying the charity only funds animal research after grant applications have gone through an independent peer review process and follows the  three Rs  principles when considering such grants. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3806", "text": "In 2016, the BHF was fined by the UK  Information Commissioner's Office  which ruled that the charity had breached data protection legislation by employing external bodies to analyse the financial status of supporters in order to appeal to them for further donations, a practice known as 'wealth screening'. [ 37 ]   BBC News Online  reported that, \"Information Commissioner Elizabeth Denham said donors had not been informed of the charity's practices, and were therefore unable to consent or object to them.\" She suggested other charities could also be engaged in similar activities. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3807", "text": "The charity's chief executive stated that \"The ICO's conclusions were 'wrong, disproportionate and inconsistent [\u2026] We find the decision surprising, as earlier this year in June the ICO praised our data handling. Our trustees will therefore consider whether it's in the interests of our supporters and beneficiaries to challenge this decision.\" [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3808", "text": "The  Canadian Cardiovascular Society  ( CCS ) is the national voice for cardiovascular physicians and scientists in Canada. The CCS is a membership organization that represents more than 1,800 professionals in the cardiovascular field. Its mission is to promote cardiovascular health and care through knowledge translation, professional development and leadership in health policy. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3809", "text": "The official journal of the Canadian Cardiovascular Society is the  Canadian Journal of Cardiology  (editor-in-chief \u2013 Stanley Nattel)."}
{"_id": "WikiPedia_Cardio$$$corpus_3810", "text": "On April 2, 2014, the Society released a list of \"Five Things Physicians and Patients Should Question\" as part of the Choosing Wisely Canada campaign. [ 2 ]  CCS recommendations include:"}
{"_id": "WikiPedia_Cardio$$$corpus_3811", "text": "1. Don\u2019t perform stress cardiac imaging or advanced non-invasive imaging when initially evaluating patients when there are no cardiac symptoms present unless the patient has high-risk markers.\n [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3812", "text": "2. Don\u2019t perform annual stress cardiac imaging or advanced non-invasive imaging in asymptomatic patients in a routine follow-up. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3813", "text": "3. Don\u2019t perform stress cardiac imaging or advanced non-invasive imaging in pre-operative assessment for patients who are scheduled to undergo low-risk non-cardiac surgery. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3814", "text": "4. Don\u2019t perform echocardiography in routine follow-up for adult patients who have mild, asymptomatic native valve disease with no change in signs or symptoms. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3815", "text": "5. Don\u2019t order annual electrocardiograms (ECGs) in patients who are low-risk and do not have any symptoms. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3816", "text": "The Canadian Cardiovascular Society Angina Grading Scale is commonly used for the classification of severity of  angina : [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3817", "text": "It is similar to the  New York Heart Association Functional Classification  of  heart failure ."}
{"_id": "WikiPedia_Cardio$$$corpus_3818", "text": "Cardiac Risk in the Young  ( CRY ) is a humanitarian  charitable organisation  helping to raise awareness of young  sudden cardiac death  (YSCD, SCD), including  sudden arrhythmic death syndrome  (SADS, SDS). CRY was established in May 1995 by Alison Cox  MBE  and is based in the  United Kingdom ."}
{"_id": "WikiPedia_Cardio$$$corpus_3819", "text": "The charity supports the families of victims of YSCD, facilitates the heart screening of young people through cardiac testing programmes and contributes to  medical research ."}
{"_id": "WikiPedia_Cardio$$$corpus_3820", "text": "The CRY General Election Manifesto 2015 states: \u201cThrough awareness, support and screening many deaths can be prevented, and research into these conditions will be the key to providing the knowledge crucial to saving these young lives.\u201d [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3821", "text": "CRY offers support to those who have suffered tragedies through a network of trained volunteer bereavement supporters, [ 2 ]  counselling groups and medical information. [ 3 ]  The charity also offers support and regular meetings to young people diagnosed with a cardiac condition through their myheart Network. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3822", "text": "CRY holds regular subsidised  ECG  screening clinics for those aged 14 to 35 across the UK, [ 5 ]  with the majority of events funded by bereaved families and free to the public."}
{"_id": "WikiPedia_Cardio$$$corpus_3823", "text": "The charity funds an expert centre for fast-track cardiac pathology in the UK, the CRY Centre for Cardiac Pathology [ 6 ]  (CRY CCP) at  St George's Hospital , London. The centre is directed by Professor Mary Sheppard. Pathology is free of charge when the cause of death is unascertained and the deceased was aged 35 or under. CRY also funds the CRY Centre for Inherited Cardiovascular Disease and Sports Cardiology at St George\u2019s Hospital. Professor Sanjay Sharma, medical director of the  London Marathon , is CRY\u2019s consultant cardiologist and leads their research programme. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3824", "text": "On 15 July 2004 CRY launched its National Postcard Campaign [ 8 ]  to highlight the deaths of eight young people per week from undiagnosed heart problems by featuring their pictures. The campaign was launched at a Parliamentary Reception in  Westminster . From August 2004 the Postcard has been re-launched as region specific including South West, North East, South, North West, Scotland and Wales versions.\nIn February 2009 the postcard campaign was updated to \"12 a week\" [ 9 ]  and continues to draw attention the number of young people with undetected heart conditions."}
{"_id": "WikiPedia_Cardio$$$corpus_3825", "text": "Cardiovascular Cell Therapy Research Network  ( CCTRN ) is a network of  physicians ,  scientists , and support staff dedicated to studying  stem cell therapy  for treating  heart disease . The CCTRN is funded by the  National Institutes of Health  (NIH) and includes expert researchers with experience in cardiovascular care at seven stem cell centers in the  United States .  The goals of the Network are to complete research studies that will potentially lead to more effective treatments for patients with  cardiovascular disease , and to share knowledge quickly with the  healthcare  community."}
{"_id": "WikiPedia_Cardio$$$corpus_3826", "text": "The mission of the CCTRN is to achieve  public health  advances for the treatment of cardiovascular diseases, through the conduct and dissemination of collaborative research leading to  evidence-based treatment  options and improved outcome for patients with heart disease. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3827", "text": "The sponsor"}
{"_id": "WikiPedia_Cardio$$$corpus_3828", "text": "The  National Heart, Lung, and Blood Institute  ( NHLBI ) is one of 27 institutes/centers of the National Institutes of Health (NIH) and supports research related to the causes, prevention, diagnosis, and treatment of  heart ,  blood vessel ,  lung , and  blood diseases ; and  sleep disorders . The NHLBI plans and directs research in the development and evaluation of interventions and devices related to prevention, treatment, and rehabilitation of patients with such diseases and disorders."}
{"_id": "WikiPedia_Cardio$$$corpus_3829", "text": "The Coordinating Center for Clinical Trials"}
{"_id": "WikiPedia_Cardio$$$corpus_3830", "text": "Since 1971, the  Coordinating Center for Clinical Trials  ( [1] ) at The  University of Texas School of Public Health  has played a leading role in cardiovascular disease and vision research by serving as a coordinating center for 25 nationwide multicenter  clinical trials . The CCCT's primary function is to provide and coordinate all operations, procedures, and activities of a large-scale randomized controlled clinical trial. The CCCT serves as the Data Coordinating Center for the CCTRN. The DCC was led by Lemuel Moye (2006-2019) and  Barry R. Davis  (2019-2021)."}
{"_id": "WikiPedia_Cardio$$$corpus_3831", "text": "The clinical sites"}
{"_id": "WikiPedia_Cardio$$$corpus_3832", "text": "The CCTRN includes seven stem cell centers in the United States with experience and expertise in clinical trials studying treatments for heart disease and peripheral artery disease. These sites include:"}
{"_id": "WikiPedia_Cardio$$$corpus_3833", "text": "In July 2008, the CCTRN opened enrollment in two studies in patients who had recently had   heart attacks : TIME [ 2 ]  ( (NCT00684021) ) and LateTIME [ 3 ]  ( (NCT00684060) ).  The purpose of these studies was to determine if  stem cells  safely taken from an individual's  bone marrow  could be  transplanted  back into the injured heart muscle of the individual and improve the heart's ability to pump following a heart attack, as well as to determine the best time for transplanting the cells following a heart attack.  The results of both studies were presented at the American Heart Association (AHA) Scientific meetings in 2011 (LateTIME) and 2012 (TIME), and simultaneously published in JAMA. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3834", "text": "In March 2009, the CCTRN opened enrollment in a  heart failure  study: FOCUS  [ 6 ]  ( (NCT00824005) ).  The purpose of this study was to determine the safety and effectiveness of injecting bone marrow stem cells into heart muscle in an attempt to promote blood vessel growth that could potentially improve the  blood supply  in  hearts that are failing .  This study recruited patients who had heart failure, but would no longer benefit from other forms of standard treatment such as surgery or  coronary artery  repair procedures such as  balloon angioplasty  or  stent  placement.  The results of this study were presented at the American College of Cardiology (ACC) Annual Meeting in 2012 and simultaneously published in JAMA. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3835", "text": "In June 2013, CCTRN opened enrollment in a study in  peripheral artery disease : PACE  [ 8 ]  ( (NCT01774097) ).  The purpose of this study was to determine the safety and effectiveness of bone marrow-derived stem cell therapy on improving blood flow and walking ability in patients with peripheral artery disease.  The results of this study were published in Circulation in 2017. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3836", "text": "In October 2015, CCTRN opened enrollment in a study in  heart failure : CONCERT-HF  [ 10 ]   (NCT02501811) . The purpose of the study was to determine whether giving autologous Mesenchymal Stem Cells (MSCs) and/or C-kit+ cells to patients with heart muscle damage is safe and to help us learn whether these treatments improve heart function for people who are not ideal candidates for other forms of standard therapy such as surgery.  The results of this study were published in the European Journal of Heart Failure in 2021. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3837", "text": "In September 2016, CCTRN opened enrollment in a study in  anthracycline-induced cardiomyopathy  (AIC): SENECA  [ 12 ]   (NCT02509156) . The purpose of the study was to determine whether giving allogeneic mesenchymal stem cells (MSCs) to patients with AIC is safe and whether these treatments improve heart function. The results of this study were published in JACC CardioOncology in 2020. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3838", "text": "The Cardiovascular System Dynamics Society  (CSDS), founded on 5 October 1976 in  Philadelphia, Pennsylvania , by organ system  physiologist  and  biomedical engineers , was a historic first in its mathematical and quantitative approach to cardiovascular mechanics. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3839", "text": "Currently the society includes investigators in muscle and vascular biology, subcellular and  sarcomere  dynamics, the microcirculation, cardiovascular biology, clinical disease, and modeling.  The primary theme remains cardiovascular function, its physiologic and molecular mechanisms, with an aim to understand how these features integrate to achieve overall performance.  An important component of the overall approach remains inclusion of mathematical predictive and causal models for the micro to the macro level. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3840", "text": "Biannual conferences rotate between Europe, North America and Japan. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3841", "text": "This article about  biomedical engineering  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3842", "text": "The  Children's Cardiomyopathy Foundation  ( CCF ) is a national  501(c)(3)   nonprofit organization  focused on the pediatric forms of  cardiomyopathy , a rare and chronic heart condition. [ 1 ]  Founded in New Jersey, CCF has grown into a global community of families, physicians, and scientists focused on accelerating the search for causes and cures for pediatric cardiomyopathy through increased research, education, awareness, and advocacy. [ 2 ]  The organization also provides support and resources to affected children and their families. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3843", "text": "CCF was founded in 2002 by Eddie Yu and Lisa Yue, who lost two children to cardiomyopathy. At the time, cardiomyopathy was a poorly understood disease in young children with low public awareness. [ 4 ]  Due to the lack of research being conducted on pediatric cardiomyopathy, the Foundation established a research grant program and formed research partnerships with the  American Heart Association ,  American Academy of Pediatrics , and  National Heart, Lung, and Blood Institute -funded Pediatric Cardiomyopathy Registry. [ 1 ]  The Foundation also organizes international scientific conferences to encourage collaboration among researchers across medical centers. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3844", "text": "CCF's investment into research and education has led to more than 420 medical presentations and peer-reviewed publications on pediatric cardiomyopathy and a four-fold increase in the number and dollar amount of pediatric cardiomyopathy studies funded by the  National Institutes of Health . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3845", "text": "In a 2017 paper published in the  Journal of the American College of Cardiology , \u201cSurvival Without Cardiac Transplantation Among Children with Dilated Cardiomyopathy,\u201d it was shown that there was a 50% reduction in diagnosed children dying and needing a heart transplant because of better care guidelines and collaborative research efforts made possible by CCF's support of the Pediatric Cardiomyopathy Registry. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3846", "text": "Through CCF's advocacy work, the Cardiomyopathy Health Education Awareness Risk Assessment and Training in the Schools Act was the first bill on cardiomyopathy to be introduced in the  United States House of Representatives  and  United States Senate . [ 7 ] [ 8 ]  In 2020, it was reintroduced as a bipartisan bill in the House of Representatives."}
{"_id": "WikiPedia_Cardio$$$corpus_3847", "text": "Congenital Heart Surgeons' Society (CHSS)  is a professional membership organization of heart surgeons who specialize in treating  congenital heart defects . The society is a  non-profit organization  registered in the United States."}
{"_id": "WikiPedia_Cardio$$$corpus_3848", "text": "The history of the group goes back to the early days of cardiac surgery in the mid 1950s, when 16 surgeons met annually to relate their early pioneering experience in operating on children with congenital heart defects. The CHSS' purpose is to associate persons interested in, and carry on activities related to, the science and practice of congenital heart surgery. It also strives to encourage and stimulate investigation and study with an aim to increase the knowledge of congenital cardiac physiology, pathology and therapy, and to correlate and disseminate such knowledge. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3849", "text": "Congenital Heart Surgeons who have a significant interest in congenital heart surgery may apply for membership in the Congenital Heart Surgeons' Society (CHSS). There are three types of membership in the CHSS: Active, Emeritus and Honorary. Currently the CHSS has over 140 member surgeons from more than 70 hospitals. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3850", "text": "In 1985 Dr. John Kirklin and Dr. Eugene Blackstone proposed that the centers pool their experience and data in managing infants with rare congenital anomalies of the heart. Data collection required the establishment of a Data Center, initially in  Birmingham, Alabama . [ 1 ]  In 1997, the Data Center moved to  The Hospital for Sick Children  in  Toronto ,  Canada . The CHSS sponsors and oversees multi-institutional clinical studies evaluating the application of surgical interventions in congenital heart disease. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3851", "text": "The mission of the Data Center is to improve care for patients with congenital heart disease through collaborative research. Some of the CHSS studies involve treatment of heart defects like the  transposition of the great arteries , congenital  valvular heart disease ,  coarctation of aorta ,  hypoplastic left heart syndrome ,  anomalous aortic origin of a coronary artery  among others. Approximately 6000 patients have participated in CHSS research studies, of which about 4000 patients are being actively followed by the Data Center. [ 3 ]  The CHSS also collaborates with other professional organizations to advance care of the children with heart diseases. They include Society of Thoracic Surgeons, European Association of Congenital Heart Surgeons, etc. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3852", "text": "Corindus, Inc.  was founded in Israel in 2002 by  Rafael Beyar , an  interventional cardiologist , and his student at the Technion, Tal Wenderow. The company's original goal was to use remote control and robotics to move coronary  guidewires  and balloon/stent catheters. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3853", "text": "Corindus Vascular Robotics, Inc. (NYSE: CVRS) was later moved to the United States to be headquartered in  Waltham, Massachusetts . The company's FDA-cleared CorPath\u00ae System became the first medical device that allows  interventionalists  to manipulate guidewires and balloon/stents from an interventional cockpit. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3854", "text": "The company went public in August 2014 and traded on the  New York Stock Exchange  under the ticker symbol  CVRS ."}
{"_id": "WikiPedia_Cardio$$$corpus_3855", "text": "Under the leadership of CEO Mark Toland and CFO David Long, the company continued to grow and received additional clearances from the FDA. Investments in the development of next generation products and expanded regulatory clearances lead to the negotiation of a potential strategic transaction. In August 2019,   Siemens Healthineers  publicly announced its intention to acquire Corindus for $1.1 billion. The final transaction closed in October 2019, representing one of the largest  MedTech  deals in 2019.  [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3856", "text": "This United States corporation or company article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3857", "text": "The  Deutsche Gesellschaft f\u00fcr Kardiologie  ( DGK ;  German Cardiac Society  in English) is a German medical research organization based in  D\u00fcsseldorf .  It is a member of the  European Society of Cardiology , [ 1 ]  and the  World Heart Federation . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3858", "text": "They award the  Arthur Weber Prize  for excellence in the field of  cardiology . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3859", "text": "This article about an organisation based in Germany is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3860", "text": "The  Deutsches Herzzentrum Berlin  ( DHZB ) is a medical research centre in  Berlin ,  Germany , specialised in  cardiovascular  disease, as well as  cardiopulmonary transplantation . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3861", "text": "The hospital has two  CMR  scanners. [ 2 ]  A new heart centre is planned to be built in 2018 and finish construction in 2021. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3862", "text": "52\u00b032\u203232\u2033N   13\u00b020\u203249\u2033E \ufeff / \ufeff 52.542222\u00b0N 13.346944\u00b0E \ufeff /  52.542222; 13.346944"}
{"_id": "WikiPedia_Cardio$$$corpus_3863", "text": "The  European Association for Cardio-Thoracic Surgery  ( EACTS ) is a membership organisation devoted to the practice of  cardiothoracic surgery . The mission statement of the association is to advance education in the field of cardiac, thoracic and vascular interventions; and promote research into cardiovascular and thoracic physiology, pathology and therapy, with the aim to correlate and disseminate the results for the public benefit. Within the EACTS there is a large number of committees working on various issues in order to improve cardio-thoracic surgery. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3864", "text": "EACTS was founded as a  European  organisation. However, its membership is now spread all over the world in all continents representing some 70 countries. Since its foundation in 1986 more than 3500 members have been admitted, and the interest in applying for membership has grown considerably during the last few years. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3865", "text": "The EACTS Annual Meeting is the largest cardio-thoracic meeting in the world [ citation needed ]  focusing on scientific developments and research in the following specialities: Acquired Cardiac Disease, Congenital Heart Disease, Vascular Disease and Thoracic Disease. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3866", "text": "The EACTS publishes two journals focused on high-quality research and cardio thoracic surgery education and one website featuring video based cardio-thoracic tutorials these are:  European Journal of Cardio-Thoracic Surgery (EJCTS) ,  Interactive Cardiovascular and Thoracic Surgery (ICVTS) , and  Multimedia Manual of Cardio-Thoracic Surgery (MMCTS)   [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3867", "text": "The Quality Improvement Programme was launched in 2012 to facilitate continuing improvement of clinical outcomes in adult cardiac surgery through improving education, and various research initiatives. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3868", "text": "The organisation has collaborated with the  European Society of Cardiology , the  American Heart Association ,  Oxford University , and other organizations to produce clinical practice guidelines and consensus statements related to the treatment of cardiovascular disease. [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3869", "text": "The  European Society of Cardiology  ( ESC ) is an independent  non-profit , non-governmental  professional association  that works to advance the prevention, diagnosis and management of diseases of the heart and blood vessels, and improve scientific understanding of the heart and vascular system. [ 2 ]  This is done by:"}
{"_id": "WikiPedia_Cardio$$$corpus_3870", "text": "Most of the approximately 100,000 ESC members are cardiologists, cardiovascular nurses and allied professionals wishing to increase their knowledge and update their skills.\nThe association adheres to the Alliance for Biomedical Research in Europe Code of Conduct."}
{"_id": "WikiPedia_Cardio$$$corpus_3871", "text": "The ESC was founded in 1950. Its headquarters is located in the technology park of  Sophia Antipolis  between Nice and Cannes, in the south of France. The first ESC-organised congress, The European Congress of Cardiology was held in London in September 1952. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3872", "text": "In February 2013, the ESC opened the  European Heart Agency in Brussels , close to the European Parliament complex, in order to have a base in the political and legislative capital of Europe. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3873", "text": "The ESC is governed by an elected board of volunteers who are cardiovascular experts. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3874", "text": "Its activities are overseen by dedicated committees made up of more than 2,000 volunteers. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3875", "text": "Employed staff support ESC volunteers in the development and management of its activities. ESC staff report to the chief executive officer, who reports to the president and management group of the ESC Board. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3876", "text": "The ESC comprises  57 National Cardiac Societies, 7 sub-specialty associations and 22 sub-specialty working groups and councils. [ 7 ]  Since 2013, [ 8 ]  additional support has been developed within the sub-specialty communities to address the special interests and needs of young physicians. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3877", "text": "The ESC organises numerous cardiology congresses each year, including the largest cardiology congress in the world,  ESC Congress ."}
{"_id": "WikiPedia_Cardio$$$corpus_3878", "text": "Annual or biennial sub-specialty congresses address acute cardiac care (Acute CardioVascular Care), cardiac imaging (EuroEcho), prevention, rehabilitation and sports cardiology (ESC Preventive Cardiology), nuclear cardiology and cardiac CT (ICNC-CT), magnetic resonance (EuroCMR congress), interventional cardiology (EuroPCR), heart failure (Heart Failure), heart rhythm and electrophysiology (EHRA), as well as basic science (Frontiers in CardioVascular Biolomedicine). [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3879", "text": "The ESC produces clinical practice guidelines for  cardiology  professionals from evidence-based clinical trials data. The guidelines aim to present all the relevant evidence on a particular clinical issue in order to help physicians weigh the benefits and risks of particular diagnostic or therapeutic procedures. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3880", "text": "A Fellow of the European Society of Cardiology is a cardiologist considered to be a person who has had a significant experience in the field and who has distinguished themself individually in clinical, educational, investigational, organisational or professional aspects of cardiology. Fellows have the right to use the postnominal designation of the FESC. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3881", "text": "The ESC publishes 17 periodicals covering cardiovascular medicine and research: [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3882", "text": "The ESC publishes numerous books for those studying cardiology and subspecialties in the field: [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3883", "text": "The ESC supports continuing medical training and development by offering a broad portfolio of needs-based education initiatives, including online and in-person courses as well as post-graduate programmes led by experts in cardiology. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3884", "text": "Grants to help offset education costs are offered by the association. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3885", "text": "Among the educational products produced by the ESC are interactive webinars that include case-based presentations, online assessments, and live discussions with key opinion leaders in cardiology. [ 16 ]  The society hosts an online platform for these presentations called ESC 365. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3886", "text": "Despite advances in cardiovascular medicine, cardiovascular disease (CVD) remains the world's biggest killer. The ESC collects cardiovascular data from across its 57 members countries through its 'Atlas of Cardiology' to better understand why and how CVD mortality can be reduced. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3887", "text": "This compendium underlines major healthcare gaps and inequalities and provides robust data for budget owners and decision-makers who can improve population health at a European level. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3888", "text": "The ESC operates a registry programme supported by  pharmaceutical industry  sponsors. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3889", "text": "The ESC leverages the knowledge, network and influence of the cardiology profession to promote policy, regulation and research funding that advances cardiovascular science, supports high quality healthcare, and encourages evidence-based decision making. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3890", "text": "The  Herz und Diabeteszentrum (Heart and Diabetes Centre) , is a heart clinic in the German town  Bad Oeynhausen . It is known for performing the most heart transplants in Germany (over 2,700 since 1989)."}
{"_id": "WikiPedia_Cardio$$$corpus_3891", "text": "Besides having a lot of cooperations with the clinics and institutes of the Ruhr-Universit\u00e4t Bochum, it has a lot of national and international cooperations.\nInternational cooperations are: [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3892", "text": "The general orientation of the HDZ NRW is to improve the quality of living of cardiac and diabetes patients by a great amount. The patients get the best treatment with a low risk due to their high performance technology. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3893", "text": "The  Heart and Stroke Foundation of Canada  is a Canadian charity dedicated to advocacy, education, and the funding of  research  surrounding  heart disease  and  stroke . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3894", "text": "In November 2016, the organization re-branded as  Heart & Stroke  and introduced a new logo; the new branding is meant to signify a more \"personal\" approach to its marketing, with a wider targeting of younger demographics and immigrants. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3895", "text": "Heart and Stroke works with medical doctors and healthcare institutions to reduce mortality from cardiovascular events. [ 2 ]  Key institutional stakeholders include provincial ministries of health, hospital associations, and healthcare institutes. [ 2 ]  They have collaborated with the Canadian Stoke Society and the Health Canada Laboratory Centre for Disease Control to create the Stroke System Coalition. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3896", "text": "Heart and Stroke fund and take part in research and fund publications of research that addresses the way in which women and other demographic groups are particularly affected by cardiovascular incidents. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3897", "text": "In early February 2018, the organization released  Ms Understood , a report about how women's early warning signs of a heart attack are frequently missed. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3898", "text": "Heart and Stroke operates a number of fundraising events, including the \"Big Bike\" event, in which 29 riders power one big red bike for twenty minutes. [ 6 ]  \"Jump Rope for Heart\" is an  elementary school -based fundraising initiative involving physical activities centered around skipping. [ 7 ]  Jump Rope for Heart celebrated its 35th anniversary in 2017, with close to 4,000 schools participating across Canada. Heart and Stroke's \"Ride for Heart\" is an annual summer running and cycling event based in  Toronto ,  Ontario , taking place on part of the  Gardiner Expressway  and  Don Valley Parkway , both of which are closed for the event. In 2017, Ride for Heart celebrated its 30th anniversary with 15,000 riders and 5,000 runners and walkers. Its title sponsor is  Manulife Financial . [ 8 ] [ 9 ]  In 2018, Toronto city councilor  Stephen Holyday  requested that the event be moved to inner city streets rather than  Gardiner Expressway , to ease traffic congestion. [ 10 ]  Proceeds from Heart & Stroke's annual lottery goes toward supporting grants for research at teaching hospitals and universities across the province of Ontario. [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3899", "text": "The Heart and Stroke Foundation of Canada advices people to reduce intake of  saturated fat  and replace saturated fats with monounsaturated and polyunsaturated fats to reduce  LDL-cholesterol . [ 13 ] [ 14 ]  They recommend a healthy diet consisting of fruit, legumes, vegetables,  whole grains , low-fat  dairy products , dairy alternatives, fish and poultry. [ 13 ]  They also recommend a limit on processed food such as  processed meats  and  sweetened beverages . [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3900", "text": "The  Heart Institute,  University of S\u00e3o Paulo  ( Portuguese :  Instituto do Cora\u00e7\u00e3o da Universidade de S\u00e3o Paulo , or  InCor ) is one of the clinical  institutes  of the central University's teaching  hospital  ( Hospital das Cl\u00ednicas da Universidade de S\u00e3o Paulo ) and recognized [ citation needed ]  as one of the world's academic and clinical excellence centers in  cardiology ,  cardiovascular medicine  and  cardiovascular surgery ."}
{"_id": "WikiPedia_Cardio$$$corpus_3901", "text": "The Heart Institute was founded in 1963  (62\u00a0years ago) \u00a0( 1963 )  by the noted  cardiovascular   surgeon  and professor of the Faculty of Medicine of the University of S\u00e3o Paulo, Dr.  Euryclides de Jesus Zerbini . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3902", "text": "23\u00b033\u203225\u2033S   46\u00b040\u203204\u2033W \ufeff / \ufeff 23.557040\u00b0S 46.667729\u00b0W \ufeff /  -23.557040; -46.667729"}
{"_id": "WikiPedia_Cardio$$$corpus_3903", "text": "This article about a Brazilian building or structure is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3904", "text": "This article related to a hospital in South America is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3905", "text": "The  Heart Research Institute  ( HRI ) is a not-for-profit  research facility , originally based in  Camperdown ,  New South Wales ,  Australia  and currently based in  Newtown , New South Wales."}
{"_id": "WikiPedia_Cardio$$$corpus_3906", "text": "Established in 1989 by a group of cardiologists at  Royal Prince Alfred Hospital , HRI is an internationally-recognised medical research institute that performs groundbreaking cardiovascular research."}
{"_id": "WikiPedia_Cardio$$$corpus_3907", "text": "The Heart Research Institute was officially opened on 17 March 1989, spearheaded by a group of cardiologists at Sydney's  Royal Prince Alfred Hospital , led by David Richmond, and also supported by The  University of Sydney ."}
{"_id": "WikiPedia_Cardio$$$corpus_3908", "text": "The original vision was to create NSW's first medical research institute dedicated to the detection, prevention and treatment of heart disease."}
{"_id": "WikiPedia_Cardio$$$corpus_3909", "text": "In September 2009, the Institute relocated from its Camperdown, New South Wales site to its present site in Newtown, New South Wales. [ 1 ]  The Institute was opened by  Quentin Bryce   AC , the  Governor-General of Australia . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3910", "text": "HRI has maintained a strong tradition of clinical research ever since that has led to multiple breakthroughs and groundbreaking discoveries."}
{"_id": "WikiPedia_Cardio$$$corpus_3911", "text": "The HRI, currently located within a purpose-built building on 7 Eliza Street, Newtown, New South Wales, is closely located to the Royal Prince Alfred Hospital and the  University of Sydney . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3912", "text": "The HRI has state-of-the-art research laboratories and support facilities. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3913", "text": "Heart Research UK  is a national charity organisation in the  United Kingdom . [ 1 ]  They fund medical research in to the prevention, treatment and cure of  heart disease , as well as community projects aimed at improving the public's heart health. [ 2 ] [ 3 ] [ 4 ]  Since its foundation, Heart Research UK has funded over \u00a325\u00a0million of research into heart disease and related conditions. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3914", "text": "Heart Research UK was founded as the 'National Heart Research Fund' in  Leeds  in 1967 by eminent cardiovascular surgeon Mr David Watson, with the aim of making heart surgery safer. Following the death of a young patient after a long heart operation, Mr Watson launched an appeal with the  Yorkshire Evening Post  to raise funds to research ways to improve the safety of heart surgery. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3915", "text": "Heart Research UK funded the first hospital-based cardiac research unit in the UK, at Killingbeck Hospital in Leeds.\u00a0 Whilst working here, Mr Watson developed a tissue valve in 1976 which became the prototype for many of the valves used in surgery today. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3916", "text": "In 1979, Heart Research UK funded six of the first eight successful heart transplants in the UK, which were carried out by  Sir Terence English  at  Papworth Hospital  in  Cambridgeshire . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3917", "text": "In 2000, Heart Research UK funded the implantation of the world's first permanent artificial heart in to  Peter Houghton , at the  John Radcliffe Hospital ,  Oxford . Mr Houghton was fitted with a Jarvik 2000 pump, and is to this day a Guinness World Record holder for the 'Longest surviving artificial heart transplant patient.' [ 9 ] [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3918", "text": "In 2005, The National Heart Research Fund changed its name to Heart Research UK and later opened up a regional office in  Birmingham . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3919", "text": "Heart Research UK funds medical research through a programme of grants. Novel and Emerging Technologies (NET) Grants, of up to \u00a3250,000, are awarded to research projects which focus on the development of new technologies to diagnose, treat and prevent heart disease and related conditions and Translational Research Project (TRP) Grants, are awarded for projects that transfer breakthroughs into practical tools that can be used for patient care. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3920", "text": "Heart Research UK also awards dedicated grants for  Northern Ireland , aimed at encouraging applications and supporting research at hospitals and universities across the whole of the UK. [ 13 ]  In 2018, building on the success of the Northern Ireland Grants, Heart Research UK launched a similarly dedicated grant for  Scotland . [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3921", "text": "Current medical research being funded by Heart Research UK includes a project with the  University College London  and  Great Ormond Street Hospital  to develop a much faster technique for imaging the hearts of babies born with  congenital heart disease  (CHD), [ 15 ]  a project at the  University of Leicester  using  electrocardiograms  (ECG's) to measure the risk of  sudden cardiac death  (SDC), [ 16 ]  and a project at the Bristol Heart Institute to repair the hearts of babies born with congenital heart disease (CHD) using stem cells from the  umbilical cord . [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3922", "text": "Since 2012, Heart Research UK have funded 'Masterclasses', in which leading international and UK experts give surgeons, doctors, nurses, physiotherapists and other health professionals the opportunity to gain new skills and knowledge. By the end of 2018, 15 masterclasses will have taken place, covering topics such as heart transplantation, imaging, mitral valve surgery, aortic surgery and exercise prescription for congenital heart disease. [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3923", "text": "Since 2009, Heart Research UK has been partnered with  Subway  to support customers' choice for a low fat option. Together, they run the Heart Research UK and Subway Healthy Heart grant scheme, an initiative that funds community projects to promote heart health across the UK. These grants are funded by in-store collections and a programme of 5K runs across the UK. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3924", "text": "Heart Support of America  is an American  non-profit organization , a  501(c)(3)  charity, based in  Knoxville, Tennessee , also known as \"Veteran's Heart Relief\".  The mission of the organization is to provide financial assistance directly to individuals who have  cardiac  problems and grants to social organizations involved in assisting patients with cardiac problems.  Patients or their families can apply for aid via an online application form accessible from the organization's homepage. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3925", "text": "Jim Halliburton founded the organization sometime after 1991 when he had a  near-death experience  following a massive heart attack. A former patient of  Dr. Ron Rosedale , Mr. Halliburton publishes and distributes a work entitled  Heart Support of America  which advocates Dr. Rosedale's metabolic approach to the treatment of heart disease."}
{"_id": "WikiPedia_Cardio$$$corpus_3926", "text": "Heart Support of America has been criticized for giving an overly low percentage of their funds to the causes that they represent. [ 1 ] [ unreliable source? ]  It was listed as one of \"America's worst charities\" in a 2013  Tampa Bay Times / CNN / Center for Investigative Reporting  report because of its fundraising and spending practices. [ 2 ]  Charitable organizations differ in and are often compared on the basis of their methods of  fundraising  and the percentage of funds going toward primary mission aims versus administrative overhead.  Information available from 2004 indicates that Heart Support of America distributes less than 40% of funds collected to the patients and social organizations that figure in its mission statement; the remaining 60% of funds raised were expended on a mixture of expenses incurred in raising funds and overall administrative expenses.  Fundraising is conducted by the organization through a combination of direct solicitation and indirectly through professional solicitors."}
{"_id": "WikiPedia_Cardio$$$corpus_3927", "text": "The  IACC  (Indian Association of Clinical Cardiologists), a non-profit organisation for non invasive cardiologists, was founded in 2008 by  Dr. Rajesh Rajan , 4  Padma Shri  doctors (such as  Padma Bhushan   Dr. Devi Prasad Shetty  and Padma Shri  Dr. Govindan Vijayaraghavan ), Mohammed Shafiq and five other colleagues from  Kerala Institute of Medical Sciences . Based in  Kerala , this association works towards the prevention of  Cardiovascular Diseases  (CVD) and the reduction of cardiovascular mortality in rural India. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3928", "text": "The association is affiliated with the  European Society of CardioVascular Surgery ,  American College of Cardiology , and  American Heart Association . [ 3 ]  It has partnered with the  World Heart Federation  to raise awareness of cardiovascular diseases and nutrition diets. [ 4 ]  Additionally, It has also worked towards increasing awareness about the co-relation between cardiovascular diseases and the environment."}
{"_id": "WikiPedia_Cardio$$$corpus_3929", "text": "The Indian College of Cardiology, the Cardiological Society of India, and the Kerala Heart Rhythm Society engaged in a public disagreement with the association in 2015. These organizations asserted that practicing cardiology by MBBS doctors with a  Postgraduate Diploma in Clinical Cardiology  (PGDCC) was both illegal and unethical. The Association argued that PGDCC is a full-time, two-year residency program in non-invasive cardiology that is taught by renowned cardiology professors and  conducted in top teaching tertiary care institutions including government medical colleges.  The American College of Cardiology ,  the American Heart Association , and the  European Society of Cardiology  have also recognized it. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3930", "text": "The official publication of the Indian Association of Clinical Cardiologists is \"Annals of Clinical Cardiology,\" which is published by  Wolters Kluwer . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3931", "text": "The IACC Cardiozone 2015 held its inaugural zonal conference in July 2015 in  Kozhikode, Kerala . [ 8 ]  It was attended by international clinical cardiologists, general physicians, and medical students. [ 9 ] [ 10 ]   U. T. Khader , then  Minister for Health and Family Welfare  of  Karnataka , had previously attended their 4th national conference in 2013. [ 11 ]  Following that, in 2016, Gruppo Ospedaliero San Donato (Milan) and IACC organised a conference in  Dubai , concentrating on interdisciplinary approaches in cardiac care. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3932", "text": "The National Annual Conference of Indian Association of Clinical Cardiologists (IACCCON) is a yearly event organised by the IACC and is one of the largest conference for clinical cardiology in India. [ 13 ]  The objective of the conference is to establish a program to train a larger number of graduates in  clinical cardiology  to deal with the early recognition, management and prevention of cardiovascular diseases and associated diseases like  diabetes  and  hypertension . [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3933", "text": "The  Indian Heart Association  ( IHA ), along with the  Indian Stroke Association  ( ISA ), is an organization dedicated to raising cardiovascular and stroke health awareness among the  South Asian  population. [ 1 ] \nThe organisation was founded by  Harvard Medical School  and  Berkeley-UCSF  affiliates Dr. Sevith Rao and Dr. Sishir Rao. The organization has sponsored and conducted cardiac health camps in India to raise awareness about  cardiovascular disease  and is headquartered in  Jubilee Hills ,  Hyderabad, India ."}
{"_id": "WikiPedia_Cardio$$$corpus_3934", "text": "The organization was appointed to the  Thoracic  and Cardiovascular Surgery Instruments Sectional Committee for the  Bureau of Indian Standards , Ministry of Health in 2013. The organization was featured in articles in prominent newspapers such as  The Hindu  and  Eenadu  as well as the front page of the  Rice University  webpage. [ 2 ]  In 2019, the organization was appointed to the Board of Directors for the Asia Pacific Heart Association, the leading interdisciplinary cardiovascular association in the Asia Pacific Region."}
{"_id": "WikiPedia_Cardio$$$corpus_3935", "text": "The IHA was featured in a 2018  The Economist  case study on the heart disease epidemic in South Asia. [ 3 ] \nThe IHA also operates an affiliated organization, the Indian Stroke Association, focused on raising awareness about stroke."}
{"_id": "WikiPedia_Cardio$$$corpus_3936", "text": "Public health estimates indicate that India accounts will account for approximately 60% of the world's heart disease burden, despite having less than 20% of the world's population.  Heart disease  is the number one cause of mortality and a silent epidemic among South Asians. In addition, South Asians are at high risk for stroke, accounting for 40% of global stroke deaths. [ 4 ] [ full citation needed ]  The Indian Heart Association was founded to focus on the goals of primary and secondary prevention of cardiovascular disease and stroke. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3937", "text": "The Indian Heart Association has been invited to numerous global cardiac health organization summits including the  World Heart Federation  Annual Meeting and  The Economist  Heart Health in Asia meetings. The IHA has also been recognised as a full member of the Cardiac subcommittee for the Bureau of Indian Standards in the Ministry of Health in India. The organization has prominent supporters and advisers including National Medal of Science Laureate Dr.  C.R. Rao  and former Science Advisor to the President of the United States Dr.  Neal Francis Lane . Late Former President of India Dr.  A. P. J. Abdul Kalam  was an advisor for the Indian Heart Association. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3938", "text": "To date, the organization has partnered with prominent physicians including Cardiologists and Surgeons from  Apollo Hospitals , KIMS, and Vishnu Hospital. The IHA has conducted or sponsored cardiac screening camps in  Andhra Pradesh ,  Maharashtra ,  Telangana , and  Tamil Nadu  and has sponsored or advised other events throughout India. The organisation has also joined hands with the Indian Medical Student Association (IMSA), the largest medical student representative body in the country. In 2015, the IHA has partnered with the Child Heart Foundation, a non-profit in Delhi, India to raise funds for treatment of congenital heart disease for families with financial hardship. In 2018, the IHA partnered with Syybol, the world's largest Bollywood dance workout community. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3939", "text": "The  Institute of Cardiovascular & Medical Sciences  ( ICAMS ) is the purpose-built  British Heart Foundation  cardiovascular research facility at the  University of Glasgow . [ 1 ]  The Director of this Institute is  Rhian Touyz , MSc (Med), PhD. ICAMS is part of the College of Medical, Veterinary & Life Sciences, which was formed in 2010."}
{"_id": "WikiPedia_Cardio$$$corpus_3940", "text": "There were around 175 research and support staff, as well as PhD & MD students (116 in 2017\u201318). Research is the primary purpose and activity of this Institute."}
{"_id": "WikiPedia_Cardio$$$corpus_3941", "text": "The staff of this institute also run and contribute to the following post-graduate programmes:- MSc Cardiovascular Sciences, MSc Clinical Pharmacology, MSc Clinical Trials, and Stratified Medicine, MSc Sports & Exercise Science & Medicine, and MSc Stratified Medicine and Pharmacological Innovation."}
{"_id": "WikiPedia_Cardio$$$corpus_3942", "text": "The  Interamerican Society of Cardiology  (SIAC for its  Spanish  acronym) is a nongovernmental association formed by the National Societies of Cardiology of the American Continent.\nThe Interamerican Society of Cardiology, together with the  European Society of Cardiology , founded in 1950, the Asian Pacific Society of Cardiology, founded in 1956, and the African Society of Cardiology founded in 1981 are the four Intercontinental Professional Societies of Cardiology of the  World Heart Federation  (WHF for its acronym in English). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3943", "text": "The Interamerican Society of Cardiology (SIAC) was founded in  Mexico  on 18 April 1944, at the initiative of Doctor  Ignacio Ch\u00e1vez . That year, the occasion being the inauguration of the National Institute of Cardiology in Mexico City its founder and director, Dr. Ignacio Ch\u00e1vez, invited distinguished  cardiologists  from North, Central and South America and the Caribbean to the ceremony. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3944", "text": "After a fruitful exchange of ideas at this meeting, it was concluded that, in fact, the event had actually constituted an Interamerican Congress and the suggestion was to acknowledge it as such. Those attending did so and decided to form the Interamerican Society of Cardiology and to recognize the event as the first Interamerican Congress of Cardiology. It was also decided to delegate upon Dr. Chavez the task of drawing up the articles of incorporation and bylaws of the Society, and he was requested to convene another Interamerican Congress of Cardiology in Mexico City when  World War II  ended. Dr. Ignacio Chavez was unanimously elected as President of the Interamerican Society of Cardiology. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3945", "text": "The main purpose of the Society is to group together the Societies of Cardiology of all the countries of the Americas for the advancement of  cardiology , to promote  research , teaching and the association of  physicians ,  surgeons , and researchers specialized in this field. It also strives to promote optimal  cardiovascular  health in the population of the Americas through the education and ongoing  professional development  of its members. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3946", "text": "To unite the Cardiovascular Societies representing all the countries of the Americas in order to facilitate the advancement of cardiovascular science, by:"}
{"_id": "WikiPedia_Cardio$$$corpus_3947", "text": "At present there are 26 national professional societies of cardiology members of SIAC forming the General Assembly to bring together more than 40,000 cardiologists."}
{"_id": "WikiPedia_Cardio$$$corpus_3948", "text": "Since the founding of the SIAC and according to the bylaws in force, the Secretary-Treasurer is permanently based at the  National Institute of Cardiology  in Mexico City."}
{"_id": "WikiPedia_Cardio$$$corpus_3949", "text": "The Interamerican Congress of Cardiology is held every two years in a country of the American continent. The XXIV Interamerican Congress of Cardiology held from the 18th to 20 October 2013 in  Buenos Aires , Argentina, had 9946 attendees, including cardiologists, teachers and students, of which 781 were foreigners from 22 different countries. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3950", "text": "The XXV Interamerican Congress of Cardiology will take place from the 4th to 7 December 2015 in Santiago de Chile. At the last General Assembly the city of  S\u00e3o Paulo , Brazil was approved as host of the XXVI Interamerican Congress of Cardiology to be held in 2017."}
{"_id": "WikiPedia_Cardio$$$corpus_3951", "text": "The Interamerican Society of Cardiology currently has the following associations and scientific Councils:"}
{"_id": "WikiPedia_Cardio$$$corpus_3952", "text": "www.siacardio.com"}
{"_id": "WikiPedia_Cardio$$$corpus_3953", "text": "The  International Society for Heart Research  began as an \"International Study Group for  Research  in  Cardiac  Metabolism\" in  Dubrovnik  in 1968; at the 1976 World Congress in Tokyo, it adopted the name \"International Society for Heart Research\". It currently has over 3,000 members and comprises 7 international Sections (Australasian, Chinese, European, Indian, Japanese, Latin American and North American).  The current president is Dr. Yoshihiko Saito Nara."}
{"_id": "WikiPedia_Cardio$$$corpus_3954", "text": "The  Society  publishes its own journal ( Journal of Molecular and Cellular Cardiology [ 1 ] )  and newsletter (Heart News and Views [ 2 ] )."}
{"_id": "WikiPedia_Cardio$$$corpus_3955", "text": "The ISHR has developed a number of awards (Peter Harris Distinguished Scientist Award, Research Achievement Award, Outstanding Investigator Award, three named Distinguished Lecture Awards and Distinguished Leader Award for Faculty). [ 3 ]   It also gives the  Richard J. Bing  Award for Young Investigators, an award named after its first President and founder."}
{"_id": "WikiPedia_Cardio$$$corpus_3956", "text": "This article about an  international organization  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3957", "text": "The Krishna Heart and Super Specialty Institute , also known as  Krishna Heart Institute  or  Krishna Hospital , located in  Ahmedabad ,  India , was established in 2000 as a high-end medical facility, specialising in  heart diseases . The hospital expanded its field of work into different medical branches and has performed over 25,000 procedures including 4,000  bypass  surgeries. The hospital was acquired by  Shalby Ltd.  in 2012. It is a facility that seeks to gain income from the increase seen in  medical tourism in India ."}
{"_id": "WikiPedia_Cardio$$$corpus_3958", "text": "Krishna Hospital was the first corporate hospital to be located in  Ahmedabad . [ 1 ]  It was conceived by Dr. Atul Chokshi, an  interventional cardiologist  practising in  New York City , his brother Animesh Chokshi and 100 other doctors, most of them living in the United States. [ 1 ]  Dr. Chokshi being a devote of the Hind deity  Krishna  and a reader of  Bhagavad Gita , named the establishment \"Krishna Heart Institute\". [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3959", "text": "Krishna Hospital is partnered with MedSolution, a  medical tourism  company located in  Vancouver, British Columbia , Canada. [ 3 ]  It was built with a capacity of 140 beds and specialised operating theaters. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3960", "text": "The number of patients treated by Krishna Hospital declined. In October 2012,  Shalby Ltd.  announced that they had acquired 86% of the share in Yogeshwar Healthcare Ltd. which ran the Krishna Hospital. The cost of the acquisition was not revealed, but was speculated to be around  \u20b9 75 crore  (US$8.8\u00a0million)- \u20b9 80 crore  (US$9.4\u00a0million). Krishna Hospital would now serve as a place to direct the over-flow of the patients from Shalby hospital. A plan to renovate the hospital was passed and 110 beds were to be added to the 140-bed hospital. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3961", "text": "Krishna Hospital, has some patients from the local areas of  North Gujarat ,  Saurashtra  and  Rajasthan , [ 1 ]  but also markets its services to foreign nationals. [ 4 ]  It provides  diagnostic  and treatment procedures in  cardiology  and  joint replacement . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3962", "text": "The hospital provides: [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3963", "text": "The institute was the first hospital in the local area to set up a specialised ISO-100 operating theatre, [ 7 ]  where the air in the operating theatre is refreshed 130 times per hour. [ 6 ]  As of 2010 [update] , Krishna hospital is reported to have performed over 25,000 procedures including 4,000 open heart bypass surgeries. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3964", "text": "Lourdes Heart Institute and Neuro Centre  (LHINC) is a new block set up in  Lourdes Hospital ,  Cochin ,  Kerala ,  India , to cater to tertiary level care for the entire spectrum of cardiovascular and neurological disease. It was inaugurated on 16 March 2007, by Mr.  A. K. Antony , the  Defence Minister of India . This institute was started to meet a long-felt need to provide cardiac and neurological interventional facilities, and especially to provide interventional neurological facilities for the treatment of strokes, including selective thrombolysis and primary angioplasty for stroke which was hitherto unavailable in this part of India."}
{"_id": "WikiPedia_Cardio$$$corpus_3965", "text": "Lourdes Heart Institute has the first biplane digital flat panel  cathetherisation laboratory  in South Asia, which is especially suited for neurological and cardiological intervention work, including carotid stenting, intra-cerebral vessel stenting, primary angioplasty, valvotomy, electrophysiologic procedures and pediatric cardiology."}
{"_id": "WikiPedia_Cardio$$$corpus_3966", "text": "A new building was built behind the main Lourdes hospital block, with outpatient departments and invasive cardiology on the ground level, the cath lab and ICCU suites on the first level and rooms on the higher levels. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3967", "text": "The LHINC  Cath lab  is capable of handling every type of interventional cardiology procedure, with the advantage of its biplane system, it has the unique capability of performing interventional procedures in less time with the advantage of using far lesser contrast than in a routine single plane cath lab, such a facility is rare, this being the first in South Asia, and even as late as December, 2007, there were only 8 such labs in the United States. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3968", "text": "LHINC has round the clock, 24/7 availability of primary  angioplasty  which is the standard treatment for  heart attacks  and results in the best results and the lowest mortality and morbidity. Other facilities include regular, elective angioplasties, day care angiography, which is done via the artery in the wrist, the  radial artery  which allow the patient to be discharged in a few hours and does not require extended lying down, radial angioplasty; temporary and permanent  pacemaker  implantations; mitral valvuloplasty, which enables the opening of narrowed heart valves, without the need for open heart surgery, with a minimally invasive \"pinhole\" incision in the groin; Automated  Implantable cardioverter-defibrillator  or AICD implantation for the prevention of sudden cardiac death in individuals at high risk and non surgical closure of \"holes in the heart\"."}
{"_id": "WikiPedia_Cardio$$$corpus_3969", "text": "LHINC provides cardiac surgery in adult patients including  coronary artery bypass surgery , both on pump and off pump surgery, aortic surgery, valve replacement and repair and endovascular aortic stent procedure. The unit did for the first time in Kerala, 'key hole' mitral valve replacement surgery on two patients."}
{"_id": "WikiPedia_Cardio$$$corpus_3970", "text": "Mended Hearts  is a  United States -based charity which functions as a support group for individuals suffering from  heart disease . It was founded in 1951 by  cardiac surgeon   Dwight Harken . [ 1 ]  Harken was the first surgeon in history to repeatedly perform successful heart surgery. Harken invited post-surgery and prospective heart patients to meet for mutual encouragement and support. These patients spoke of their \"mended hearts\". Mended Hearts offers a program for the families of children born with congenital heart defects known as  Mended  Little  Hearts . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3971", "text": "Mended Hearts partners with 460 hospitals and rehabilitation clinics across the United States, with 285 chapters employing 21,000 volunteers."}
{"_id": "WikiPedia_Cardio$$$corpus_3972", "text": "The  Montreal Heart Institute (MHI)  (French:  Institut de Cardiologie de Montr\u00e9al ), in  Montreal ,  Quebec , is a specialty  hospital  dedicated to the development of  cardiology , which is affiliated with the  Universit\u00e9 de Montr\u00e9al . The MHI is founded in 1954 by  Paul David , and along with the  Ottawa Heart Institute  is considered one of the largest cardiology institutes in the world, which is the first educational hospital on  cardiovascular diseases  in Canada, and is ranked as one of the largest  preventive medicine  centres in Quebec. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3973", "text": "Prominent Montreal businessman  J. Louis Levesque  was a  major benefactor whose initial $1 million donation in 1969 doubled the research department's budget. Levesque supported the Institute for more than a quarter of a century, donating more than $10 million. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3974", "text": "The MHI was ranked number one research hospital in Canada for researcher intensity, and research expenditure per researcher, on the 2015 list of \"Canada's Top 40 Research Hospitals\" published by Research Infosource. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3975", "text": "This Canadian hospital\u2013related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_3976", "text": "The Montreal Heart Institute Foundation  ( French :  Fondation de l\u2019Institut de Cardiologie de Montr\u00e9al ) is a non-profit group associated to  Montreal Heart Institute , in  Montreal ,  Quebec , which aims to raise and administer funds to support the research, teaching, care, and prioritize the innovative cardiovascular research projects. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3977", "text": "Alain Gignac is the President and CEO of the MHIF. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3978", "text": "Mount Sinai Medical Center  is a  hospital  located at 4300 Alton Road in  Miami Beach, Florida , and is the largest private, independent  not-for-profit  teaching  hospital  in Florida. The institution was incorporated on March 11, 1946, and opened on its current location on December 4, 1949. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3979", "text": "Mount Sinai Medical Center includes six locations throughout  Miami-Dade County . In 2009, Mount Sinai Medical Center began an affiliation with  Columbia University , allowing for students and patients to treat, research, and study between  Miami  and  New York City . As part of the affiliation, the Mount Sinai Heart Institute and the Columbia University Divisions of Cardiology and Urology at Mount Sinai were created. This institution is not affiliated with the  Mount Sinai School of Medicine  or  Mount Sinai Hospital , established in 1852 in New York."}
{"_id": "WikiPedia_Cardio$$$corpus_3980", "text": "The center's five satellite locations include a freestanding emergency department, physician offices, diagnostic center and cancer center in  Aventura , physician offices in  Coral Gables ,  Hialeah  and  Key Biscayne  and a diagnostic catheterization and sleep lab in Coral Gables. Mount Sinai includes more than 700 physicians, 3,500 employees and 500 volunteers."}
{"_id": "WikiPedia_Cardio$$$corpus_3981", "text": "As of 2020 [update] , the medical center has 589 staffed beds. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_3982", "text": "Mount Sinai purchased Miami Heart Institute in 2000 for $75 million on the theory that consolidating the two hospitals would slowly ease the competition of the two nearby facilities and improve their image. [ 3 ]  Many of Miami Heart Institute's Doctors, nurses and skilled technical staff were transferred over to Mount Sinai as part of the acquisition. In February 2012, Mount Sinai Medical Center sold the Miami Heart Institute building, which was redeveloped into a luxury condo under the  Ritz-Carlton  brand. [ 4 ]  As of 2020 [update] , Mount Sinai Medical Center is the only hospital and largest employer on Miami Beach."}
{"_id": "WikiPedia_Cardio$$$corpus_3983", "text": "Mount Sinai Medical Center provides following clinical services:"}
{"_id": "WikiPedia_Cardio$$$corpus_3984", "text": "Mount Sinai currently has 15 different buildings/pavilions and they are as follows:"}
{"_id": "WikiPedia_Cardio$$$corpus_3985", "text": "25\u00b048\u203247\u2033N   80\u00b08\u203227\u2033W \ufeff / \ufeff 25.81306\u00b0N 80.14083\u00b0W \ufeff /  25.81306; -80.14083"}
{"_id": "WikiPedia_Cardio$$$corpus_3986", "text": "Multan Institute of Cardiology  (MIC), is a hospital located in  Multan  city in  Pakistan . It was established by  Chaudhry Pervaiz Elahi , the former chief minister of  Punjab  province, in 2005."}
{"_id": "WikiPedia_Cardio$$$corpus_3987", "text": "It was a project for the establishment of a specialised, tertiary care centre for patients with cardiovascular diseases. In early 2003, Pervaiz Elahi, the Chief Minister of Punjab, prioritised this initiative, evident by his appointment of Col. (Ret) Prof M A Cheema as the Project Director of MIC. He has been a pioneer in cardiac surgery within Pakistan and had previously established the Punjab Institute of Cardiology, in Lahore. The centre initiated its outpatient services in 2005, while inpatient services commenced in 2005. The first  open heart surgery  was performed on 29 October 2007 and by March 2008 over 50 open heart operations were conducted without any surgical mortality."}
{"_id": "WikiPedia_Cardio$$$corpus_3988", "text": "After the completion of the project Prof M A Cheema, was succeeded by Prof Syed Ali Raza Gardezi to assume the responsibilities of the first  Executive Director  of the institute. Prof. Dr. Syed Ali Raza Gardezi is an accomplished cardiologist who came from the respectable Gardezi family of Multan. The institute achieved several milestones during the tenure of Prof Gardezi. The construction of a modular operation theatre suite was an achievement despite the medical  Fraternity  in Punjab not being convinced of the benefits of modular theatres."}
{"_id": "WikiPedia_Cardio$$$corpus_3989", "text": "Prof. Dr. Muhammad Mujtaba Ali Siddiqui is the current Executive Director of CPEIC after Prof Rana Altaf Ahmed and Prof. Syed Ali Raza Gardezi."}
{"_id": "WikiPedia_Cardio$$$corpus_3990", "text": "CPE Institute of Cardiology Multan is a  tertiary care hospital  providing comprehensive services of cardiology and cardiac surgery for both adult and  congenital heart diseases . It has one of the largest Modular Operation Theater suites in the country. There are five operating rooms with dedicated preparation and scrub areas. The construction of this modular theater complex was completed in 2009 and the first surgery in the new complex was performed in March 2009. [ 1 ]  The intensive care has a capacity of 20 beds. The hospital has three  Cardiac Catheterization  Laboratories. The Institute also has facilities of Cardiac CT-scan, Nuclear Cardiology, Exercise Tolerance Testing and Echocardiography."}
{"_id": "WikiPedia_Cardio$$$corpus_3991", "text": "The department of anesthesia is led by an the Professor of Anesthesia. Their main area of service is associated with post operative care for cardiac patients in the  intensive care units  (ICU) and providing other anesthetic services to the whole hospital on a 24 hours basis."}
{"_id": "WikiPedia_Cardio$$$corpus_3992", "text": "On an average over 1300 surgeries are performed annually."}
{"_id": "WikiPedia_Cardio$$$corpus_3993", "text": "The types of surgeries offered include:"}
{"_id": "WikiPedia_Cardio$$$corpus_3994", "text": "\u2022 Coronary artery bypass surgery."}
{"_id": "WikiPedia_Cardio$$$corpus_3995", "text": "\u2022 Valve replacements and repair"}
{"_id": "WikiPedia_Cardio$$$corpus_3996", "text": "\u2022 Surgery for aortic dissection and aneurysms."}
{"_id": "WikiPedia_Cardio$$$corpus_3997", "text": "\u2022 Repair of atrial and ventricular septal defects."}
{"_id": "WikiPedia_Cardio$$$corpus_3998", "text": "\u2022 Repair of Fallot\u2019s Tetralogy"}
{"_id": "WikiPedia_Cardio$$$corpus_3999", "text": "\u2022 PDA"}
{"_id": "WikiPedia_Cardio$$$corpus_4000", "text": "\u2022 Surgery for Coarctation of aorta"}
{"_id": "WikiPedia_Cardio$$$corpus_4001", "text": "\u2022 PA banding"}
{"_id": "WikiPedia_Cardio$$$corpus_4002", "text": "\u2022 Right Heart bypass in uni ventricular heart"}
{"_id": "WikiPedia_Cardio$$$corpus_4003", "text": "\u2022 Surgery for peripheral artery disease"}
{"_id": "WikiPedia_Cardio$$$corpus_4004", "text": "The department is led by a professor, an associate professor and two assistant professors for adult cardiac surgery, and  two assistant professors for Paediatric Cardiac Surgery. The department is evolving into an entirely independent Paediatric Cardiac Surgery Department in near future."}
{"_id": "WikiPedia_Cardio$$$corpus_4005", "text": "The cardiology department provides diagnostic and therapeutic services to patients with heart diseases. The department has a twelve bedded emergency and twenty bedded  CCU  for critical patients. The department is headed by Professor of cardiology and its faculty consists of one Associate Professor and four Assistant Professors."}
{"_id": "WikiPedia_Cardio$$$corpus_4006", "text": "The following diagnostic facilities are available:"}
{"_id": "WikiPedia_Cardio$$$corpus_4007", "text": "The Department has two  Angiography  labs where following procedures are done:"}
{"_id": "WikiPedia_Cardio$$$corpus_4008", "text": "Being a highly specialized field, its importance emerges from the high incidence of  congenital  and acquired disorders found in children. It provides services in all diagnostic and several therapeutic areas. The department consists of two consultant pediatric cardiologists. The department is doing regular cardiac catheterization for congenital lesions and has started transcatheter treatment of suitable congenital disorders like  ASD ,  PDA ,  pulmonary stenosis  and mitral stenosis."}
{"_id": "WikiPedia_Cardio$$$corpus_4009", "text": "The department has modern equipment and provides a complete array of routine and specialized tests."}
{"_id": "WikiPedia_Cardio$$$corpus_4010", "text": "It provides comprehensive diagnostic imaging facilities round the clock. The following tests are routinely done:"}
{"_id": "WikiPedia_Cardio$$$corpus_4011", "text": "The department has facilities of processing digital images which are displayed online."}
{"_id": "WikiPedia_Cardio$$$corpus_4012", "text": "The primary aim of the dental section is to provide preoperative dental clearance of the patients undergoing valve surgery. However any patient requiring dental treatment is provided this service within the institute saving them the trouble and cost of visiting the Dental Hospital. The Dental clinic is located on the first floor and is run by two consultant dental surgeons."}
{"_id": "WikiPedia_Cardio$$$corpus_4013", "text": "CSSD is one of the systems installed in Pakistan and ensures sterilized surgical instruments and linen used in the operation theatres and the catheterization laboratories."}
{"_id": "WikiPedia_Cardio$$$corpus_4014", "text": "The laundry system of this hospital is of European make and is able to clean and wash bulk of hospital linen."}
{"_id": "WikiPedia_Cardio$$$corpus_4015", "text": "Textbooks and international journals for doctors, nurses, and paramedics are available here. It remains open till late evening."}
{"_id": "WikiPedia_Cardio$$$corpus_4016", "text": "According to the policy of the Government of Punjab, the hospital pharmacy provides the supply of free medicines to the poor patients. For the convenience of paying patients a retail pharmacy is established in the hospital. It provides medicines at lower than market price. It is located on the ground floor opposite the office of the Executive Director. The retail pharmacy is being updated and upgraded."}
{"_id": "WikiPedia_Cardio$$$corpus_4017", "text": "The department of cardiac surgery has a state of the art electronic database donated by Dr. Anjum Jalal, one of the developers of the software. The database presently has complete records of over 4000 patients who underwent surgery from 2009 onwards. It retrieves records quickly so is extremely useful in maintaining consistency of follow-ups. The dynamic lookup facility of the database is also helpful in conducting heavyweight research studies. Such database software is extremely costly, usually over 30000 dollars per year. The role of the database has been recognized and appreciated by both the local and international community of cardiac surgeons. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4018", "text": "Multan institute of cardiology is primarily serving the poor people living in the region of  south Punjab . However, due to its convenient geographic location many patients from upper  Sindh ,  Balochistan  and Khyber-Pakhtunkhwa also visit for treatment of heart diseases. In 2016 a total of 474,552 patients visited the Outpatients Department, 1568 patients underwent open heart surgery, 6468 patients had angiographies and 2947 patients underwent PCI. The institute provided free medicines, as per Government policy, to over 292,900 patients."}
{"_id": "WikiPedia_Cardio$$$corpus_4019", "text": "In 2017, the institute is going to complete its 10-years of its indoor services of clinical excellence. The data presented above has put the institute among some of the best centers in the world. The charts given below show clinical performance: [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4020", "text": "Besides such a large number of patients served, the institute has also achieved distinction for performing highly complex interventions and surgical operations. A large number of adult congenital operations have been performed by the team of cardiac surgeons with exceptional results. Complex aortic root replacements have also been performed routinely. Surgical correction of extremely rare conditions (like aorto-ventricular tunnel and ruptured  sinus of Valsalva ) have also been performed with excellent outcomes. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4021", "text": "The institute has a record of having prominent names in its faculty. Prof Haider Zaman, Prof Rana Altaf Ahmed, Prof Ijaz Ahmed are respectable names among the academia of cardiac surgery and cardiology. As a result of the tireless efforts of its faculty, the institute was accredited by the  College of Physicians & Surgeons  soon after its establishment.  It has trained several cardiologists and cardiac surgeons. The academic activities are a regular feature of the institute. Cath. Meetings, Audit Meetings, and GP training programs are on the regular academic calendar of the institute. The institute has hosted several national meetings including the annual meetings of Pakistan Society of Cardiovascular and Thoracic Surgeons as well as Pakistan Hypertension League."}
{"_id": "WikiPedia_Cardio$$$corpus_4022", "text": "Some of the publications done by the doctors of MIC include the following:"}
{"_id": "WikiPedia_Cardio$$$corpus_4023", "text": "The institute also publishes a monthly news letter under the editorship of Dr. Kashif Hashmi. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4024", "text": "30\u00b011\u203230\u2033N   71\u00b027\u203201\u2033E \ufeff / \ufeff 30.19167\u00b0N 71.45028\u00b0E \ufeff /  30.19167; 71.45028"}
{"_id": "WikiPedia_Cardio$$$corpus_4025", "text": "The  UK Health Forum  (UKHF) (formerly National Heart Forum) is a  charitable organisation  in the  UK  allying over 60 charities,  non-governmental  and  medical professional organizations  in reducing the risks of  coronary heart disease  (CHD) and such related conditions as  stroke ,  diabetes  and  cancer . Established in 1984, the NHF has three primary functions: (1) to facilitate the work of its members by providing a forum for communication and by coordinating their actions; (2) to encourage sound national and international action by researching CHD and related conditions and educating others about them; and (3) to aid policy makers and UKHF members in effective collaboration. Members include such organisations as the  British Medical Association , the  British Heart Foundation ,  Which?  and  Cancer Research UK . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4026", "text": "Among other areas of interest, the UKHF has spoken publicly against irresponsible advertising of  junk food  to children. [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4027", "text": "It has a commercial subsidiary Micro Health Simulations. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4028", "text": "This article related to a non-profit organization is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_4029", "text": "National Heart Foundation  is a health advocacy group and welfare organisation and is located in  Dhaka , Bangladesh. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4030", "text": "National Heart Foundation was founded in 1979. The foundation established the  Heart Diseases Institute and Hospital  in Mirpur. [ 3 ] [ 4 ]  Brigadier General  Abdul Malik , national professor of Bangladesh, founded the foundation. [ 5 ]  The foundation released a smartphone app for heart patients in Bangladesh. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4031", "text": "On 31 May 2018, the NHFD received the a World No Tobacco Day award by the governmental Health Service Division of  Ministry of Health & Family Welfare  for its \"contribution to tobacco control\" in the country and the vital role played \"for prevention & control of cardiovascular disease (CVD) in Bangladesh\". [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4032", "text": "For the first time, The National Heart Foundation of Bangladesh (NHFB) had conducted MICS. [ 8 ]  Dr. Asraful Hoque Sium was the surgeon of this operation. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4033", "text": "This article about a  Bangladeshi  organisation is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_4034", "text": "The  National Heart Foundation of Australia  (known as the  Heart Foundation ) is a charity established in 1959. Its activities have been funding cardiovascular research, supporting health professionals in their practice, developing health promotion activities, informing and educating the public and assisting people with cardiovascular disease. It describes its mission as \"to reduce heart disease and improve the heart health and quality of life of all Australians through our work in Risk Reduction, Support, Care and Research.\" [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4035", "text": "The organisation emerged after  tuberculosis  had been effectively removed as a health concern and after the successful establishment of the  Heart and Stroke Foundation of Canada . A group of concerned Sydney professionals meet with the trustees of R.T Hall Trust and members of the New South Wales government health services in July 1958 and decided to form the National Heart Foundation of Australia. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4036", "text": "The foundation provides people with, and at risk of,  cardiovascular disease  information and guidance on how to minimise their risk. Annually, the organisation distributes more than 1.3\u00a0million heart health brochures. Each year, the Heart Foundation's information service and its website provides heart health information to thousands of Australians."}
{"_id": "WikiPedia_Cardio$$$corpus_4037", "text": "The foundation supports and works with all levels of government, other health organisations, the media and community groups and food manufacturers to implement policies and programmes that attempt to improve the cardiovascular health of Australians. This includes programmes on cardiovascular health risks such as smoking or physical inactivity, through to  recovery  and  rehabilitation  and diet. The foundation has partnered with the  Health Star Rating System  by assisting in monitoring the uptake and compliance of the  Health Star Rating  on applicable products. [ 4 ]  The foundation's collected data has been used in the formal reviews of the  Health Star Rating  and provided help in making the system more effective and accurate. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4038", "text": "The foundation claims to take the latest research and creates practical treatment tools for  health practitioners . The foundation attempts to bridge gaps in care through programs specifically targeting those Australians at higher risk of cardiovascular disease."}
{"_id": "WikiPedia_Cardio$$$corpus_4039", "text": "The foundation supports local governments that change neighbourhoods to create healthier communities. Initiatives by councils, such as building cycleways and upgrading walking paths are eligible for Heart Foundation Local Government Awards (to be renamed Heart Foundation Healthy Community Awards in 2011)."}
{"_id": "WikiPedia_Cardio$$$corpus_4040", "text": "Through community education campaigns and media activities, the foundation promotes lifestyle changes to improve the heart health of Australians. Recent examples include the Warning Signs campaign, which raises awareness of the symptoms of a heart attack and of the need to phone 000 so that sufferers can get early treatment to have the best chance for survival."}
{"_id": "WikiPedia_Cardio$$$corpus_4041", "text": "The foundation's \"Healthy Eating Principles\" include plenty of fruit, vegetables and  whole grains  with a variety of protein sources such as fish and seafood, lean poultry with a restriction on  red meat . [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4042", "text": "The foundation recommends a diet low in  saturated fat  and trans fat whilst rich in monounsaturated and  polyunsaturated fats  such as avocados, unsalted nuts, seeds and oily fish like salmon and sardines. [ 8 ] [ 9 ]  The foundation have noted that milk, yoghurt and cheese can be eaten as part of a heart-healthy diet but butter, cream and ice cream are not recommended as heart-healthy. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4043", "text": "A 2017 review by the Sax Institute for the National Heart Foundation of Australia on dietary patterns and cardiovascular disease outcomes found that the  DASH diet  is the most beneficial dietary pattern to reduce CVD risk in healthy populations. [ 12 ]  Another review published the same year that examined the evidence for the association between dietary fat and cardiovascular disease found that saturated fat consumption is associated with higher mortality and that replacement of saturated fat with polyunsaturated fat decreases risk of cardiovascular disease events and mortality. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4044", "text": "In 2018 the Sax Institute for the National Heart Foundation of Australia reviewed evidence on the heart health effects of eating unprocessed  red meat  and  poultry . The report concluded that \"the totality of evidence reviewed in this report suggests that white meat (poultry, turkey and rabbit) have relatively neutral, whereas unprocessed red meat (beef, pork, veal, and lamb) likely have moderately adverse outcomes on cardiovascular effects, particularly related to weight gain and stroke risk.\" [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4045", "text": "In 2019, the foundation lifted their limit on full fat  dairy products  and  eggs  for the general population. [ 11 ] [ 15 ]  The recommended limit remains for those with heart disease, high cholesterol or type 2 diabetes. [ 11 ] [ 16 ]  The foundation published a position statement on full fat dairy products, \"Based on current evidence, there is not enough evidence to recommend full fat over reduced fat products or reduced fat over full fat products for the general population. For people with elevated cholesterol and those with existing coronary heart disease, reduced fat products are recommended.\" [ 10 ]  The position statement also noted that the \"evidence for milk, yoghurt and cheese does not extend to butter, cream, ice-cream and dairy-based desserts; these products should be avoided in a heart healthy eating pattern\". [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4046", "text": "The foundation's 2019 position statement on dietary fat and heart healthy eating recommends replacing saturated fat with polyunsaturated fat, monounsaturated fat and whole grains to lower risk of a cardiovascular disease. [ 17 ]  The foundation's 2021 position statement on  alcohol  and heart health for the general population is to reduce consumption to no more than 10 standard drinks per week and no more than 4 standard drinks on any one day which supports the  National Health and Medical Research Council 's recommendation levels. The foundation has stated that alcohol consumption is harmful to people with atrial fibrillation so such individuals may need to drink less or none at all. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4047", "text": "The  National Heart Foundation of New Zealand  (known as the Heart Foundation) is a registered New Zealand heart health  charity  established in 1968. It funds research into heart disease, and provides education to promote healthy lifestyles to prevent  heart disease . It has awarded over $78 million to fund research and specialist training for  cardiologists  since 1970. The funding has provided over 1,800 research and training grants awarded in New Zealand."}
{"_id": "WikiPedia_Cardio$$$corpus_4048", "text": "There are 18 [ 1 ]  Heart Foundation branches located through New Zealand."}
{"_id": "WikiPedia_Cardio$$$corpus_4049", "text": "The Heart Foundation's work includes:"}
{"_id": "WikiPedia_Cardio$$$corpus_4050", "text": "In 1968, a group of cardiologists established the National Heart Foundation with the aim of making an impact on New Zealand's heart disease epidemic. New Zealand's death rates due to heart disease were among the highest in the world at the time. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4051", "text": "In 2015 the foundation released a television advertisement asking viewers \"who gives the most realistic performance of a heart attack?\", and showing several people acting as if they are experiencing a heart attack. In the end, the advertisement points to a person sitting in the background. It was designed to teach people that heart attacks are not as dramatic as what are portrayed in cinema. [ 2 ]  The advertisement received multiple awards. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4052", "text": "The foundation recommends a diet low in  saturated fat  and high in unsaturated fats (monosaturated and polyunsaturated) from nuts, seeds, plant oils, avocado and oily fish to reduce heart disease risk. They advice that 40% of the food trolley should be filled with fruit and vegetables. [ 4 ]  The foundation recommends people to replace  refined grains  with  whole grains  and consume at least three servings of whole grains per day for heart health. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4053", "text": "In 2017, the foundation published a Dairy and Heart Health  umbrella review  which found an \"overall neutral effect of  dairy  on cardiovascular risk for the general population\". [ 6 ]  Their position paper stated that \"the evidence overall suggests dairy products can be included in a heart-healthy eating pattern and choosing reduced-fat dairy over full-fat dairy reduces risk for some, but not all, cardiovascular risk factors\". [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4054", "text": "In 2020, the foundation\u2019s Expert Nutrition Policy (ENP) issued a position statement that concluded that high consumption of  red meat  increases risk of heart disease and stroke by 16% therefore one should aim to reduce consumption of red meat below 350g per week and replace meat with plant sources of protein. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4055", "text": "The Heart Foundation is New Zealand's leading independent funder of heart research. Their funding enables medical researchers and cardiologists to undertake research projects and specialist training. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4056", "text": "Heart Foundation donors funded a Chair of Heart Health position at Auckland University. [ 10 ]  The Chair, filled by Professor Rob Doughty, was established to create a research hub to focus on improving understanding of heart disease, and to help improve heart health for New Zealanders. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4057", "text": "In 2017 the Heart Foundation funded a two-year study into the link between heart disease and mental illness, [ 11 ]  to be carried out by Professor Bart Ellenbroek and his research team at Victoria University, Wellington. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4058", "text": "The Heart Foundation of New Zealand, with other organisations including the British Heart Foundation and the Wellcome Trust, funded research published in 2011 into the use of a  polypill  to reduce the risk of heart attack and stroke. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4059", "text": "The Heart Foundation holds heart-help sessions that offer support and advice from guest speakers including health professionals. These sessions are run by regionally-based Heart Foundation staff. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4060", "text": "The Heart Foundation runs a lottery as a fundraiser. It began on 26 December 1993. Jennian Homes [ 14 ]  is the partner of the Heart Foundation Lottery."}
{"_id": "WikiPedia_Cardio$$$corpus_4061", "text": "The Heart Foundation Tick programme [ 15 ]  was used to help New Zealanders find healthy food choices. The programme ran for 25 years and was retired in 2016. [ 16 ]  An achievement of the Tick programme was its success in working with food companies to reduce the amount of salt in processed food products. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4062", "text": "Institut Jantung Negara Sdn Bhd  (also known as  National Heart Institute ; abbreviation  IJN ), is a heart surgery centre in  Jalan Tun Razak ,  Kuala Lumpur ,  Malaysia . IJN was founded in 1992 under Prime Minister  Mahathir Mohamad  tenure."}
{"_id": "WikiPedia_Cardio$$$corpus_4063", "text": "It is located adjacent to the  Kuala Lumpur Hospital ."}
{"_id": "WikiPedia_Cardio$$$corpus_4064", "text": "The IJN was first established in 1984 by a few cardiologists and general physicians and was situated at the GHKL's old blood bank office, and the current IJN's logo was created in the same year of 1984. IJN later moved to its current location in 1992. The institutes specialises in  cardiology  and  cardiothoracic surgery  services for both adult and  paediatric  cases. As the national referral centre for  cardiovascular disease , IJN sees new cases referred from all over the country and abroad and follow-up cases at the outpatient clinics."}
{"_id": "WikiPedia_Cardio$$$corpus_4065", "text": "IJN went through an expansion which was completed in late 2009. Following the expansion, the number of beds dedicated for heart treatment increased to 432, making IJN one of the largest heart centres in the region. In March 2019, pioneer surgeon  Yahya Awang  announced the takeover of IJN by the Ministry of Health from the Ministry of Finance. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4066", "text": "3\u00b010\u203213\u2033N   101\u00b042\u203232\u2033E \ufeff / \ufeff 3.170197\u00b0N 101.708937\u00b0E \ufeff /  3.170197; 101.708937"}
{"_id": "WikiPedia_Cardio$$$corpus_4067", "text": "The  Philippine Heart Center  is a hospital in  Central ,  Quezon City ,  Philippines , specializing in the treatment of heart ailments. It was established on February 14, 1975. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4068", "text": "The Philippine Heart Center is a hospital specializing in the treatment of heart ailments. It has rooms for paying patients and charity patients [ 4 ]  and admits more than 14,000 patients every year, including 3,300 that undergo heart surgery. [ 5 ]  It holds regular training programs for medical professionals. [ 6 ]  It as one of the busiest congenital heart surgery centers in Asia, according to its website. [ 2 ]   It is currently headed by  cardiothoracic surgeon  Dr. Avenilo L. Aventura, Jr. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4069", "text": "The Philippine Heart Center was established through  Presidential Decree No. 673  issued by  president   Ferdinand E. Marcos  on February 14, 1975. [ 3 ]  The building is identified with what is referred to as the Marcoses' \" edifice complex ,\" [ 9 ] [ 10 ]  defined by architect Gerard Lico as \"an obsession and compulsion to build edifices as a hallmark of greatness.\" [ 11 ]  The hospital was built using 50% of the national health budget, according to Senator  Jose W. Diokno , \"while around the country, Filipinos were dying of curable illnesses like TB [tuberculosis], whooping cough, and dysentery.\" [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4070", "text": "Its original name was the Philippine Heart Center for Asia and was changed to its current form in 1975. The first patient to be admitted to the PHC was Imelda Francisco, on April 14, 1975. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4071", "text": "Cardiovascular  specialists including  Christiaan Barnard ,  Denton Cooley , Donald Effler, and  Charles Bailey  practised there. [ 13 ] [ 14 ]  The first Director of the PHC was  Avenilo P. Aventura (1974-1986), a cardiovascular  surgeon  who performed many pioneering  operations  in the Philippines including the first successful renal transplantation in 1970, the first CABG in 1972, and developed and implanted the first  ASEAN  bioprosthesis, the PHCA porcine valve. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4072", "text": "In 2014, the Philippine Heart Center was given a Qmentum International Gold Accreditation for August 2014 \u2013 2017 by Accreditation Canada International for \"excellence in hospital practices and safety. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4073", "text": "On June 13, 2024, Marcos, Jr. appointed Avenilo \u201cJun\u201d L. Aventura Jr. M.D. as PHC's  Executive Director . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4074", "text": "The hospital building was designed by Filipino architect Jorge Ramos [ 17 ]  in what has been described as a  Brutalist  style. [ 18 ]  It was built in 1975 with a reported cost of almost US$50 million. [ 19 ] [ page\u00a0needed ]  It was co-founded by Dr. Ludgerio D. Torres. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4075", "text": "The  Pulmonary Hypertension Association  ( PHA ) is a  501(c)(3)   nonprofit organization  that provides support, education, advocacy, and awareness association for  pulmonary hypertension .  It provides information to the public about the illness and acts as a support group for those with the disease, providing medical provider location services and emotional support for those suffering from the illness."}
{"_id": "WikiPedia_Cardio$$$corpus_4076", "text": "Singer  Chloe Temtchine , who suffers from  pulmonary venoocclusive disease  (PVOD), which accounts for a small number of pulmonary hypertension cases, wrote her song \"Be Brave\" shortly after she was released from a hospital's critical care unit, and donates 50% of sales proceeds to the PHA. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4077", "text": "Three female pulmonary hypertension patients came together in 1987 with the hope of reaching other pulmonary hypertension patients. The goal was to connect pulmonary hypertension patients with one another, help locate pulmonary hypertension specialists and centers, form support groups, and publish a newsletter about the pulmonary hypertension community. In 1990, the women started a mailing newsletter,  Pathlight , to about 100 people and a fourth woman soon connected with the three pulmonary hypertension patients; the United Patients Association for Pulmonary Hypertension was formed the same year. [ 2 ]  United Patients Association for Pulmonary Hypertension officially changed its name to the Pulmonary Hypertension Association (PHA) in 1997 and hired its first full-time staff member in 1999. The organization has grown to more than 16,000 members who include patients, family members, and medical professionals. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4078", "text": "The  Punjab Institute of Cardiology  (PIC), located in  Lahore ,  Pakistan , is a 547-bed tertiary care  hospital . Wither over 1500 staff members, the institute provides  cardiac care  service nationwide, treating more than 300,000 patients annually. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4079", "text": "In addition to its cardiac consultation services, the Punjab Institute of Cardiology offers a comprehensive range of medical services, including an Outpatient Department (OPD) and an array of advanced diagnostic services such as  Electrocardiograms  (ECG),  Exercise Tolerance Tests  (ETT),  Angiography ,  Angioplasty ,  Electrophysiology  studies, and  CT scans . These diagnostic tools play a pivotal role in the accurate assessment and management of cardiovascular diseases. [ 2 ]  - ECG, ETT,  Angiography ,  Angioplasty ,  Electrophysiology ,  CT Scan"}
{"_id": "WikiPedia_Cardio$$$corpus_4080", "text": "The hospital offers outpatient services, advanced diagnostics, interventional and invasive cardiology, as well as  cardiac surgery . The hospital also provides fully equipped cardiac ambulatory services 24/7. Each year, more than 160,000 patients are examined in the OPD, with over 17,000 admissions. As the second largest cardiac centre in Pakistan, after NICVD Karachi, PIC performs 31,000  echocardiograms , 4,000  nuclear medicine  procedures, 16,000  angiograms , 3,500  angioplasties  (including 5,000  stents  placements), and 2,500 cardiac surgeries annually. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4081", "text": "Punjab Institute of Cardiology is also actively involved in research and postgraduate training in cardiology, cardiac surgery and anesthesia. It is the first  ISO  certified hospital in the government sector. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4082", "text": "In 2015, the  College of Physicians and Surgeons Pakistan  selected the Punjab Institute of Cardiology for training in Electrophysiology and Interventional Cardiology. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4083", "text": "90% of patients at the Punjab Institute of Cardiology (PIC) receive free treatment; it is a government-funded hospital. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4084", "text": "An expanded emergency department is to open in March 2016 and was near completion in January 2016. This will help the hospital handle heavy workload better at the emergency department. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4085", "text": "An incident that occurred in January 2012 at this institution showed a problem with drug packaging. That month more than 100 heart patients died of overdoses from a particular drug that had inadequate labeling. Hundreds more patients suffered nonfatal adverse reactions from this drug. This problem, while bringing unwanted attention to the Punjab Institute of Cardiology, was not unique to that hospital system. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4086", "text": "On 11 December 2019, in an unprecedented assault on a hospital led to death of 3 patients and injuries to several others.  However, the Young Doctors Association (YDA) of Pakistan reports for death of 12 patients during the attack at hospital. [ 7 ]  Reportedly a large number of lawyers started marching from Mall Road Lahore and gathered outside the Punjab Institute of Cardiology to protest against a mocking viral video. They closed the hospital's entrance and exit points, within no time their protest turned violent and remained catastrophic for hours. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4087", "text": "Rabindranath Tagore International Institute of Cardiac Sciences  ( RTIICS ), also known as  Rabindranath Tagore Hospital , in  Mukundapur ,  Kolkata , West Bengal, India, is a multispeciality,  tertiary care  unit of  Narayana Health  group. It is a 681-bedded  NABH  accredited multi-super-speciality quaternary care hospital established in the year 2000. RTIICS has 16 fully equipped operation theatres, 4th Generation Da Vinci Robot, and four state-of-the-art Catheterisation laboratories with 24-hour emergency facilities. RTIICS provides services not only to the people of West Bengal and the neighbouring states in Eastern India and Northeastern India, it is a global healthcare hub catering to patients from countries such as Bangladesh, Bhutan, Myanmar, Nepal as well as African countries. It is equipped with clinical and technical expertise proven over time. The institute has set benchmarks in providing quaternary care services [ 1 ]  in Cardiac Surgery, Heart Transplants, LVAD, Interventional Cardiology, Pacemaker and Device Therapy, Electro Physiology and Preventive Cardiology. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4088", "text": "RTIICS is the group's main hospital in Eastern India, with a primary  catchment area  of Kolkata. The hospital also treats patients from neighbouring districts, North-Eastern states as well as from neighbouring countries and continents such as Bangladesh, Nepal, Bhutan, Africa and Myanmar. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4089", "text": "RTIICS, a unit of Asia Heart Foundation, was established in April 2000 by Dr.  Devi Prasad Shetty , founder and chairman of Narayana Health. Early in 2016, RTIICS announced the establishment of \u2018Stride\u2019, [ 4 ]  a clinical centre offering multidisciplinary care for  vascular diseases  and traumas. Apart from  vascular surgery , Stride is supported by an  endocrinologist ,  radiologist ,  physiotherapist , counselor and other specialists. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4090", "text": "It specialises in  cardiology ,  neurology ,  neurosurgery ,  nephrology  and  urology . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4091", "text": "Resuscitation Council UK  (RCUK) is a healthcare charity focused on resuscitation education and training for healthcare professionals and bystander  CPR  awareness for the public."}
{"_id": "WikiPedia_Cardio$$$corpus_4092", "text": "It is the United Kingdom body responsible for setting central standards for CPR and related disciplines. RCUK is a member of the European Resuscitation Council, [ 1 ]  which is part of the international standards body, the International Liaison Committee on Resuscitation (ILCOR). [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4093", "text": "Resuscitation Council UK was formed in 1983 by a group of medical professionals with a shared interest in research-based resuscitation methods and instruction. Its objective is to educate both the general public and health care professionals in the most effective resuscitation methods. [ 4 ]  RCUK's resuscitation guidelines [ 5 ]  and quality standards [ 6 ]  provide guidance for healthcare professionals regarding adult,  paediatric  and newborn resuscitation. The organisation has an established set of professional training courses that operate across the UK and train healthcare professionals in  immediate  and  advanced life support . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4094", "text": "In more recent years, Resuscitation Council UK has also been involved in various campaigns to support the public in learning CPR. RCUK leads the UK's effort on Restart a Heart Day, working with St John Ambulance, NHS Ambulance Services, British Heart Foundation, British Red Cross and the Saving Lives for Scotland to raise awareness of out-of-hospital  cardiac arrest  and encourage people to learn CPR skills. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4095", "text": "RCUK also works to raise awareness of the importance of CPR decision-making, and has developed the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) Process, which has been adopted in numerous regions across the UK. [ 10 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4096", "text": "Resuscitation Council UK aims to: [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4097", "text": "The  Society for Cardiovascular Magnetic Resonance  ( SCMR ) is an international non-profit medical society based in  East Dundee , in the  United States . [ citation needed ]   It was established as international representative and advocate for   physicians ,  scientists , and  technologists  working in cardiovascular magnetic resonance ( CMR ) imaging.  It works to improve patient outcomes through education, training, standards, research and development. [ 1 ]  The society has published more than 40 professional guidelines and expert consensus statements to help standardize and guide education, research and patient management with CMR. [ 2 ] [ 3 ] [ 4 ]  The society's members are physicians, scientists, technologists and trainees. In 2018, it is led by Matthias Stuber."}
{"_id": "WikiPedia_Cardio$$$corpus_4098", "text": "The society was established in 1994. [ 5 ]   Its first president was  Gerald M. Pohost, elected in 1996."}
{"_id": "WikiPedia_Cardio$$$corpus_4099", "text": "In 1998, the organization began holding annual scientific meetings.  The meeting has grown to include a conference with about 1000 attendees. [ 6 ]  SCMR has organized joint scientific meetings with EACVI, as well as Joint Workshops with ISMRM."}
{"_id": "WikiPedia_Cardio$$$corpus_4100", "text": "The society has regional  working groups  and affiliates in Asia, Australia/New Zealand,  Canada , Europe, India, Latin America, [ citation needed ]  the Middle East, [ citation needed ]  and the United States. [ citation needed ]  The role of these working groups is to promote CMR in these regions. [ citation needed ]  There are also special interest groups focusing on Pediatrics/ Congenital  and Interventional CMR. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4101", "text": "The Canadian Society for Cardiovascular Magnetic Resonance, an independent chapter of SCMR, was established in 2005; in 2013 it published guidelines for the analysis and reporting of CMR studies. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4102", "text": "The SCMR is governed by its officers, including the president, vice-president, secretary, vice-secretary, past-president, and the board of trustees. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4103", "text": "The Society presents an annual award, The Gold Medal Award, for distinguished and extraordinary service to the field of CMR and to the Society. [ 7 ]   Recipients have been:"}
{"_id": "WikiPedia_Cardio$$$corpus_4104", "text": "The society publishes an open access journal, the  Journal of Cardiovascular Magnetic Resonance . [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4105", "text": "SCMR has worked with other cardiovascular societies (e.g.  AHA ,  ACC ,  SCCT ,  ASE , ASNC) in establishing cardiovascular guidelines and appropriateness use criteria. [ 4 ] [ 16 ]  These guidelines and consensus statements are based on published research studies and expert opinions in the field to help improve cardiovascular patient care.  SCMR also joined the  Choosing Wisely  campaign in 2014 to reduce excessive testing. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4106", "text": "The society also provides online introductory training in Cardiovascular Magnetic Resonance. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4107", "text": "Sri Jayadeva Institute of Cardiovascular Sciences and Research (SJICR)  is a  tertiary care  autonomous healthcare institute run by the  Government of Karnataka , in  Bengaluru , with additional centers in  Mysuru  and  Kalaburagi . At the Bengaluru campus, it presently has 1150 in-patient beds for  cardiology ,  cardiothoracic surgery  and pediatric cardiology, spread over two twin eight story buildings and is considered one of the largest dedicated heart hospitals in Asia. This new building which was opened in 2001 and was built at a cost of US$17 million. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4108", "text": "The original building for SJICR was located in the campus of  Victoria Hospital , which is the main teaching hospital of the  Bangalore Medical College and Research Institute . The hospital moved to its new buildings at  Bannerghatta Road  in 2001. This building was built solely by the efforts of Dr. Prabudev and team. Dr. Prabudev was the first director of this institute. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4109", "text": "SJICR campus in Bengaluru consist of twin eight story towers, with a separate facility for library and Cath labs. The emergency rooms are located in the basement with access from  Bannerghatta road [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4110", "text": "The hospital caters to approximately 165,000 patients a year and both cardiology, cardio-thoracic and pediatric cardiology OPDs run Monday to Saturday from 9 am to 4 pm. The average patient volume per day is around 1000-1200 OPD visits."}
{"_id": "WikiPedia_Cardio$$$corpus_4111", "text": "There are more than 1150 in patient beds, spread over 8 floors of the two buildings most of them being in general wards and intensive care units and only a few in two private wards. It is considered to be the best cardiology set up in India and Asia and the super specialty training program is considered to be one of the best in India at par with AIIMS cardiology."}
{"_id": "WikiPedia_Cardio$$$corpus_4112", "text": "Expansion to other cities"}
{"_id": "WikiPedia_Cardio$$$corpus_4113", "text": "The Kalaburagi campus was opened to public on 24 April 2016 and the Mysuru campus was opened to public on 24 February 2018."}
{"_id": "WikiPedia_Cardio$$$corpus_4114", "text": "SJIC has 4 cardiac intensive care units. In total, the cardiology ICU bed numbers around 100 and are well equipped with individual ventilators, touch panel monitors, infusion pumps, powered beds and all necessary ancillary medical equipment. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4115", "text": "The echo lab is one of the busiest in the state with an average daily echo turnover of 160 trans-thoracic echo-cardiograms and 10 trans-esophageal echo-cardiograms. Each year around lakhs and lakhs echo is being done, the highest in India and Asia. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4116", "text": "Average interventional cardiology workload ranges between 150 cases a day of which 700-800 cases per month are percutaneous coronary interventions, there are six Philips digital  Cath labs , of which one is the only swing  Cath lab  in the region, enabling large case volumes and more efficient patient care.one Cath lab is dedicated Esp. for electrophysiology and one for pediatric cardiology. SJICR interventional cardiology includes both adult and pediatric cardiology, and every form of interventional procedure, from primary  angioplasty , to  septal ablation   (Sigwart procedure)  is performed on a regular basis. It has the distinction of performing the highest number of percutaneous mitral valvulotomy procedures in the world for stenosis of the  mitral valve . Pediatric cardiology in SJIC performs all standard pediatric interventional procedures, including  percutaneous  closure for  Atrial septal defect ,  ventricular septal defect  and also the relatively rare procedure of percutaneous closure of peri membranous ventricular septal defects. The angioplasty work carried out in hospital is around 32000 per year the highest in India for a government set up. The institute boasts of the latest instruments and for most of the latest procedures in cardiology or Cath Lab, it is the pioneer in India."}
{"_id": "WikiPedia_Cardio$$$corpus_4117", "text": "SJIC is the only government centre in the state of Karnataka to run post doctoral courses in cardiology, cardio-thoracic surgery, paediatric cardiology and cardiac anaesthesia. There are presently 21 seats for Doctorate in Medicine (DM) Cardiology and Master Chirurgiae (MCh) Cardio-thoracic surgery and 8 seats for Cardiac Anaesthesia every year. These three-year courses are akin to the fellowship courses in cardiology and cardiothoracic surgery in other countries, and are entered to after a three year residency (MD/DNB) in either Medicine or Surgery, and are thus considered \"Post Doctoral\" courses or fellowships. These fellowships are much in demand partly since they are the only government sponsored courses in the state and also due to the high patient volume at SJIC which results in a higher degree of interventional experience after having completed the course, and, as such, are determined after an intensely contested all - India level examination conducted by the government of India. The patient load is one of the highest in India and so the choice of most of the post graduate doctorate trainees."}
{"_id": "WikiPedia_Cardio$$$corpus_4118", "text": "In 2008, the number of DM seats was increased to an unprecedented 21 per year and MCh seats to 12 per year, making it one of the largest Super-specialty training courses in India and Asia."}
{"_id": "WikiPedia_Cardio$$$corpus_4119", "text": "The present director is  Padma Shri  Professor  C. N. Manjunath , an academic and interventional cardiologist. Manjunath is reported to have been the innovator of a new method of balloon mitral valvuloplasty. His researches have been published in several articles and scientific papers published in peer reviewed national and international journals; PubMed, an online repository of medical data has listed 73 of his articles. He is known to have performed over 26,000 interventional procedures and is credited with the highest number of balloon mitral valvuloplasty using Accura balloon catheter in India. He is associated with Mallige Medical Centre, Bangalore as a consultant and is a member of the Indian Medical Association. He has also served as the president of the Indian College of Cardiology. The Government of Karnataka awarded him the Rajyotsava Prashasti in 1998 and he received the fourth highest Indian civilian honour of the Padma Shri in 2007. Rajiv Gandhi University of Health Sciences (RGUHS) honoured him in 2012 with the degree of Doctor of Science (Honoris causa)."}
{"_id": "WikiPedia_Cardio$$$corpus_4120", "text": "Surgeons of Hope  (SOH) is a  New York City -based  nonprofit organization  established in 2001. It deals with  heart defects  in children and the  related surgery ."}
{"_id": "WikiPedia_Cardio$$$corpus_4121", "text": "Surgeons of Hope began its work [ when? ]  with pilot programs in  Cambodia ,  Mozambique ,  Senegal , and  Afghanistan . [ 1 ]  In 2008, it shifted focus to efforts in  Latin America .  In 2013, Surgeons of Hope opened the only pediatric heart center in Nicaragua. [ 2 ]  As of 2018, Surgeons of Hope has programs in  Nicaragua  and  Costa Rica . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4122", "text": "The  Tanzania Heart Institute  ( THI ) is a specialized cardiac clinic located in  Ada Estate  of  Kinondoni  Ward in  Kinondoni District  of  Dar es Salaam ,  Tanzania , managed by a non-profit organization. It is located in the northern part of the city, in the residential district of  Ada Estate ."}
{"_id": "WikiPedia_Cardio$$$corpus_4123", "text": "It was founded by Dr. Ferdinand Masau. [ 1 ]  The institute was closed by the government in 2012."}
{"_id": "WikiPedia_Cardio$$$corpus_4124", "text": "This  Tanzania -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_4125", "text": "The Texas Heart Institute  is a not-for-profit cardiology and heart surgery center located within the  Texas Children's Hospital  and  St. Luke's Episcopal Hospital  at the  Texas Medical Center  in  Houston, Texas . [ 1 ] [ 2 ] [ 3 ]  In 2010, in its annual survey of \u201cAmerica's Best Hospitals,\u201d  U.S. News & World Report  ranked the Texas Heart Institute at St. Luke's Episcopal Hospital number 4 in the United States for heart care, making this its 20th consecutive year as one of the top 10 heart centers in the country. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4126", "text": "29\u00b042\u203229\u2033N   95\u00b023\u203258\u2033W \ufeff / \ufeff 29.7081\u00b0N 95.3994\u00b0W \ufeff /  29.7081; -95.3994"}
{"_id": "WikiPedia_Cardio$$$corpus_4127", "text": "Tiny Tickers  is a  charitable  organisation [ 1 ]  in the United Kingdom that aims to improve the early detection, diagnosis, and care of babies with congenital heart disease through a combination of improving standards, providing specialised training and equipment, spreading awareness of congenital heart disease and supporting families."}
{"_id": "WikiPedia_Cardio$$$corpus_4128", "text": "Tiny Tickers charity was founded in 1999 by world-renowned fetal cardiologist Dr Helena Gardiner, when she realised many of the babies she was caring for could have been helped earlier.  She had experience of, and was concerned about, the low prenatal detection rate of  congenital heart disease (CHD)."}
{"_id": "WikiPedia_Cardio$$$corpus_4129", "text": "1 in every 125 babies born in the UK has a serious heart condition, which is around one baby born every two hours fighting congenital heart disease (CHD). Tiny Tickers is the only UK charity dedicated to the early detection and care of those babies. Spotting a heart defect early improves a baby's chances of survival and long-term quality of life. 1,000 heart babies leave UK hospitals every year with no-one knowing they have a life-threatening heart condition, putting them in grave danger of going into heart failure."}
{"_id": "WikiPedia_Cardio$$$corpus_4130", "text": "Tiny Tickers trains sonographers to have the skills and confidence to detect heart defects at pregnancy scans. The antenatal detection rate of heart defects in the UK has more than doubled from 23% to 53.5% since they started their work (NICOR)."}
{"_id": "WikiPedia_Cardio$$$corpus_4131", "text": "Tiny Tickers also places potentially life-saving pulse oximetry machines in maternity wards to further improve the early detection of CHD."}
{"_id": "WikiPedia_Cardio$$$corpus_4132", "text": "Pulse oximetry  testing helps to detect heart defects by measuring oxygen levels (oxygen saturation) in the blood. It uses a light sensor to assess the level of oxygen in the baby\u2019s blood. Not every baby will be born displaying signs and symptoms and with this machine many more life-threatening defects can be detected."}
{"_id": "WikiPedia_Cardio$$$corpus_4133", "text": "At present, pulse oximetry testing is not a mandatory newborn test within  NHS  hospitals, and many maternity units do not have the means to introduce these life-saving machines. For these reasons, Tiny Tickers places pulse oximetry testing kits in maternity units across the UK which can then be used as part of standard newborn tests."}
{"_id": "WikiPedia_Cardio$$$corpus_4134", "text": "The charity teaches new parents and those working with babies to recognise the five key signs a baby may have an undiagnosed heart defect ( Think HEART )."}
{"_id": "WikiPedia_Cardio$$$corpus_4135", "text": "Another core part of the charity's work is supporting the families of babies with CHD. They provide detailed information, share CHD stories and connect heart parents through support group forums and peer support groups."}
{"_id": "WikiPedia_Cardio$$$corpus_4136", "text": "Tiny Tickers receives no government funding. The charity is entirely funded by the generosity of individuals and grant makers."}
{"_id": "WikiPedia_Cardio$$$corpus_4137", "text": "Tiny Tickers has featured in a number of high profile media campaigns, including a 2017  BBC Lifeline appeal  and a 2023  Global's Make Some Noise Appeal , where charity staff and supporters were interviewed on Heart Radio by  Amanda Holden  and  Jamie Theakston ."}
{"_id": "WikiPedia_Cardio$$$corpus_4138", "text": "Uganda Heart Institute  (UHI) is a specialized, public, tertiary care medical facility owned by the  Uganda Ministry of Health . It is a component of  Mulago National Referral Hospital , the largest hospital in  Uganda , which serves as the teaching hospital of  Makerere University College of Health Sciences . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4139", "text": "The Institute is located on  Mulago Hill  in the northern part of the city of  Kampala . It sits within the  Mulago Hospital Complex , the teaching hospital of the  Makerere University College of Health Sciences . This location is approximately 4.5 kilometres (2.8\u00a0mi) north of the central business district of Kampala, the capital and largest city of Uganda. [ 2 ]  The coordinates of the Institute are 0\u00b020'17.0\"N, 32\u00b034'31.0\"E (Latitude:0.338056; Longitude:32.575278). [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4140", "text": "Uganda Heart Institute (UHI) was established as an autonomous body by an Act of Parliament (The Uganda Heart Institute ACT, 2016). The Institute is now a provider of cardiovascular services and the only National Referral Facility for heart diseases in Uganda. Currently, UHI, using a modest investment and an enabling legal framework has trained cardiac specialists and installed a  cardiac catheterization laboratory  and  operating theatre , which have enabled them to conduct heart surgeries and interventions. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4141", "text": "Uganda Heart Institute handles over 20,000 patients annually. The Institute started carrying out Open Heart Surgery in 2007 and to-date; over 7000 heart operations have been performed. This in effect means the Uganda Heart Institute can handle over 95 percent of the adult cases and 85 percent of the cases among children in Uganda. This is in line with the  National Development Plan II  (NDP2) strategy of reducing referrals abroad to less than 5 percent. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4142", "text": "In order to improve access to heart care, UHI is developing capacity to operationalize regional centers in collaboration with the Ministry of Health and Regional Referral Hospitals. The Institute is partnering with various stakeholders including civil society, to promote health through advocating for a healthy lifestyle. The preventive programs are being addressed through a multi-sectoral approach with the Ministry of Health and other local and international partners. What Uganda Heart Institute needs now is more working space and lager operational budgets to enable it fulfill its mandate. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4143", "text": "In 1988, the  Uganda Heart Foundation , in collaboration with the  Uganda Ministry of Health ,  Makerere University  and  Mulago National Referral Hospital , started the  Uganda Heart Institute , using space provided on Ward 1C, in the New Mulago Hospital Complex. This resurrected plans to establish a specialized cardiac unit at Mulago, began in 1958, but were killed in 1972, with the expulsion of the Ugandan Asians by dictator  Idi Amin . [ 1 ]  Since 1988, the Institute has received valuable contribution from national and international donors including the  Rotary Club . [ 6 ]  Media reports indicate that of the 1.5 million children born every year in Uganda, about 15,000 have heart defects at birth (congenital heart abnormalities). Of those, about 8,000 children require corrective surgeries. Uganda's only heart institute has the capacity to perform only 1,000 heart operations annually. That leaves a backlog of 7,000 youngsters every year. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4144", "text": "Beginning in August 2015, the  Government of Uganda  had plans to break ground for a new 200 bed hospital to be named  Uganda Institute of Cardiothoracic Diseases , to replace the current Uganda Heart Institute. The new hospital will have three operating theatres, cardiac catheterization laboratories, an Intensive Care Unit, and research facilities. The construction will be funded by a US$64.9 million (UGX:169 billion) loan from the  Islamic Development Bank . It is anticipated that the Institute will seek financial autonomy to raise funds, hire staff, pay salaries, and procure supplies, independent of Mulago Hospital, similar to the autonomy enjoyed by the  Uganda Cancer Institute . [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4145", "text": "The  New Vision  newspaper, reported in November 2016, that Uganda Heart Institute had acquired land measuring 2.5 acres (10,000\u00a0m 2 ) along  Owen Road  in the  Mulago  neighborhood, where it was going to build its new headquarters. The new complex will consist of three towers: (a) the first tower will house the outpatient clinics and hospital beds, including an  intensive care unit  (b) the second tower will include research laboratories and conference rooms and (c) the third tower will house critical staff, such as research fellows, residents and biomedical engineers. Total cost for the entire project is budgeted at US$65 million, of which US$51 million is for construction and the US$14 million balance is for equipment. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4146", "text": "In April 2022,  Dr John Omagino , the Executive director of UHI disclosed that the institute had acquired 10 acres (4.0\u00a0ha) of land in the  Naguru \u2013 Nakawa  Government Complex. The institute plans to build a 250-bed hospital here, expandable to 1,000 beds over time. The new hospital is expected to save the government of Uganda an estimated US$73 million that is spent on treating high ranking government officials overseas annually. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4147", "text": "In July 2022, the UHI disclosed that a consortium comprising the  Saudi Fund for Development , the  OPEC Fund for International Development  and the  Arab Bank for Economic Development in Africa  had agreed to lend US$75 million (UGX 285 billion) \"for establishing a state-of-the-art heart surgery and treatment centre\", at  Naguru , in Kampala. This new hospital will be capable of performing 5,000 heart surgeries annually, up from the current 1,000 performed in the limited space at Mulago. [ 12 ]  IN March 2024, the  New Vision  newspaper reported that total amount borrowed from the three  Middle Eastern  lenders totaled Ush223 billion (US$61 million in 2024 money). [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4148", "text": "The plan calls for a 250- bed hospital in the first phase, expandable to 500 beds in the second phase and to 1,000 beds in the third phase. [ 5 ]  The construction of the new headquarters and hospital is budgeted at US$73 million. The table below illustrates the sources of finding for the project. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4149", "text": "The  engineering, procurement and construction  (EPC) contract was awarded to  Arab Contractors Uganda Limited  at a contract price of US$45.4 million. Two Chinese construction companies, who did not win the bid, complained to a government tribunal that adjudicates such disputes in the country. In Q3 2024, the tribunal ruled in favor of Arab Contractors. Construction is expected to begin in Q4 2024. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4150", "text": "On Monday 22 January 2018, an all-Ugandan team of 14 healthcare specialists performed the first  coronary artery bypass  surgery operation by an all Ugandan team, in the history of the heart institute. The successful 10-hour operation was billed at USh18 million (approx. US$5,000), compared to USh300 million (approx. US$83,000), if it were done in a private hospital in South Africa, a common destination for Ugandan patients with means. [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4151", "text": "In April 2018, a cohort of 11 patients with abnormal heart rhythms, underwent a procedure called  catheter ablation  using the  radiofrequency ablation  method. All eleven of the patients benefited and recovered well. This was the first time this type of procedure was performed in Uganda. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4152", "text": "As of August 2021 [update]  the following constituted the nine-member UHI board of Directors. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4153", "text": "The following cardiologists and cardiothoracic surgeons have served as the director of the Uganda Heart Institute since its foundation in 1988: [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4154", "text": "United OneHeart Foundation  is a non-profit research and development organisation. Its stated mission is as a  non-profit  organisation to help people to improve the quality of life by fostering improvements in medicine with the aim of decreasing impact of  cardiovascular diseases  with focus on  India  and  South Asia ."}
{"_id": "WikiPedia_Cardio$$$corpus_4155", "text": "The organisation focuses on health-related activities in the Indian state  Karnataka  while advocating to decrease the impact of heart diseases all over country mainly among children and youth.  It has centers in  Bangalore  and  Mangalore ."}
{"_id": "WikiPedia_Cardio$$$corpus_4156", "text": "On the activities scale, the foundation work is uniquely global in its approach, concentrating on its work entirely on public health and medical education in the last decade, it aims mainly on cardiovascular disease management. Its focus is primarily on developing countries like India [ 1 ]  and on medical care for youths. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4157", "text": "United OneHeart Foundation  was envisioned in Bangalore, India in 1994 by  Rahul Shetty , at the time a University Medical Student."}
{"_id": "WikiPedia_Cardio$$$corpus_4158", "text": "The foundation aims to inform people around the world and tries to engage them in the global effort for health and development in developing countries. They advocate reducing the impact of heart diseases through the advancement of research and its application and the promotion of healthy and well balanced living. They partner regularly with other organizations like the  World Heart Federation  based in Geneva, Switzerland. It participates in  World Heart Day  activities every year."}
{"_id": "WikiPedia_Cardio$$$corpus_4159", "text": "The Foundation conducts regular Heart Disease screening activities in state of Karnataka, [ 3 ]  India to increase the awareness of cardiac disease and its potential impact and to detect heart diseases at an early stage. They also distribute  health related articles for the benefit of community to increase awareness about heart disease."}
{"_id": "WikiPedia_Cardio$$$corpus_4160", "text": "To enable high-quality learning resources and technologies accessible to students and teachers from low-income communities, it conducts research on making this a reality. To this aim it has contributed over half a million Indian rupees towards research and development efforts."}
{"_id": "WikiPedia_Cardio$$$corpus_4161", "text": "United OneHeart Foundation also fosters sustainable developments by producing innovations that improve practices of health and health education in cardiovascular disease management, it conducts research and development for new low cost medical technologies which aims to benefit communities in developing countries."}
{"_id": "WikiPedia_Cardio$$$corpus_4162", "text": "In October, 2006, the Foundation entered into a partnership with the  IBM Corporation  agreeing to encourage the community members to contribute their idle PC time to assist humanitarian research and focus on medical issues by joining  World Community Grid  Project."}
{"_id": "WikiPedia_Cardio$$$corpus_4163", "text": "The  University of Ottawa Heart Institute  (UOHI)  (French: Institut de cardiologie de l'Universit\u00e9 d'Ottawa  (ICUO))  is Canada's largest  cardiovascular health  centre. It is located in  Ottawa ,  Ontario , Canada. It began as a department in  The Ottawa Hospital , and since has evolved into a complete cardiac centre, encompassing prevention, diagnosis, treatment, rehabilitation, research, and education. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4164", "text": "UOHI cares for more than 60,000 cardiac patients each year, and patient satisfaction is among the highest in Ontario, averaging 87 percent. [ 2 ]  The Heart Institute is affiliated with the Ottawa Hospital and the  University of Ottawa , specifically the  Faculty of Medicine ."}
{"_id": "WikiPedia_Cardio$$$corpus_4165", "text": "The institute also provides training to more than 100 physicians annually and runs an extensive cardiovascular research program, with 65 research faculty and research funding of approximately $65 million a year."}
{"_id": "WikiPedia_Cardio$$$corpus_4166", "text": "UOHI was founded in 1976 by Dr.  Wilbert Keon , with financial support from the Ontario Ministry of Education. Keon worked with numerous partners, including all of the hospitals in the region, the University of Ottawa, and the Ottawa Hospital Regional District Planning council, to ensure the vision of a world-renowned institute would unfold as planned. The first phase of the Heart Institute\u2014the Cardiac Unit, as it was then known\u2014officially opened on May 11, 1976."}
{"_id": "WikiPedia_Cardio$$$corpus_4167", "text": "UOHI is the sole, independent provider of specialized cardiovascular care for 14 hospitals within the Ottawa region, home to over 1 million people (9 percent of the population of Ontario), and serves more than 40 referral hospitals throughout the province."}
{"_id": "WikiPedia_Cardio$$$corpus_4168", "text": "In 2004, UOHI recruited Dr. Robert Roberts from  Baylor College of Medicine  to serve as President and Chief Executive Officer. Roberts, an internationally recognized investigator in the field of molecular genetics, was brought in to place a greater emphasis on research within the institute. Shortly afterwards, UOHI established the Ruddy Canadian Cardiovascular Genetics Centre, the first such centre in Canada and one of only a handful worldwide dedicated to cardiovascular genetics."}
{"_id": "WikiPedia_Cardio$$$corpus_4169", "text": "In April 2014, former Heart Institute Chief of Cardiac Surgery  Dr. Thierry Mesana  took over as the third President and CEO of UOHI."}
{"_id": "WikiPedia_Cardio$$$corpus_4170", "text": "In April 2024, former Heart Institute Deputy Director General  Dr. Rob Beanlands  became the fourth President and CEO of UOHI."}
{"_id": "WikiPedia_Cardio$$$corpus_4171", "text": "The institute has been responsible for numerous \u2018firsts\u2019, including:"}
{"_id": "WikiPedia_Cardio$$$corpus_4172", "text": "UOHI maintains a clinical staff of over 700, including physicians, nurses, technicians, and other health professionals. In addition to standard care, approximately 100 clinical trials are underway at the institute at any time."}
{"_id": "WikiPedia_Cardio$$$corpus_4173", "text": "More than 1,900 open-heart procedures at UOHI each year require anesthesia, including coronary artery bypass, valve replacement, heart transplant, pulmonary thromboendarterectomy, mechanical circulatory assist devices and others. Clinical anesthesia is also provided for a growing number and variety of pacemaker and implantable cardioverter-defibrillator, percutaneous aortic valve, and arrhythmia procedures."}
{"_id": "WikiPedia_Cardio$$$corpus_4174", "text": "UOHI is a national centre for cardiac imaging. The institute employs all standard imaging modalities and evaluates experimental techniques and applications. UOHI also has the rare capability to develop and produce novel, short-lived nuclear tracers on site. The on-site cyclotron lets the institute produce many of its own medical isotopes, particularly for PET imaging. UOHI\u2019s Nuclear Cardiology Program is the largest such clinical program in Canada."}
{"_id": "WikiPedia_Cardio$$$corpus_4175", "text": "UOHI's cardiac surgeons perform more than 1,900 open-heart procedures annually, and the institute is known for its reconstructive heart-valve surgery program. Dr. Pierre Voisine is the Chief of Cardiac Surgery. It has among the lowest mortality rates and largest patient volumes in North America, especially for high-risk patients. Surgical specialties include:"}
{"_id": "WikiPedia_Cardio$$$corpus_4176", "text": "The Heart Institute is the provincial centre for pulmonary thromboendarterectomy."}
{"_id": "WikiPedia_Cardio$$$corpus_4177", "text": "The Cardiac Prevention and Rehabilitation program focuses its efforts in five areas: cardiac rehabilitation, prevention and wellness (for patient and public education), the Champlain Cardiovascular Disease Prevention Network, the Ottawa Model for Smoking Cessation [ 5 ]  (implemented in more than 200 medical institutions across Canada), and behavioral and risk modification research."}
{"_id": "WikiPedia_Cardio$$$corpus_4178", "text": "Approximately 60,000 patients a year visit UOHI\u2019s cardiology clinics for testing and treatment of heart disorders. The Cardiology program operates a number of specialized clinics that address various conditions and risk factors for heart disease."}
{"_id": "WikiPedia_Cardio$$$corpus_4179", "text": "The institute's cardiologists conduct more than 12,000 non-surgical interventions annually."}
{"_id": "WikiPedia_Cardio$$$corpus_4180", "text": "The ST-Elevation Myocardial Infarction (STEMI) Protocol, developed at UOHI, specifies that paramedic in Ottawa identify patients with a STEMI heart attack and transport them directly to the Institute. The program has cut mortality rates from heart attack in Ottawa by half. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4181", "text": "UOHI\u2019s division of nursing manages or supports programs and units within the Heart Institute, including the cardiac catheterization and electrophysiology labs, the cardiac operating rooms, the cardiac surgery intensive care unit and the intensive cardiac care unit."}
{"_id": "WikiPedia_Cardio$$$corpus_4182", "text": "UOHI offers specialized cardiac nursing training and education in a number of areas, such as critical care, provincial programs in cardiac CT, cardiac PET, artificial hearts, and pulmonary thromboendarterectomy."}
{"_id": "WikiPedia_Cardio$$$corpus_4183", "text": "Since 2004, a concerted effort to grow research funding at UOHI has resulted in a 300 percent increase in total grant awards. The Institute has more than 65 research faculty and 130 research staff members whose work encompasses all aspects of cardiovascular medicine. Research programs include:"}
{"_id": "WikiPedia_Cardio$$$corpus_4184", "text": "Heart Institute investigators:"}
{"_id": "WikiPedia_Cardio$$$corpus_4185", "text": "UOHI trains physicians, nurses, technologists, technicians, and other health professionals, as well as graduate students and post-doctoral students in the life and biomedical sciences. The Heart Institute also provides continuing education and best practice training for health care professionals and institutions, and develops patient education tools and programs to facilitate and support self-management of cardiovascular risk factors."}
{"_id": "WikiPedia_Cardio$$$corpus_4186", "text": "The institute is certified by the Royal College of Physicians and Surgeons of Canada for residency and fellowship training in cardiac surgery, cardiology, and cardiac anesthesiology."}
{"_id": "WikiPedia_Cardio$$$corpus_4187", "text": "The  Victor Chang Cardiac Research Institute  ( VCCRI ) is an Australian  non-profit   medical   research facility  that is dedicated to finding cures for  cardiovascular disease . With headquarters located in  Darlinghurst ,  New South Wales , the research hub is home to more than 20 research laboratories and the Victor Chang Cardiac Research Institute Innovation Centre. The institute's mission is \"the relief of pain and suffering, and the promotion of well-being, through an understanding of the fundamental mechanisms of cardiovascular disease\". Its key research is focused on the prevention and treatment of various  heart diseases , including  arrhythmia ,  cardiac arrest ,  cardiomyopathy ,  congenital heart disease ,  heart attack ,  heart failure ,  high cholesterol ,  obesity ,  spontaneous coronary artery dissection  (SCAD) and  stroke . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4188", "text": "The Victor Chang Cardiac Research Institute was founded in memory of pioneering  cardiac surgeon   Victor Chang   AC . [ 2 ]  Established on 14 February 1994, approximately three years after Chang's death, and opened by then  Prime Minister   Paul Keating , [ 3 ]  the institute has become a world-class research and research training facility. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4189", "text": "The Victor Chang Cardiac Research Institute was officially launched on 14 February 1994, by  Prime Minister Paul Keating , with  Kerry Packer  AC as patron, and  Professor Robert Graham  as executive director. The institute was originally founded under the auspices of the Sisters of Charity and St Vincent's Hospital. It was named in honour of  heart transplant  surgeon  Victor Chang , who died in  Sydney  under tragic circumstances on 4 July 1991. Dr Chang passionately believed in the ability for research to better the lives of many more than surgery ever could, saying \"you can save hundreds of lives through surgery but you could save millions through medical research\". On 27 February 1995, the institute was accredited as an independent research facility with  Neville Wran   AC ,  QC  as its inaugural chairman. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4190", "text": "On 1 November 1996,  Diana, Princess of Wales  officially opened the Victor Chang Cardiac Research Institute's temporary premises in Darlinghurst at the  Garvan Institute of Medical Research , touring several heart research laboratories. The Princess attended the Victor Chang Cardiac Research Institute Royal Ball as the Guest of Honour on 31 October 1996. [ 7 ]   Following the death of Diana, the institute established the inaugural Princess' Lecture which was first delivered by Professor Sir  Magdi Yacoub  in 1998."}
{"_id": "WikiPedia_Cardio$$$corpus_4191", "text": "In 2000 Dr Victor Chang was voted Australian of the Century by the people of Australia. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4192", "text": "On 4 March 2005,  Crown Princess Mary of Denmark  was the guest of honour at the second Victor Chang Royal Ball. The Royal Ball aimed to raise funds to develop a purpose-built, world class research centre in honour of Victor Chang. With the help of  Atlantic Philanthropies , construction of the Lowy Packer Building [ 9 ]  commenced in August 2006 with a groundbreaking ceremony in Darlinghurst. The ten-storey Lowy Packer Building would become the Victor Chang Cardiac Research Institute's new home. Construction was completed in 2008 and on 3 September, the Lowy Packer Building was formally opened by Crown Princess Mary of Denmark. [ 10 ]  Crown Princess Mary also attended a dinner with  Crown Prince Frederik  held inside the new complex. Queen Mary is an Honorary Life Governor of the Victor Chang Cardiac Research Institute."}
{"_id": "WikiPedia_Cardio$$$corpus_4193", "text": "In 2008 former NSW Premier  Neville Wran  retired as chairman, becoming a patron of the institute.  Steven Lowy  AM took up the position. In 2013 Lowy stood down as chairman, leaving the board after six years as chairman and 19 years as a director of the institute. Matthew Grounds AM was appointed chairman of the board. In 2013, the Victor Chang Cardiac Research Institute established an additional research laboratory based at the  University of Western Australia . Led by Professor Livia Hool, the expansion marks the initial phase of the institute's plans to enhance cardiovascular research in  Western Australia . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4194", "text": "In 2019 the institute celebrated its 25th anniversary with a dinner at the  Sydney Opera House . In 2020 the founding executive director of the institute,  Professor Robert Graham  stepped down after 25 years, handing over the leadership to  Professor Jason Kovacic . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4195", "text": "In 2022 the institute and  The University of Western Australia  announced an official partnership. Along with the new strategic partnership, an additional Victor Chang Cardiac Research Institute laboratory was opened at the university. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4196", "text": "The Victor Chang Cardiac Research Institute focuses on medical research, centered around;"}
{"_id": "WikiPedia_Cardio$$$corpus_4197", "text": "The Victor Chang Cardiac Research Institute, located within the purpose-built Lowy Packer Building, [ 9 ]  is a major partner in the St Vincent's Hospital Research Precinct in Darlinghurst, Sydney. Other partners in the precinct are the  Garvan Institute of Medical Research , the St Vincent's Centre for Applied Medical Research, and  St Vincent's Hospital  itself. [ 4 ]  The institute was funded by grants from the  Government of Australia  and a donation from Kerry Packer. [ 14 ]  The Lowy Packer Building was funded by the grants from the Government of Australia and the Government of New South Wales and donations from the  Atlantic Philanthropies , the  Lowy  and Packer families, the  National Australia Bank ,  ANZ Bank ,  Citigroup , and other donors. [ 4 ]  The budget for the building was A$80 m. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4198", "text": "The Victor Chang Cardiac Research Institute's laboratories in Western Australia are located on the grounds of  The University of Western Australia , which is approximately ten minutes from  Perth  CBD."}
{"_id": "WikiPedia_Cardio$$$corpus_4199", "text": "The VCCRI has state-of-the-art research laboratories and support facilities. The institute holds itself to the highest standards of excellence in research, research training and efforts to translate each new discovery into practical medical applications. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4200", "text": "The institute is governed by its board of directors, chaired by Matthew Grounds, an investment banker. [ 16 ] :\u200a13"}
{"_id": "WikiPedia_Cardio$$$corpus_4201", "text": "As of 31\u00a0December\u00a02017 [update]  the institute had a team of over 300 research and support staff work across six research divisions, being: [ 16 ] :\u200a12"}
{"_id": "WikiPedia_Cardio$$$corpus_4202", "text": "In addition, the institute has a business unit responsible for administration and core facilities and another unit that drives fund development. [ 16 ] :\u200a12"}
{"_id": "WikiPedia_Cardio$$$corpus_4203", "text": "The Victor Chang Institute is also affiliated with the  University of New South Wales , accredited by Australia's  National Health and Medical Research Council  (NHMRC) as an independent biomedical research facility; and is a member of the Association of Australian Medical Research Institutes (AAMRI). The institute is also a Research Ministry within the Mary Aikenhead Ministries."}
{"_id": "WikiPedia_Cardio$$$corpus_4204", "text": "Acute cardiac unloading  is any maneuver, therapy, or intervention that decreases the power expenditure of the  ventricle  and limits the hemodynamic forces that lead to  ventricular remodeling  after insult or injury to the  heart . This technique is being investigated as a therapeutic to aid after damage has occurred to the heart, such as after a  heart attack . The theory behind this approach is that by simultaneously limiting the oxygen demand and maximizing oxygen delivery to the heart after damage has occurred, the heart is more fully able to recover. This is primarily achieved by using temporary minimally invasive mechanical circulatory support to supplant the pumping of blood by the heart. Using mechanical support  decreases the workload of the heart, or unloads it."}
{"_id": "WikiPedia_Cardio$$$corpus_4205", "text": "Cardiac traumas such as  myocardial infarction  (commonly called a heart attack),  myocarditis ,\u00a0 peripartum cardiomyopathy ,  cardiogenic shock \u00a0, and  takotsubo cardiomyopathy  result in an impaired ability of the heart to pump blood. Without proper blood flow the person will ultimately die. Maintaining sufficient  cardiac output  is the primary objective of therapeutic approaches treating these cardiac conditions. However, many therapies aimed at increasing cardiac output place further stress on the heart. In this way a well-document vicious cycle begins in which increased cardiac output is required, but in order to achieve this the heart must work harder. This exacerbated stress leads to poorer outcomes. [ 1 ]  With the exception of  cardiopulmonary bypass , current therapeutic approaches do not allow the heart to rest and recover. The workload of the heart (pumping blood) is never uncoupled from heart function. Acute cardiac unloading is able to functionally uncouple [ 2 ]  the heart from cardiac output, allowing the heart to rest and recover from damage."}
{"_id": "WikiPedia_Cardio$$$corpus_4206", "text": "The pumping of blood is considered the workload of the heart and requires power expenditure. Acute cardiac unloading is any maneuver, therapy, or intervention that decreases the power expenditure of the ventricle while maintaining cardiac output. Oxygen consumption (MVO2) is a direct measure of the total energy requirements of the heart, including the energy needed to pump blood. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4207", "text": "Pressure-volume (PV) loop analysis  provides a framework for understanding how acute cardiac unloading reduces MVO2 in the heart. [ 4 ] [ 5 ]  The\u00a0PV loop characterizes the events occurring during a single cardiac cycle (a single heartbeat). The total area bound by the PV loop is the mechanical energy ( pressure-volume work ) used to actively pump blood every beat, measured in mmHg\u00b7mL (aka, a  joule \u00a0). This is known as the  stroke work (SW).  The remaining area bound by the  ESPVR  and  EDPVR  that is outside of the loop is the potential energy (PE) that resides in the  myofilaments  that was not transduced into the work of pumping blood. The sum of these two areas (PE + SW) is known as the pressure-volume area (PVA). PVA is a first order approximation of MVO2. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4208", "text": "Acute cardiac unloading decreases the workload of and the oxygen demand of the heart.  This can be visualized as an overall decrease in the PVA of the PV loop. [ 3 ] [ 2 ]  Mechanical unloading of the heart by a percutaneous ventricular support device such as the  Impella  device can achieve this in two ways. First, the device is a continuous flow device. It directly aspirates blood from the  ventricle  into the  aorta . This decreases the  preload  and results in a left-shift and loss of the normal isovolumic contraction line. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4209", "text": "Under conditions of mechanical support, mean aortic pressure (MAP) is maintained independent of native ventricular function, and ventricular and aortic pressures become uncoupled. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4210", "text": "When the heart is damaged by a  myocardial infarction  a portion of muscle is permanently lost. The heart has a limited innate  ability to replace dead muscle with new, functional muscle . [ 6 ]  The dead heart muscle is replaced by non-contractile fibrotic tissue, forming the  myocardial scar . Scar tissue does not contract, and it does not help the heart pump blood.  This persistently stresses the heart and increases the workload of the lasting myocardium as measured by MVO2. Clinical research indicates that as the size of the myocardial scar increases, so does the likelihood of the patient to develop heart failure. [ 7 ]   Acute cardiac unloading decreases cardiac MVO2 and has been demonstrated to limit the amount of scar tissue that forms, thus preserving heart function after a heart attack. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4211", "text": "Cardiac catheterization  ( heart cath ) is the insertion of a  catheter  into a  chamber  or  vessel  of the  heart . This is done both for diagnostic and interventional purposes."}
{"_id": "WikiPedia_Cardio$$$corpus_4212", "text": "A common example of cardiac catheterization is  coronary catheterization  that involves catheterization of the  coronary arteries  for  coronary artery disease  and  myocardial infarctions  (\"heart attacks\"). Catheterization is most often performed in special laboratories with  fluoroscopy  and highly maneuverable tables. These \"cath labs\" are often equipped with cabinets of catheters,  stents ,  balloons , etc. of various sizes to increase efficiency. Monitors show the fluoroscopy imaging,  electrocardiogram  (ECG), pressure waves, and more."}
{"_id": "WikiPedia_Cardio$$$corpus_4213", "text": "Coronary angiography is a diagnostic procedure that allows visualization of the coronary vessels. Fluoroscopy is used to visualize the lumens of the arteries as a 2-D projection. Should these arteries show narrowing or blockage, then techniques exist to open these arteries.  Percutaneous coronary intervention  is a blanket term that involves the use of mechanical stents, balloons, etc. to increase blood flow to previously blocked (or occluded) vessels. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4214", "text": "Measuring pressures in the heart is also an important aspect of catheterization. The catheters are fluid filled conduits that can transmit pressures to outside the body to  pressure transducers . This allows measuring pressure in any part of the heart that a catheter can be maneuvered into. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4215", "text": "Measuring blood flow is also possible through several methods. Most commonly, flows are estimated using the  Fick principle  and thermodilution. These methods have drawbacks, but give invasive estimations of the cardiac output, which can be used to make clinical decisions (e.g.,  cardiogenic shock ,  heart failure ) to improve the person's condition. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4216", "text": "Cardiac catheterization can be used as part of a therapeutic regimen to improve outcomes for survivors of out-of-hospital cardiac arrest. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4217", "text": "Cardiac catheterization often requires the use of  fluoroscopy  to visualize the path of the catheter as it enters the heart or as it enters the coronary arteries. The coronary arteries are known as \"epicardial vessels\" as they are located in the epicardium, the outermost layer of the heart. [ 2 ]  The use of fluoroscopy requires radiopaque contrast, which in rare cases can lead to contrast-induced kidney injury (see  Contrast-induced nephropathy ). People are constantly exposed to low doses of  ionizing radiation  during procedures. [ 3 ]  Ideal table positioning between the x-ray source and receiver, and  radiation monitoring  via  thermoluminescent dosimetry , are two main ways of reducing a person's exposure to radiation. [ 3 ]  People with certain  comorbidities  (people who have more than one condition at the same time) have a higher risk of adverse events during the cardiac catheterization procedure. [ 3 ]  These comorbidity conditions include  aortic aneurysm ,  aortic stenosis , extensive three-vessel  coronary artery disease ,  diabetes , uncontrolled  hypertension ,  obesity ,  chronic kidney disease , and  unstable angina . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4218", "text": "Left heart catheterization (LHC) is an ambiguous term and sometime clarification is required: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4219", "text": "technique is also used to assess the amount of occlusion (or blockage) in a coronary artery, often described as a percentage of occlusion. A thin, flexible wire is inserted into either the  femoral artery  or the  radial artery  and threaded toward the heart until it is in the ascending  aorta . Radial access is not associated with an increased risk of stroke over femoral access. [ 5 ]  At this point, a catheter is guided over the wire into the ascending aorta, where it can be maneuvered into the coronary arteries through the coronary ostia. [ 4 ]  In this position, the interventional cardiologist can inject contrast and visualize the flow through the vessel. If necessary, the physician can utilize percutaneous coronary intervention techniques, including the use of a  stent  (either bare-metal or  drug-eluting ) to open the blocked vessel and restore appropriate blood flow. In general, occlusions greater than 70% of the width of the vessel lumen are thought to require intervention. However, in cases where multiple vessels are blocked (so-called \"three-vessel disease\"), the interventional cardiologist may opt instead to refer the patient to a cardiothoracic surgeon for coronary artery bypass graft (CABG; see  Coronary artery bypass surgery ) surgery. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4220", "text": "Right heart catheterization (RHC) allows the physician to determine the pressures within the heart (intracardiac pressures). The heart is most often accessed via the internal jugular or femoral vein; arteries are not used. Values are commonly obtained for the right atrium, right ventricle, pulmonary artery, and pulmonary capillary \"wedge\" pressures. Right heart catheterizations also allow the physician to estimate the cardiac output, the amount of blood that flows from the heart each minute, and the cardiac index, a hemodynamic parameter that relates the cardiac output to a patient's body size.  Determination of cardiac output  can be done by releasing a small amount of saline solution (either chilled or at room temperature) in one area of the heart and measuring the change in blood temperature over time in another area of the heart. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4221", "text": "Right heart catheterization is often done for  pulmonary hypertension ,  heart failure , and  cardiogenic shock . The pulmonary artery catheter can be placed, used, and removed, or it can be placed and left in place for continuous monitoring. The latter can be done an  intensive care unit  (ICU) to permit frequent measurement of the hemodynamic parameters in response to interventions. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4222", "text": "Parameters obtainable from a right heart catheterization: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4223", "text": "Coronary catheterization is an invasive process and comes with risks that include stroke, heart attack, and death. Like any procedure, the benefits should outweigh the risks and so this procedure is reserved for those with symptoms of serious heart diseases and is never used for screening purposes. Other, non-invasive tests are better used when the diagnosis or certainty of the diagnosis is not as clear. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4224", "text": "Indications for cardiac catheterization include the following: [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4225", "text": "Right heart catheterization, along with  pulmonary function testing  and other testing should be done to confirm  pulmonary hypertension  prior to having  vasoactive   pharmacologic treatments  approved and initiated. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4226", "text": "Placement of internal  pacemakers  and  defibrillators  are done through catheterization as well. An exception to this is placement of electrodes on the outer surface of the heart (called epicardial electrodes). Otherwise, electrodes are placed through the venous system into the heart and left there permanently. Typically, these devices are placed in the left upper chest and enter the left  subclavian vein  and electrodes are placed in the right atrium, right ventricle, and coronary sinus (for the left ventricle stimulation). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4227", "text": "Echocardiography  is a non-invasive method to evaluate the heart valves. However, sometimes the valve pressure gradients need to be measured directly because echo is equivocal for the severity of valve disease. Invasive assessment of the valve can be done with catheterization by placing a catheter across the valve and measuring the pressures simultaneously on each side of the valve to obtain the pressure gradient. [ 8 ]  In conjunction with a right heart catheterization, the valve area can be estimated. For example, in  aortic valve area calculation  the Gorlin equation can be used to calculate the area if the cardiac output, pressure gradient, systolic period, and heart rate are known. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4228", "text": "Evaluation of the blood flow to the lungs can be done invasively through catheterization. Contrast is injected into the pulmonary trunk, left or right pulmonary artery, or segment of the pulmonary artery. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4229", "text": "Cardiac shunts  can be evaluated through catheterization. Using oxygen as a marker, the  oxygen saturation  of blood can be sampled at various locations in and around the heart. For example, a left-to-right  atrial septal defect  will show a marked increase in oxygen saturation in the right atrium, ventricle, and pulmonary artery as compared to the  mixed venous oxygen saturation  from the oxygenated blood from the lungs mixing into the venous return to the heart. Utilizing the  Fick principle , the ratio of blood flow in the lungs (Qp) and system circulations (Qs) can calculate the Qp:Qs ratio. Elevation of the Qp:Qs ratio above 1.5 to 2.0 suggests that there is a hemodynamically significant left-to-right shunt (such that the blood flow through the lungs is 1.5 to 2.0 times more than the systemic circulation). This ratio can be evaluated non-invasively with  echocardiography  too, however. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4230", "text": "A \"shunt run\" is often done when evaluating for a shunt by taking blood samples from  superior vena cava  (SVC),  inferior vena cava  (IVC),  right atrium ,  right ventricle ,  pulmonary artery , and system arterial. Abrupt increases in oxygen saturation support a left-to-right shunt and lower than normal systemic arterial oxygen saturation supports a right-to-left shunt. Samples from the SVC & IVC are used to calculate  mixed venous oxygen saturation . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4231", "text": "By injecting contrast into the left ventricle, the outline of the ventricle can be measured in both systole and diastole to estimate the  ejection fraction  (a marker of heart function). Due to the high contrast volumes and injection pressures, this is often not performed unless other, non-invasive methods are not acceptable, not possible, or conflicting. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4232", "text": "Advancements in cardiac catheterization have permitted replacement of heart valves by means of blood vessels. This method allows  valve replacement  without  open heart surgery  and can be performed on people who are high-risk for such a surgery. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4233", "text": "Catheterization can also be used to perform  balloon septostomy , which is the widening of a  foramen ovale ,  patent foramen ovale  ( PFO ), or  atrial septal defect  ( ASD ) using a  balloon catheter . This can be done in certain congenital heart diseases in which the mechanical shunting is required to sustain life such as in  transposition of the great vessels . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4234", "text": "Hypertrophic cardiomyopathy  is a disease in which the myocardium is thickened and can cause blood flow obstruction. If hemodynamically significant, this excess muscle can be removed to improve blood flow. Surgically, this can be done with  septal myectomy . However, it can be done through catheterization and by injecting  ethanol  to destroy the tissue in an  alcohol septal ablation . This is done by selected an appropriate septal artery supplying the intended area and, essentially, causing a localized, controlled  myocardial infarction  of the area with ethanol. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4235", "text": "Complications of cardiac catheterization and tools used during catheterization include, but not limited to: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4236", "text": "The likelihood of these risks depends on many factors that include the procedure being performed, the overall health state of the patient, situational (elective vs emergent), medications (e.g.,  anticoagulation ), and more. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4237", "text": "\"Cardiac catheterization\" is a general term for a group of procedures. Access to the heart is obtained through a peripheral artery or vein. Commonly, this includes the  radial artery ,  internal jugular vein , and  femoral artery / vein . Each blood vessel has its advantages and disadvantages. Once access is obtained, plastic catheters (tiny hollow tubes) and flexible wires are used to navigate to and around the heart. Catheters come in numerous shapes, lengths, diameters, number of lumens, and other special features such as electrodes and balloons. Once in place, they are used to measure or intervene. Imaging is an important aspect to catheterization and commonly includes fluoroscopy but can also include forms of  echocardiography  ( TTE ,  TEE ,  ICE ) and ultrasound ( IVUS ). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4238", "text": "Obtaining access uses the  Seldinger technique  by puncturing the vessel with a needle, placing a wire through the needle into the lumen of the vessel, and then exchanging the needle for a larger plastic sheath. Finding the vessel with a needle can be challenging and both ultrasound and fluoroscopy can be used to aid in finding and confirming access. Sheaths typically have a side port that can be used to withdraw blood or injection fluids/medications, and they also have an end hole that permits introducing the catheters, wires, etc. coaxially into the blood vessel. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4239", "text": "Once access is obtained, what is introduced into the vessel depends on the procedure being performed. Some catheters are formed to a particular shape and can really only be manipulated by inserting/withdrawing the catheter in the sheath and rotating the catheter. Others may include internal structures that permit internal manipulation (e.g.,  intracardiac echocardiography ). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4240", "text": "Finally, when the procedure is completed, the catheters are removed and the sheath is removed. With time, the hole made in the blood vessel will heal.  Vascular closure devices  can be used to speed along hemostasis."}
{"_id": "WikiPedia_Cardio$$$corpus_4241", "text": "Much equipment is required for a facility to perform the numerous possible procedures for cardiac catheterization."}
{"_id": "WikiPedia_Cardio$$$corpus_4242", "text": "General: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4243", "text": "Percutaneous coronary intervention: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4244", "text": "Electrophysiology: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4245", "text": "The history of cardiac catheterization dates back to  Stephen Hales  (1677-1761) and  Claude Bernard  (1813-1878), who both used it on animal models. Clinical application of cardiac catheterization begins with Dr.  Werner Forssmann  in 1929, who inserted a catheter into the vein of his own forearm, guided it fluoroscopically into his right atrium, and took an  X-ray  picture of it. [ 9 ]  However, even after this achievement, hospital administrators removed Forssmann from his position owing to his unorthodox methods. [ 9 ] \nDuring  World War II ,  Andr\u00e9 Fr\u00e9d\u00e9ric Cournand , a physician at  NewYork-Presbyterian/Columbia , then Columbia-Bellevue, opened the first catheterization lab. In 1956, Forssmann and Cournand were co-recipients of the Nobel Prize in Physiology or Medicine for the development of cardiac catheterization.\nDr.  Eugene A. Stead  performed research in the 1940s, which paved the way for cardiac catheterization in the USA. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4246", "text": "Cardiac contractility modulation  is a  therapy  which is intended for the treatment of patients with moderate to severe  heart failure  ( NYHA class II\u2013IV ) with symptoms despite optimal medical therapy who can benefit from an improvement in cardiac output. The short- and long-term use of this therapy enhances the strength of ventricular  contraction  and therefore the heart's pumping capacity by modulating (adjusting) the  myocardial contractility . This is provided by a  pacemaker -like device that applies  non-excitatory electrical signals  adjusted to and synchronized with the electrical action in the  cardiac cycle . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4247", "text": "In cardiac contractility modulation therapy, electrical stimulation is applied to the cardiac muscle during the absolute  refractory period . In this phase of the cardiac cycle, electrical signals cannot trigger new  cardiac muscle  contractions, hence this type of stimulation is known as a non-excitatory stimulation. However, the electrical signals increase the influx of  calcium   ions  into the cardiac muscle cells ( cardiomyocytes ). [ 4 ] [ 5 ]  In contrast to other electrical stimulation treatments for heart failure, such as  pacemaker  therapy or  implantable cardioverter defibrillators  (ICD), cardiac contractility modulation does not directly affect cardiac rhythm. Rather, the aim is to enhance the heart's natural contraction (the native cardiac contractility) sustainably over long periods of time. Furthermore, unlike most interventions that increase cardiac contractility, cardiac contractility modulation is not associated with an unfavorable increase in oxygen demand by the heart (measured in terms of Myocardial Oxygen Consumption or MVO 2 ). This may be explained by the beneficial effect the therapy has in improving cardiac efficiency. [ 6 ] [ 7 ] [ 8 ]  A meta-analysis in 2014 [ 2 ]  and an overview of device-based treatment options in heart failure in 2013 [ 9 ]  concluded that cardiac contractility modulation treatment is safe, [ 1 ] [ 9 ]  that it is generally beneficial to patients [ 1 ] [ 9 ]  and that the treatment increases the  exercise tolerance  (ET) and  quality of life  (QoL) of patients. [ 2 ]  Furthermore, preliminary long-term  survival data  shows that cardiac contractility modulation is associated with lower long-term  mortality  in heart failure patients when compared with expected rates among similar patients not treated with cardiac contractility modulation. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4248", "text": "Based on the results of the pivotal FIX-HF-5C trial, [ 11 ]  the FDA approved cardiac contractility modulation therapy for use in the United States on March 21, 2019. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4249", "text": "The FDA approved the OPTIMIZER Smart System, which delivers cardiac contractility modulation therapy, as indicated to improve 6-minute hall walk distance, quality of life, and functional status of NYHA Class III heart failure patients who remain symptomatic despite guideline directed medical therapy, who are in normal sinus rhythm, are not indicated for cardiac resynchronization therapy, and have a left ventricular ejection fraction ranging from 25% to 45%. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4250", "text": "Based on the results of clinical trials, [ 3 ] [ 13 ]  cardiac contractility modulation devices are approved and available for clinical use in all  European Union  countries and in  Australia ,  Turkey ,  India  and  Hong Kong , as well as in other countries that recognize  CE marking  for  medical devices . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4251", "text": "Based on the approval of cardiac contractility modulation devices, the therapy is a treatment option for patients that are at least 18 years old who suffer from  heart failure symptoms  due to left ventricular systolic dysfunction (LVSD) despite adequate medical treatment. Further clinical research are under way to identify which patient group within the scope of the device approval benefits most from cardiac contractility modulation treatment. [ 1 ] [ 2 ] [ 3 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4252", "text": "Criteria for the classification of patients with left ventricular systolic heart failure include the severity of the disease based on functional parameters (NYHA classification), the average percentage of blood volume ejected by the left ventricle with each heart beat (left ventricular  ejection fraction  or LVEF) and the duration of the QRS complex seen in the electrocardiogram (ECG). Most clinical studies on cardiac contractility modulation therapy have involved heart failure patients who were classified initially as NYHA Class II, III or IV and had a normal QRS duration (QRS duration \u2264 120 ms). The efficacy of cardiac contractility modulation on patients in an earlier stage of heart failure has not yet been studied. [ 2 ] [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4253", "text": "A subsequent evaluation study (subgroup analysis) has already suggested a particular patient group that responds exceptionally well to cardiac contractility modulation therapy. The patients were characterized by a disease severity of NYHA class III and a left ventricular ejection fraction of \u2265 25%. [ 1 ] [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4254", "text": "Although studies on cardiac contractility modulation therapy have focused on patients with a normal QRS duration (i.e. \u2264 120 ms), it is possible to use the therapy in patients who meet the treatment indication but who do not have a normal QRS duration. [ 3 ] [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4255", "text": "A preliminary study has previously shown that cardiac contractility modulation may be safe and effective in such patients who have not responded to  cardiac resynchronization therapy  (CRT). [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4256", "text": "Cardiac resynchronization therapy (CRT; also known as biventricular pacing) has proven to be an effective treatment in heart failure. [ 20 ]  However, CRT is generally recommended exclusively for patients with a preserved sinus rhythm and a prolonged QRS complex (\u2265 120 ms) who also suffer from  left bundle branch block  (LBBB), or for patients without left bundle branch block but who have a preserved sinus rhythm and a QRS complex with a width of \u2265 150 ms. [ 20 ]  However, only 30-40% of all heart failure patients show such a prolonged QRS complex, and therefore the 60-70% of patients who have a normal QRS complex cannot be treated with CRT. In addition, around 30% of the patients eligible for CRT treatment do not respond to CRT. [ 2 ] [ 15 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4257", "text": "Until recently, the only other available device-based treatment was the  left ventricular assist device  (LVAD). LVAD therapy is indicated in patients with severe illness and is associated with several hours of surgery (involving a  cardiopulmonary bypass ). It is usually considered as a therapy providing a \"bridge to transplant\" for heart failure patients classified as NYHA class IV, and is intended to support heart function until a  heart transplant  is received. [ 2 ] [ 15 ] [ 17 ]  Current research results suggest that the therapeutic gap described above could now be closed by the cardiac contractility modulation therapy. [ 2 ] [ 15 ] [ 17 ]  Additionally, a long-term study showed that the cardiac contractility modulation was able to stop the common and prognostically unfavorable long-term prolongation of QRS duration in heart failure patients. This result was interpreted as signaling the safety of the treatment and as an indicator that patients could benefit from cardiac contractility modulation therapy in the long term. If the QRS-stabilizing effect were to be confirmed in further studies, the cardiac contractility modulation would become the first device-based treatment for heart failure with the potential to halt QRS prolongation, a factor associated with a poor prognosis. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4258", "text": "The  guidelines  issued by the  European Society of Cardiology  (ESC) in 2016, mention cardiac contractility modulation therapy as a therapy option to be considered in selected group of patients with HF. Mostly these guidelines are endorsed by national cardiac societies in individual countries within the European Union. [ 20 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4259", "text": "Cardiac contractility modulation has proven to be effective and safe in randomized controlled trials involving several hundred patients. [ 23 ] [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4260", "text": "The nature and extent of the effect of cardiac contractility modulation have been the subject of numerous investigations. Although various individual publications, as well as one of two meta-analyses, have presented the efficacy and significant potential of cardiac contractility modulation in the treatment of heart failure, medical evaluation of the therapy efficacy is not yet complete. Scientists point out, however, that this was also the case for CRT therapy when it was first introduced, advocating the provision of cardiac contractility modulation to suitable patients before further studies are completed. [ 3 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4261", "text": "To date (February 2015), there are at least two meta-analyses studying the efficacy of cardiac contractility modulation therapy on heart failure, [ 2 ] [ 26 ]  a large number of review articles (e.g. [ 3 ] [ 17 ] [ 18 ] [ 27 ] [ 28 ] ) and at least two survey articles on device-based treatments of advanced heart failure [ 1 ] [ 15 ]  which address cardiac contractility modulation. Furthermore, there are more than 70 individual publications focusing specifically on cardiac contractility modulation therapy. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4262", "text": "Further randomized controlled trials studying the effect of cardiac contractility modulation on the progression of heart failure have been initiated and are currently (as of February 2015) recruiting patients. [ 3 ] [ 14 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4263", "text": "Giallauria et al. evaluated the three  randomized controlled trials  (RCTs) currently available on cardiac contractility modulation as a treatment for heart failure patients. [ 2 ] [ 23 ] [ 24 ]  The three trials included a total of 641 patients and assessed the effect of cardiac contractility modulation either in comparison to a sham treatment [ 23 ] [ 24 ]  or in comparison to the best medical treatment. [ 25 ]  In contrast to an earlier meta-analysis by Kwong et al. [ 26 ]  the study did not evaluate the data based on summarized results alone, but on the basis of the individual data sets of the 641 enrolled patients."}
{"_id": "WikiPedia_Cardio$$$corpus_4264", "text": "The study concluded that cardiac contractility modulation significantly improved important markers of cardiac performance. These included the  maximal oxygen uptake  (peak VO2 or pVO2 \u2013 measured by ventilatory parameters during a cardiopulmonary exercise test), which is indicative of improved survival, [ 30 ]  and the  6-minute walk test . The quality of life of participating patients, measured by the Minnesota Living with Heart Failure Questionnaire (MLWHFQ), also improved significantly. However, both meta-analyses demanded additional and larger randomized controlled trials in order to evaluate the effect of the therapy more precisely. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4265", "text": "Giallauria et al. describe the success of cardiac contractility modulation and the further potential of the therapy. Particular emphasis is given to the possibility that cardiac contractility modulation therapy may close the  therapeutic gap  in heart failure treatment if previous study outcomes are confirmed. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4266", "text": "As of February 2015, the effect of cardiac contractility modulation therapy on the long-term mortality rates of heart failure patients has not been studied in a randomized controlled trial. Some preliminary single-center studies have been reported though. [ 10 ]  Kuschyk et al. evaluated the long-term efficacy and survival of patients with cardiac contractility modulation. [ 10 ]  Their analysis included 81 patients with a disease severity of NYHA class II, III or IV and a mean follow-up of around 3 years. The analysis compared the observed mortality rate with the prediction of the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) model [ 31 ] [ 32 ]  which is based on the records of over 39,000 heart failure patients. Unlike a previous long-term outcome study of cardiac contractility modulation, [ 33 ]  this study was not limited by a widely heterogeneous group of patients."}
{"_id": "WikiPedia_Cardio$$$corpus_4267", "text": "Following long-term observation, the study concluded that cardiac contractility modulation improved quality of life, exercise tolerance, NYHA class, left ventricular ejection fraction (LVEF) and  brain natriuretic peptide  (BNP) levels. Mortality rates were significantly lower than predicted at year 1, and lower than predicted but not statistically significant at year 3. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4268", "text": "Heart failure is a chronic disease that usually progresses gradually. [ 20 ]  The rate of progression and the degree of symptoms of the disease varies between different patients. Cardiac contractility modulation therapy aims to treat heart failure through a medium- to long-term treatment, over the course of weeks and months. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4269", "text": "According to large implanting clinics, after the implantation wound is healed, the lifestyle of a patient is not restricted by the implanted device. [ 34 ]  Leisure, travel (by car, train, ship or plane), hobbies and sex life will not be restricted. The patient may perceive an improved capacity for these activities and overall enhanced performance and exercise capacity in response to the actual therapy. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4270", "text": "In the past, the most important contraindication in cardiac contractility modulation treatment was permanent and long-standing persistent  atrial fibrillation . The signal application in current cardiac contractility modulation devices was timed and triggered according to the electrical activity of the  atrium . In atrial fibrillation, electrical activity in the atrium is severely disturbed and is therefore not a reliable basis for the triggering of cardiac contractility modulation signals. This also applies to other diseases involving severe disturbance in electrical atrial sensing. [ 35 ]  Requests have been raised in scientific literature for an improved cardiac contractility modulation algorithm which would allow the therapy to be delivered independently from any atrial signal. A pioneering study had shown that an improved cardiac contractility modulation algorithm could make the therapy an effective treatment for patients with persistent atrial fibrillation. [ 35 ]  Following these study results the new generation was developed and can now offer cardiac contractility modulation therapy also for patients with atrial fibrillation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4271", "text": "Other irregular rhythms, including frequent  premature ventricular contractions  (ventricular extra systoles) or a distinct signal transduction disorder in the heart (untreated  AV block  of more than 300 ms), may represent contraindications. CRT treatment should be considered in lieu of cardiac contractility modulation in patients with left bundle branch block (LBBB) and a QRS duration of over 120 ms, or when the QRS duration is greater than 150 ms and independent of LBBB. [ 9 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4272", "text": "As with conventional pacemaker therapy, the cardiac contractility modulation device cannot be implanted if the leads cannot be positioned appropriately in the heart. In cases where there is an  artificial heart valve  between the right atrium and ventricle (a mechanical prosthetic tricuspid valve), the valve function could be greatly affected by the ventricular leads. In some instances it may be impossible to guide the leads through the main veins in the upper half of the body to the heart due to  venous thrombosis , for example  VVI pacemakers , in the case of 100% stimulation, are also contraindicated. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4273", "text": "The most frequently encountered adverse events related to cardiac contractility modulation therapy are lead fracture or lead dislodgement. [ 25 ]  Other reported complications include:"}
{"_id": "WikiPedia_Cardio$$$corpus_4274", "text": "These side effects are similar to those that occur with other electrical stimulation therapies, such as pacemakers, CRT devices or ICD devices. [ 30 ]  Furthermore, recorded complications did not differ between patients with activated or deactivated cardiac contractility modulation devices. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4275", "text": "Overall, cardiac contractility modulation treatment was demonstrated to have no negative impact on health markers. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4276", "text": "Similarly to patients with other electrical stimulation devices, patients with a cardiac contractility modulation device must follow certain precautions arising from the device implantation and its function."}
{"_id": "WikiPedia_Cardio$$$corpus_4277", "text": "The  mechanism of action  of cardiac contractility modulation has been subject to continuous research since its initial discovery. Based on  animal testing  and experiments on human myocardial tissue obtained by  biopsies , essential parts of the mechanism of action have been identified. [ 4 ] [ 39 ]  According to current understanding (as of February 2015), the mechanism of action of cardiac contractility modulation may be summarized in the following manner: The signals applied during the electrical non-excitatory state of the cardiac muscle cells (the absolute refractory period) cause an increase in myocyte calcium in the cytosol during systole. This increases the muscle contraction strength. Additionally, within minutes, cell  metabolism  and  gene expression , which are typically abnormal in heart failure, improve towards their normal state. [ 39 ]  This beneficial effect occurs initially only in the area adjacent to the electrodes, but with time also spreads to remote areas of the cardiac muscle. [ 39 ]  Cardiac contractility modulation therefore restores the structure and function of damaged cells back towards their normal state. In some cases, disease-related changes in the ventricular heart structure can be partially reversed by cardiac contractility modulation through a process known as reverse remodeling of the heart. [ 3 ] [ 4 ] [ 5 ] [ 18 ] [ 40 ] [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4278", "text": "Development of cardiac contractility modulation began in the late 1990s. [ 42 ] [ 43 ]  Studies on individual cardiac muscle cells using a patch-clamp technique had already shown, in 1969, that a voltage applied during the absolute refractory period through leads between the interior of the cell and its outside environment increased the calcium influx through the cell membrane and improved the contraction of cardiac muscle cells. [ 44 ] [ 45 ]  In 2001, scientists observed that a similar effect occurs even if the voltage is applied exclusively outside the cardiac muscle cells. [ 46 ]  Additionally, it was observed that therapeutically useful effects on the cardiac muscle were achieved if the electrical signals were applied not only to single cells but to large areas using larger leads, as used in conventional cardiac pacemakers. The contractility of both a healthy heart and a damaged heart could be increased through application of appropriate signals during the absolute refractory period of the cardiac muscle cells. [ 47 ] [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4279", "text": "An implantable cardiac contractility modulation device was received by a patient for the first time in 2001. [ 49 ] [ 50 ]  The first study on the therapeutic effects of in humans was presented in 2004. [ 51 ]  To date, more than 3,000 heart failure patients have been treated with cardiac contractility modulation worldwide, [ 13 ]  including 641 patients under the study conditions recommended by the  Cochrane Collaboration  as being necessary for inclusion in a meta-analysis. [ 2 ]  Cardiac contractility modulation device implantation was first successfully done in India in Royal Hospital, Trivandrum, Kerala, under the leadership of Dr. C. Bharath Chandran. Advocate Harishankar was the first person in India to get the cardiac contractility modulation device implanted."}
{"_id": "WikiPedia_Cardio$$$corpus_4280", "text": "Cardiac magnetic resonance imaging perfusion  ( cardiac MRI perfusion ,  CMRI perfusion ), also known as  stress CMR perfusion , [ 1 ]  is a clinical  magnetic resonance imaging  test performed on patients with known or suspected  coronary artery disease  to determine if there are perfusion defects in the  myocardium  of the  left ventricle  that are caused by narrowing of one or more of the  coronary arteries ."}
{"_id": "WikiPedia_Cardio$$$corpus_4281", "text": "CMR perfusion is increasingly used in cardiac imaging to test for inducible myocardial ischaemia and has been well validated against other imaging modalities such as invasive angiography [ 2 ] [ 3 ]  or FFR. Several recent large-scale studies have shown non-inferiority or superiority to  SPECT  imaging. It is becoming increasingly established as a marker of prognosis in patients with coronary artery disease. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4282", "text": "There are two main reasons for doing this test: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4283", "text": "In contrast to the nuclear imaging modalities ( PET  and  SPECT ), CMR perfusion does not involve the use of ionising radiation and can therefore be used multiple times without the risk to the patient of exposure to radiation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4284", "text": "It is a non-invasive test, is generally regarded as a safe (see below) procedure and is well tolerated by patients (apart from people with claustrophobia) [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4285", "text": "The majority of scans are performed using a stress/rest protocol using adenosine as the stressor which acts to induce ischaemia in the myocardium by the coronary 'steal' phenomenon. Some centers use inotrope dobutamine to stress the heart and the images are interpreted in a similar fashion to  dobutamine stress echocardiogram . This article concentrates on adenosine stress scans. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4286", "text": "An intravenous infusion of  adenosine  is given at 140\u00a0\u03bcg/Kg/min for 3 minutes with continuous heart rate and blood pressure recording to induce  hyperaemia  (normally seen as a drop in systolic blood pressure of 10mmHg or a rise in heart rate of 10bpm). Following this, an intravenous bolus of 0.05\u00a0mmol/kg of a  gadolinium  chelate (such as gadodoteric acid) is administered via an antecubital fossa vein on the contralateral arm to the adenosine. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4287", "text": "Typically, 3 short axis slices, each of 10mm thickness, are acquired per cardiac cycle, at the basal, mid papillary and apical levels of the left ventricle. A single shot prospectively gated, balanced TFE sequence is used with a typical resolution of 2.5 x 2.5mm. The patient is then allowed to rest until the haemodynamic effects of the adenosine have stopped (typically 5 minutes). The same scan protocol is then performed at rest. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4288", "text": "The images are stored as video files and are analysed on a dedicated workstation. The majority of clinical scans are analysed qualitatively by visually comparing the stress and rest scans in parallel. In a normal scan, the wash in (1st pass) of gadolinium into the myocardium can be seen as the myocardium turning from black to mid grey uniformly throughout the whole of the left ventricle in both the stress and rest scans. In an abnormal scan an area of the myocardium will turn grey slower than the surrounding tissue as the blood (and hence gadolinium) enters more slowly due to a narrowing of the coronary artery supplying it. This is called a perfusion defect and usually represents myocardial ischaemia. It may be seen on both the rest and stress scans in which case it is called a matched perfusion defect and is probably due to an area or scar from a previous myocardial infarction. If it is only seen on the stress scan it is called an area of inducible perfusion defect (ischaemia). The position in the left ventricle of the perfusion defects are described using the AHA 17 segment model. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4289", "text": "Stress CMR cannot be performed on all patients due to the relative or absolute contraindications listed below, this is a problem, especially in patients who either have a pacemaker or severe renal failure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4290", "text": "The acquisition of the images is very sensitive to the rhythm of the heart and scans of patients with atrial fibrillation, bigeminy or trigeminy will sometimes be of low quality and may not be interpretable. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4291", "text": "Due to the high contrast between the blood pool and the myocardium it is common to get what looks like a thin subendocardial area of ischaemia called the  Gibbs artifact , this however, is less common with newer technology allowing higher resolution imaging. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4292", "text": "In patients who have had a previous myocardial infarction or previous coronary artery bypass surgery, the images may be very difficult to interpret and in such cases, the analysis of the scans is performed with the complement of another imaging modality (such as coronary angiography). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4293", "text": "It is a non-invasive test as is generally regarded as safe however, there are some patients for whom this is contraindicated and there are a number of potential complications: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4294", "text": "Contraindications are as follows: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4295", "text": "It is common for the patient to get a number of mild symptoms when they are given the Adenosine infusion, such as feeling hot and sweaty, short of breath, nauseous and noticing that their heart is beating faster. These, if they occur, resolve rapidly (normally within 60 seconds) after the Adensoine infusion has stopped. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4296", "text": "There are a number of more serious and much less common side effects, including transient heart block, bronchoconstriction and a 1 in 10,000 risk of  anaphylaxis  caused by the gadolinium contrast agent. These can invariably be successfully treated with no long term side effects. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4297", "text": "Adenosine infusion is associated with some very rare but very serious side effects, including acute  pulmonary oedema  and  cardiac arrest  (occurring in \u22481 in 1000 patients). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4298", "text": "Cardioversion  is a  medical procedure  by which an abnormally fast  heart rate  ( tachycardia ) or other  cardiac arrhythmia  is converted to a  normal rhythm  using  electricity  or  drugs ."}
{"_id": "WikiPedia_Cardio$$$corpus_4299", "text": "Synchronized electrical cardioversion  uses a therapeutic dose of  electric current  to the  heart  at a specific moment in the  cardiac cycle , restoring the activity of the  electrical conduction system of the heart . ( Defibrillation  uses a therapeutic dose of  electric current  to the  heart  at a random moment in the  cardiac cycle , and is the most effective resuscitation measure for  cardiac arrest  associated with  ventricular fibrillation  and pulseless  ventricular tachycardia . [ 1 ] )  Pharmacologic cardioversion , also called  chemical cardioversion ,  uses  antiarrhythmia medication  instead of an electrical shock. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4300", "text": "To perform synchronized electrical cardioversion, two  electrode  pads are used (or, alternatively, the traditional hand-held \"paddles\"), each comprising a metallic plate which is faced with a saline based conductive gel.  The pads are placed on the chest of the patient, or one is placed on the chest and one on the back.  These are connected by cables to a machine which has the combined functions of an  ECG  display screen and the electrical function of a  defibrillator . A synchronizing function (either manually operated or automatic) allows the cardioverter to deliver a reversion shock, by way of the pads, of a selected amount of  electric current  over a predefined number of  milliseconds  at the optimal moment in the  cardiac cycle  which corresponds to the R wave of the  QRS complex  on the  ECG ."}
{"_id": "WikiPedia_Cardio$$$corpus_4301", "text": "Timing the shock to the R wave prevents the delivery of the shock during the vulnerable period (or relative refractory period) of the  cardiac cycle , which could induce  ventricular fibrillation .  If the patient is conscious, various drugs are often used to help sedate the patient and make the procedure more tolerable.  However, if the patient is hemodynamically unstable or unconscious, the shock is given immediately upon confirmation of the  arrhythmia . When synchronized electrical cardioversion is performed as an elective procedure, the shocks can be performed in conjunction with drug therapy until  sinus rhythm  is attained. After the procedure, the patient is monitored to ensure stability of the sinus rhythm."}
{"_id": "WikiPedia_Cardio$$$corpus_4302", "text": "Synchronized electrical cardioversion is used to treat hemodynamically unstable supraventricular (or narrow complex)  tachycardias , including  atrial fibrillation  and  atrial flutter . It is also used in the emergent treatment of wide complex tachycardias, including  ventricular tachycardia , when a pulse is present. Pulseless  ventricular tachycardia  and  ventricular fibrillation  are treated with unsynchronized shocks referred to as  defibrillation . Electrical therapy is inappropriate for  sinus tachycardia , which should always be a part of the  differential diagnosis ."}
{"_id": "WikiPedia_Cardio$$$corpus_4303", "text": "Various  antiarrhythmic agents  can be used to return the heart to normal  sinus rhythm . [ 3 ]  Pharmacological cardioversion is an especially good option in patients with atrial fibrillation of recent onset. Drugs that are effective at maintaining normal rhythm after electric cardioversion can also be used for pharmacological cardioversion. Drugs like  amiodarone ,  diltiazem ,  verapamil  and  metoprolol  are frequently given before electrical cardioversion to decrease the heart rate, stabilize the patient and increase the chance that cardioversion is successful. There are various classes of agents that are most effective for pharmacological cardioversion."}
{"_id": "WikiPedia_Cardio$$$corpus_4304", "text": "Class I agents are sodium (Na) channel blockers (which slow conduction by blocking the Na+ channel) and are divided into 3 subclasses a, b and c. Class Ia slows phase 0 depolarization in the ventricles and increases the absolute refractory period.  Procainamide ,  quinidine  and  disopyramide  are Class Ia agents. Class 1b drugs lengthen phase 3 repolarization. They include  lidocaine ,  mexiletine  and  phenytoin . Class Ic greatly slow phase 0 depolarization in the ventricles (however unlike 1a have no effect on the refractory period).   Flecainide ,  moricizine  and  propafenone  are Class Ic agents.\n [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4305", "text": "Class II agents are beta blockers which inhibit SA and AV node depolarization and slow heart rate. They also decrease cardiac oxygen demand and can prevent cardiac remodeling. Not all beta blockers are the same; some are cardio selective (affecting only beta 1 receptors) while others are non-selective (affecting beta 1 and 2 receptors). Beta blockers that target the beta-1 receptor are called cardio selective because beta-1 is responsible for increasing heart rate; hence a beta blocker will slow the heart rate."}
{"_id": "WikiPedia_Cardio$$$corpus_4306", "text": "Class III agents (prolong repolarization by blocking outward K+ current):  amiodarone  and  sotalol  are effective class III agents.  Ibutilide  is another Class III agent but has a different mechanism of action (acts to promote influx of sodium through slow-sodium channels). It has been shown to be effective in acute cardioversion of recent-onset atrial fibrillation and atrial flutter."}
{"_id": "WikiPedia_Cardio$$$corpus_4307", "text": "Class IV drugs are calcium (Ca) channel blockers. They work by inhibiting the action potential of the SA and AV nodes."}
{"_id": "WikiPedia_Cardio$$$corpus_4308", "text": "If the patient is stable,  adenosine  may be used for restoration of sinus rhythm in patients with macro-reentrant supraventricular tachycardias. It causes a short-lived cessation of conduction through the atrio-ventricular node breaking the circus movement through the node and the macro-reentrant pathway restoring sinus rhythm."}
{"_id": "WikiPedia_Cardio$$$corpus_4309", "text": "Cardioversion for restoration of sinus rhythm from an atrial rhythm is largely a scheduled procedure. In addition to cardiology, anesthesiology is also usually involved to ensure comfort of the patient for the duration of the shock therapy. The presence of registered nurses, physician associates, or other medical personnel may also be helpful during the procedure."}
{"_id": "WikiPedia_Cardio$$$corpus_4310", "text": "Before starting the procedure, the patient's chest and back will be prepped for electrode placement. The skin should be free of any oily substances (e.g., lotions) and hair which may otherwise interfere with adhesion of the pads. [ 5 ]  Once this is complete, the medical team will adhere the pads to the patient using a rolling motion to ensure the absence of air pockets.  (see details on pad placement below) . The anesthesiology team will then administer a general anesthetic (e.g.,  Propofol ) in order to ensure patient comfort and amnesia during the procedure. Opioid analgesics (e.g., Fentanyl) may be combined with Propofol, although anesthesiology must weight the benefits against adverse effects including apnea. [ 6 ]  Bite blocks and extremity restraints are then utilized to prevent self-injury during cardioversion. Once these medications are administered, the  glabellar reflex  or  eyelash reflex  may be used to determine the patient's level of consciousness."}
{"_id": "WikiPedia_Cardio$$$corpus_4311", "text": "The pads are connected to a machine that can interpret the patient's cardiac rate and rhythm and deliver a shock at the appropriate time. The machine should synchronize ('sync') with the  R wave  of the rhythm strip. Although uncommon, sometimes the machine will unintentionally sync to high amplitude T waves, so it is important to ensure that the machine is synced appropriately to R waves. [ 7 ]  Interpretation of the patient's rhythm is imperative when using cardioversion to restore sinus rhythm from less emergent arrhythmias where a pulse is present (e.g.,  atrial flutter ,  atrial fibrillation ). However, if a patient is confirmed to be in  pulseless ventricular tachycardia  \"v-tach\" or  ventricular fibrillation  \"v-fib\", then a shock is delivered immediately upon connection of the pads. In this application, electrical cardioversion is more properly termed  defibrillation . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4312", "text": "Once the machine is synced with the patient's cardiac rhythm, the machine must be charged. To determine the amount of energy (measured in joules \"J\") the patient requires, many factors are considered. As a rule of thumb, recent-onset atrial arrhythmias require less energy compared to persistent atrial arrhythmias. If the cardiologist suspects that the patient may be less respondent to cardioversion, a higher energy may be utilized. Once the machine is synced and charged, a shock can be delivered to the patient. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4313", "text": "Following electrical cardioversion, the cardiologist will determine if sinus rhythm has been restored. To confirm sinus rhythm, a distinct  P wave  should be seen preceding each QRS complex. Additionally, each  R-R interval  should be evenly spaced. If sinus rhythm is restored, the pads may be disconnected, and any other medical equipment is removed from the patients (e.g., bite blocks, restraints, etc.). The patient will regain consciousness soon thereafter (the effects of Propofol generally last for only 3\u20138 minutes). However, if the arrhythmia is persistent, the machine may be re-charged to a higher energy level, and the cardioversion attempt may be repeated. It is recommended to wait 60 seconds between subsequent cardioversion attempts, but this amount of time may be adjusted based on the patient and/or provider."}
{"_id": "WikiPedia_Cardio$$$corpus_4314", "text": "Pad placement for electrical cardioversion a cardiac arrhythmia may be either anterior-posterior or anterior-lateral. In an anterior-posterior setup one pad is placed on the chest and the other pad is placed on the back. In an anterior-lateral setup, one pad is placed on the chest and the other pad is placed along the left midaxillary line. Choosing the right pad placement can be an important aspect when measuring the success of electrical cardioversion. For example, the anterior-posterior pad positioning is commonly used when attempting to restore an atrial arrhythmia as the vector between the pads predominately runs through the atria. The anterior-lateral pad positioning may be used when attempting to restore pulseless ventricular tachycardia or ventricular fibrillation as there may not be enough time or strength to apply an electrode the patient's back."}
{"_id": "WikiPedia_Cardio$$$corpus_4315", "text": "The anterior pad should be placed inferior to the right clavicle while also being vertically centered over at the level of the right 4th intercostal space. The posterior pad should be placed just lateral to the left side of the spine and vertically centered at the level of T7. [ 12 ] [ 13 ]  The inferior angle of the scapula can be used as a reference for the level of T7."}
{"_id": "WikiPedia_Cardio$$$corpus_4316", "text": "The anterior pad should be placed inferior to the right clavicle while also being vertically centered over at the level of the right 4th intercostal space. The lateral pad should be placed along the left midaxillary line at the level of the left 5th intercostal space. [ 12 ] [ 13 ]  The left nipple can be used as a reference for the level of the left 4th intercostal space. From here, the midaxillary 5th intercostal space is identified by moving inferiorly one intercostal space and laterally towards the midaxillary line."}
{"_id": "WikiPedia_Cardio$$$corpus_4317", "text": "Catheter ablation  is a procedure that uses radio-frequency energy or other sources to terminate or modify a faulty electrical pathway from sections of the  heart  of those who are prone to developing  cardiac arrhythmias  such as  atrial fibrillation ,  atrial flutter  and  Wolff-Parkinson-White syndrome . If not controlled, such arrhythmias increase the risk of  ventricular fibrillation  and sudden  cardiac arrest . The ablation procedure can be classified by energy source:  radiofrequency ablation  and  cryoablation ."}
{"_id": "WikiPedia_Cardio$$$corpus_4318", "text": "Catheter ablation may be recommended for a recurrent or persistent  arrhythmia  resulting in symptoms or other dysfunction.  Atrial fibrillation  frequently results from bursts of  tachycardia  that originate in muscle bundles extending from the  atrium  to the  pulmonary veins . [ 1 ]  Pulmonary vein isolation by transcatheter ablation can restore  sinus rhythm . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4319", "text": "Catheter ablation of most arrhythmias has a high success rate. Success rates for WPW syndrome have been as high as 95%  [ 2 ]  For  Supraventricular tachycardia  (SVT), single procedure success is 91% to 96% (95% Confidence Interval) and multiple procedure success is 92% to 97% (95% Confidence Interval). [ 3 ]  For atrial flutter, single procedure success is 88% to 95% (95% Confidence Interval) and multiple procedure success is 95% to 99% (95% Confidence Interval). [ 3 ]  For automatic atrial tachycardias, the success rates are 70\u201390%. [ citation needed ]  The potential complications include bleeding, blood clots, pericardial tamponade, and heart block, but these risks are very low, ranging from 2.6 to 3.2%."}
{"_id": "WikiPedia_Cardio$$$corpus_4320", "text": "For non-paroxysmal  atrial fibrillation , a 2016 systematic review compared catheter ablation to heart rhythm drugs. After 12 months, participants receiving catheter ablation were more likely to be free of atrial fibrillation, and less likely to need cardioversion. However, the evidence quality ranged from moderate to very low [ 4 ]  A 2006 study, including both paroxysmal and non-paroxysmal atrial fibrillation, found that the success rates are 28% for single procedures. Often, several procedures are needed to raise the success rate to a 70\u201380% range. [ 5 ]   One reason for this may be that once the heart has undergone atrial remodeling as in the case of chronic atrial fibrillation patients, largely 50 and older, it is much more difficult to correct the 'bad' electrical pathways. Young people with AF with paroxysmal, or intermittent, AF therefore have an increased chance of success with an ablation since their heart has not undergone atrial remodeling yet. [ citation needed ]  Several experienced teams of electrophysiologists in US heart centers claim they can achieve up to a 75% success rate. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4321", "text": "Pulmonary vein isolation has been found to be more effective than optimized antiarrhythmic drug therapy for improving quality of life at 12 months after treatment. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4322", "text": "Catheter ablation has been found to improve mental health outcomes in individuals with symptomatic atrial fibrillation. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4323", "text": "A 2018 study showed efficacy of cardiac ablation for treatment of  Premature Ventricular Contraction  as 94.1%. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4324", "text": "Catheter ablation is usually performed by an  electrophysiologist  (a specially trained  cardiologist ) in a  cath lab . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4325", "text": "Catheter ablation procedure involves advancing several flexible  catheters  into the patient's  blood vessels , usually either in the  femoral vein , internal jugular vein, or  subclavian vein . The catheters are then advanced towards the heart. The catheters have electrodes at the tips that can measure the electrical signals from the heart. These electrodes create a map of the abnormal pathways causing arrhythmias. Then, the electrophysiologist uses the map to identify areas from which abnormal heart rhythms originate. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4326", "text": "Once the abnormal areas are located, catheters are used to deliver energy via local heating or freezing to  ablate  (destroy) the abnormal tissue that is causing the arrhythmia. The energy is applied cautiously to avoid damaging healthy heart tissue. [ 9 ]  Originally, a  DC  impulse was used to create lesions in the intra-cardiac conduction system. [ 10 ]  However, due to a high incidence of complications, widespread use was never achieved."}
{"_id": "WikiPedia_Cardio$$$corpus_4327", "text": "In contrast to the thermal methods (extreme heat or cold)  electroporation  is being used and evaluated as a means of killing very small areas of heart muscle. The cardiac catheter delivers trains of high-voltage ultra-rapid electrical pulses that form irreversible pores in cell membranes, resulting in cell death of cardiac muscle, while not killing adjacent tissues ( esophagus  and  phrenic nerve ). [ 11 ]  It is thought to allow better selectivity than the previous thermal techniques, which used heat or cold to kill larger volumes of muscle. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4328", "text": "One type of catheter ablation is pulmonary vein isolation, where the ablation is done in the left atrium in the area where the 4 pulmonary veins connect. [ 13 ] [ 14 ]   Radiofrequency ablation for atrial fibrillation can be unipolar (one electrode) or bipolar (two electrodes). [ 15 ]  Although bipolar can be more successful, it is technically more difficult, resulting in unipolar being used more often. [ 15 ]  But bipolar is more effective in preventing recurrent atrial arrhythmias. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4329", "text": "During the procedure, the patient's heart rhythm is monitored continuously. The electrophysiologist can observe changes to the patient's cardiac electrical activity to determine the success of the ablation. If the cardiac rhythm shows no abnormal signals or arrhythmias, the catheters are withdrawn from the heart and the incision is closed."}
{"_id": "WikiPedia_Cardio$$$corpus_4330", "text": "After catheter ablation the patients are moved to a cardiac recovery unit, intensive care unit, or  cardiovascular intensive care unit  where they are not allowed to move for 4\u20136 hours.  Minimizing movement helps prevent bleeding from the site of catheter insertion.  Some people have to stay overnight for observation, some need to stay much longer and others are able to go home on the same day. This all depends on the problem, the length of the operation and whether or not  general anaesthetic  was used. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4331", "text": "Recurrence of atrial fibrillation within three months of an ablation is seen in most patients, but many of those patients become free of atrial fibrillation in the long term. [ 17 ]  For this reason the first three months after an ablation are described as the \"blanking period,\" during which no further intervention is to be attempted. [ 17 ]  Recurrence during the nine months following the blanking period, occurs in 25% to 40% of patients, the variability greatly affected by obesity and the severity of atrial fibrillation before the ablation. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4332", "text": "Some potential complications associated with the procedure include: [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4333", "text": "Patients may also experience a return of the arrhythmia after the procedure, requiring them to undergo further treatment. However, in general this procedure is considered a safe, effective, and minimally invasive method to treat arrhythmias. Studies have shown that the overall complication rate of cardiac ablation procedures is about 6%. [ medical citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4334", "text": "A  catheterization laboratory , commonly referred to as a  cath lab , is an examination room in a hospital or clinic with  diagnostic imaging  equipment used to visualize the arteries of the heart and the chambers of the  heart  and treat any  stenosis  or abnormality found."}
{"_id": "WikiPedia_Cardio$$$corpus_4335", "text": "Most catheterization laboratories are \"single plane\" facilities, those that have a single  X-ray  generator source and an  X-ray image intensifier  for  fluoroscopic  imaging. [ 1 ]  Older cath labs used  cine film  to record the information obtained, but since 2000, most new facilities are  digital . The latest digital cath labs are biplane (have two X-ray sources) and use  flat panel detectors . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4336", "text": "Cardiac catheterization laboratories are usually staffed by a multidisciplinary team. This may include a medical practitioner (normally either a consultant  cardiologist  or  radiologist ), cardiac  physiologist ,  radiographer  and  nurse . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4337", "text": "The consultant cardiologist is responsible for gaining arterial access, inserting a sheath into either the  radial  or  femoral artery , passing a wire and  catheter  into the coronary artery and selectively injecting  contrast media  into the coronary arteries. They then interpret the images taken to ascertain where the narrowed or blocked artery has the problem. They use a variety of techniques and imaging tools to measure the size of things such as balloons and  stents ."}
{"_id": "WikiPedia_Cardio$$$corpus_4338", "text": "Cardiac physiologists usually set up what is known as a  transducer  to monitor pressure in the arteries. They also have a live view of the patients  ECG  so they can tell whether or not there is a problem caused by the insertion of the catheter into the heart to the electrical pathways. [ 5 ] [ 6 ]  The physiologist will also set up a temporary pacemaker if the procedure is an angioplasty or a  percutaneous coronary intervention  (PCI). Finally, they also set up  defibrillators  on to the patient for emergency use if needed. In some locations, some of these responsibilities may be carried out by other personnel, such as trained nurses or technologists. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4339", "text": "Cardiac catheterization  is a general term for a group of procedures that are performed in the cath lab, such as  coronary angiography . Once a catheter is in place, it can be used to perform a number of procedures including  angioplasty , PCI ( percutaneous coronary intervention ) angiography,  transcatheter aortic valve replacement ,  balloon septostomy , and an  electrophysiology study  or  catheter ablation . Devices such as  pacemakers  may be fitted or  rotablation  to remove plaque can be performed. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4340", "text": "Cellular cardiomyoplasty , or cell-based cardiac repair, is a new potential therapeutic modality in which  progenitor cells  are used to repair regions of damaged or necrotic myocardium. The ability of transplanted progenitor cells to improve function within the failing heart has been shown in experimental animal models and in some human clinical trials. [ 1 ]  In November 2011, a large group of collaborators at Minneapolis Heart Institute Foundation at Abbott Northwestern found no significant difference in  left ventricular ejection fraction  (LVEF) or other markers, between a group of patients treated with cellular  cardiomyoplasty  and a group of control patients. [ 2 ]  In this study, all patients were post MI, post  percutaneous coronary intervention  (PCI) and that infusion of progenitor cells occurred 2\u20133 weeks after intervention. In a study that is currently underway (February 2012), however, more positive results were being reported: In the SCIPIO trial, patients treated with  autologous  cardiac stem cells post MI have been reported to be showing statistically significant increases in LVEF and reduction in infarct size over the control group at four months after implant. Positive results at the one-year mark are even more pronounced. [ 3 ] \nYet the SCIPIO trial \"was recently called into question\". [ 4 ] [ 5 ]  Harvard University is \"now investigating the integrity of some of the data\". [ 4 ]  The Lancet recently published a non-specific \u2018Expression of concern\u2019 about the paper. [ 6 ] \nSubsequently, another preclinical study also raised doubts on the rationale behind using this special kind of cell, [ 7 ]  as it was found that the special cells only have a minimal ability in generating new cardiomyocytes. [ 8 ]  Some specialists therefore now raise concerns to continue. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4341", "text": "To date, the ideal progenitor cells have not been found or created. With the goal of recreating human tissue, the use of embryonic stem cells (ESC) was the initial logical choice. These pluripotent cells can conceptually give rise to any  somatic cell  line in the human body and while animal studies have shown restoration of cardiac function, immunologic rejection issues and  teratoma  formation have rendered ESC's a high risk. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4342", "text": "Human-induced pluripotent stem cells (iPSCs) are a cell line derived from somatic cells which have been induced through a combination of  transcription factors . The iPSC line is very similar or identical to ESCs in many regards and also shows great promise in cardiac potential. [ 11 ]  This cell line, however, is also less than ideal in that this cell type has been unable to mature into a  homogeneous  cell culture, making it  immunogenic  and  teratogenic . [ 12 ] \nA third cell line that shows great promise and has no known safety concerns is the  adult stem cell  derived from bone marrow or from cardiac tissue explants. It has been shown in several studies that adult stem cells do have cardiogenic potential. [ 13 ] [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4343", "text": "Presently, the success of adult stem cells in regenerating human myocardium is just a fraction of what it could be. Three major challenges have been observed. Adult stem cells exhibit a minimal [ clarification needed ]  commitment to engraft into the damaged myocardium, they have low survival rates and they have limited proliferation. [ 16 ]  The positive effects observed in clinical trials today are a result of the work of donated stem cells that persist in the damaged myocardium for just days to weeks after delivery. Clearly, if cell survival is prolonged, these effects could be greatly enhanced. [ citation needed ]  This is where a majority of research is being done today and several methodologies hold great promise. [ 17 ] \n [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4344", "text": "A  coronary catheterization  is a  minimally invasive  procedure to access the  coronary circulation  and blood filled chambers of the  heart  using a  catheter . It is performed for both diagnostic and interventional (treatment) purposes."}
{"_id": "WikiPedia_Cardio$$$corpus_4345", "text": "Coronary catheterization is one of the several  cardiology diagnostic tests and procedures . Specifically, through the injection of a liquid  radiocontrast agent  and illumination with  X-rays , [ 1 ]  angiocardiography allows the recognition of  occlusion ,  stenosis ,  restenosis ,  thrombosis  or  aneurysmal  enlargement of the  coronary artery   lumens ;  heart chamber  size;  heart muscle  contraction performance; and some aspects of  heart valve  function. Important internal  heart  and  lung   blood pressures , not measurable from outside the body, can be accurately measured during the test. The relevant problems that the test deals with most commonly occur as a result of advanced  atherosclerosis  \u2013  atheroma  activity within the wall of the coronary  arteries . Less frequently,  valvular ,  heart muscle , or  arrhythmia  issues are the primary focus of the test."}
{"_id": "WikiPedia_Cardio$$$corpus_4346", "text": "Coronary artery  luminal  narrowing  reduces the flow reserve for oxygenated blood to the heart, typically producing intermittent  angina . Very advanced luminal  occlusion  usually produces a  heart attack . However, it has been increasingly recognized, since the late 1980s, that coronary catheterization does not allow the recognition of the presence or absence of coronary  atherosclerosis  itself, only significant luminal changes which have occurred as a result of end stage complications of the  atherosclerotic  process. See  IVUS  and  atheroma  for a better understanding of this issue."}
{"_id": "WikiPedia_Cardio$$$corpus_4347", "text": "The technique of angiography itself was first developed in 1927 by the Portuguese physician  Egas Moniz  at the  University of Lisbon  for  cerebral angiography , the viewing of brain vasculature by X-ray radiation with the aid of a contrast medium introduced by catheter. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4348", "text": "Heart catheterization was first performed in 1929 when the German physician  Werner Forssmann  inserted a plastic tube in his  cubital vein  and guided it to the right chamber of the heart. He took an x-ray to prove his success and published it on November 5, 1929, with the title \"\u00dcber die Sondierung des rechten Herzens\" (About probing of the right heart). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4349", "text": "In the early 1940s,  Andr\u00e9 Cournand , in collaboration with  Dickinson Richards , performed more systematic measurements of the hemodynamics of the heart. For their work in the discovery of cardiac catheterization and hemodynamic measurements, Cournand, Forssmann, and Richards shared the Nobel Prize in Physiology or Medicine in 1956. The first radial access for angiography can be traced back to 1953, where  Eduardo Pereira [ clarification needed ] , in Lisbon, Portugal, first cannulated the radial artery to perform a coronary angiogram."}
{"_id": "WikiPedia_Cardio$$$corpus_4350", "text": "In 1960  F. Mason Sones , a pediatric cardiologist at the  Cleveland Clinic , accidentally injected radiocontrast in a coronary artery instead of the left ventricle. Although the patient had a reversible cardiac arrest, Sones and Shirey developed the procedure further, and are credited with the discovery (Connolly 2002); they published a series of 1,000 patents in 1966 (Proudfit  et al. )."}
{"_id": "WikiPedia_Cardio$$$corpus_4351", "text": "Since the late 1970s, building on the pioneering work of  Charles Dotter  in 1964 and especially  Andreas Gruentzig  starting in 1977, coronary catheterization has been extended to therapeutic uses: (a) the performance of less invasive physical treatment for  angina  and some of the complications of severe  atherosclerosis , (b) treating  heart attacks  before complete damage has occurred and (c) research for better understanding of the pathology of  coronary artery disease  and  atherosclerosis . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4352", "text": "In the early 1960s, cardiac catheterization frequently took several hours and involved significant complications for as many as 2\u20133% of patients. With multiple incremental improvements over time, simple coronary catheterization examinations are now commonly done more rapidly and with significantly improved outcomes. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4353", "text": "Indications for cardiac catheterization include the following:"}
{"_id": "WikiPedia_Cardio$$$corpus_4354", "text": "The  patient  being examined or treated is usually awake during catheterization, ideally with only  local anaesthesia  such as  lidocaine  and minimal general  sedation , throughout the  procedure . Performing the procedure with the patient awake is safer as the patient can immediately report any discomfort or problems and thereby facilitate rapid correction of any undesirable events. Medical monitors fail to give a comprehensive view of the patient's immediate well-being; how the patient feels is often a most reliable indicator of procedural safety. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4355", "text": "Death,  myocardial infarction ,  stroke , serious  ventricular arrhythmia , and major vascular complications each occur in less than 1% of patients undergoing catheterization. [ 4 ]  However, though the imaging portion of the examination is often brief, because of setup and safety issues, the patient is often in the lab for 20\u201345 minutes. Any of multiple technical difficulties, while not endangering the patient (indeed added to protect the patient's interests), can significantly increase the examination time. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4356", "text": "Coronary catheterization is performed in a catheterization lab, usually located within a hospital. With current designs, the patient must lie relatively flat on a narrow, minimally padded,  radiolucent  (transparent to  X-ray ) table. The X-ray source and imaging camera equipment are on opposite sides of the patient's chest and freely move, under motorized control, around the patient's chest so images can be taken quickly from multiple angles. More advanced equipment, termed a bi-plane cath lab, uses two sets of X-ray source and imaging cameras, each free to move independently, which allows two sets of images to be taken with each injection of radio contrast agent . The equipment and installation setup to perform such testing typically represents a capital expenditure of US$2\u20135 million (2004), sometimes more, partially repeated every few years. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4357", "text": "During coronary catheterization (often referred to as a \"cath\" or \"cardiac cath\" by physicians),  blood pressures  are recorded and  fluoroscopy  ( X-ray   motion picture ) shadow-grams of the blood inside the  coronary arteries  are recorded. In order to create the X-ray pictures, a  physician  guides a small tube-like device called a catheter, typically ~2.0\u00a0mm (6-French) in diameter, through the large arteries of the body until the tip is just within the opening of one of the  coronary arteries . By design, the catheter is smaller than the lumen of the  artery  it is placed in; internal (intra-arterial) blood pressures are monitored through the  catheter  to verify that the catheter does not block blood flow (as indicated by \"dampening\" of the blood pressure). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4358", "text": "The catheter is itself designed to be  radiodense  for visibility and it allows a clear, watery, blood compatible radiocontrast agent, commonly called an X-ray dye, to be selectively injected and mixed with the blood flowing within the artery. Typically 3\u20138 cc of the radiocontrast agent is injected for each image to make the  blood flow  visible for about 3\u20135 seconds as the radiocontrast agent is rapidly washed away into the coronary  capillaries  and then coronary  veins . Without the X-ray dye injection, the blood and surrounding heart  tissues  appear, on X-ray, as only a mildly-shape-changing, otherwise uniform water density mass; no details of the blood and internal organ structure are discernible. The radiocontrast within the blood allows visualization of the blood flow within the arteries or heart chambers, depending on where it is injected. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4359", "text": "If  atheroma , or  clots , are protruding into the lumen, producing  narrowing , the narrowing may be seen instead as increased haziness within the X-ray shadow images of the blood/dye column within that portion of the artery; this is as compared to adjacent, presumed healthier, less  stenotic  areas."}
{"_id": "WikiPedia_Cardio$$$corpus_4360", "text": "For guidance regarding catheter positions during the examination, the physician mostly relies on detailed knowledge of internal anatomy, guide wire and catheter behavior and intermittently, briefly uses  fluoroscopy  and a low X-ray dose to visualize when needed. This is done without saving recordings of these brief looks. When the physician is ready to record diagnostic views, which are saved and can be more carefully scrutinized later, he activates the equipment to apply a significantly higher X-ray dose, termed  cine , in order to create better quality motion picture images, having sharper radiodensity contrast, typically at 30 frames per second. The physician controls both the contrast injection,  fluoroscopy  and cine application timing so as to minimize the total amount of radiocontrast injected and times the X-ray to the injection so as to minimize the total amount of X-ray used. Doses of radiocontrast agents and X-ray exposure times are routinely recorded in an effort to maximize safety."}
{"_id": "WikiPedia_Cardio$$$corpus_4361", "text": "Though not the focus of the test,  calcification  within the  artery  walls, located in the outer edges of  atheroma  within the artery walls, is sometimes recognizable on fluoroscopy (without contrast injection) as radiodense halo rings partially encircling, and separated from the blood filled lumen by the interceding radiolucent atheroma tissue and  endothelial  lining. Calcification, even though usually present, is usually only visible when quite advanced and calcified sections of the artery wall happen to be viewed on end  tangentially  through multiple rings of calcification, so as to create enough radiodensity to be visible on fluoroscopy."}
{"_id": "WikiPedia_Cardio$$$corpus_4362", "text": "Angiocardiography can be used to detect and diagnose congenital defects in the heart and adjacent vessels. [ 5 ]  In this context, the use of angiocardiography has declined with the introduction of  echocardiography . However, angiocardiography is still in use for selected cases as it provides a higher level of anatomical detail than echocardiography. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4363", "text": "By changing the diagnostic catheter to a guiding catheter, physicians can also pass a variety of instruments through the catheter and into the  artery  to a  lesion  site. The most commonly used are 0.014-inch-diameter (0.36\u00a0mm) guide wires and the balloon dilation catheters. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4364", "text": "By injecting radiocontrast agent through a tiny passage extending down the  balloon catheter  and into the balloon, the balloon is progressively expanded. The hydraulic pressures are chosen and applied by the physician, according to how the balloon within the  stenosis  (abnormal narrowing in a blood vessel) responds. The radiocontrast filled balloon is watched under  fluoroscopy  (it typically assumes a \"dog bone\" shape imposed on the outside of the balloon by the stenosis as the balloon is expanded), as it opens. As much  hydraulic  brute force is applied as judged needed and visualized to be effective to make the stenosis of the artery lumen visibly enlarge. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4365", "text": "Typical normal  coronary artery  pressures are in the <200 mmHg range (27 kPa). The hydraulic pressures applied within the balloon may extend to as high as 19000 mmHg (2,500 kPa). Prevention of over-enlargement is achieved by choosing balloons manufactured out of high tensile strength clear plastic membranes. The balloon is initially folded around the catheter, near the tip, to create a small cross-sectional profile to facilitate passage through luminal stenotic areas, and is designed to inflate to a specific pre-designed diameter. If over-inflated, the balloon material simply tears and allows the inflating radiocontrast agent to simply escape into the blood. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4366", "text": "Additionally, several other devices can be advanced into the artery via a guiding catheter. These include  laser  catheters,  stent  catheters,  IVUS  catheters,  Doppler  catheter, pressure or temperature measurement catheter and various  clot  and grinding or removal devices. Most of these devices have turned out to be niche devices, only useful in a small percentage of situations or for research."}
{"_id": "WikiPedia_Cardio$$$corpus_4367", "text": "Stents, which are specially manufactured expandable stainless steel mesh tubes, mounted on a balloon catheter, are the most commonly used device beyond the balloon catheter. When the stent/balloon device is positioned within the stenosis, the balloon is inflated which, in turn, expands the stent and the artery. The balloon is removed and the stent remains in place, supporting the inner artery walls in the more open, dilated position. Current stents generally cost around $1,000 to 3,000 each (US 2004 dollars), the drug-coated ones being the more expensive."}
{"_id": "WikiPedia_Cardio$$$corpus_4368", "text": "Interventional procedures have been plagued by  restenosis  due to the formation of  endothelial   tissue  overgrowth at the lesion site. Restenosis is the body's response to the injury of the vessel wall from  angioplasty  and to the  stent  as a  foreign body . As assessed in clinical trials during the late 1980 and 1990s, using only balloon angioplasty (POBA, plain old balloon angioplasty), up to 50% of patients developed significant restenosis; but that percentage has dropped to the single to lower two-digit range with the introduction of  drug-eluting stents .  Sirolimus ,  paclitaxel , and  everolimus  are the three drugs used in coatings which are currently FDA approved in the United States. [ citation needed ]  As opposed to bare metal,  drug-eluting stents  are covered with a medicine that is slowly dispersed with the goal of suppressing the restenosis reaction. The key to the success of drug coating has been (a) choosing effective agents, (b) developing ways of adequately binding the drugs to the stainless surface of the  stent  struts (the coating must stay bound despite marked handling and stent deformation stresses), and (c) developing coating controlled release mechanisms that release the drug slowly over about 30 days. One of the newest innovations in coronary stents is the development of a dissolving stent.  Abbott Laboratories  has used a dissolvable material,  polylactic acid , that will completely absorb within 2 years of being implanted. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4369", "text": "CT angiography  can act as a less invasive alternative to Catheter angiography. Instead of a catheter being inserted into a vein or artery, CT angiography involves only the injection of a CT-visible dye into the arm or hand via an IV line. CT angiography lowers the risk of arterial perforation and catheter site infection. It provides 3D images that can be studied on computer, and also allows measurement of heart ventricle size. Infarct area and arterial calcium can also be observed (however those require a somewhat higher radiation exposure). That said, one advantage retained by Catheter angiography is the ability of the physician to perform procedure such as  balloon angioplasty  or insertion of a  stent  to improve blood flow to the artery. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4370", "text": "Imaging in coronary angiograms is performed via  fluoroscopy  using X-rays, which pose a potential for increasing the patient's risk of  radiation-induced cancer . The risk increases with the exposure time, consisting of 1) time guiding the probe into and out of the heart and 2) time illuminating the contrast agent to perform the angiogram. Absorbed radiation is also a function of  body mass index , with obese patients having twice the dose of normal-weight patients; exposure to the operator was also doubled. [ 9 ]  Coronary angiograms can be done either transradial (through the wrist) or transfemoral (through the groin). [ 10 ]  The transradial route results in somewhat greater patient and operator exposure. Overall, patient exposure can range from 2 millisieverts (equivalent of about 20 chest x-ray plates) to 20 millisieverts. [ 11 ]  For a given patient, exposure can vary within an institution and between institutions by up to 121%. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4371", "text": "Radiation exposure to the operator can be reduced by the use of protective equipment. Exposure to the patient can be reduced by minimizing fluoroscopy time."}
{"_id": "WikiPedia_Cardio$$$corpus_4372", "text": "The  Cox maze procedure , also known as  maze procedure , is a type of  heart surgery  for  atrial fibrillation ."}
{"_id": "WikiPedia_Cardio$$$corpus_4373", "text": "\"Maze\" refers to the series of incisions arranged in a  maze -like pattern in the  atria . Today, various methods of minimally invasive maze procedures, collectively named  minimaze procedures , are used."}
{"_id": "WikiPedia_Cardio$$$corpus_4374", "text": "James Cox  is an American cardiothoracic surgeon. Cox received his medical degree at  University of Tennessee Medical Center  and completed his training in both General and Cardiothoracic Surgery at  Duke University Hospital . Cox and his associates at Duke, and later at  Washington University School of Medicine  developed the \"maze\" or \"Cox maze\" procedure, an \"open-heart\"  cardiac surgery  procedure intended to eliminate  atrial fibrillation  (AF)."}
{"_id": "WikiPedia_Cardio$$$corpus_4375", "text": "Incidence of stroke in patients with AF who are anticoagulated is still around 2-5% per year. The first such procedure was performed by Dr. Cox at St. Louis' Barnes Hospital\u2014now  Barnes-Jewish Hospital \u2014in 1987. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4376", "text": "The intention was to eliminate AF by using incisional scars to block abnormal electrical circuits (atrial macroreentry) that initiate and perpetuate the abnormal electrical waves of AF. This required an extensive series of full-thickness incisions through the walls of both atria, a median sternotomy (vertical incision through the sternum), and cardiopulmonary bypass (heart-lung machine;  extracorporeal circulation ). After the introduction of the initial procedure, a series of improvements were made, culminating in 1992 in the Cox maze III procedure, which is now considered to be the \"gold standard\" for effective surgical cure of AF. It was quite successful in eliminating AF but had drawbacks as well. [ 2 ]  The Cox maze III is sometimes referred to as the \"traditional maze\", the \"cut-and-sew maze\", or simply the \"maze.\" [ citation needed ]  Damiano and colleagues have described a Cox-Maze IV procedure in 2002 in which they modified the Cox-Maze III technique using a combination of bipolar radiofrequency and cryothermal ablation lines. [ 3 ]  Since then, the Cox-Maze IV procedure is the gold standard surgical treatment for AF with conversion to normal sinus rhythm and freedom from AF at 1 year postoperatively of 93%, [ 4 ] [ 5 ]  but the results are institution dependent. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4377", "text": "During the past 10 years, [ when? ]  several energy sources, such as unipolar radiofrequency, bipolar radiofrequency, microwave, laser, high-intensity focused ultrasound, and cryothermia, were incorporated into various devices in order to create some of the lesions of the Cox maze III procedure  without actually cutting into the atrial walls .  Microwave and laser therapy have both been withdrawn from the market, but the other devices continue to be utilized to treat AF surgically. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4378", "text": "External counterpulsation  therapy  ( ECP ) is a procedure that may be performed on individuals with  angina ,  heart failure , or  cardiomyopathy ."}
{"_id": "WikiPedia_Cardio$$$corpus_4379", "text": "The FDA approved the CardiAssist\u00a0ECP system for the treatment of angina, acute myocardial infarction and cardiogenic shock under a 510(k) submission in 1980 [ 1 ]   [ failed verification ] Since then, additional ECP devices have been cleared by the FDA for use in treating stable or unstable angina pectoris, acute myocardial infarction, cardiogenic shock, and congestive heart failure. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4380", "text": "Studies have found EECP to be beneficial for patients with erectile dysfunction and some COPD patients. Additionally, improvements in exercise endurance in the non-diseased patient has been found in research studies. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4381", "text": "Some reviews did not find sufficient evidence that it was useful for either angina or heart failure. [ 5 ] [ 6 ]  Other reviews found tentative benefit in those with angina that does not improve with medications. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4382", "text": "For  stroke  due to lack of blood flow, a 2012 Cochrane review found significant neurological  improvement, but insufficient evidence to make reliable conclusions. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4383", "text": "External counterpulsation therapy significantly improved the exercise endurance of normal adults, low endurance adults, and COPD patients. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4384", "text": "While an individual is undergoing ECP, they have pneumatic cuffs on their legs and is connected to  telemetry  monitors that monitor heart rate and rhythm. The most common type in use involves three cuffs placed on each leg (on the calves, the lower thighs, and the upper thighs (or buttocks)). The cuffs are timed to inflate and deflate based on the individual's  electrocardiogram . The cuffs should ideally inflate at the beginning of  diastole  and deflate at the beginning of  systole . During the inflation portion of the cycle, the calf cuffs inflate first, then the lower thigh cuffs, and finally the upper thigh cuffs. Inflation is controlled by a pressure monitor, and the cuffs are inflated to about 200  mmHg . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4385", "text": "Of note, therapies are tailored on an individual basis but beginning regimens tend to include daily one-hour treatments that occur 5 days of the week and last 6\u20138 weeks with an average overall of 35 hours. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4386", "text": "One theory is that ECP exposes the coronary circulation to increased  shear stress , and that this results in the production of a cascade of growth factors that result in new blood vessel formation in the heart (arteriogenesis and  angiogenesis ). [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4387", "text": "To best understand the pathophysiology of the therapy it is easiest to understand what each step does. To begin with, as the cuffs on each leg inflate, starting at the calf and working up to the upper thighs, blood is propelled back to the heart thereby increasing the venous return or preload. This increase in preload occurs simultaneously with diastole which happens to be the time during the cardiac cycle in which coronary perfusion occurs. So, by increasing the coronary perfusion, you allow more oxygen to perfuse the heart and ultimately generate more collateral circulation without actually increasing the work of the heart. Additionally, cardiac output is increased via the Frank-Starling mechanism secondary to the increased venous return. As the cardiac cycle progresses to systole, the cuffs on the extremities deflate, allowing for the increased cardiac output to adequately perfuse all tissues including the extremities. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4388", "text": "\u201cHeal Your Heart with EECP\u201d by Debra Braverman, MD."}
{"_id": "WikiPedia_Cardio$$$corpus_4389", "text": "The  handgrip maneuver  is performed by clenching one's fist forcefully for a sustained time until fatigued. Variations include squeezing an item such as a rolled up washcloth. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4390", "text": "The handgrip maneuver increases  afterload [ 1 ]  by squeezing the  arterioles  and increasing  total peripheral resistance . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4391", "text": "Since increasing afterload will prevent blood from flowing in a normal forward path, it will increase any murmurs that are due to backwards flowing blood. [ 3 ] \nThis includes  aortic regurgitation  (AR),  mitral regurgitation  (MR), and a  ventricular septal defect  (VSD). [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4392", "text": "Mitral valve prolapse : The click and the murmur of mitral valve prolapse are delayed because left atrial volume also increases due to mitral regurgitation along with increased left ventricular volume. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4393", "text": "Murmurs that are due to forward flowing of blood such as  aortic stenosis , and  hypertrophic cardiomyopathy  decrease in intensity. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4394", "text": "The effect of reducing the intensity in forward flowing murmurs is much more evident in aortic stenosis rather than mitral stenosis. The reason for this is that there is a larger pressure gradient across the aortic valve. [ 6 ]  A complementary maneuver for differentiating disorders is the  Valsalva maneuver , which decreases preload. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4395", "text": "Hybrid coronary revascularization  ( HCR ) or  hybrid coronary bypass  is a relatively new type of  heart surgery  that provides an alternative to traditional  coronary artery bypass surgery  (CABG) or  percutaneous coronary intervention  (PCI or PTCA) by combining the two into one operation. It is this combining aspect that \" hybrid \" refers to. HCR is one of several types of  hybrid cardiac surgery ; it is not to be confused with a  MIDCAB  (minimally invasive direct coronary artery bypass) procedure, which uses the smaller  thoracotomy  incision but does not involve  coronary stenting . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4396", "text": "Hybrid bypass offers all the benefits of a  MIDCAB , although there are some disadvantages."}
{"_id": "WikiPedia_Cardio$$$corpus_4397", "text": "A 2018 Meta Analysis with over 4000 patient cases found HCR to have significant advantages compared with conventional  CABG . Reduced incidence of  Blood Transfusion , reduced hospital stay duration and reduced  intubation  duration were all reported. In contrast, HCR was found to be  significantly more expensive  compared to CABG. [ 8 ] \nHowever, 2018 guidelines recommend (Level 2B recommendation) that hybrid coronary revascularization may be considered in specific patient subsets at experienced centres. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4398", "text": "The  instantaneous wave-free ratio  ( iFR , sometimes referred to as the  instant wave-free ratio  or  instant flow reserve ) is a  diagnostic tool  used to assess whether a  stenosis  is causing a limitation of blood flow in  coronary arteries  with subsequent  ischemia . iFR is performed during  cardiac catheterisation  ( angiography ) using invasive coronary pressure wires which are placed in the coronary arteries that are to be assessed. Pressure wires are commonly used by  interventional cardiologists  to guide decisions to perform revascularization, either by  stenting  or  bypass surgery ."}
{"_id": "WikiPedia_Cardio$$$corpus_4399", "text": "Coronary artery blockages or stenoses that limit blood flow to the heart muscle can cause  angina  and can be treated by  stenting  or  bypass surgery . Relief of a stenosis by stenting aims to restore vessel patency with improvement in blood flow leading to a reduction in angina symptoms. However, if stenoses are not flow limiting, then they can be safely left alone without stenting or surgery and this help reduce patient's exposure to unnecessary procedures and potential complications. Identifying stenoses that cause flow limitation, or ischaemia, can be done in a variety of ways. Non-invasive tests can include  stress testing  such as exercise electrocardiograms, stress echocardiography, or  perfusion imaging  tests such as  scintigraphy  or  SPECT . Alternatively, invasive tests can be performed at the time of angiography, and these include those that measure coronary flow velocity in the vessel,  CFR  or index flow against pressure gradients such as hyperaemic or basal stenosis resistance (HSR or BSR). More commonly coronary pressure measurements are used as a surrogate for flow measurement and techniques include iFR and  fractional flow reserve  (FFR). Cardiologists use a combination of these investigations together with the patient's history, symptoms and clinical risk factors to decide if a stenosis requires further treatment. An example of use in clinical practice is seen here. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4400", "text": "Instantaneous wave-free ratio is performed using high fidelity pressure wires that are passed distal to the coronary stenosis. iFR isolates a specific period in diastole, called the wave-free period, and uses the ratio of distal coronary pressure (Pd) to the pressure observed in the aorta (Pa) over this period. During this wave-free period, the competing forces (waves) that affect coronary flow are quiescent meaning pressure and flow are linearly related as compared to the rest of the cardiac cycle. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4401", "text": "When stenoses are flow limiting, Pd and Pa pressures over the wave-free period diverge; a normal ratio is 1.0 and iFR values of below 0.90 suggest flow limitation. iFR can be calculated using dedicated consoles available for medical use and typically uses an average over 5 heart beats but can be performed using a single heart beat. iFR is measured at rest, without the need for pharmacological vasodilators or stressors and compares well to other invasive and non-invasive markers of ischemia or flow limitation. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4402", "text": "A number of studies using the Imperial College developed iFR algorithm have been conducted. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4403", "text": "The ADVISE study was a proof of concept study that demonstrated that the wave-free period, usually isolated using wave-intensity analysis, [ 5 ]  could be reliably determined using a pressure-only approach. [ 6 ]  This was shown across a variety of stenosis severities and demonstrated that over that specific period in diastole, microcirculatory resistance was the lowest and most stable compared to the rest of the cardiac cycle. During this specific period, pressure and flow are linearly related, allowing pressure-only inferences of transtenotic flow limitation. iFR was compared to the current clinically-used reference standard, FFR, and demonstrated good diagnostic lesion classification. Furthermore, iFR was consistent in utility for the left and right coronary artery, and the wave-free period was stable from beat-to-beat and even in the presence of arrhythmia. The study however was relatively underpowered to determine a clinical cut-point. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4404", "text": "The ADVISE-Registry was a larger study in which pressure wire data collected from patients undergoing functional assessment for clinical management, was analysed to compare iFR and FFR. [ 7 ]  This study recognised that matching FFR was limited by the capacity of FFR to match itself with repeated measures and accordingly presented per-range agreements. An independent consecutive blinded comparison of iFR and FFR in Asian patients reported similar results. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4405", "text": "The CLARIFY study was a physiological study in which iFR and FFR were compared to an independent third measure, hyperaemic stenosis resistance (HSR) which uses a combination of pressure and flow assessment to detect ischemia. [ 8 ]  Both measures compared equally well to this flow-based index.  In stenoses classified as ischemic, the wave-free period provided a similar reduction in microvascular resistance as adenosine-mediated hyperaemia over the whole cardiac cycle. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4406", "text": "The Hybrid iFR-FFR approach has been proposed as method of minimising patient exposure to adenosine or other vasodilators. [ 9 ]  In this approach, an iFR can be measured, and stenoses with an iFR >0.93 may be deferred while those with an iFR <0.86 can be treated by revascularization. Stenoses with an iFR between 0.86-0.93 can undergo an FFR assessment to guide therapy. This range can be changed by the physician according to how closely they want to match an FFR-classification of lesions. Using this typical range, almost 60% of stenoses can be spared from needing vasodilator infusion. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4407", "text": "ADVISE-II has prospectively assessed the hybrid approach in an independent international multi-centre study which confirmed the findings of the earlier Hybrid analysis. Interim results were reported by Javier Escaned at EuroPCR, the final findings were presented at TCT 2013. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4408", "text": "These findings have been in keeping with an international collaborative study, RESOLVE, which pooled retrospective data from many centres worldwide with independent core-lab analysis of raw pressure traces. [ 11 ]  Conflicting data, when re-analysed using the clinically available iFR-algorithms produced results similar to the ADVISE-Registry and ADVISE Hybrid studies. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4409", "text": "iFR has also been compared to FFR and the resting Pd/Pa ratio in the post-coronary intervention setting. In a manner similar to FFR, iFR can be used to measure the haemodynamic change induced by stent placement and detect the impact of any residual stenoses. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4410", "text": "The ADVISE-in-Practice study reported the first clinical experience of the commercially available iFR console. [ 14 ]  Video examples of iFR technology in clinical use are available here  [1] ."}
{"_id": "WikiPedia_Cardio$$$corpus_4411", "text": "Two outcome studies, DEFINE-FLAIR [ 15 ]  and the iFR-SWEDEHEART [ 16 ]  will assess whether patient outcomes differ if stenoses are treated according to iFR or FFR classification of stenosis severity. DEFINE-FLAIR, which aims to recruit 2500 patients, will be the largest physiological study to date and will provide the first randomised data of the use of iFR and FFR in patients with both stable coronary disease and acute coronary syndromes. It will also provide the first randomised data of the clinical utility of FFR in guiding and deferring coronary intervention outside of the FAME and DEFER studies. Both DEFINE-FLAIR and iFR-SWEDEHEART have harmonised clinical endpoints which will enable combined analysis of over 4500 patients. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4412", "text": "SYTNAX II is a modern PCI study assessing the clinical utility of stenting three-vessel coronary disease. [ 17 ]  Patients with three-vessel coronary disease whom the Heart Team decide are in equipoise between surgical revascularization or PCI intervention, undergo physiologically guided stenting. The SYNTAX II clinical risk calculator is used to determine equipoise. All major vessels undergo pressure wire assessment using the iFR-FFR hybrid approach, and only those positive for ischaemia undergo stenting. Intravascular ultrasound is used to ensure optimal stent delivery. Clinical outcomes will be compared to a historical surgical cohort from SYNTAX-I study. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4413", "text": "The instantaneous wave-free ratio can also be calculated on a beat-to-beat basis. If performed during the slow withdrawal of a pressure wire (referred to as 'pullback') under resting conditions, it is possible to plot the change of iFR or trans-stenotic gradient over the wave-free period throughout the vessel. [ 18 ] [ 19 ]  This can help identify focal and diffuse coronary disease potentially amenable to revascularisation. An example of pullback in clinical use can be seen  in this video . The pressure wire data can be co-registered with the angiographic findings to aid ease of interpretation. With mechanised pullback approaches which move the pressure wire at a fixed speed, the physiological length of a stenosis can be determined. With advanced live co-registration this is also feasible with during manual pullback. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4414", "text": "Advanced computer processing can utilise iFR-pullback data to predict the hemodynamic consequences of performing percutaneous coronary intervention (PCI) to a chosen segment of the coronary vessel. The predicted iFR values produced by the virtual-PCI on the iFR-pullback are closely related to those observed after PCI in the coronary vessel. [ 18 ]  This predictive capacity may provide added advantage to Interventional Cardiologists when assessing multiple coronary stenoses in a single vessel and planning the treatment approach. iFR-pullback technologies are undergoing evaluation in European centres. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4415", "text": "Alternative iFR computation systems have been proposed, for example incorporating part of systole into the definition of diastole and optionally different time-shifts between Pd and Pa signals, [ 21 ]  yielding unsatisfactory results. [ 22 ]  The same datasets reanalysed using the standard algorithms confirm the mainstream findings. [ 11 ]  Various explanations have been proposed. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4416", "text": "A  diagnosis of myocardial infarction  is created by integrating the history of the presenting illness and physical examination with  electrocardiogram  findings and  cardiac markers  ( blood tests  for  heart muscle  cell  damage ). [ 1 ] [ 2 ]  A  coronary angiogram  allows visualization of narrowings or obstructions on the heart vessels, and therapeutic measures can follow immediately. At  autopsy , a  pathologist  can diagnose a  myocardial infarction  based on  anatomopathological  findings."}
{"_id": "WikiPedia_Cardio$$$corpus_4417", "text": "A  chest radiograph  and routine blood tests may indicate complications or precipitating causes and are often performed upon arrival to an  emergency department . New regional wall motion abnormalities on an  echocardiogram  are also suggestive of a myocardial infarction. Echo may be performed in equivocal cases by the on-call cardiologist. [ 3 ]  In stable patients whose symptoms have resolved by the time of evaluation,  Technetium (99mTc) sestamibi  (i.e. a \"MIBI scan\"),   thallium-201 chloride  or  Rubidium-82  Chloride can be used in  nuclear medicine  to visualize areas of reduced blood flow in conjunction with physiologic or pharmacologic stress. [ 3 ] [ 4 ]  Thallium may also be used to determine viability of tissue, distinguishing whether non-functional myocardium is actually dead or merely in a state of hibernation or of being stunned. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4418", "text": "According to the WHO criteria as revised in 2000, [ 6 ]  a cardiac  troponin  rise accompanied by either typical symptoms, pathological Q waves, ST elevation or depression or coronary intervention are diagnostic of MI."}
{"_id": "WikiPedia_Cardio$$$corpus_4419", "text": "Previous WHO criteria [ 7 ]  formulated in 1979 put less emphasis on cardiac biomarkers; according to these, a patient is diagnosed with myocardial infarction if two (probable) or three (definite) of the following criteria are satisfied:"}
{"_id": "WikiPedia_Cardio$$$corpus_4420", "text": "The general appearance of patients may vary according to the experienced symptoms; the patient may be comfortable, or restless and in severe distress with an increased  respiratory rate . A cool and  pale skin  is common and points to  vasoconstriction . Some patients have low-grade fever (38\u201339\u00a0\u00b0C).  Blood pressure  may be elevated or decreased, and the  pulse  can become  irregular . [ 8 ] [ 9 ] :\u200a1444"}
{"_id": "WikiPedia_Cardio$$$corpus_4421", "text": "If heart failure ensues, elevated  jugular venous pressure  and  hepatojugular reflux , or swelling of the legs due to peripheral  edema  may be found on inspection. Rarely, a cardiac bulge with a pace different from the pulse rhythm can be felt on  precordial examination . Various abnormalities can be found on  auscultation , such as a third and fourth  heart sound ,  systolic murmurs , paradoxical splitting of the second heart sound, a  pericardial  friction rub and  rales  over the lung. [ 8 ] [ 9 ] :\u200a1450"}
{"_id": "WikiPedia_Cardio$$$corpus_4422", "text": "The primary purpose of the  electrocardiogram  is to detect  ischemia  or acute coronary injury in broad, symptomatic  emergency department  populations. A serial ECG may be used to follow rapid changes in time. The standard 12 lead ECG does not directly examine the  right ventricle , and is relatively poor at examining the posterior basal and lateral walls of the  left ventricle . In particular, acute myocardial infarction in the distribution of the circumflex artery is likely to produce a nondiagnostic ECG. [ 10 ]  The use of additional ECG leads like right-sided leads V3R and V4R and posterior leads V7, V8, and V9 may improve sensitivity for right ventricular and posterior myocardial infarction. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4423", "text": "The 12 lead ECG is used to classify patients into one of three groups: [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4424", "text": "A normal ECG does not rule out acute myocardial infarction. Mistakes in interpretation are relatively common, and the failure to identify high risk features has a negative effect on the quality of patient care. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4425", "text": "It should be determined if a person is at high risk for myocardial infarction before conducting imaging tests to make a diagnosis. [ 13 ]  People who have a normal ECG and who are able to exercise, for example, do not merit routine imaging. [ 13 ]  Imaging tests such as stress radionuclide  myocardial perfusion imaging  or stress  echocardiography  can confirm a diagnosis when a person's history, physical exam, ECG and cardiac biomarkers suggest the likelihood of a problem. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4426", "text": "Cardiac markers or cardiac enzymes are proteins that leak out of injured myocardial cells through their damaged cell membranes into the bloodstream. Until the 1980s, the enzymes  SGOT  and  LDH  were used to assess cardiac injury. Now, the markers most widely used in detection of MI are  MB  subtype of the enzyme  creatine kinase  and cardiac  troponins  T and I as they are more specific for myocardial injury. The cardiac troponins T and I which are released within 4\u20136 hours of an attack of MI and remain elevated for up to 2 weeks, have nearly complete tissue specificity and are now the preferred markers for assessing myocardial damage. [ 14 ] \n Heart-type fatty acid binding protein  is another marker, used in some home test kits.\nElevated troponins in the setting of chest pain may accurately predict a high likelihood of a myocardial infarction in the near future. [ 15 ]  New markers such as  glycogen phosphorylase isoenzyme BB  are under investigation. [ 16 ]  Note that only the cardiac troponins are used clinically for myocardial infarction as creatine kinase adds little value in diagnosing MI while adding to system cost. [ 17 ] [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4427", "text": "The diagnosis of myocardial infarction requires two out of three components (history, ECG, and enzymes).  When damage to the heart occurs, levels of cardiac markers rise over time, which is why  blood tests  for them are taken over a 24-hour period. Because these enzyme levels are not elevated immediately following a heart attack, patients presenting with chest pain are generally treated with the assumption that a myocardial infarction has occurred and then evaluated for a more precise diagnosis. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4428", "text": "In difficult cases or in situations where intervention to restore blood flow is appropriate, coronary  angiography  can be performed. A  catheter  is inserted into an artery (typically the  radial  or  femoral artery [ 21 ] ) and pushed to the vessels supplying the heart. A radio-opaque dye is administered through the catheter and a sequence of x-rays (fluoroscopy) is performed. Obstructed or narrowed arteries can be identified, and  angioplasty  applied as a therapeutic measure (see below). Angioplasty requires extensive skill, especially in emergency settings. It is performed by a physician trained in  interventional cardiology . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4429", "text": "Histopathological  examination of the heart may reveal infarction at  autopsy .  Gross examination  may reveal signs of myocardial infarction. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4430", "text": "Under the microscope, myocardial infarction presents as a circumscribed area of ischemic, coagulative  necrosis  (cell death). On gross examination, the infarct is not identifiable within the first 12 hours. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4431", "text": "Although earlier changes can be discerned using  electron microscopy , one of the earliest changes under a normal microscope are so-called  wavy fibers . [ 23 ]  Subsequently, the myocyte  cytoplasm  becomes more  eosinophilic  (pink) and the cells lose their transversal striations, with typical changes and eventually loss of the  cell nucleus . [ 24 ]  The interstitium at the margin of the infarcted area is initially infiltrated with  neutrophils , then with  lymphocytes  and  macrophages , who  phagocytose  (\"eat\") the myocyte debris. The necrotic area is surrounded and progressively invaded by  granulation tissue , which will replace the infarct with a fibrous ( collagenous )  scar  (which are typical steps in  wound healing ). The interstitial space (the space between cells outside of blood vessels) may be infiltrated with  red blood cells . [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4432", "text": "These features can be recognized in cases where the perfusion was not restored; reperfused infarcts can have other hallmarks, such as  contraction band necrosis . [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4433", "text": "These tables gives an overview of the histopathology seen in myocardial infarction by time after obstruction. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4434", "text": "Differential diagnoses for myocardial fibrosis:"}
{"_id": "WikiPedia_Cardio$$$corpus_4435", "text": "Management of acute coronary syndrome  is targeted against the effects of reduced blood flow to the affected area of the  heart muscle , usually because of a  blood clot  in one of the  coronary arteries , the vessels that supply oxygenated blood to the myocardium. This is achieved with urgent hospitalization and medical therapy, including drugs that relieve  chest pain  and reduce the size of the infarct, and drugs that inhibit clot formation; for a subset of patients invasive measures are also employed ( coronary angiography  and  percutaneous coronary intervention ). Basic principles of management are the same for all types of  acute coronary syndrome . However, some important aspects of treatment depend on the presence or absence of  elevation of the ST segment  on the  electrocardiogram , which classifies cases upon presentation to either  ST segment  elevation  myocardial infarction  (STEMI) or non-ST elevation acute coronary syndrome (NST-ACS); the latter includes  unstable angina  and non-ST elevation myocardial infarction (NSTEMI). Treatment is generally more aggressive for STEMI patients, and  reperfusion therapy  is more often reserved for them. Long-term therapy is necessary for prevention of  recurrent events  and  complications . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4436", "text": "Acute coronary syndromes are caused by sudden and critical reduction of blood flow in one of the coronary arteries, the vessels that supply oxygenated blood to the myocardium (heart muscle), typically by a blood clot. The principal symptom is typically chest pain, known as angina pectoris; people who present with angina must prompt evaluation for possible acute coronary syndrome. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4437", "text": "Acute coronary syndromes are classified to two major categories, according to the patient's electrocardiogram, and specifically the presence or absence of persistent (>20 min)  ST segment elevation  (or  left bundle branch block ). [ 2 ]  Patients with acute coronary syndrome and ST elevation are said to have ST-elevation myocardial infarction (STEMI) and they tend to have one of their coronary arteries totally blocked. [ 3 ]  Damage is reversible for approximately 20 [ 4 ] -30 [ 5 ]  minutes after complete obstruction of blood flow; thereafter myocardial  cell death  ensues and progresses as time passes. Therefore, complete and sustained restoration of blood flow must be as prompt as possible to ensure maximum salvage of functional myocardium, a principle expressed in the maxim \"time is muscle\". [ 6 ]  This is achieved with reperfusion therapy, which is based on invasive reopening of the affected coronary artery with primary percutaneous coronary intervention, or non-invasive breaking up of the responsible blood clot with a  thrombolytic drug . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4438", "text": "Patients without ST segment elevation are said to have non-ST-elevation acute coronary syndrome and tend not to have full occlusion of a coronary artery. If there is evidence of myocardial cell death (especially elevated  cardiac biomarkers ) they are considered to have a non-ST-elevation myocardial infarction (NSTEMI); otherwise they are classified with unstable angina. [ 8 ]  Their management is based on the estimation of their risk for adverse events. Patients at low risk can be adequately treated with medical therapy, in many ways similar to the one used for STEMI (but excluding thrombolytics). Those at moderate to high risk benefit from an early invasive strategy, which includes  coronary angiography  and, if necessary,  revascularization  with percutaneous coronary intervention or  coronary artery bypass surgery . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4439", "text": "Medical therapy for acute coronary syndromes is based on drugs that act against ischemia and resultant angina and limit the infarct size (i.e., the area of myocardium that is affected), as well as drugs that inhibit clot formation. The latter include  antiplatelet agents , which block the activation and aggregation of  platelets  (cellular blood components that contribute to clot formation), and  anticoagulant agents  (which attenuate the  coagulation cascade ). Long-term therapy in acute coronary syndrome survivors is targeted against recurrence and long-term complications ( secondary prevention ). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4440", "text": "Women are taken less seriously than men when they have a heart attack leading to higher mortality among women. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4441", "text": "Because of the relationship between the duration of myocardial ischemia and the extent of damage to  heart muscle, public health services encourage people experiencing possible  acute coronary syndrome symptoms  or those around them to immediately call  emergency medical services . [ 11 ] [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4442", "text": "Patients with known  coronary artery disease  who have been prescribed  nitroglycerin  should promptly take one dose, and call emergency medical services if their symptoms do not improve within 2\u20135 minutes. Chewing non\u2212enteric-coated  aspirin  is encouraged (unless there are  contraindications )."}
{"_id": "WikiPedia_Cardio$$$corpus_4443", "text": "Patients should stay calmed in a comfortable position. In case of heart attack, [ 14 ]  it would not usually be lying down, but sitting down or sitting down with folded knees (but patients would notice the position that fits for them)."}
{"_id": "WikiPedia_Cardio$$$corpus_4444", "text": "Patients should not be transported to hospital by private vehicles instead of an ambulance, unless evacuation by land or air ambulance is impossible (e.g., dangerous weather in a very remote area), and if they must be, it should be done if possible with someone trained in cardiac first aid.  [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4445", "text": "Health care professionals are responsible for teaching their patients at risk of acute coronary syndrome what the symptoms of this condition are, and that it is imperative to seek urgent medical attention in case they present. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4446", "text": "Emergency Medical Services (EMS) Systems vary considerably in their ability to evaluate and treat patients with suspected acute myocardial infarction. Some provide as little as first aid and early defibrillation. Others employ highly trained paramedics with sophisticated technology and advanced protocols. [ 17 ]  Paramedic services are capable of providing  oxygen , IV access, sublingual  nitroglycerine ,  morphine , and  aspirin .  Some advanced paramedic systems can also perform 12-lead ECGs. [ 18 ]   If a STEMI is recognized the paramedic may be able to contact the local PCI hospital and alert the emergency room physician, and staff of the suspected AMI. Some Paramedic services are capable of providing  thrombolytic therapy  in the prehospital setting, allowing reperfusion of the myocardium. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4447", "text": "With  primary PCI  emerging as the preferred therapy for ST-segment elevation myocardial infarction,  EMS  can play a key role in reducing  door-to-balloon  intervals (the time from presentation to a hospital  ER  to the restoration of coronary artery blood flow) by performing a 12-lead  ECG  in the field and using this information to triage the patient to the most appropriate medical facility. [ 21 ] [ 22 ] [ 23 ] [ 24 ]  In addition, the 12-lead ECG can be transmitted to the receiving hospital, which enables time saving decisions to be made prior to the arrival of the patient. This may include a \"cardiac alert\" or \"STEMI alert\" that calls in off duty personnel in areas where the  cardiac cath lab  is not staffed 24 hours a day. [ 25 ]   Even in the absence of a formal alerting program, prehospital 12-lead ECGs are independently associated with reduced door to treatment intervals in the emergency department. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4448", "text": "In patients with symptoms typical of myocardial ischemia an electrocardiogram must be immediately obtained - e.g., within 10 minutes from first contact with medical or paramedical personnel, including  prehospital  setting; the  electrocardiographic findings  will guide the subsequent management. Patients with  elevation of the ST segment  (or presumed new  left bundle branch block ) are treated based on guidelines for  ST elevation myocardial infarction  (STEMI) and must undergo reperfusion therapy as soon as possible. Serum  cardiac biomarkers  are routinely obtained and their elevation is necessary for confirming diagnosis of myocardial infarction; [ 27 ]  however, reperfusion must not be delayed by waiting for the results. Patients without the above findings are initially classified with non ST elevation  acute coronary syndrome , and subsequent cardiac biomarker results will differentiate between true  non ST elevation myocardial infarction  (NSTEMI) and  unstable angina . [ 28 ] [ 29 ] [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4449", "text": "Relief of the pain of angina is of paramount importance, not only for humane reasons but because the pain is associated with  sympathetic activation  that causes  vasoconstriction  and increases the workload of the heart. [ 28 ]  The pain of myocardial ischemia is likely to respond to any intervention that improves the relationship between oxygen demand and supply, like  nitrates ,  beta blockers  and  oxygen . [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4450", "text": "Nitrates, like  nitroglycerin , dilate blood vessels, which is beneficial against myocardial ischemia in two ways: By increasing blood flow in the coronary arteries and the amount of oxygen that arrives to heart muscle; and by relaxing all blood vessels in the body, thereby reducing the workload that heart needs to produce against them and the oxygen it consumes. The preferred mode of administration is  sublingually . By relaxing blood vessels nitrates also reduce blood pressure, which must be carefully  monitored ; they must not be used if  hypotension  is present. They must also be avoided in patients who have taken  sildenafil  or other  phosphodiesterase type 5 inhibitors  (used for  erectile dysfunction ) within the previous 24\u201348 hours, as the combination of the two could cause a serious drop in blood pressure. [ 31 ] [ 32 ] [ 33 ]   Intravenous  nitrates are useful in patients with hypertension or  pulmonary edema . [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4451", "text": "By reducing  sympathetic  stimulation of the heart,  beta blockers  decrease heart rate, blood pressure and  cardiac output , and hence heart oxygen consumption. Beta-blockers alleviate ischemic pain, and have also been proved to reduce the size of infarcted heart muscle, the risk of  arrhythmias , and the proportion of patients with acute coronary syndrome who actually evolve STEMI. However, they have also been shown to increase the risk of  acute heart failure . Their early use is contraindicated if there are signs of  congestive heart failure  (e.g.,  Killip class  II or above) or hypotension, along with other  contraindications to beta blockers  ( slow heart rate ,  atrioventricular block ); in the absence of contraindications beta blocker therapy should begin in the first 24 hours. It may be prudent to prefer oral rather than intravenous forms. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4452", "text": "Initial administration of oxygen to all patients with acute coronary syndrome is common practice; however, there is no evidence to support or refute that supplemental oxygen might be harmful or beneficial for cardiac patients who do not need it. [ 36 ]  It is currently recommended to give oxygen only to breathless patients or when  blood oxygen saturation  is low, e.g. <90%. [ 31 ] [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4453", "text": "Analgesic agents that are most commonly used are  opioids , and especially  morphine , which is considered the analgesic of choice in patients with ST elevation. Along with its pain-controlling properties, morphine also reduces the work of breathing, alleviates breathlessness, reduces anxiety and has favorable action on  hemodynamic  parameters and cardiac oxygen consumption. [ 31 ] [ 38 ] [ 39 ]  However, in patients presenting without ST elevation, morphine has been shown to have adverse events potential, and its use is considered acceptable only after inadequate pain relief by medication specific against  angina . [ 40 ]   Non-steroidal anti-inflammatory drugs  are contraindicated for both categories of patients. [ 40 ] [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4454", "text": "All patients with acute coronary syndrome must immediately receive  antiplatelet therapy , including aspirin and generally a second oral antiplatelet agent. [ 42 ]  Bleeding is the most important side-effect of antiplatelets. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4455", "text": "Aspirin inhibits  platelet  aggregation and formation of blood clots. It is effective across the entire spectrum of acute coronary syndromes; it has been shown to reduce the  rate of death  in patients with STEMI and in patients presenting without ST elevation.  Aspirin is contraindicated in patients with documented allergy or known platelet disorder. Patients who have had gastrointestinal symptoms while on long-term aspirin therapy are usually able to tolerate aspirin in the short term. For patients with true intolerance to aspirin  clopidogrel  is recommended. Lower doses need days to achieve full antiplatelet effect, therefore a  loading dose  is necessary for patients who are not already on aspirin. [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4456", "text": "Aside from aspirin, three antiplatelet agents taken by mouth have been approved for use in acute coronary syndromes, clopidogrel,  ticagrelor  and  prasugrel ; all reduce platelet aggregation by inhibiting the  P2Y 12  receptor , a type of  adenosine phosphate  receptor, on the surface of platelets. Not all three of them are equally indicated in all types of acute coronary syndromes. In patients with ST elevation the choice of P2Y 12  inhibitor depends on reperfusion strategy; for patients undergoing primary  percutaneous coronary intervention  ticagrelor and prasugrel are considered superior to clopidogrel, as they are more potent and have more rapid onset of action, at the cost of some increase in bleeding risk; for STEMI patients who are treated with  fibrinolysis  and those who do not undergo reperfusion treatment only clopidogrel is indicated. Prasugrel must not be given to patients with a history of  ischemic stroke  or aged 75 years or older. In patients with non-ST elevation acute coronary syndrome current guidelines also recommend immediate administration of dual antiplatelet therapy upon diagnosis; clopidogrel and ticagrelor are indicated in this setting, with ticagrelor considered superior for patients undergoing early invasive strategy (see later). However, emerging evidence questions this strategy. [ 44 ]  As with aspirin, it is necessary to administer a loading dose. [ 45 ] [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4457", "text": "Glycoprotein IIb/IIIa inhibitors  are a class of intravenous antiplatelet agents used in patients undergoing percutaneous coronary intervention, consisting of  abciximab ,  eptifibatide  and  tirofiban . Patients presenting with ST elevation that will be reperfused with percutaneous coronary intervention may receive one of the above agents at the time of  catheterization , or perhaps before. Administering eptifibatide or tirofiban may also be reasonable in patients presenting with NST-ACS who are considered of intermediate or high risk and are treated with early invasive strategy. [ 47 ] [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4458", "text": "Anticoagulants in acute coronary syndrome are targeted against the coronary blood clot, as well as towards prevention of thrombotic complications, like formation of blood clots in the  ventricles ,  stroke ,  pulmonary embolism  or  deep vein thrombosis . [ 49 ]  Patients undergoing PCI also need an anticoagulant to prevent  catheter  thrombosis. Options include  unfractionated heparin ,  enoxaparin  (a  low molecular weight heparin ),  fondaparinux  (a  pentasaccharide  antagonist of  factor Xa ) and  bivalirudin  (a  direct thrombin inhibitor ); all the above agents are given  parenterally  (subcutaneously or  intravenously ). Unfractionated heparin has the disadvantage of requiring dose adjustment based on a laboratory exam,  activated partial thromboplastin time  (APTT). In STEMI patients choice depends on the reperfusion strategy used (see below); bivalirudin is used when PCI is employed only, while in the same case fondaparinux is not preferred. [ 50 ]  Similarly, in Non-STE ACS bivalirudin too is only used when an early invasive strategy is chosen. [ 51 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4459", "text": "The concept of reperfusion has become so central to the modern treatment of acute myocardial infarction, that we are said to be in the reperfusion era. [ 53 ] [ 54 ]  Patients who present with suspected acute myocardial infarction and ST segment elevation (STEMI) or new bundle branch block on the 12 lead  ECG  are presumed to have an occlusive thrombosis in an epicardial coronary artery. They are therefore candidates for immediate reperfusion, either with  thrombolytic therapy ,  percutaneous coronary intervention  (PCI) or when these therapies are unsuccessful,  bypass surgery . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4460", "text": "Individuals without ST segment elevation are presumed to be experiencing either unstable angina (UA) or non-ST segment elevation myocardial infarction (NSTEMI). They receive many of the same initial therapies and are often stabilized with  antiplatelet drugs  and  anticoagulated . If their condition remains ( hemodynamically ) stable, they can be offered either late  coronary angiography  with subsequent restoration of blood flow (revascularization), or  non-invasive   stress testing  to determine if there is significant ischemia that would benefit from revascularization.  If hemodynamic instability develops in individuals with NSTEMIs, they may undergo urgent coronary angiography and subsequent revascularization. The use of thrombolytic agents is contraindicated in this patient subset, however. [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4461", "text": "The basis for this distinction in treatment regimens is that ST segment elevations on an ECG are typically due to complete occlusion of a coronary artery. On the other hand, in NSTEMIs there is typically a sudden narrowing of a coronary artery with preserved (but diminished) flow to the distal myocardium. Anticoagulation and antiplatelet agents are given to prevent the narrowed artery from occluding. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4462", "text": "At least 10% of patients with STEMI do not develop myocardial necrosis (as evidenced by a rise in cardiac markers) and subsequent Q waves on EKG after reperfusion therapy. Such a successful restoration of flow to the infarct-related artery during an acute myocardial infarction is known as \"aborting\" the myocardial infarction. If treated within the hour, about 25% of STEMIs can be aborted. [ 56 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4463", "text": "Additional objectives are to prevent life-threatening arrhythmias or conduction disturbances. This requires monitoring in a  coronary care unit  and protocolized administration of  antiarrhythmic agents .  Antiarrhythmic agents are typically only given to individuals with life-threatening arrhythmias after a myocardial infarction and not to suppress the  ventricular ectopy  that is often seen after a myocardial infarction. [ 57 ] [ 58 ] [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4464", "text": "Cardiac rehabilitation  aims to optimize function and  quality of life  in those affected by a heart disease. This can be with the help of a physician, or in the form of a cardiac rehabilitation program. [ 60 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4465", "text": "Physical exercise  is an important part of  rehabilitation  after a myocardial infarction, with beneficial effects on cholesterol levels, blood pressure, weight,  stress  and  mood . [ 60 ]  Some patients become afraid of exercising because it might trigger another infarct. [ 61 ]  Patients are encouraged to exercise, and should only avoid certain exerting activities. Local authorities may place limitations on  driving   motor vehicles . [ 62 ]  In most cases, the advice is a gradual increase in physical exercise during about 6\u20138 weeks following an MI. [ 63 ]  If it doesn't feel too hard for the patient, the advice about exercise is then the same as applies to anyone else to gain health benefits, that is, at least 20\u201330 minutes of moderate exercise on most days (at least five days per week) to the extent of getting slightly short of breath. [ 63 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4466", "text": "Some people are afraid to have  sex  after a heart attack. Most people can resume sexual activities after 3 to 4 weeks. The amount of activity needs to be dosed to the patient's possibilities. [ 64 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4467", "text": "Cocaine  associated myocardial infarction should be managed in a manner similar to other patients with acute coronary syndrome, except that  beta blockers  should not be used and  benzodiazepines  should be administered early. [ 65 ]   The treatment itself may have complications. If attempts to restore the blood flow are initiated after a critical period of only a few hours, the result may be a  reperfusion injury  instead of amelioration. [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4468", "text": "In  wilderness first aid , a possible heart attack justifies  evacuation  by the fastest available means, often meaning the initiation of a  MEDEVAC . The suspicion or provisional diagnosis of an MI means that it is inappropriate for the patient to walk out of the wilderness setting and will require them to be carried or conveyed in a vehicle.  Aspirin, nitroglycerin, and oxygen can all be given with relative ease in a wilderness setting and should be administered as soon as possible in suspected cases of MI.  Wilderness management of  cardiac arrest  differs slightly from that carried out in an urban setting in that it is generally considered acceptable to terminate a resuscitation attempt after 30 minutes if there has been no change in the patient's condition. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4469", "text": "Certified personnel traveling by commercial aircraft may be able to assist an MI patient by using the on-board  first aid kit , which may contain some cardiac drugs (such as  glyceryl trinitrate  spray,  aspirin , or  opioid  painkillers), an  AED , [ 67 ]  and  oxygen . Pilots may divert the flight to land at a nearby airport.  Cardiac monitors  are being introduced by some airlines, and they can be used by both on-board and ground-based physicians. [ 68 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4470", "text": "Percutaneous coronary intervention  ( PCI ) is a minimally invasive non-surgical procedure used to treat  narrowing  of the  coronary arteries  of the  heart  found in  coronary artery disease . [ 2 ]  The procedure is used to place and deploy  coronary stents , a permanent wire-meshed tube, to open narrowed coronary arteries. PCI is considered 'non-surgical' as it uses a small hole in a peripheral artery (leg/arm) to gain access to the arterial system; an equivalent surgical procedure would involve the opening of the chest wall to gain access to the heart area. The term ' coronary angioplasty  with stent' is synonymous with PCI. The procedure visualises the blood vessels via  fluoroscopic  imaging and  contrast dyes . PCI is performed by an  interventional cardiologists  in a  catheterization laboratory  setting. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4471", "text": "Patients who undergo PCI broadly fall into two patient groups. Those who are suffering from a  heart attack  and are in a critical care emergency room setting and patients who are clinically at a high risk of suffering a heart attack at some future point. PCI is an alternative to the invasive surgery  coronary artery bypass grafting  ( CABG , often referred to as \"bypass surgery\"), which bypasses narrowed arteries by grafting vessels from other locations in the body. Coronary angioplasty was first introduced in 1977 by  Andreas Gruentzig  in Switzerland. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4472", "text": "PCI is used to open a blocked coronary artery/arteries and to restore arterial blood flow to heart muscle, without requiring open-heart surgery. In patients with acute coronary syndromes, PCI may be appropriate; guidelines and best practices are constantly evolving. [ 5 ]  Heart attack 'onset to treatment time' is important and significantly influences clinical outcomes of PCI procedures. The rapid  reperfusion  of heart muscle is critical in preventing further heart muscle damage caused by heart attacks, this time is often referred to as 'Onset-to-Door' and ' Door-to-balloon'  time, shortening this time is an important goal within an emergency care/ hospital setting. A number of initiatives have been active sponsored by a variety of organizations and hospital groups since the late 1990s to reduce this time to treatment. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4473", "text": "The use of PCI in addition to  anti-angina medication  in stable angina\u200a may reduce the number of patients with angina attacks for up to 3 years following the therapy, [ 7 ]  but does not reduce the risk of death, future myocardial infarction or need for other interventions. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4474", "text": "PCI is widely practiced and has a number of risks; [ 9 ]  however, major procedural complications are uncommon. PCI is performed using minimally invasive  catheter-based procedures  by an interventional cardiologist, a medical doctor with special training in the treatment of the heart. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4475", "text": "For most patients who are not receiving primary PCI (not having PCI to treat a heart attack) the patient is usually awake during PCI, and chest discomfort may be experienced during the procedure.  Bleeding from the insertion point in the groin (femoral artery) or wrist (radial artery) is common, in part due to the use of  antiplatelet drugs . Some  bruising  is common, but occasionally a  hematoma  may form. This may delay hospital discharge as flow from the artery into the hematoma may continue (pseudoaneurysm) which requires surgical repair. Infection at the skin puncture site is rare and  dissection  (tearing) in the interior wall of an arterial blood vessel is uncommon.  Allergic reaction  to the contrast dye used is possible, but has been reduced with the newer agents. [ 11 ]  Deterioration of kidney function can occur in patients with pre-existing kidney disease, but kidney failure requiring dialysis is rare. Vascular access complications are less common and less serious when the procedure is performed via the radial artery. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4476", "text": "The most serious risks are  death ,  stroke ,  ventricular fibrillation  (non-sustained  ventricular tachycardia  is common),  myocardial infarction  (heart attack, MI), and  aortic dissection . A heart attack during or shortly after the procedure occurs in 0.3% of cases; this may require emergency  coronary artery bypass surgery . [ 13 ]  Heart muscle injury characterized by elevated levels of  CK-MB ,  troponin I , and  troponin T  may occur in up to 30% of all PCI procedures. Elevated enzymes have been associated with later clinical outcomes such as higher risk of death, subsequent MI, and need for repeat revascularization procedures. [ 14 ] [ 15 ]  Angioplasty carried out shortly after an MI has a risk of causing a  stroke , but this is less than the risk of a stroke following thrombolytic drug therapy. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4477", "text": "As with any procedure involving the heart, complications can sometimes, though rarely, cause death. The mortality rate during angioplasty is 1.2%. [ 17 ]  Sometimes chest pain can occur during angioplasty because the balloon briefly blocks off the blood supply to the heart.\nThe risk of complications is higher in: [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4478", "text": "Balloon angioplasty  is the inflation of a balloon (often part of an integrated medical device combining a balloon, guidewire, and stent) within the coronary artery to 'crush' the plaque causing the occlusion into the walls of the artery. Balloon angioplasty is still often performed as a part of PCI procedure, it is rarely the only activity performed. Procedures commonly associated with PCI are:"}
{"_id": "WikiPedia_Cardio$$$corpus_4479", "text": "PCI consists of preparation of the skin area to be accessed (groin or arm), by shaving and swabbing the area with a bacteriostatic agent, usually a  chlorhexidine  based product. An introducer needle is inserted into the target artery. Once the access is gained, a \"sheath introducer\" is inserted to keep the artery open. This procedure is termed  percutaneous  access. As of 2023, catheter systems used in PCI procedures are often fully integrated medical devices. They are usually referred to as \"over the wire\" or OTW catheters. [ 19 ]  Typically having two lumen paths (a cavity within any tubular structure), the larger one for the navigating highly flexible guidewire and the smaller one for inflating and deflating the balloon or balloon/catheter assembly. The guidewire lumen extends the total length of the catheter. A balloon-stent is often part of the assembled device, other features may also be part of the medical device design depending on the nature of the procedure. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4480", "text": "The interventional cardiologist uses the entry point created during the percutaneous access step, to introduce the catheter system and guides it to the  occluded  area of the coronary artery being treated, using  fluoroscopy  and  radiopaque  dyes as an imaging tool. The device and its balloon/stent components can be inflated to open the  stenotic  diseased artery area. When a stent is used, the stent tube mesh is initially collapsed onto the balloon component of the catheter. In this collapsed state, it is small enough to be passed though relatively narrow peripheral arteries and then inflated by the underlying balloon and pressed firmly against the diseased coronary artery wall. It  is expanded by pressure introduced by injecting physiological saline into the device through the lumen of the still attached catheter. Inflation time and pressure used are recorded during this placement procedure. After the balloon inflation/deflation or the deposition of the stent, the placement device/deflated balloon are removed leaving the stent in place. [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4481", "text": "The interventional cardiologist decides how to treat the blockage in the best way during the PCI/stent placement, based on real-time data. The cardiologist uses imaging data provided by both  intravascular ultrasound  (IVUS), and  fluoroscopic  imaging (combined with a  radiopaque  dye) during the procedure. The information obtained from these two sources enables the cardiologist to track the path of the catheter-device as it moves through the arterial vessels. This information also helps determine both the location and physical characteristics of plaque(s) causing narrowing in the arteries. Data from these two techniques is used to correctly position the stent and to obtain detailed information relating to the coronary arterial anatomy. This anatomy varies greatly among individuals, having this information becomes crucial for effective treatment. The obtained data is recorded on video and is of value in cases when future treatment is needed. [ 23 ] [ 24 ] [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4482", "text": "Older  bare-metal  stents (BMS) provide a mechanical framework that holds the artery wall open, preventing stenosis, or narrowing, of coronary arteries. Newer  drug-eluting stents  (DES) are traditional stents with a polymer coating containing drugs that prevent cell proliferation. The antiproliferative drugs are released slowly over time to help prevent tissue growth."}
{"_id": "WikiPedia_Cardio$$$corpus_4483", "text": "DES stents have been shown to help prevent  restenosis  of the artery through mechanisms that rely upon the suppression of tissue growth at the stent site and local modulation of the body's inflammatory and immune responses. The first two drug-eluting stents to be utilized were the  paclitaxel -eluting stent and the  sirolimus -eluting stent, both of which have received approval from the U.S. Food and Drug Administration. Most current FDA-approved drug-eluting stents use sirolimus (also known as rapamycin),  everolimus  and  zotarolimus . Biolimus A9-eluting stents, which utilize biodegradable polymers, are approved outside the U.S. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4484", "text": "Newer-generation PCI technologies aim to reduce the risk of late stent thrombosis or other long-term adverse events. Some DES products market a biodegradable polymer coating with the belief that the permanent polymer coatings of DES contribute to long-term inflammation. Other strategies: A more recent study proposes that in the case of population with diabetes mellitus\u2014a population particularly at risk\u2014a treatment with paclitaxel-eluting balloon followed by BMS may reduce the incidence of coronary restenosis or myocardial infarction compared with BMS administered alone. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4485", "text": "After placement of a stent or scaffold, the patient needs to take two antiplatelet medications (aspirin and one of a few other options) for several months to help prevent blood clots. The length of time a patient needs to be on dual antiplatelet therapy is individualized based risks of ischemic events and bleeding risk. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4486", "text": "In primary PCI,  angiography  may demonstrate  thrombus  (blood clots) inside the coronary arteries. Various studies have been performed to determine whether aspirating these clots (thrombus aspiration or manual thrombectomy) is  beneficial. At the moment there is no evidence that routine clot aspiration improves outcomes. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4487", "text": "Lesions with a high degree of calcium deposition within the vessel wall, especially if the calcium is circumferential, are considered to be hard to dilate in regards to balloon  angioplasty . Complex lesions are one of the key predictors of poor outcome in percutaneous coronary intervention (PCI), [ 31 ]  hence calcium lesion modification is needed before implantations of stents. The aim is to create cracks in the calcium within the vessel wall in order to increase the likelihood of successful expansion of the stenosis and delivery of the final stent. [ 32 ] [ 33 ]  This is traditionally achieved by balloon  angioplasty  or debulking strategies including rotational, orbital and laser atherectomy. However, coronary intravascular  lithotripsy  using acoustic shockwaves is a novel approach for treating superficial and deep calcium in the vessel wall. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4488", "text": "For many patients the stenting procedures does not require an in-hospital stay. Much of the time spent in immediate recovery post stenting is to ensure the access site is not bleeding. The patient is generally monitored using ECG etc. Medications to prevent a blood clots from forming generally and in the stent are given directly after the stenting procedure, commonly in the form of an immediate loading dose of the potent anticoagulant (blood thinner)  Plavix  administered as a tablet. Other anticoagulant medicines are also used and the combination of aspirin and Plavix is a typical anticoagulant practice. For patients who have had a heart attack, the length of hospitalization is largely dependent on the muscle damage caused by the event. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4489", "text": "If a stent has been placed as part of the PCI procedure, the patient will be given a 'medical device card' (US) with information about the implanted stent such as a medical device serial number, this is important as it informs clinicians performing future potential medical procedures, this is also the case with arterial closure systems which are also medical devices. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4490", "text": "There is usually significant soreness at the point of entry into the arterial system, and fairly large  hematomas  (significant bruising) are very common, this soreness usually improves after a week or so. Patients are generally advised to 'take it easy' for a week or two and are instructed to be cautious not to lift any substantial weight, this is primarily to ensure the access site heals. Follow up appointments within a week or two of the procedure with a cardiologist or primary care provider/GP are a standard global practice. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4491", "text": "It is a standard practice to have further follow-up examinations every three to six months for the first year, though these practices do vary by region and practitioners. Further diagnostic  coronary angiography  is not routinely indicated after coronary stent implantation. If progression of heart disease is suspected, a stress test will be performed; patients who develop symptoms or show evidence of ischemia in a stress test may undergo diagnostic cardiac re-catheterization. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4492", "text": "Physical examinations play an important role after PCI-stenting procedures. Those patients at high risk of suffering from complications and those with more complexed coronary issues, angiography may be indicated regardless of the findings of non-invasive stress tests. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4493", "text": "Cardiac rehabilitation  activities are dependent on many factors, but largely are connected to the degree of heart muscle damage prior to the PCI/DES procedure. Many patients who undergo this procedure have not had a heart attack, and may have no notable damage to their hearts. Others may have had a serious heart attack and the amount of damage to their heart's ability to supply the body with oxygenated blood might be impaired. Rehabilitation activities are prescribed to fit each individuals needs. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4494", "text": "Percutaneous coronary angioplasty is one of the most common procedures performed during U.S. hospital stays; it accounted for 3.6% of all operating room procedures performed in 2011. [ 38 ]  Between 2001 and 2011, however, its volume decreased by 28%, from 773,900 operating procedures performed in 2001 to 560,500 procedures in 2011. [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4495", "text": "Conflicting data exists relating to clinical outcomes comparing PCI/Stenting and CABG surgery. The preponderance of studies do suggest that CABG offers advantages in reducing death and myocardial infarction in people with multivessel blockages compared with PCI. [ 40 ]  The assessments are complicated by considerations such as the fact that PCI is a minimally invasive procedure and CABG is significant surgery. [ 41 ]  Different modeling studies have come to opposing conclusions on the relative cost-effectiveness of PCI and CABG in people with myocardial ischemia that does not improve with medical treatment. [ 42 ] [ 43 ] [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4496", "text": "Coronary angioplasty, also known as  percutaneous  transluminal coronary angioplasty (PTCA), because it is done through the skin and through the lumen of the artery, was first developed in 1977 by  Andreas Gruentzig . The first procedure took place Friday Sept 16, 1977, at  Zurich ,  Switzerland . [ 45 ]  Adoption of the procedure accelerated subsequent to Gruentzig's move to  Emory University  in the United States. Gruentzig's first fellow at Emory was  Merril Knudtson , who, by 1981, had already introduced it to  Calgary ,  Alberta ,  Canada . [ 46 ]  By the mid-1980s, many leading medical centers throughout the world were adopting the procedure as a treatment for  coronary artery disease . [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4497", "text": "Current concepts recognize that after three months the artery has adapted and healed and no longer needs the stent. [ 48 ]  Complete revasculariztion of all stenosed coronary arteries after a STEMI is more efficacious in terms of major adverse cardiac events and all-cause mortality, while being safer than culprit-vessel-only approach. [ 49 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4498", "text": "In 2007 the  New England Journal of Medicine  published the results of a trial called COURAGE. [ 50 ]  The study compared stenting as used in PCI to medical therapy alone in symptomatic stable  coronary artery disease  (CAD). [ 50 ]  This showed there was no mortality advantage to stenting in stable CAD, though there was earlier relief of symptoms which equalized by five years. After this trial there were widely publicized reports of individual doctors performing PCI in patients who did not meet any traditional criteria. [ 51 ]  A 2014 meta-analysis showed there may be improved mortality with second generation  drug-eluting stents , which were not available during the COURAGE trial. [ 52 ]  Medical societies have since issued guidelines as to when it is appropriate to perform percutaneous coronary intervention. [ 53 ] [ 54 ]  In response the rate of inappropriate stenting was seen to have declined between 2009 and 2014. [ 55 ]  Statistics published related to the trends in U.S. hospital procedures, showed a 28% decrease in the overall number of PCIs performed in the period from 2001 to 2011, with the largest decrease notable from 2007. [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4499", "text": "The 2017 ORBITA study [ 56 ]  has also caused much controversy, in that it found that following percutaneous coronary intervention there was no statistically significant difference in exercise time compared with medical therapy. The study authors believe that angina relief by PCI is largely a placebo effect. [ 57 ]  Others have noted the small sample size with insufficient power to detect outcome differences and the short 6 week duration of the trial. [ 58 ]  85% of patients in the medical therapy arm elected to have PCI at the end of the trial. [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4500", "text": "The 2019 ISCHEMIA trial [ 60 ]  has confirmed that invasive procedures (PCI or CABG) do not reduce death or heart attacks compared to medical therapy alone for stable angina. Patients with angina experienced improved quality of life with PCI compared to medical therapy. [ 61 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4501", "text": "Precordial thump  is a  medical procedure  used in the treatment of  ventricular fibrillation  or pulseless  ventricular tachycardia  under certain conditions. The procedure has a very low success rate, but may be used in those with witnessed, monitored onset of one of the \"shockable\"  cardiac rhythms  if a  defibrillator  is not immediately available. [ 1 ] [ 2 ]  It should not delay  cardiopulmonary resuscitation  (CPR) and defibrillation, nor should it be used in those with unwitnessed out-of-hospital  cardiac arrest . [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4502", "text": "In a precordial thump, a provider strikes at the middle of a person's  sternum  with the  ulnar  aspect of the fist. [ 4 ]  The intent is to interrupt a potentially life-threatening rhythm. The thump is thought to produce an electrical  depolarization  of 2 to 5  joules . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4503", "text": "The precordial thump may only be effective if administered within seconds of the onset of  ventricular fibrillation  or pulseless  ventricular tachycardia . [ 5 ]  It is not helpful for treating ventricular fibrillation if too much time has passed. [ 6 ]  It also has very low effectiveness for treating  ventricular arrhythmia [ 7 ]  (possibly even making it worse), [ 4 ] [ 7 ]  and ventricular tachycardia, [ 2 ]  especially when compared to CPR and defibrillation as alternatives."}
{"_id": "WikiPedia_Cardio$$$corpus_4504", "text": "Historically, it was recommended as the initial action to take when addressing such witnessed and monitored cardiac arrests in a hospital setting. [ 5 ]  More recently, European guidelines recommend it should no longer be routinely used with available evidence suggesting it does not improve survival to hospital discharge. [ 8 ]  However, American guidelines continue advocating its use by healthcare professionals. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4505", "text": "There are concerns that the precordial thump can result in worsening of a person's heart rhythm more often than it improves it. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4506", "text": "The use of the precordial thump technique has sometimes been shown in famous  movies  and  television , such as in  The Good Doctor  Season 2 episode 5 in which it is performed by Dr. Brown, and  The Resident  Season 1 episode 2 in which it is performed by Conrad Hawkins, usually in passing without any explanation.  Untrained laypersons have been known to attempt it, and sometimes cause additional injury to the person as the blow must be carefully aimed. If applied incorrectly it may cause further injury, for instance inducing  cardiac arrest by blunt trauma , or breaking  the tip of the sternum , risking fatal damage to the  liver  or other abdominal organs. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4507", "text": "At one time, the technique was also taught as part of standard CPR training with the requirement that it must be administered within 60 seconds of the onset of symptoms.  That time restriction, combined with a number of injuries caused by improper technique, [ citation needed ]  resulted in the procedure being removed from CPR training."}
{"_id": "WikiPedia_Cardio$$$corpus_4508", "text": "James E. Pennington and  Bernard Lown  at  Harvard University  are credited with formalizing this technique in the medical literature. They published their report in the  New England Journal of Medicine  in the early 1970s.  Richard S. Crampton  and George Craddock, at the  University of Virginia  helped to promote the  paramedic  use of chest thump through a curious accident. In 1970, the Charlottesville-Albemarle Rescue Squad (VA) was transporting a patient with an unstable  cardiac rhythm  in what was then called a  Mobile Coronary Care Unit . When the vehicle inadvertently hit a speed bump in a shopping center parking lot, the patient's normal heart rhythm was restored. Further research confirmed that chest thumping patients with life-threatening  arrhythmias  could save lives. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4509", "text": "Percussion pacing or fist pacing was proposed as a method of delivering  mechanical pacing  to someone in cardiac arrest. There is little evidence to support its use. [ 11 ]  In 1920, German physician Eduard Schott originally described percussion pacing, and a 2007 BJA article describes good benefit to this technique. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4510", "text": "quantium Medical Cardiac Output  ( qCO ) uses  impedance cardiography  in a simple, continuous, and non-invasive way to estimate the  cardiac output  (CO) and other hemodynamic parameters such as the  stroke volume  (SV) and  cardiac index  (CI). The CO estimated by the qCO monitor is referred to as the \"qCO\". The  impedance plethysmography  allows determining changes in volume of the body tissues based on the measurement of the  electric impedance  at the body surface. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4511", "text": "The assessment of cardiac output (CO) is important because it reveals the main cardiac function: the supply of blood to tissues. CO reflects the hemodynamic flow and hence the transport of oxygen; its clinical applications by non-invasive continuous  hemodynamic monitoring  are especially useful for some medical specialties like  anaesthesiology ,  emergency care  and  cardiology , for example to prevent  hypoperfusion  and to guide fluid administration."}
{"_id": "WikiPedia_Cardio$$$corpus_4512", "text": "Several authors advocate the high reliability and good correlation of cardiography impedance compared to others techniques more established. [ 4 ] [ 5 ] [ 6 ]  Nevertheless, some detractors complain about the sensitivity of the technique to artefacts such as the  electromyography  or breathing movements. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4513", "text": "The Impedance Cardiography (ICG or Ztot) signal represents the changes in the thoracic impedance due to variations in the blood flow. In practice, the raw Ztot signal (in O) is transformed to the \u2013dZ/dt waveform (filtered negative  first derivative , in O x s-1) by using the first derivative to remark the  inflection points  of the raw Ztot signal. The most important characteristic points of the \u2013dZ/dt waveform are B, C, and X points (see figure 2). All these points are associated with distinct physiological events within the systolic part of the  cardiac cycle , i.e., located after the  QRS complex  onset. In that sense, the R wave from the  ECG  signal can be an important reference for detecting such events. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4514", "text": "The ICG signal is extremely sensitive to artifacts due to movements and respiration. Baseline variations can considerably alter the dZ/dtmax point and the dependent hemodynamic parameters. High-frequency interferences also can affect the  accuracy  in estimating some characteristics points, essentially the B point, affecting the LVET dependent parameters. The qCO's algorithm uses classical and advanced adaptive filtering techniques to minimize such problems with good results. The algorithm applies a  band-pass filtering stage , which attenuates both the baseline drifts (due to movement or respiration) and the high-frequency signal. Also, it features  Adaptive Neuro-Fuzzy Inference System (ANFIS) , for higher accuracy, which is able to obliterate even artifacts such as the electrosurgical noise. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4515", "text": "Since its discovery, the use of CO monitoring has been restricted to certain kinds of patients because of the risk of the classical procedures. Lately, new kinds of methods and devices have been developed. Nowadays, in practice, the method election is determined mainly by the features of the patients and the possibilities of the hospital to accede to this technology.\nDifferent CO monitor methods can be characterized by their invasiveness or their ability to measure continuously. The most ideal should be reliable, continuous, non-invasive, easy to use, and cost-effective. [ 10 ]  The invasive methods like the still gold standard method  Swan-ganz catheter  ( pulmonary artery catheter ), based on transcardiac thermodilution, are being replaced by its invasiveness; hence these systems will not be inspected in this document.\nThe minimally invasive methods also require catheterization, but less harmful. One of them is the  Thermodilution Transpulmonary (TDTP) , developed in the late 1990s, which presents risk of  iatrogenic effect  effects such as  pneumothorax ,  Bleeding ,  infection ,  thrombosis  or  vascular ischemia , inherent to the requirement of both  arterial and central venous catheter . As a calibrating method, this system performs a thermodilution curve by measuring the changes in blood temperature due to the injection of cold serum and calculates the CO intermittently through a modified equation of Stewart-Hamilton. [ 11 ]  Furthermore, this method lets a continuous reading of the CO through the analysis of the  arterial Pulse Pressure  (PP) wave.\nAdmittedly, these systems have some limitations, related for example to the thermodilution, such as thermic artifacts due to the injection of another serum or during the extracorporeal purification treatment (this therapy is required by approximately the 5% of patients in critical areas). [ 12 ]  Most of the monitors able to provide a continuous measure of the CO, are based on the analysis of the  arterial blood pressure (BP) curve, called pulse contour methods. [ 13 ]  They are founded by the fact that the pulse pressure is proportional to the ejection volume; however, this is only true when aortic resistance remains constant, hence, these methods have some limitations such as  obesity , which affects the arterial distensibility, or  aortic regurgitation . Furthermore, the values may be modified in patients with  Intra-Aortic Balloon Pumps (IABP)  or unstable arterial signal as in cases of severe arrhythmias or  ventricular extrasystolia . The signal can be altered also by shock or hypothermia states because of the peripheral vasoconstriction or arterial spasm. Usually, for calculating the stroke volume, the methods based on pulse wave analysis need previous and periodic calibrations that must be done in the same patient, which is a drawback.\nThe main non-invasive methods can be classified into two groups. The first group is formed by different variations of the echocardiography and  echo-Doppler techniques  and the second group is comprised by the aortic bioimpedance and bioreactance.  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4516", "text": "Doppler or echocardiography systems cannot assess the CO continuously. The continuous assessment capability is the major advantage of the qCO device. This is especially important to predict if the patient is fluid responsive in cases of hemodynamic instability or circulatory shock, which can be assessed with a simple test named  Passive Leg Raising  (PLR, described in detail below), for which, the quick variations in the CO should be detected.\nAnother benefit is the fact that qCO is fully non-invasive, thus avoiding risks for the patient. Further, it does not need to be calibrated, which allows accelerating and simplifying the monitoring, thereby, providing a large benefit for both the patients and clinicians.\nThe Pulse Pressure Variation (PPV) method is influenced by mechanical ventilation, due to changes in the pleural pressure, hence, such monitoring should not be recommended for patients who are not being mechanically ventilated with a regular tidal volume. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4517", "text": "The average resting CO is 5.6 L/min for a healthy male and 4.9 L/min for a female, decreasing with age and increasing with Body Surface Area (BSA).\nChanges in the CO can be determined by  Heart rate  (HR) and Stroke Volume (SV). The SV in turn, depends on three general factors:  pre-load ,  post-load  and  myocardial contractility . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4518", "text": "In the field of anesthesia, the main reason for CO monitoring during surgery are complications that can arise after the immediate postoperative period (such as hypoxemia, tachycardia, or oliguria) and also, if the therapeutic intervention becomes complex. Despite some clinicians believe that the CO monitor can be introduced only when complications emerge, it is recommended to monitor since before the induction in order to have a baseline.\nFluid administration in the intraoperative period is part of the daily practice in anesthesiology. Several studies have demonstrated that the time of administering fluid therapy can be more important than the volume dispensed; thus the treatment guided by BP is primitive, whereas the functional parameters CO and SV can detect easily and quickly the preload variations\nIn the branch of medical intensive care, the CO and other related parameters may be useful for the differential diagnosis of shock states such as hypovolemic shock, cardiogenic or septic."}
{"_id": "WikiPedia_Cardio$$$corpus_4519", "text": "The rise of volume is the main therapy elected to improve oxygen delivery. However, approximately, only 50% of subjects respond to fluids by increasing SV. The treatment of non-responsive patients can promote deleterious effects in the pulmonary system due to the increase in extravascular fluid. Hence it is important to have a tool to determine this condition.\nIt is called SVV to the physiological variations, due to changes in intra-thoracic pressure of spontaneous breathing, which diminish the arterial pulse pressure during inspiration and increase it during inspiration; however if the SVV decreases too much, it can be termed paradoxical pulse and can be related to different pathologies such EPOC or pericarditis.\nIn mechanically ventilated patients, the same process takes place in reverse, due to the positive pressure. Therefore, the normal values of SVV depend on the ventilation mode, and it can be calculated through the SV with the formula:  \n \n \n \n S \n V \n V \n = \n ( \n S \n \n V \n \n m \n a \n x \n \n \n \u2212 \n S \n \n V \n \n m \n i \n n \n \n \n ) \n \n / \n \n S \n \n V \n \n m \n e \n a \n n \n \n \n \n \n {\\displaystyle SVV=(SV_{max}-SV_{min})/SV_{mean}} \n \n , by a respiratory cycle or other period of time.\nDuring mechanical ventilation the goal is to maintain SVV between 10 and 15%, higher values along with a low SV may indicate the need for volume resuscitation.  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4520", "text": "SVV may be fairly sensitive and specific used as a dynamic indicator of the volume status to answer the question: \u201cIs your patient fluid responsive?\u201d, compared to the conventional parameters. However, using the SVV should not be recommended to interpret the situation of patients with arrhythmias or vasodilator therapy. Also, to avoid natural variations, the patients must be under mechanical ventilation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4521", "text": "A critical point for fluid management in some medical specialties is to adjust the intravascular volume replacement. An incorrect practice can seriously affect the organ function and hence the outcome. Guiding fluid management using standard physiologic variables such as BP and HR, because of their regulated nature, is usually insensitive to changes in intravascular volume and may be misleading for example occulting a hypo-perfusion state. Therefore, optimizing the cardiac preload with fluid administration guided by BP is not reliable. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4522", "text": "With the formula to achieve objectives, called Goal-Directed Therapy (GDT), Rivers (2001) demonstrated how to reduce mortality in patients with severe sepsis and septic shock through the optimization of different hemodynamic variables for a dynamic and individualized view, instead of maintaining only an adequate Arterial Pressure (AP). Later publications support that the intraoperative GDT, used to maintain adequate systemic oxygenation, can safeguard organs especially sensible from perioperative hypo-perfusion. High-risk patients or even less pernicious patients to major surgery could profit from GDT by reducing the incidence of postoperative complications, thus, improving and accelerating the outcome.  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4523", "text": "The CO measurement in cardiology provides rewarding diagnostic and prognostic information for the management of patients with left- and right-sided cardiac dysfunction. Pulmonary Arterial Hypertension (PAH) may diminish the CO and promote right-sided heart failure, which untreated could be fatal. A simultaneous measurement of the preload also enables to assay the blood flow levels to discard states of hypovolemia or hypervolemia. [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4524", "text": "For the fluid responsiveness evaluation, a small amount of solution can be previously administered as a tester, though this method is not recommended because it is irreversible. Another option is the passive leg raising test, which consists of inducing a fast and transient hemodynamic challenge without fluid infusion. By modifying the patient's position, a volume of venous blood from the lower body toward the right heart it is transferred, simulating an infusion of approximately 300\u00a0ml. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4525", "text": "An increase in the CO (of = 10%) and AP within the next 60\u201390 seconds after leg elevation indicates a positive result, suggesting that the patient is fluid responsive and might benefit from additional fluid. By contrast if the test is negative, the patient should not be treated as it would be harmful. The fluid overload can raise extravascular water causing deleterious side effects in lungs. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4526", "text": "The basic mechanisms for the hemodynamic regulation are: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4527", "text": "The explanation why the heart is capable of adapting to growing volumes of blood flow is called 'Frank-Starling's mechanism', which says that the more distended is the muscle during the filling, the more strength of contraction and quantity of blood pumped by the left ventricle to the aorta. When the heart reaches a physiological limitation, then blood pumping cannot increase, although the venous return is further increased. The SVV contributes to knowing the state of euvolemia in ventilated patients and designates the point on the Frank-Starling curve where the patient is. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4528", "text": "In addition to cardiac function, the qCO also evaluates indirectly other related fields as is the  parasympathetic nervous system  (PNS), through the evaluation of the R-R intervals and Heart Rate Variability (HRV or beat-to-beat variation). Since 1960 the HRV has been analyzed. Nowadays, it has become a widely used tool for study the ANS modulation in clinical areas such as cardiology. Even though, its utility is not well known yet. The interest lies in its profound relationship with breathing, ANS, and cardiac autonomic regulation.  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4529", "text": "The most relevant and validated capacity is to prognosticate the coronary heart disease patients, accordingly, a reduced HRV is related to a high risk of mortality after myocardial infarction. Another important point is the fact that Inflammation is stimulated by the effect of the parasympathetic nervous system and inhibited by the sympathetic, thereby, could also be measured through the R-R intervals to guide the physician. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4530", "text": "Several reports maintain that the HRV analysis is a highly accurate indicator of the autonomic dysfunction in alcoholic and diabetic subjects. Also, it is growing interest in applying the HRV to evaluate a neurologic function, and the best results have been found out in psychiatric patients. Regarding the anesthesia and critical care fields, the ANS dysfunction should be considered because it is related to high morbidity and mortality in patients undergoing surgery under the general anesthesia effect. Naturally, events as the tracheal intubation and inhalation agents can produce quick variations in ANS. Also, should be regarded in critical patients who may show a worse outcome when it is added to certain illnesses such as sepsis [24,25]. [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4531", "text": "The HRV depends on the age, sex, and also other physiological variations such as hormonal components, genetics, exercise, environmental factors, thermoregulation, etc. A controlled recording could explain variations in ANS due to physiology, pharmacology or pathology [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4532", "text": "There exist several systems for quantifying the HRV, nevertheless, none of them have shown better result than others. [ 27 ]  The most widely used methods for the HRV analysis can be grouped under time-domain and frequency-domain, the qCO offers the following values:"}
{"_id": "WikiPedia_Cardio$$$corpus_4533", "text": "The  Relative Atrial Index (RAI)  is a numeric parameter used to assess for  cardiac shunt  defects.  It is calculated from the  standard transthoracic Doppler  echocardiogram  measurements of the right atrial area divided by the left atrial area.  RAI = right atrial area / left atrial area. [ 1 ]  These measurements are made from the apical four chamber view. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4534", "text": "Large validation studies [ 2 ]  in patients with known atrial septal defects showed that the RAI > 1.0 in the majority of cases. This is in contrast to matched and population controls, where the RAI was significantly below 1.0.  This simple numeric parameter has found a role in the diagnostic work-up for possible shunt defects on standard tranthorcaic  echocardiograms . The RAI rapidly normalizes within 24 hours of percutaneous closure [ 3 ]  of atrial septal defects. [ 4 ]  Secondary validation studies have confirmed the data in discrete patient populations. [ 5 ]   This parameter has been shown to predict long-term survival after acute pulmonary embolism. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4535", "text": "The RAI was conceptualized in response to observed clinical inadequacies of standard transthoracic echocardiography in some shunt conditions. The same author [ 7 ]  had developed several Doppler echocardiographic  numeric parameters  over the last two decades to assess cardiac diastolic function. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4536", "text": "Remote ischemic conditioning  (RIC) is an experimental medical procedure that aims to reduce the severity of  ischaemic injury  to an organ such as the heart or the brain, most commonly in the situation of a  heart attack  or a  stroke , or during procedures such as heart surgery when the heart may temporary suffer ischaemia during the operation, by triggering the body's natural protection against tissue injury. [ 1 ] [ 2 ]  Although noted to have some benefits in experimental models in animals, this is still an experimental procedure in humans and initial evidence from small studies have not been replicated in larger clinical trials. Successive clinical trials have failed to identify evidence supporting a protective role in humans. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4537", "text": "The procedure involves repeated, temporary cessation of blood flow to a limb to create  ischemia  (lack of  oxygen  and  glucose ) in the tissue. This \"conditioning\" activates the body's natural protective physiology against  reperfusion injury  and the tissue damage caused by low oxygen levels [ 4 ] \u2014a protection present in many mammals. [ 5 ]  RIC essentially mimics the cardio-protective effects of exercise; [ 6 ]  in fact, exercise can be considered a form of RIC in which the stimulus is distant from the organ being protected. RIC has been termed \"exercise in a device\", especially suited for patients who are unable or unwilling to work out. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4538", "text": "The phenomenon of  ischemic preconditioning  (IPC) was discovered in 1986 by C. E. Murry and colleagues, [ 8 ]  who observed that repeated, temporary cross-clamping of the  left anterior descending artery  (LAD) in  dogs  protected the LAD territory of the heart against a subsequent prolonged ischemic event, reducing  infarct  size by 75%. This was thought to be a local effect and was termed local ischemic preconditioning. The phenomenon was confirmed by other researchers in dogs,  pigs ,  mice , and  rats . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4539", "text": "In 1993, Karin Przyklenk and colleagues began using the term \"remote\" when they observed that cross-clamping on the right side of the heart ( right circumflex artery ) protected the left side of the heart (LAD territory) from ischemia: that is, the protective trigger was remote from the observed effect. [ 9 ]  Other researchers confirmed this remote effect and found that performing the preconditioning protocol on  kidney  or  gastrointestinal  tissue also provided protection to the heart. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4540", "text": "In 2002, Raj Kharbanda and Andrew Redington, working at the  Hospital for Sick Children  in  Toronto , showed that non-invasively stopping and starting blood flow in the arm provided the same protection as invasive preconditioning of the heart. [ 11 ]  This adaptation of the RIC protocol significantly improved its safety and applicability, and resulted in a surge of clinical interest in the technique. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4541", "text": "More than 10,000 patients worldwide have completed clinical trials involving RIC, and another 20,000 are enrolled in ongoing trials. [ citation needed ]  The first human clinical trial of RIC was conducted by Dr. Redington in pediatric patients undergoing  heart surgery  at the Hospital for Sick Children. [ 12 ]  The patients treated with RIC prior to surgery exhibited less heart damage, as measured by the biomarker  troponin , as well as less need for supportive drugs. This trial was followed by others measuring the effects of RIC on rates and outcomes of  heart attacks ,  heart failure ,  stroke , and cardiothoracic intervention. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4542", "text": "In multiple  randomized controlled trials , [ which? ]  remote ischemic conditioning reduced infarct size in  ST-elevation  myocardial infarction (STEMI) patients when used in the ambulance [ 14 ]  or  emergency department [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ]  as an adjunct therapy to primary  percutaneous coronary intervention  (PCI), or when used with  thrombolytic drugs . [ 20 ]  In seven trials comprising 2,372 STEMI patients, infarct size\u2014a measure of damage to the heart\u2014was reduced by 17\u201330% on average, and the reduction was greatest (~60%) in the largest infarcts. Further analysis of a Danish study (CONDI-1), in which patients were treated in the ambulance, [ 21 ]  showed that those who received RIC did not show a decline in myocardial salvage index (a measure of a healthy heart) when they experienced a delay in treatment, while the  control group  experienced a significant decline in salvage index. [ 22 ]  The RIC treatment therefore resulted, effectively, in an extension of the \" golden hour \", the period in which medical treatment for heart attacks is most effective. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4543", "text": "Infarct size is a predictor of future cardiovascular events as well as mortality, [ 23 ]  and researchers doing long-term follow-up on STEMI patients treated with RIC found that the reduction in heart damage at the time of the heart attack resulted in clinical improvement four years later: MACCE ( m ajor  a dverse  c ardiovascular and  c erebrovascular  e vent) rates were reduced by 47% (13.5% vs. 25.6%, p=0.018). [ 24 ]  This improvement resulted in mean cumulative cardiovascular medical care costs that were \u20ac2,763 lower in the RIC-treated group than in the control group (\u20ac12,065 vs. \u20ac14,828) [ 25 ] \u2014savings of approximately 20%."}
{"_id": "WikiPedia_Cardio$$$corpus_4544", "text": "There are currently two large randomized controlled trials of RIC treatment in STEMI patients ongoing in Europe, [ 26 ] [ 27 ]  both of which will examine the effects of RIC treatment on coronary death and hospitalization for heart failure after one year. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4545", "text": "Remote ischemic conditioning significantly reduced heart damage (as measured by troponin elevations) in four randomized controlled trials involving 816 elective (non-emergency) PCI patients. [ 28 ] [ 29 ] [ 30 ] [ 31 ]  The myocardial damage and troponin elevations seen in elective PCI patients are less than that in emergency STEMI patient, because there is less acute reperfusion injury in elective PCI, and damage instead results from distal embolization and side-branch occlusion. [ 32 ]  Nevertheless, myocardial damage during elective PCI remains a significant predictor of morbidity and mortality, as patients exhibiting any increase in troponin are at a significantly increased risk of future cardiovascular events. [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4546", "text": "Researchers at  Papworth Hospital  in  Cambridge  conducted the first large study of RIC in elective PCI patients (the CRISP study) [ 28 ]  and found that patients treated with RIC prior to  stenting  showed a 62% reduction in troponin levels, less chest discomfort, and reduced six-month hospitalization rates. Long-term follow-up of the CRISP [ 34 ]  study showed that this single RIC treatment resulted in a 35% reduction in six-year MACCE rates. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4547", "text": "RIC has been shown to reduce  Contrast-induced nephropathy  (CIN) and contrast-induced  acute kidney injury  (CI-AKI), two serious complications that can occur when patients are given  contrast media  during imaging or invasive procedures such as angioplasty or  percutaneous aortic valve replacement . The incidence of CIN is 13% in an unselected population and can be as much as 57% in patients with poor kidney function and congestive heart failure. [ 36 ]  The development of CIN after percutaneous coronary intervention is independently associated with an increased risk of short- and long-term ischemic and hemorrhagic events. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4548", "text": "RIC provided a statistically significant benefit in five randomized clinical trials comprising 480 patients. The first report was in an observational study of patients in the United States, [ 38 ]  and the first randomized clinical trial to show a benefit in patients at extremely high risk of injury (those with Stage 3 or 4 kidney disease,  diabetes , or heart failure) was done in Germany. [ 39 ]  The German study showed a reduced incidence of CIN (a 70% reduction, from 40% to 12%, p=0.002), with no patients in the treated arm needing in-hospital  dialysis  (compared with 14% in the control group), and reduced six-week readmission rates (a 60% reduction, from 36% to 14%). Similar protection was seen in cancer patients undergoing contrast-enhanced  computed tomography  (CECT): Researchers found a 35% reduction in CIN across the population, [ 40 ]  and the patients at highest risk benefited the most, with a 60% reduction."}
{"_id": "WikiPedia_Cardio$$$corpus_4549", "text": "These results, confirmed in subsequent clinical trials involving cardiac patients, [ 41 ] [ 18 ] [ 42 ]  show that RIC can protect the kidneys as well as the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_4550", "text": "Yetgin and colleagues conducted a systematic review and analysis of RIC in cardiac surgery, [ 43 ]  examining thirteen trials involving 891 patients, and found that RIC treatment reduced troponin levels by 21% to 49%. In addition, they concluded that trials in which the primary measure was a validated biomarker (e.g., 72-hour cardiac troponin  AUC ) [ 44 ]  showed a benefit from RIC treatment, while trials in which a non-validated biomarker (e.g., 24-hour troponin AUC) was the primary measure did not show a benefit. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4551", "text": "In the first prospectively designed trial to examine the effect of RIC on clinical outcomes in  coronary artery bypass grafting  (CABG), Thielmann and colleagues showed that RIC treatment reduced troponin levels and improved long-term morbidity and mortality. [ 45 ]  However, while patients who received the anesthetic  isoflurane  benefited from the treatment, the anesthetic  propofol  blocked the effects of RIC. [ 46 ]  Investigations in Dr. Gerd Heusch's lab showed that propofol abolishes the  phosphorylation  of  STAT5 , [ 47 ]  a key survival molecule that is activated by RIC. Two other trials in CABG surgery (ERICCA [ 48 ]  and RIP-HEART [ 49 ] ) reported neutral results for the clinical benefit of RIC, but both of these trials used propofol as the initiating anesthetic. In a viewpoint letter that followed the publication of the ERICCA and RIP-HEART trials, Heusch and Dr. Bernard Gersh wrote that the use of propofol rather than  volatile anesthesia  appeared to be a common denominator in all studies that failed to find protection with RIC. [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4552", "text": "A 2015 trial in high-risk CABG patients showed a reduced incidence of surgical acute kidney injury in RIC-treated patients (37.5% vs. 52.5%, p=0.02), a reduced need for dialysis, and shorter stays in the  intensive care unit . [ 51 ]  This study did not use propofol, and a three-month follow-up found that RIC treatment improved clinical outcomes. [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4553", "text": "Researchers are working to expand the clinical applications of RIC beyond cardiovascular indications. Because RIC modifies the  expression of genes  involved in  inflammation ,  coagulation , and  complement pathways , [ 53 ]  researchers believe repeated treatments (chronic conditioning) could aid recovery or prevent disease progression in a variety of chronic conditions. The areas of research that are most advanced are in heart failure and stroke recovery. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4554", "text": "Despite advances in the treatment of heart attacks, survivors are at a significant risk of heart failure and death within five years because of adverse remodeling processes in the heart. [ 54 ] [ 55 ]  The acute inflammatory process that occurs soon after a heart attack is necessary for healing and scar formation, [ 56 ]  but can be harmful if it continues for an extended period of time. Continued  oxidative stress  results in inflammation, death of heart cells,  fibrosis of the ventricles , and  hypertrophy  (enlargement) of the heart, [ 57 ]  progressing to heart failure. Studies show that repeated daily RIC treatments lead to significant  downregulation  of  neutrophil  activation and proinflammatory responses in humans, [ 58 ]  and could reduce post-heart-attack inflammation."}
{"_id": "WikiPedia_Cardio$$$corpus_4555", "text": "In rodent models of post-heart-attack heart failure, daily RIC treatment for 28 days resulted in reduced markers of inflammation (including  TGF-b ), improved ventricular function, and improved survival over 100 days, in a dose-dependent manner. [ 59 ]  This study provided the scientific rationale for the CRIC-RCT clinical trial ( NCT01817114 ). There are two other ongoing randomized controlled trials of chronic conditioning in heart-failure patients:  NCT01664611  and  NCT02248441 ."}
{"_id": "WikiPedia_Cardio$$$corpus_4556", "text": "In addition to its efficacy in cardiological settings, RIC is thought to remotely recruit neuroprotective pathways, and its safety, feasibility, and low cost give it high potential in a wide variety of neurological conditions. [ 7 ]  Like the heart, the brain has self-protective abilities and can adapt to stress and injury (e.g.,  hypoxia  or ischemia) by activating cellular protective pathways. [ 60 ]  RIC not only confers protection against ischemia-reperfusion injury, but also increases cerebral blood flow, which may contribute to the neuroprotective effect. [ 61 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4557", "text": "The first randomized trial of RIC in acute stroke patients was done by Hougaard and colleagues in Denmark. [ 62 ]  Compared with standard treatment, RIC increased tissue survival after one month and reduced the risk of infarction in high-risk tissue. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4558", "text": "Two randomized trials of RIC have also been conducted in patients with intracranial atherosclerotic stenosis (ICAS), a significant risk factor for stroke with a high risk of recurrence. The first\u2014which included 68 Chinese patients under the age of 80 who had intracranial arterial stenosis of 50\u201399% and had experienced a stroke or  transient ischemic attack  (TIA) within the previous 30 days [ 63 ] \u2014evaluated the effects of 300 days of brief, repetitive, bilateral arm ischemic conditioning on stroke recurrence. It found that the conditioning reduced the incidence of recurrent stroke from 23.3% to 5% at 90 days, and from 26.7% to 7.9% at 300 days; it also improved the rate of recovery (measured with the  modified Rankin scale ) and cerebral  perfusion . The second trial examined the effect of 180 days of RIC on symptomatic ICAS in Chinese people aged 80\u201395 years, as invasive stenting is not always suitable for elderly patients, and less-invasive methods are needed. RIC safely prevented stroke and TIA recurrence and reduced inflammation in these patients. [ 64 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4559", "text": "Delayed  cerebral infarction  after  subarachnoid hemorrhage  is a major cause of morbidity. Two Phase I clinical trials have shown that RIC after subarachnoid hemorrhage is feasible, safe, and well tolerated, and can prevent delayed neurological deficits. [ 65 ] [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4560", "text": "Traumatic brain injury  (TBI) shares many pathophysiological pathways with acute stroke, and ischemic preconditioning increases the brain's resistance to injury. [ 67 ]  Animal models of stroke (both open-skull and closed-skull models) [ 68 ]  show that RIC improves cerebral blood flow; reduces ischemic injury,  edema , and cell death; and improves functional outcomes. A small randomized clinical trial in severe TBI also showed that patients who received RIC had lower levels of brain injury biomarkers. [ 69 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4561", "text": "Reduced cerebral blood flow is an early finding in  vascular cognitive impairment  (VCI). Cardiovascular risk factor control is currently the only management option for VCI, but observational studies suggest that exercise slows down cognitive decline. [ 70 ]  In a mouse model that reproduced the damage seen in patients with VCI ( white matter  damage, cerebral hypoperfusion, inflammation,  blood\u2013brain barrier  damage, and cognitive deficits), daily RIC for two weeks increased cerebral blood flow, and this increase persisted for one week after cessation of conditioning. Moreover, mice that underwent RIC had less inflammation, less white and  gray matter  damage, less  \u03b2\u2011amyloid  deposition, and improved cognition. [ 71 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4562", "text": "In  laparoscopic procedures , CO2  pneumoperitoneum  is essential for adequate visualization but can lead to elevated intra-abdominal pressure, potentially causing splanchnic hypoperfusion and capillary microcirculation impairment. This scenario predisposes to  ischemia-reperfusion injury , characterized by an upsurge in  reactive oxygen species  (ROS), culminating in a spectrum of peritoneal pathologies, including mesothelial cell damage, inflammatory cascades, and adhesion formation."}
{"_id": "WikiPedia_Cardio$$$corpus_4563", "text": "Ischemic preconditioning (IPC), entailing transient ischemic episodes prior to prolonged ischemia, has emerged as a prophylactic strategy to ameliorate such iatrogenic oxidative insults. In vitro and in vivo studies elucidate that IPC augments cellular anti-oxidative defenses and modulates inflammatory mediators, potentially attenuating  peritoneal  injury sequelae. [ 72 ] [ 73 ]  Despite the theoretical mechanistic plausibility and encouraging preclinical data, the translatability of these findings to human laparoscopy remains tentative. Human trials in laparoscopic contexts have shown IPC's potential in modulating biomarkers associated with oxidative stress and alleviating clinical symptoms. Notably, a study involving remote ischemic conditioning applied to the upper arm exhibited enhanced skin microcirculation in the lower extremities, suggesting systemic microcirculatory benefits. [ 74 ]  Furthermore, in a trial involving patients undergoing laparoscopic surgery, those subjected to IPC demonstrated notable improvements in systemic antioxidant capacity, as evidenced by elevated  glutathione  levels. Additionally, these patients reported a significant reduction in pain intensity, highlighting IPC's potential in enhancing patient comfort and recovery. [ 75 ]  These findings, while preliminary, underscore IPC's promise in laparoscopic surgery, suggesting its role in reducing oxidative stress and improving postoperative outcomes."}
{"_id": "WikiPedia_Cardio$$$corpus_4564", "text": "The RIC stimulus can be applied to different tissues in the body. Either the upper limb (arm) or the lower limb (leg) may be used; however, because it is easier and more comfortable, most clinical trials use the upper limb. [ 76 ]  Researchers investigating the optimal dosing for the RIC stimulus have concluded that the upper limb is superior to the lower limb, [ 76 ]  that RIC on one limb generates an equivalent response to RIC on two limbs, [ 77 ]  and that maximal benefit occurs at 4\u20136 cycles. [ 77 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4565", "text": "The non-invasiveness and ease of application of RIC have allowed it to be studied in more situations than the original, invasive ischemic preconditioning, which was only realistically applicable in elective surgery. Studies have examined the effects of RIC applied at different times:  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4566", "text": "The term \"post-conditioning\" is used to describe short, intermittent inflations of an intra-coronary balloon at the time of reperfusion, and does not refer to RIC on a limb. Delayed post-conditioning is synonymous with chronic conditioning. [ 78 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4567", "text": "Remote ischemic conditioning on the limb is mostly done by healthcare professionals, using a manual  blood-pressure cuff  and a stopwatch. The standard RIC protocol, used in the majority of clinical trials, consists of four cycles of five minutes of inflation at 200mmHg, followed by five minutes of deflation. This is the original conditioning protocol described by Murry et al. [ 79 ]  based on examinations of energetic depletion of the cell."}
{"_id": "WikiPedia_Cardio$$$corpus_4568", "text": "One automated device is approved in Europe and Canada for the delivery of remote ischemic conditioning: the autoRIC Device, [ 80 ]  which delivers four cycles of five minutes of inflation at 200mm Hg followed by five minutes of deflation to the upper limb. In a comparative study of this device and manual conditioning, the autoRIC Device was shown to be much easier to use. [ 81 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4569", "text": "Reperfusion therapy  is a medical treatment to restore blood flow, either through or around, blocked arteries, typically after a heart attack ( myocardial infarction  (MI)). Reperfusion therapy includes  drugs  and  surgery . The drugs are  thrombolytics  and  fibrinolytics  used in a process called  thrombolysis . Surgeries performed may be  minimally-invasive   endovascular procedures  such as a  percutaneous coronary intervention  (PCI), which involves  coronary angioplasty . The angioplasty uses the insertion of a  balloon  and/or  stents  to open up the artery. [ 1 ]  Other surgeries performed are the more invasive  bypass surgeries  that graft arteries around blockages."}
{"_id": "WikiPedia_Cardio$$$corpus_4570", "text": "If an MI is presented with  ECG  evidence of an  ST elevation  known as  STEMI , or if a  bundle branch block  is similarly presented, then reperfusion therapy is necessary. In the absence of an ST elevation, a non-ST elevation MI, known as an  NSTEMI , or an  unstable angina  may be presumed (both of these are indistinguishable on initial evaluation of symptoms). ST elevations indicate a completely blocked artery needing immediate reperfusion. In NSTEMI the blood flow is present but limited by  stenosis . In NSTEMI, thrombolytics must be avoided as there is no clear benefit of their use. [ 2 ]  If the condition stays stable a  cardiac stress test  may be offered, and if needed subsequent  revascularization  will be carried out to restore a normal blood flow. If the blood flow becomes unstable an urgent angioplasty may be required. In these unstable cases the use of thrombolytics is contraindicated. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4571", "text": "At least 10% of treated cases of STEMI do not develop  necrosis  of the  heart muscle . A successful restoration of blood flow is known as aborting the heart attack. About 25% of STEMIs can be aborted if treated within the hour of symptoms onset. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4572", "text": "Thrombolytic therapy  is indicated for the treatment of STEMI \u2013 if it can begin within 12 hours of the onset of symptoms, and the person is eligible based on exclusion criteria, and a  coronary angioplasty  is not immediately available. [ 5 ]  Thrombolysis is most effective in the first 2 hours. After 12 hours, the risk of  intracranial bleeding  associated with thrombolytic therapy outweighs any benefit. [ 3 ] [ 6 ] [ 7 ]  Because irreversible injury occurs within 2\u20134 hours of the infarction, there is a limited window of time available for reperfusion to work. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4573", "text": "Thrombolytic drugs are contraindicated for the treatment of unstable angina and NSTEMI [ 3 ] [ 8 ]  and for the treatment of individuals with evidence of  cardiogenic shock . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4574", "text": "Although no perfect thrombolytic agent exists, ideally it would lead to rapid reperfusion, have a high sustained patency rate, be specific for recent thrombi, be easily and rapidly administered, create a low risk for  intracerebral bleeding  and systemic bleeding, have no  antigenicity , adverse  hemodynamic effects , or clinically significant  drug interactions , and be  cost effective . [ 10 ]  Currently available thrombolytic agents include  streptokinase ,  urokinase , and  alteplase  (recombinant  tissue plasminogen activator , rtPA).  More recently, thrombolytic agents similar in structure to rtPA such as  reteplase  and  tenecteplase  have been used. These newer agents boast efficacy at least as well as rtPA with significantly easier administration. The thrombolytic agent used in a particular individual is based on institution preference and the age of the patient."}
{"_id": "WikiPedia_Cardio$$$corpus_4575", "text": "Depending on the thrombolytic agent being used, additional  anticoagulation  with  heparin  or  low molecular weight heparin  may be of benefit. [ 11 ] [ 12 ]  With tPa and related agents (reteplase and tenecteplase), heparin is needed to keep the coronary artery open. Because of the anticoagulant effect of fibrinogen depletion with streptokinase [ 13 ]  and urokinase [ 14 ] [ 15 ] [ 16 ]  treatment, it is less necessary there. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4576", "text": "Thrombolytic therapy to abort a myocardial infarction is not always effective. The degree of effectiveness of a thrombolytic agent is dependent on the time since the myocardial infarction began, with the best results occurring if the thrombolytic is used within two hours of the onset of symptoms. [ 17 ] [ 18 ]  Failure rates of thrombolytics can be as high as 50%. [ 19 ]  In cases of failure of the thrombolytic agent to open the infarct-related coronary artery, the person is then either treated conservatively with anticoagulants and allowed to \"complete the infarction\" or  percutaneous coronary intervention  (and coronary angioplasty) is then performed. [ 20 ]   Percutaneous coronary intervention in this setting is known as \"rescue PCI\" or \"salvage PCI\". Complications, particularly bleeding, are significantly higher with rescue PCI than with primary PCI due to the action of the thrombolytic. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4577", "text": "Intracranial bleeding (ICB) and subsequent  stroke  is a serious  side effect  of thrombolytic use. The  risk factors  for developing intracranial bleeding include a previous episode of intracranial bleed, advanced age of the individual, and the thrombolytic regimen that is being used. In general, the risk of ICB due to thrombolytics is between 0.5 and 1 percent. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4578", "text": "The benefit of prompt,  primary angioplasty over thrombolytic therapy for acute STEMI is now well established. [ 21 ] [ 22 ] [ 23 ]  When performed rapidly, an angioplasty restores flow in the blocked artery in more than 95% of patients compared with the reperfusion rate of about 65% achieved by thrombolysis. [ 21 ]  Logistic and economic obstacles seem to hinder a more widespread application of angioplasty, [ 24 ]  although the feasibility of providing regionalized angioplasty for STEMI is currently being explored in the United States. [ 25 ]  The use of a coronary angioplasty to abort a myocardial infarction is preceded by a primary  percutaneous coronary intervention . The goal of a prompt angioplasty is to open the artery as soon as possible, and preferably within 90 minutes of the patient presenting to the emergency room. This time is referred to as the  door-to-balloon  time. Few hospitals can provide an angioplasty within the 90 minute interval, [ 26 ]  which prompted the  American College of Cardiology  (ACC) to launch a national Door to Balloon (D2B) Initiative in November 2006. Over 800 hospitals have joined the D2B Alliance as of March 16, 2007. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4579", "text": "One particularly successful implementation of a primary PCI protocol is in the  Calgary Health Region  under the auspices of the  Libin Cardiovascular Institute of Alberta .  Under this model,  EMS  teams responding to an emergency can transmit the ECG directly to a digital archiving system that allows emergency room staff to immediately confirm the diagnosis. This in turn allows for redirection of the EMS teams to those facilities that are ready to conduct time-critical angioplasty. This protocol has resulted in a median time to treatment of 62 minutes. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4580", "text": "The current guidelines in the United States restrict angioplasties to hospitals with available emergency bypass surgery as a backup, [ 5 ]  but this is not the case in other parts of the world. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4581", "text": "A PCI involves performing a coronary  angiogram  to determine the location of the infarcting vessel, followed by  balloon angioplasty  (and frequently deployment of an intracoronary stent) of the  stenosed  arterial segment.  In some settings, an extraction catheter may be used to attempt to aspirate (remove) the thrombus prior to balloon angioplasty.  While the use of intracoronary  stents  do not improve the short term outcomes in primary PCI, the use of stents is widespread because of the decreased rates of procedures to treat  restenosis  compared to balloon angioplasty. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4582", "text": "Adjuvant therapy  during an angioplasty includes intravenous  heparin ,  aspirin , and  clopidogrel .   Glycoprotein IIb/IIIa inhibitors  are often used in the setting of primary angioplasty to reduce the risk of ischemic complications during the procedure. [ 31 ] [ 32 ]   Due to the number of antiplatelet agents and anticoagulants used during primary angioplasty, the risk of bleeding associated with the procedure is higher than during an elective procedure. [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4583", "text": "Emergency bypass surgery for the treatment of an acute myocardial infarction (MI) is less common than PCI or thrombolysis. From 1995 to 2004, the percentage of people with  cardiogenic shock  treated with primary PCI rose from 27.4% to 54.4%, while the increase in  coronary artery bypass graft surgery  (CABG) was only from 2.1% to 3.2%. [ 34 ]   Emergency CABG is usually undertaken to simultaneously treat a mechanical complication, such as a ruptured papillary muscle, or a ventricular septal defect, with ensuing cardiogenic shock. [ 35 ]  In uncomplicated MI, the  mortality rate  can be high when the surgery is performed immediately following the infarction. [ 36 ]  If this option is entertained, the patient should be stabilized prior to surgery, with supportive interventions such as the use of an  intra-aortic balloon pump . [ 37 ]  In patients developing cardiogenic shock after a myocardial infarction, both PCI and CABG are satisfactory treatment options, with similar survival rates. [ 38 ] [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4584", "text": "Coronary artery bypass surgery involves an artery or vein from the patient being implanted to bypass  narrowings  or occlusions in the coronary arteries. Several arteries and veins can be used, however  internal mammary artery  grafts have demonstrated significantly better long-term patency rates than  great saphenous vein  grafts. [ 40 ]  In patients with two or more coronary arteries affected, bypass surgery is associated with higher long-term  survival rates  compared to percutaneous interventions. [ 41 ]  In patients with single vessel disease, surgery is comparably safe and effective, and may be a treatment option in selected cases. [ 42 ]  Bypass surgery has higher costs initially, but becomes  cost-effective  in the long term. [ 43 ]  A surgical bypass graft is more  invasive  initially but bears less risk of recurrent procedures (but these may be again  minimally invasive ). [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4585", "text": "Accelerated idioventricular rhythm  which looks like slow  ventricular tachycardia  is a sign of a successful reperfusion. [ 44 ]   No treatment of this rhythm is needed as it rarely changes into a more serious rhythm. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4586", "text": "Transcatheter aortic valve replacement  ( TAVR ) is the implantation of the  aortic valve  of the  heart  through the blood vessels without actual removal of the native valve (as opposed to the aortic valve replacement by  open heart surgery , surgical  aortic valve replacement , AVR). The first TAVI was performed on 16 April 2002 by  Alain Cribier , which became a new alternative in the management of high-risk patients with severe aortic stenosis. [ 2 ] [ 3 ]  The implantated valve is delivered via one of several access methods: transfemoral (in the upper leg), transapical (through the wall of the heart), subclavian (beneath the collar bone), direct aortic (through a minimally invasive surgical incision into the aorta), and transcaval (from a temporary hole in the aorta near the navel through a vein in the upper leg), among others."}
{"_id": "WikiPedia_Cardio$$$corpus_4587", "text": "Severe symptomatic  aortic stenosis  carries a poor prognosis. At present, there is no treatment via medication, making the timing of aortic valve replacement the most important decision to make for these patients. [ 4 ]  Until recently,  surgical aortic valve replacement  was the standard treatment for adults with severe symptomatic aortic stenosis. However, the risks associated with surgical aortic valve replacement are increased in elderly patients and those with concomitant severe systolic  heart failure  or  coronary artery disease , as well as in people with comorbidities such as  cerebrovascular  and  peripheral arterial disease ,  chronic kidney disease , and chronic respiratory dysfunction."}
{"_id": "WikiPedia_Cardio$$$corpus_4588", "text": "Patients with symptomatic severe aortic stenosis have a mortality rate of approximately 50% at 2 years without intervention. [ 5 ]  In patients who are deemed too high risk for open heart surgery, TAVI significantly reduces the rates of death and cardiac symptoms. [ 6 ]  Until about 2017 TAVI was not routinely recommended for low-risk patients in favor of aortic valve replacement, however it is increasingly being offered to intermediate risk patients, based on studies finding that it is not inferior to surgical aortic valve replacement. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4589", "text": "Transapical TAVI is reserved for patients for whom other approaches are not feasible: an evidence-based  BMJ Rapid Recommendation  made a strong recommendation against  transapical  TAVI in people who are also candidates for either  transfemoral  TAVI or surgery. [ 8 ]  People who have the option of either transfemoral TAVI or surgical replacement are likely to choose surgery if they are younger than 75 and transfemoral TAVI if they are older than 75. [ 8 ]  The rationale for age-based recommendations is that surgical aortic valve replacements are known to be durable long-term (average of durability of 20 years), so people with longer life expectancy would be at higher risk if TAVI durability is worse than surgery. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4590", "text": "Medtronic 's CoreValve Transcatheter Aortic Valve is constructed of a self-expanding  Nitinol (nickel titanium)  frame and delivered through the  femoral artery . This device received  FDA  approval in January 2014. [ 10 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4591", "text": "Boston Scientific 's Lotus Valve system was awarded  CE approval  in October 2013. It allows the final position to be assessed and evaluated before release and has been designed to minimise regurgitation. [ 12 ]   Boston Scientific  has since retired the device as of January 11, 2021. [ 13 ]  This was primarily due to difficulty regarding the ability to reposition and recapture the valve."}
{"_id": "WikiPedia_Cardio$$$corpus_4592", "text": "St Jude Medical 's Portico Transcatheter aortic valve received European  CE mark  approval in December 2013. The valve is repositionable before release to ensure accurate placement helping to improve patient outcomes. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4593", "text": "Edwards ' Sapien aortic valve is made from  bovine   pericardial tissue  and is implanted via a  catheter -based delivery system. It is approved by the FDA for use in the US. [ 10 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4594", "text": "The devices are implanted without open heart surgery. The valve delivery system is inserted in the body, the valve is positioned and then implanted inside the diseased aortic valve, and then the delivery system is removed. The catheter-based delivery system can be inserted into the body from one of several sites. [ 14 ]  Pre-procedural planning includes aortic valve annulus measurements and possible procedural complication likelihood. The standard for preoperative plans is to perform a multi-detector computed angiotomography (MDCT), which delivers the information required. Magnetic resonance imaging (MRI) and 3D echocardiography is an alternative. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4595", "text": "The transfemoral approach requires the catheter and valve to be inserted via the femoral artery. Similar to coronary artery stenting procedures, this is accessed via a small incision in the groin, through which the delivery system is slowly fed along the artery to the correct position at the aortic valve. A larger incision in the groin may be required in some circumstances. [ 14 ]  The femoral artery (via transfemoral approach) is the traditional access for percutaneous aortic valve implantation. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4596", "text": "The transapical approach sees the catheter and valve inserted through the tip of the heart and into the left ventricle. Under general anesthesia, a small surgical incision is made between the ribs, followed by a small puncture of the heart. The delivery system is then fed slowly to the correct position at the aortic valve. The puncture in the heart is then sutured shut. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4597", "text": "The transaortic approach sees the catheter and valve inserted through the top of the right chest. Under general anesthesia, a small surgical incision is made alongside the right upper breastbone, followed by a small puncture of the aorta. The delivery system is then fed slowly to the correct position at the aortic valve. The hole in the aorta is then sutured shut. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4598", "text": "The transcaval approach has been applied to a smaller number of patients who are not eligible for transfemoral, transapical, or transaortic approaches. In the transcaval approach a tube is inserted via the femoral vein instead of the femoral artery, and a small wire is used to cross from the inferior vena cava into the adjacent abdominal aorta. Once the wire is across, a large tube is used to place the transcatheter heart valve through the femoral vein and inferior vena cava into the aorta and from there the heart. This otherwise resembles the transfemoral approach. Afterwards, the hole in the aorta is closed with a self-collapsing  nitinol  device designed to close holes in the heart. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4599", "text": "In the subclavian approach, an incision is made under the collarbone under general anesthesia, and the delivery system is advanced into the correct position in the aortic valve. The delivery system is then removed and the incision is sutured closed. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4600", "text": "Regular medical checkups and imaging tests are required after TAVI. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4601", "text": "The  Mayo Clinic  says that blood thinners ( anticoagulants ) are prescribed to prevent blood clots after TAVI. Artificial heart valves are susceptible to bacterial infection; most bacteria that cause heart valve infections come from the mouth, so that good dental hygiene and routine dental cleaning are recommended. Antibiotics are prescribed for use before certain dental procedures. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4602", "text": "New or worse post-procedure symptoms that require attention include dizziness or light-headedness, swelling of the ankles, sudden weight gain, extreme fatigue with activity, and signs of infection. Emergency attention is required for chest pain, pressure or tightness, severe, sudden shortness of breath, or fainting. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4603", "text": "When PAVR surgery is performed an important and difficult aspect that affects the patient is the orientation, uniformity and depth at which the valve is inserted. When the valve is not inserted correctly, when there is incomplete sealing between the native heart valve and the stented valve, paravalvular leak (PVL) can occur.  Key properties associated with paravalvular leak are the regurgitation volume, the PVL orifice location (anterior or posterior) and the associated fluid dynamic effects that occur from the interactions between the regurgitated flow and the normal transmitral flow. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4604", "text": "Morisawa  et al. [ 20 ] [ unreliable medical source? ]  carried out  quantitative research  to determine how the PVL flow effected normal transmitral flow based on three different  in-vitro  situations: no PVL, anterior orifice PVL and posterior orifice PVL. The results showed that while the two PVL cases worsened the fluid dynamics of the normal transmitral flow seen without leakage, the posterior orifice PVL was worse, leading to a higher circulation and kinetic energy, requiring the heart to work harder and consume more energy to maintain normal bodily functions."}
{"_id": "WikiPedia_Cardio$$$corpus_4605", "text": "Additionally, the \"Big 5 of TAVI complications\" include paravalvular leakage (PVL), major bleeding or vascular complications, acute kidney injury (AKI), stroke, and conduction abnormalities, such as high-degree AV-block with need for permanent pacemaker implantation must be monitored to ensure successful procedural outcomes such as low mortality and morbidity. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4606", "text": "There is a ~3% risk of  stroke  associated with TAVI due to embolism or altered hemodynamics during or after the procedure. [ 22 ]  Approximately 70% of patients undergoing TAVI show signs of clinically silent  brain infarcts  on  neuroimaging  afterwards. [ 23 ] [ 22 ]  Further, levels of the neuroaxonal damage biomarker  neurofilament light chain  are elevated in  blood plasma  after TAVI. [ 24 ]  Whereas clinical stroke is associated with reduced quality of life and cognitive impairment, the significance of silent brain infarcts and elevated levels of neurofilament light is presently unclear."}
{"_id": "WikiPedia_Cardio$$$corpus_4607", "text": "Within 24 hours post-operation, patients are encouraged to be walking. It is common for patients to have an overnight hospital stay post operatively. Follow-up examinations (Chest X-ray, EKG, and Cardiac US) ensure heart functioning. Incision sites are monitored closely. Pts. are encouraged not to drive for 72 hours post operatively, and to avoid physical activity for up to 10 days. Most patients resume activity within 2 weeks. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4608", "text": "A 2018 study that interviewed nineteen elderly patients six months after a transapical TAVI procedure found that participants felt weak and tired at first after TAVI, some more than before the procedure. Some reported a later \"surprisingly simple rehabilitation\" with rapid recovery, while others had a \"demanding rehabilitation\", with slow recovery, fatigue, and weakness. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4609", "text": "The durability of transcatheter prostheses, in terms of all-cause mortality and the need of re-intervention, was not reliably known as of 2021 [update]  due to the lack of long-term follow-up data. A narrative review published in 2021 reported that a 2015 study involving simulation on first-generation prostheses suggested a TAVI durability limited to 7\u20138 years. Later prostheses have improved durability. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4610", "text": "Bioprosthetic valve disfunction (BVD) has historically been divided into SVD (structural valve deterioration, including irreversible intrinsic changes of the prosthetic valve structure), NSVD (non-structural valve deterioration, including irreversible intra- or para-prosthetic regurgitation, prosthesis malposition, and patient-prosthesis mismatch), valve thrombosis, and endocarditis (which can be potentially reversible). Durability seems to be similar between TAVI and surgical implantation (SAVR), but there is a lack of long-term data, with only computed simulation models available. In many respects TAVI and SAVR are comparable, but TAVI still has a higher rate of NSVD. In elderly patients the prostheses should outlive the patient. The 2021 review suggested that in younger patients (with longer average life expectancy) choosing TAVI might still be premature, due to the increased likelihood of the need for future re-operation with worse prognostic impact. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4611", "text": "The catheter procedure was invented and developed in Aarhus University Hospital Denmark in 1989 by Henning Rud Andersen, [ 28 ]  who performed the first animal implantations that year. [ 29 ]  The first implantation in a human was performed on 16 April 2002 by  Alain Cribier  in Hopital Charles Nicolle, at the  University of Rouen , France. [ 30 ]  Technology experts Stan Rowe and Stan Rabinowitz partnered with physicians Alain Cribier and Martin Leon of  NewYork\u2013Presbyterian  Hospital and others to create the company Percutaneous Valve Technologies (PVT) in 2002. The company was purchased by  Edwards Lifesciences  in 2004; its valve became the Sapien valve. [ 31 ] [ 32 ]  It was the first aortic valve device to receive FDA approval, in November 2011 for use in inoperable patients and in October 2012 for use in patients at high surgical risk. [ 33 ]  The device is effective in improving functioning in patients with severe aortic stenosis. It is now approved in more than 50 countries. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4612", "text": "Internationally famous pop singer  Mick Jagger  had the procedure in March 2019 at NewYork\u2013Presbyterian, [ 34 ]  which was said to have raised public awareness. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4613", "text": "Transcatheter pulmonary valve replacement  ( TPVR ), also known as  percutaneous pulmonary valve implantation  ( PPVI ), is the replacement of the pulmonary valve via catheterization through a vein. It is a significantly less invasive procedure in comparison to open heart surgery and is commonly used to treat conditions such as  pulmonary atresia . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4614", "text": "TPVR can be used to repair  congenital defects  in the  pulmonary valve  or right  ventricular outflow tract  dysfunction, such as  pulmonary atresia ,  Tetralogy of Fallot , or  persistent truncus arteriosus . [ 4 ]  TPVR can also be used to replace dysfunctional  artificial heart valves . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4615", "text": "For those experiencing symptoms, TPVR is indicated when the right ventricular  systolic pressure  is above 60 mmHg and/or when there is moderate to severe  pulmonary regurgitation . [ 4 ]  For those not experiencing any symptoms, TPVR is indicated if there is severe right ventricular outflow tract narrowing and/or severe pulmonary insufficiency, with decreased exercise capacity, progressive right  ventricular dilation , progressive right ventricular dysfunction, progressive  tricuspid valve regurgitation , right ventricular systolic pressure above 80 mmHg, or cardiac  fibrillation . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4616", "text": "For dysfunctional artificial conduits, TPVR immediately resolves pulmonary regurgitation and normalizes the right ventricular outflow tract gradient, and is associated with significant improvements in symptoms and improvements in long-term ventricular function. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4617", "text": "Active infection, central vein occlusion, coronary occlusion, and need for other surgeries such as for  arrhythmia  are contraindications for TPVR. [ 4 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4618", "text": "If coronary compression (which impairs  coronary blood flow ) is observed with  balloon dilation  in the right ventricular outflow tract, TPVR is also contraindicated. [ 4 ]  This test is performed to prevent potentially fatal complications, for which approximately 5% of candidates are at risk. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4619", "text": "TPVR is not recommended for tracts that are less than 16\u00a0mm [ 4 ]  or more than 29\u00a0mm in diameter. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4620", "text": "There is a low incidence of major complications, which is likely due to pre-procedural assessments preventing individuals with unfavourable anatomy from undergoing the procedure. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4621", "text": "The most common complication is fracture of the stent frame. [ 4 ]  This is seen in up to 30% of cases. [ 4 ]  The majority of stent fractures are diagnosed by routine imaging and are not clinically relevant. [ 4 ]  Stent fractures leading to obstruction of the right ventricular outflow tract is the most common reason for repeat intervention and can be treated with valve-in-valve procedures (placing a new valve inside the failed valve). [ 4 ]  More severe fractures may require surgery. [ 4 ]  Risk factors for stent fractures include younger age, smaller tract diameter, and position of the valve directly below the  sternum . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4622", "text": "Tears or ruptures of the right ventricular outflow tract may occur during the procedure, especially if the tract is already heavily calcified. [ 4 ]  This is reported to occur in up to 9% of procedures. [ 4 ]  Most cases are manageable by using a covered stent and do not lead to severe bleeding. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4623", "text": "Infective endocarditis  occurs at a rate of about 1%-3%. [ 1 ]  Most cases do not directly impact the implanted valve, and most cases can be treated with antibiotics. [ 4 ]  However, infective endocarditis can also cause valve explantation or  sepsis , which can lead to death. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4624", "text": "Rare complications that may require urgent surgery include valve migration, valve  embolization ,  pulmonary artery  occlusion, pulmonary artery rupture, or  coronary artery  compression impeding blood flow. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4625", "text": "Death is rare, and is usually attributable to other  comorbidities  rather than from the implantation procedure itself. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4626", "text": "Several tests are performed before the procedure to assess whether the procedure is suitable for the individual and to record their anatomy in preparation for the procedure. [ 4 ] [ 6 ]  Ventricular function and size are assessed with an  echocardiogram . [ 4 ]  The right ventricle and the anatomy of the outflow tract, including any anatomical variations, are also assessed with  cardiac magnetic resonance imaging . [ 4 ] [ 6 ]  The severity of the outflow tract defect or pulmonary regurgitation is assessed with  Doppler ultrasonography . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4627", "text": "TPVR is a  percutaneous procedure , meaning the device is brought into the body through the skin and into a vein. Patients are put under  general anesthesia . [ 4 ]  The heart is typically reached by passing through the  femoral vein ,  jugular vein , or  subclavian vein . [ 4 ]  A balloon dilation test is performed first, to confirm that coronary compression will not occur and the procedure can continue. [ 4 ] [ 6 ]  Stent fractures can be prevented by using pre-stenting, using a bare metal stent before TPVR. [ 5 ]  After the valve is implanted, balloon dilation is used to create the diameter of the valve. [ 6 ]  At the end of the procedure, pressure is applied to the area to encourage  hemostasis  (stop bleeding). [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4628", "text": "Patients undergoing TPVR are typically ambulatory within 6 hours of finishing the procedure and can be discharged home within 24 hours. [ 6 ]  As  cardiopulmonary bypass  is not required, a stay in the intensive care unit and an extended hospital stay are generally not needed. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4629", "text": "TPVR was developed as a less invasive alternative to other treatment options requiring  open heart surgery , such as patch augmentation, replacing the native valve with an  artificial heart valve , or using a  valved conduit . [ 4 ]  These surgeries typically require repeat surgeries to repair issues including pulmonary regurgitation,  valve narrowing , kinking of the conduit, or calcification, leading to significant morbidity. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4630", "text": "The first TPVR was performed in 2000. [ 4 ] [ 7 ]  This device was further developed into the Melody transcatheter pulmonary valve by  Medtronic . [ 4 ] [ 6 ]  The Melody device received approval from Health Canada in 2006 and from the US Food and Drug Administration (FDA) in 2010. [ 6 ]  A similar device, the Edwards Sapien pulmonic transcatheter heart valve, produced by  Edwards Lifesciences , first received FDA approval in 2015. [ 4 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4631", "text": "The comparatively lower risks of TPVR and reduced need for reintervention compared to traditional surgical treatments has led to a paradigm shift favouring earlier treatment for right ventricular outflow tract defects, which were previously postponed due to the risks of traditional surgery. [ 1 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4632", "text": "Transmyocardial laser revascularization  ( TMR ) is a procedure used to treat inoperable  heart disease [ 1 ]  in people with persistent  angina  that is not relieved by any other  revascularization  method."}
{"_id": "WikiPedia_Cardio$$$corpus_4633", "text": "Most people with  coronary artery disease  are treated with  angioplasty  and  stenting  or  coronary bypass surgery  and medications to improve blood flow to the heart muscle. The objective of each of these approaches is to increase  blood flow  through the  coronary arteries  to the heart. When these treatment options are exhausted, the patient is left with no viable surgical alternative other than, in limited cases,  heart transplantation .  Without a viable surgical alternative, the patient is generally managed with drug therapy, often with significant lifestyle limitations."}
{"_id": "WikiPedia_Cardio$$$corpus_4634", "text": "TMR, or transmyocardial laser revascularization, is a newer treatment aimed at improving blood flow to areas of the heart that were not treated by angioplasty or surgery."}
{"_id": "WikiPedia_Cardio$$$corpus_4635", "text": "TMR is a surgical procedure. It is performed through a small incision in the left side of the chest. Frequently, it is performed along with coronary bypass surgery, occasionally alone."}
{"_id": "WikiPedia_Cardio$$$corpus_4636", "text": "When performing TMR a qualified cardiac surgeon delivers a precise laser therapy (either with a Holmium:YAG  laser  or  CO 2 ), directly to the target area(s) of the heart muscle. When performed as a primary therapy, it is done through a small incision between the ribs ( thoracotomy ) with the patient under  general anesthesia .  Transmyocardial laser revascularization (TMR) can also be performed as a secondary procedure in patients that have ischemic heart disease with areas of the heart that cannot be bypassed. The precise laser therapy is delivered to create small channels into the heart chamber. During a typical procedure, approximately 10 \u201350 channels are made in each targeted region of the  heart muscle ."}
{"_id": "WikiPedia_Cardio$$$corpus_4637", "text": "The channels in the heart muscle seal over almost immediately with little blood loss while the new channels allow fresh blood to perfuse the heart wall immediately.The CO 2  Heart Laser uses a computer to direct laser beams to the appropriate area of the heart in between heartbeats, when the ventricle is filled with blood and the heart is relatively still."}
{"_id": "WikiPedia_Cardio$$$corpus_4638", "text": "TMR is a treatment option for patients who:"}
{"_id": "WikiPedia_Cardio$$$corpus_4639", "text": "TMR has shown positive clinical benefits for patients who may require one or two bypass grafts, yet also have other areas of the heart that are not able to be bypassed by direct bypass-surgery.  This is often seen in patients with  diabetes .  The surgeon will bypass the targeted blockages and use the CO 2  Heart Laser on the heart muscle with diffuse disease to achieve more complete blood flow to the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_4640", "text": "TMR is not suitable for patients whose:"}
{"_id": "WikiPedia_Cardio$$$corpus_4641", "text": "A ventriculotomy  is a heart surgery that involves an incision into one or both  ventricles . It is a component of many heart surgeries, including  infarctectomy  and many  congenital heart defect surgeries . In the long-term, a prior ventriculotomy can increase the risk of ventricular  arrhythmia . Right ventriculotomy often causes  right bundle branch block  if it is extensive. Modern congenital surgery techniques have reduced the long-term effects of ventriculotomy and its repair. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4642", "text": "The  Wasserman 9-Panel Plot , often called a  Nine-Panel Plot , is a standard layout for the  graphical representation  of  data  produced by a  cardiopulmonary exercise test . [ 1 ]  The layout was updated in 2012. The graphs give an overview of  cardiovascular , ventilatory, and  gas exchange  parameters. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4643", "text": "The Wasserman 9-Panel Plot is named for  American   physiologist  Professor  Karlman Wasserman  M.D. Ph.D., who first displayed the data in this manner. [ 3 ]  Professor Wasserman worked extensively on  pulmonary  physiology, and also described the \"gear wheel model\" used for explaining results obtained from the test. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4644", "text": "Acute decompensated heart failure  ( ADHF ) is a sudden worsening of the signs and symptoms of  heart failure , which typically includes difficulty breathing ( dyspnea ),  leg or feet swelling , and  fatigue . [ 1 ]  ADHF is a common and potentially serious cause of  acute respiratory distress . The condition is caused by severe congestion of multiple organs by fluid that is inadequately circulated by the failing heart. An attack of  decompensation  can be caused by underlying medical illness, such as  myocardial infarction , an  abnormal heart rhythm ,  infection , or  thyroid disease ."}
{"_id": "WikiPedia_Cardio$$$corpus_4645", "text": "Heart failure or cardiovascular insufficiency can be acute without being decompensated from a chronic condition. In this case, the signs of congestion such as weight gain and edema will not yet have developed. This is commonly due to pump failure or cardiovascular insufficiency after   myocardial infarction  when a significant loss of cardiac function occurs. Such patients will, have  shortness of breath  due to poor tissue perfusion, tissue hypoxia and  metabolic acidosis .  [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4646", "text": "Cardiac symptoms of heart failure include chest pain/pressure and  palpitations . Common noncardiac signs and symptoms of heart failure include  loss of appetite , nausea, weight loss, bloating, fatigue, weakness,  low urine output ,  waking up at night to urinate , and cerebral symptoms of varying severity, ranging from anxiety to memory impairment and confusion. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4647", "text": "Flash Pulmonary Edema or Crash Pulmonary Edema is a clinical characterization of acute heart failure with a dramatic presentation. [ 4 ]  It is an acute cardiac disease precipitated by cardiac events and usually associated with severe hypertension."}
{"_id": "WikiPedia_Cardio$$$corpus_4648", "text": "Chronic stable  heart failure  may easily  decompensate . This most commonly results from an intercurrent illness (such as  pneumonia ),  myocardial infarction  (a heart attack),  abnormal heart rhythms  (such as  atrial fibrillation ), uncontrolled  high blood pressure , or the person's failure to maintain a fluid restriction, diet, or medication. [ 5 ]   Other well recognized precipitating factors include  anemia  and  hyperthyroidism  which place additional strain on the heart muscle. Excessive fluid or salt intake, and medication that causes fluid retention such as  NSAIDs  and  thiazolidinediones , may also precipitate decompensation. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4649", "text": "A  jugular venous distension  is the most sensitive clinical sign for acute decompensation. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4650", "text": "In acute decompensated heart failure, the immediate goal is to re-establish adequate perfusion and oxygen delivery to end organs. This entails ensuring that  airway, breathing, and circulation  are adequate. Management consists of propping up the head of the patient, giving oxygen to correct hypoxemia, administering morphine, diuretics like  furosemide , addition of an ACE inhibitor, use of nitrates and use of  digoxin  if indicated for the heart failure and if arrhythmic. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4651", "text": "Supplemental oxygen may be administered if  blood levels of oxygen are low ; the Heart Failure Society of America, however, has recommended that it not be used routinely. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4652", "text": "Initial therapy of acute decompensated heart failure usually includes some combination of a vasodilator such as nitroglycerin, a  loop diuretic  such as  furosemide , and  non-invasive positive pressure ventilation  (NIPPV). [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4653", "text": "A number of different medications are required for people who are experiencing heart failure. Common types of medications that are prescribed for heart failure patients include  ACE inhibitors ,  vasodilators ,  beta blockers ,  aspirin ,  calcium channel blockers , and  cholesterol  lowering medications such as  statins . Depending on the type of damage a patient has suffered and the underlying cause of the heart failure, any of these drug classes or a combination of them can be prescribed. Patients with heart pumping problems will use a different medication combination than those who are experiencing problems with the heart's ability to fill properly during  diastole . Potentially dangerous drug interactions can occur when different drugs mix together and work against each other. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4654", "text": "Nitrates such as  nitroglycerin  ( glyceryl trinitrate ) and  isosorbide dinitrate  are often used as part of the initial therapy for ADHF. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4655", "text": "Another option is  nesiritide , although it should only be considered if conventional therapy has been ineffective or contraindicated as it is much more expensive than nitroglycerin and has not been shown to be of any greater benefit. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4656", "text": "A 2013 Cochrane review, compared nitrates and other pharmacological, non-pharmacological, and placebo interventions. [ 9 ]  The review found no significant difference between the interventions in terms of symptom control or haemodynamic stability. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4657", "text": "The  National Institutes for Health and Care Excellence  (NICE) guidelines do not recommend routinely offering nitrates in acute heart failure. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4658", "text": "Heart failure is usually associated with a volume overloaded state. Therefore, those with evidence of fluid overload should be treated initially with intravenous loop diuretics. In the absence of symptomatic low blood pressure intravenous nitroglycerin is often used in addition to diuretic therapy to improve congestive symptoms. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4659", "text": "Volume status should still be adequately evaluated. Some heart failure patients on chronic diuretics can undergo excessive diuresis. In the case of diastolic dysfunction without systolic dysfunction, fluid resuscitation may, in fact, improve circulation by decreasing heart rate, which will allow the ventricles more time to fill. Even if the patient is edematous, fluid resuscitation may be the first line of treatment if the person's blood pressure is low. The person may, in fact, have too little fluid in their blood vessels, but if the low blood pressure is due to  cardiogenic shock , the administration of additional fluid may worsen the heart failure and associated low blood pressure. If the person's circulatory volume is adequate but there is persistent evidence of inadequate end-organ perfusion, inotropes may be administered. In certain circumstances, a  left ventricular assist device  (LVAD) may be necessary."}
{"_id": "WikiPedia_Cardio$$$corpus_4660", "text": "Once the person is stabilized, attention can be turned to treating pulmonary edema to improve oxygenation. Intravenous furosemide is generally the first line. However, people on long-standing diuretic regimens can become tolerant, and dosages must be progressively increased. If high doses of furosemide are inadequate, boluses or continuous infusions of bumetanide may be preferred. These  loop diuretics  may be combined with  thiazide diuretics  such as oral  metolazone  or intravenous  chlorothiazide  for a synergistic effect. Intravenous preparations are physiologically preferred because of more predictable absorption due to intestinal edema, however, oral preparations can be significantly more cost effective. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4661", "text": "The effectiveness and safety of  ACE inhibitors  and  angiotensin receptor blockers  (ARBs) acutely in ADHF have not been well studied, but are potentially harmful.  A person should be stabilized before therapy with either of these medication classes is initiated. [ 14 ]  Individuals with poor kidney perfusion are especially at risk for kidney impairment inherent with these medications. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4662", "text": "Beta-blockers  are stopped or decreased in people with acutely decompensated heart failure and a low blood pressure. However, continuation of beta-blockers may be appropriate if the blood pressure is adequate. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4663", "text": "Inotropes  are indicated if low blood pressure (  SBP  < 90 mmHg ) is present."}
{"_id": "WikiPedia_Cardio$$$corpus_4664", "text": "The  National Institutes for Health and Care Excellence  (NICE) guidelines do not recommend routinely offering inotropes in acute heart failure. [ 12 ]  However, they recommend it be considered in patients with ADHF and potentially reversible caradiogenic shock. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4665", "text": "Opioids  have traditionally been used in the treatment of the  acute pulmonary edema  that results from acute decompensated heart failure. A 2006 review, however, found little evidence to support this practice. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4666", "text": "The  National Institutes for Health and Care Excellence  (NICE) guidelines do not recommend routinely offering opioids in acute heart failure. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4667", "text": "Continuous positive airway pressure  may be applied using a face mask; this has been shown to improve symptoms more quickly than oxygen therapy alone, [ 18 ]  and has been shown to reduce the risk of death. [ 19 ] [ 20 ]  Severe  respiratory failure  requires treatment with  endotracheal intubation  and  mechanical ventilation ."}
{"_id": "WikiPedia_Cardio$$$corpus_4668", "text": "Ultrafiltration  can be used to remove fluids in people with ADHF associated with  kidney failure . Studies have found that it decreases health care utilization at 90 days. [ 21 ] \nOne such method is  aquapheresis ultra-filtration"}
{"_id": "WikiPedia_Cardio$$$corpus_4669", "text": "A 2022 Cochrane review on the benefits, efficacy, and safety of ultrafiltration compared to diuretic therapy found that ultrafiltration probably reduces the incidence of heart-failure related hospitalisation in the long term. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4670", "text": "The  National Institutes for Health and Care Excellence  (NICE) guidelines do not recommend routinely offering ultrafiltration in acute heart failure. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4671", "text": "In some cases, doctors recommend  surgery  to treat the underlying problem that led to heart failure. [ 23 ]  Different procedures are available depending on the level of necessity and include  coronary artery bypass surgery ,  heart valve  repair or replacement, or  heart transplantation . During these procedures, devices such as heart pumps,  pacemakers , or  defibrillators  might be implanted. The treatment of heart disease is rapidly changing and thus new therapies for acute heart failure treatment are being introduced to save more lives from these massive attacks. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4672", "text": "Bypass surgery  is performed by removing a vein from the arm or leg, or an artery from the chest and replacing the blocked artery in the heart. This allows the blood to flow more freely through the heart. Valve repair is where the valve that is causing heart failure is modified by removing excess valve tissues that cause them to close too tightly. In some cases,  annuloplasty  is required to replace the ring around the valves. If the repair of the valve is not possible, it is replaced by an  artificial heart valve . The final step is heart replacement. When severe heart failure is present and medicines or other heart procedures are not effective, the diseased heart needs to be replaced."}
{"_id": "WikiPedia_Cardio$$$corpus_4673", "text": "Another common procedure used to treat heart failure patients is an  angioplasty . Is a procedure used to improve the symptoms of  coronary artery disease  (CAD), reduce the damage to the heart muscle after a  heart attack , and reduce the risk of death in some patients. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4674", "text": "A  pacemaker  is a small device that's placed in the chest or abdomen to help control abnormal heart rhythms. [ 26 ]   They work by sending electric pulses to the heart to prompt it to beat at a rate that is considered to be normal and are used to treat patients with arrhythmias. They can be used to treat hearts that are classified as either a  tachycardia  that beats too fast, or a  bradycardia  that beats too slow."}
{"_id": "WikiPedia_Cardio$$$corpus_4675", "text": "Athletic heart syndrome  ( AHS ) is a non- pathological  condition commonly seen in  sports medicine  in which the human  heart  is  enlarged , and the resting  heart rate  is  lower  than normal."}
{"_id": "WikiPedia_Cardio$$$corpus_4676", "text": "The athlete's heart is associated with physiological  cardiac remodeling  as a consequence of repetitive cardiac loading. [ 3 ]  Athlete's heart is common in athletes who routinely exercise more than an hour a day, and occurs primarily in  endurance  athletes, though it can occasionally arise in heavy  weight trainers . The condition is generally considered benign, but may occasionally hide a serious medical condition, or may even be mistaken for one. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4677", "text": "Athlete's heart most often does not have any physical  symptoms , although an indicator would be a consistently low resting heart rate. Athletes with AHS often do not realize they have the condition unless they undergo specific medical tests, because athlete's heart is a normal,  physiological  adaptation of the body to the stresses of physical conditioning and aerobic exercise. [ 5 ]  People diagnosed with athlete's heart commonly display three  signs  that would usually indicate a heart condition when seen in a regular person:  bradycardia ,  cardiomegaly , and  cardiac hypertrophy ."}
{"_id": "WikiPedia_Cardio$$$corpus_4678", "text": "Bradycardia is a slower than normal heartbeat, at around 40\u201360 beats per minute. Cardiomegaly is the state of an enlarged heart, and cardiac hypertrophy the thickening of the muscular wall of the heart, specifically the  left ventricle , which pumps oxygenated blood to the  aorta . Especially during an intensive workout, more blood and oxygen are required to the peripheral tissues of the arms and legs in highly trained athletes' bodies. A larger heart results in higher  cardiac output , which may allow it to beat more slowly at rest, as more blood is pumped out with each beat. [ medical citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4679", "text": "Another sign of athlete's heart syndrome is an  S3 gallop , which can be heard through a  stethoscope . This sound can be heard as the  diastolic pressure  of the irregularly shaped heart creates a disordered blood flow. However, if an  S4 gallop  is heard, the patient should be given immediate attention. An S4 gallop is a stronger and louder sound created by the heart, if diseased in any way, and is typically a sign of a serious medical condition. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4680", "text": "Athlete's heart is a result of dynamic physical activity, such as aerobic training more than 5 hours a week rather than static training such as weightlifting. During intensive prolonged  endurance  or  strength training , the body signals the heart to pump more blood through the body to counteract the  oxygen deficit  building in the  skeletal muscles . Enlargement of the heart is a natural physical adaptation of the body to deal with the high pressures and large amounts of blood that can affect the heart during these periods of time. Over time, the body will increase both the chamber size of the  left ventricle , and the  muscle mass  and wall thickness of the heart. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4681", "text": "Cardiac output , the amount of blood that leaves the heart in a given time period (i.e. liters per minute), is proportional to both the chamber sizes of the heart and the rate at which the heart beats. With a larger left ventricle, the heart rate can decrease and still maintain a level of cardiac output necessary for the body. Therefore, athletes with AHS commonly have lower  resting heart rates  than nonathletes. [ medical citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4682", "text": "The heart becomes enlarged, or hypertrophic, due to intense cardiovascular workouts, creating an increase in  stroke volume , an enlarged left ventricle (and  right ventricle ), and a decrease in resting heart rate along with irregular rhythms. The wall of the left ventricle increases in size by about 15\u201320% of its normal capacity. No decrease of the  diastolic function  of the left ventricle occurs. [ 9 ]  The athlete may also experience an irregular  heartbeat  and a resting  pulse rate  between 40 and 60 beats per minute (bradycardia). [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4683", "text": "The level of physical activity in a person determines what physiological changes the heart makes. The two types of exercise are static (strength-training) and dynamic (endurance-training). Static exercise consists of weight lifting and is mostly  anaerobic , meaning the body does not rely on  oxygen  for performance. It also moderately increases heart rate and stroke volume ( oxygen debt ). Dynamic exercises include running, swimming, skiing, rowing, and cycling, which rely on oxygen from the body. This type of exercise also increases both heart rate and stroke volume of the heart. Both static and dynamic exercises involve the thickening of the left ventricular wall due to increased cardiac output, which leads to physiologic hypertrophy of the heart. Once athletes stop training, the heart returns to its normal size. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4684", "text": "Athlete's heart is usually an  incidental finding  during a routine screening or during tests for other medical issues. An enlarged heart can be seen at  echocardiography  or sometimes on a  chest X-ray . Similarities at presentation between athlete's heart and clinically relevant cardiac problems may prompt  electrocardiography  (ECG) and exercise  cardiac stress tests . The ECG can detect  sinus bradycardia , a resting heart rate of fewer than 60 beats per minute. This is often accompanied by  sinus arrhythmia . The pulse of a person with athlete's heart can sometimes be irregular while at rest, but usually returns to normal after exercise begins. [ 12 ] [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4685", "text": "Regarding  differential diagnosis ,  left ventricular hypertrophy  is usually indistinguishable from athlete's heart and at ECG, but can usually be discounted in the young and fit. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4686", "text": "It is important to distinguish between athlete's heart and  hypertrophic cardiomyopathy  (HCM), a serious cardiovascular disease characterized by thickening of the heart's walls, which produces a similar ECG pattern at rest. This genetic disorder is found in one of 500 Americans and is a leading cause of  sudden cardiac death  in young athletes (although only about 8% of all cases of sudden death are actually exercise-related). [ 17 ] [ 18 ]  The following table shows some key distinguishing characteristics of the two conditions. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4687", "text": "Athlete's heart should not be confused with bradycardia that occurs secondary to  relative energy deficiency in sport  or  anorexia nervosa , which involve slowing of metabolic rate and sometimes shrinkage of the heart muscle and reduced heart volume. [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4688", "text": "The  medical history  of the patient (endurance sports) and  physical examination  (bradycardia, and maybe a  third  or  fourth heart sound ), can give important hints."}
{"_id": "WikiPedia_Cardio$$$corpus_4689", "text": "Because of several well-known and high-profile cases of athletes experiencing sudden unexpected death due to cardiac arrest, such as  Reggie White  and  Marc-Vivien Fo\u00e9 , a growing movement is making an effort to have both professional and school-based athletes screened for cardiac and other related conditions, usually through a careful medical and health history, a good family history, a comprehensive physical examination including  auscultation  of heart and lung sounds and recording of  vital signs  such as  heart rate  and  blood pressure , and increasingly, for better efforts at detection, such as an electrocardiogram. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4690", "text": "An  electrocardiogram  (ECG) is a relatively straightforward procedure to administer and interpret, compared to more invasive or sophisticated tests; it can reveal or hint at many circulatory disorders and arrhythmias. Part of the cost of an ECG may be covered by some insurance companies, though routine use of ECGs or other similar procedures such as  echocardiography  (ECHO) are still not considered routine in these contexts. Widespread routine ECGs for all potential athletes during initial screening and then during the yearly physical assessment could well be too expensive to implement on a wide scale, especially in the face of the potentially very large demand. In some places, a shortage of funds, portable ECG machines, or qualified personnel to administer and interpret them (medical technicians, paramedics, nurses trained in cardiac monitoring, advanced practice nurses or nurse practitioners, physician assistants, and physicians in internal or  family medicine  or in some area of cardiopulmonary medicine) exist. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4691", "text": "If sudden cardiac death occurs, it is usually because of pathological hypertrophic enlargement of the heart that went undetected or was incorrectly attributed to the benign \"athletic\" cases. Among the many alternative causes are episodes of isolated arrhythmias which degenerated into lethal VF and asystole, and various unnoticed, possibly asymptomatic cardiac congenital defects of the vessels, chambers, or valves of the heart. Other causes include  carditis ,  endocarditis ,  myocarditis , and  pericarditis  whose symptoms were slight or ignored, or were asymptomatic. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4692", "text": "The normal treatments for episodes due to the pathological look-alikes are the same mainstays for any other episode of  cardiac arrest :  cardiopulmonary resuscitation , defibrillation to  restore normal sinus rhythm , and if initial defibrillation fails, administration of  intravenous   epinephrine  or  amiodarone . The goal is avoidance of infarction, heart failure, and/or lethal arrhythmias ( ventricular tachycardia ,  ventricular fibrillation ,  asystole , or  pulseless electrical activity ), so ultimately to restore normal  sinus rhythm . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4693", "text": "Athlete's heart is not dangerous for athletes (though if a nonathlete has symptoms of bradycardia, cardiomegaly, and cardiac hypertrophy, another illness may be present). Athlete's heart is not the cause of sudden cardiac death during or shortly after a workout, which mainly occurs due to  hypertrophic cardiomyopathy  and  arrhythmogenic cardiomyopathy  (ARVC), two genetic disorders. Although a link between intensive exercise and exercise-induced arrhythmogenic right ventricular cardiomyopathy exists. [ 3 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4694", "text": "No treatment is required for people with athletic heart syndrome; it does not pose any physical threats to the athlete, and despite some theoretical concerns that the  ventricular remodeling  might conceivably predispose for serious arrhythmias, [ 26 ]  no evidence has been found of any increased risk of long-term events. [ 27 ]  Athletes should see a physician and receive a clearance to be sure their symptoms are due to athlete's heart and not another heart disease, such as cardiomyopathy. If the athlete is uncomfortable with having athlete's heart or if a differential diagnosis is difficult,  deconditioning  from exercise for a period of three months allows the heart to return to its regular size. However, one long-term study of elite-trained athletes found that dilation of the left ventricle was only partially reversible after a long period of deconditioning. [ 28 ]  This deconditioning is often met with resistance to the accompanying lifestyle changes. The real risk attached to athlete's heart is if athletes or nonathletes simply assume they have the condition, instead of making sure they do not have a life-threatening heart illness. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4695", "text": "The athlete's heart syndrome was first described in 1899 by  Salomon Henschen . He compared the heart size of cross-country skiers to those who lived  sedentary  lives. He noticed that those who participated in competitive sports displayed symptoms of athlete's heart syndrome. Henschen believed the symptoms were a normal adjustment to exercise, and felt concern was not needed. [ 9 ]  Henschen believed that the entire heart became enlarged. He also believed athletes with AHS lived shorter lives than those who did not acquire the syndrome. Because his research occurred throughout the 19th century, technology was limited, and it became difficult to devise appropriate ways to measure the hearts of athletes. Few believed in Henschen's theory about athletes having larger hearts than those who did not participate in sports. The latter, however, in addition to Henschen's belief of an enlargement of the entire heart among athletes is in agreement with the four-chamber dilation seen with modern imaging modalities in individuals with athlete's heart. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4696", "text": "An  atrioventricular fistula  is a  fistula  between an  atrium  and a  ventricle  of the  heart . [ citation needed ] \nFormation of an AVF is a potential complication of  catheter ablation . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4697", "text": "This article about a medical condition affecting the circulatory system is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_4698", "text": "Cardiovascular disease , including  heart disease , is a major cause of death in Australia. [ 1 ]  Heart disease is an overall term used for any type of  Cardiovascular disease  that affects the heart reducing blood supply to the heart. It is also often referred as Cardiac disease and Coronary heart disease. It is generally a lifelong condition where damage to the artery and blood vessel cannot be cured. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4699", "text": "Cardiovascular disease (CVD) continues to have a major impact on the health of  Australians  in terms of prevalence,  mortality ,  morbidity , burden of disease and expenditure. From 2007 to 2008, an estimated 3.4 million Australians were diagnosed with CVD. [ 3 ]  Cardiovascular disease remains Australia's leading cause of death. In 2009, 46,106 deaths in Australia were directly linked with CVD (21,935 males and 24,171 females); this figure represents a total of 33% of all deaths in Australia. [ 4 ]  It was reported in 2010 that almost 16% of the total projected burden of disease was a result of CVD. [ 5 ]  This then made individuals with CVD susceptible to co-morbid conditions later in life, making them \"at risk\" for depression and anxiety."}
{"_id": "WikiPedia_Cardio$$$corpus_4700", "text": "There are number of conditions that involves the heart such as:"}
{"_id": "WikiPedia_Cardio$$$corpus_4701", "text": "According to Chenzbraun (2010), symptoms of the heart disease varies, and should not be ignored. The symptoms of heart disease are not always intense and varies according to factors such as age and gender.  [ citation needed ] The most common symptoms of heart disease is:"}
{"_id": "WikiPedia_Cardio$$$corpus_4702", "text": "This is a major risk factor of heart disease resulting in death. The rate of smoking is low in Australia according to the health survey: 14% of women and 18% of men being daily smokers (Nichols, 2014)."}
{"_id": "WikiPedia_Cardio$$$corpus_4703", "text": "58% of Australians lack physical activity. Those who undertake low levels of physical activity are at higher risk of developing heart disease. Men were classified as moderately active than women (Nichols & Peterson, 2014)."}
{"_id": "WikiPedia_Cardio$$$corpus_4704", "text": "Alcohol plays a huge role in Australian culture and its social circumstance. According to the Australian Bureau of statistics, 87.6% of males and 77.3% of females had consumed alcohol in the past year. Alcohol  consumed at a limit, reduces the risk of developing heart disease. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4705", "text": "Being overweight and obese is very common in Australia especially children and teens. Almost 69.7% of male and 55.7% of female are overweight. The rate for both men and women of obesity is 27.5% (Australian Bureau of statistics). It is one of the leading cause of heart disease and  cardiovascular disease . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4706", "text": "High blood pressure ( hypertension ) causes stress to the heart and its function that leads to heart disease. Males experience heart disease caused by hypertension than women. One in five Australians with high blood pressure has heart disease (Nichols, 2014)."}
{"_id": "WikiPedia_Cardio$$$corpus_4707", "text": "A key step to prevent any type of heart disease is addressing the risk factors. Such as not smoking or use of drugs, regular exercising, have healthy diet, maintain healthy weight and have regular health screening to check up on blood pressure. These lifestyle changes reduces the risk of developing heart disease (Wood & Gordon, 2011)."}
{"_id": "WikiPedia_Cardio$$$corpus_4708", "text": "Prescribed medications are given to help improve blood flow, low blood pressure and to relax blood vessel walls. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4709", "text": "A non-surgical procedure called,  Angioplasty , could be done to help dilate the narrowed arteries. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4710", "text": "Coronary artery bypass surgery  is also another way to treat coronary heart disease. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4711", "text": "Although there are treatments available to treat heart disease, it is a lifelong condition restricting some daily lifestyle routine and incurable. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4712", "text": "Heart disease is the leading cause of death in Australia. [ 7 ]  In 2007-8 about 3.5 million people were diagnosed with heart disease (especially cardiovascular disease). Although there are significant advances in the treatments, heart disease still remains the lead cause of death in Australia especially with people in lower socioeconomic groups (AIHW, 2011)."}
{"_id": "WikiPedia_Cardio$$$corpus_4713", "text": "The number and rate of deaths from CVD have fallen considerably from the peak levels experienced in the late 1960s and early 1970s when CVD was responsible for around 60,000 deaths annually, or roughly 55% of all deaths each year. [ 8 ]  These major gains have been attributed to a combination of research, improvements in prevention and detection of cardiovascular disease, and better clinical management of people with the disease. There is a close interrelationship between CVD and other important chronic conditions, including  diabetes  and  chronic kidney disease . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4714", "text": "Cardiovascular disease kills one Australian every 11 minutes, and 3\u00b74 million of the country's population are affected, with the Indigenous Australians having a 30% higher rate. In their lifetime, 1\u00b75 million Australians are estimated to have diabetes and one in six Australians are suspected to have a stroke. The Baker Heart and Diabetes Institute, based in Melbourne, is one of the most well known cardiovascular disease research institutes. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4715", "text": "One of the studies directed by an Australian-Dutch research team, led by, Karin Jandeleit-Dahm from Harald Schmidt from Maastricht University, Netherlands, has identified the role of an enzyme which accelerates the development of diabetic atherosclerosis. Researchers were able to substantially reduce the development of artery plaques by suppressing or inhibiting this enzyme with a new drug, which will allow prevention and treatment of cardiovascular disease in people with diabetes. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4716", "text": "Another team, led by Bronwyn Kingwell, [ 10 ]  Head of the Baker Institute's Metabolic and Vascular Physiology, have found a new use for an old drug. The researchers found that after taking the standard anti-hypertensive drug Ramipril, patients with peripheral arterial disease (PAD), which restricts mobility due to leg pain, enjoyed a longer and less painful time on their feet. For some patients, this could be the difference between living independently and living under the care of others for the rest of their lives. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4717", "text": "Autoimmune   heart   diseases  are the effects of the body's own  immune  defense system mistaking cardiac  antigens  as foreign and attacking them leading to  inflammation  of the heart as a whole, or in parts. The commonest form of autoimmune heart disease is rheumatic heart disease or  rheumatic fever ."}
{"_id": "WikiPedia_Cardio$$$corpus_4718", "text": "Aetiologically, these are most commonly seen in children with a history of  sore throat  caused by a  streptococcal infection . This is similar to the post-streptococcal  glomerulonephritis . Here, the anti-bacterial  antibodies  cross react with the heart antigens causing inflammation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4719", "text": "Inflammatory damage leads to the following: [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4720", "text": "These are the typical mechanisms of  autoimmunity .  Autoantibodies  or auto-toxic  T-lymphocyte  mediated tissue destruction. The process is aided by  neutrophils , the  complement system ,  tumor necrosis factor alpha , etc. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4721", "text": "These depend on the amount of  inflammation . These are covered in their relevant articles."}
{"_id": "WikiPedia_Cardio$$$corpus_4722", "text": "Intensive cardiac care and  immunosuppressives  including  corticosteroids  are helpful in the acute stage of the disease.  Colchicine  can also be used to help prevent recurrences in Pericarditis."}
{"_id": "WikiPedia_Cardio$$$corpus_4723", "text": "When the condition becomes  chronic , treatment can include debility control and supportive care."}
{"_id": "WikiPedia_Cardio$$$corpus_4724", "text": "Bernheim syndrome  is a presumed  disorder  wherein the  right ventricle  is severely compressed due to a shift in the  ventricular septal wall  of the  heart , leading to  heart failure . It was first described by  Hippolyte Bernheim  in 1910. Today, it is argued whether or not Bernheim syndrome is indeed a  syndrome  or a  side effect  of other  cardiac conditions , such as  left ventrical heart failure  where the  left ventricle  is substantially enlarged, encroaching on the space of the  right ventricle . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4725", "text": "Signs and symptoms  of Bernheim syndrome are ill-defined and typically follow those of  heart failure . Bernheim distinguished Bernheim syndrome from the typical  heart failure  manifestations via the engorgement of  veins  due to congestion without evidence of  pulmonary congestion . [ 2 ]  There is also evidence of venous blockage going into  pulmonary circulation  and is therefore isolated to the  right side of the heart . Manifestations of Bernheim syndrome include symptoms of  hypertension , ronchi in the lungs,  edema ,  vein distention , and signs of poor  perfusion . [ 2 ]  It is important to note that there are no manifestations of  dyspnea  nor  pulmonary congestion  until it is presumed  to be a terminal stage of Bernheim  syndrome . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4726", "text": "Bernheim syndrome is believed to be the rightward shift of the ventricular septum compressing the right ventricle without causing  pulmonary congestion . [ 3 ]  This was first described by Hippolyte Bernheim in which he presented 10 patients with signs and symptoms of right sided heart failure whose  postmortem autospy  reveals a ventricular septum that invaded the  right ventricle  space. [ 1 ]  This opposed the traditional view of right sided heart failure,  right ventricular hypertrophy , where the right ventricle is enlarged. Bernheim describes right ventricles the size of a slit,which was due to the bulging ventricular  septum wall . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4727", "text": "Bernheim syndrome is believed to occur in two stages: the anatomical and clinical stages. During the anatomical stage, there are no clinical signs of the syndrome, but the  stenosis  of the right ventricle makes it difficult to fill to its normal capacity. This is a offset by the dilation of the  right atrium  as it takes in different  volume . In the clinical period, there are signs and  symptoms  present. In the clinical period, there are two stages. In the first stage of the clinical signs of venous obstruction due to the right ventricular stenosis become apparent while pulmonary  blood flow  continues normally. In the second stage of the symptoms of poor circulation becomes apparent such as systemic venous engorgement. [ 2 ]  It is at this point where the patient appears to have  heart failure . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4728", "text": "Most cases of Bernheim syndrome have been identified  postmortem  in  necropsy . A cross-sectional view of the heart muscle will show a greatly reduced  right ventricle  size. In necropsy, it is typical for the heart and lungs to be weighed with a higher weight indicating a build up of blood in the lungs:  pulmonary congestion . The weight of the lungs is therefore expected to be within normal limits to rule out  pulmonary congestion  (900-1,280g). [ 4 ]  The weight of the  liver  was also part of diagnosis with a significantly greater weight than what is in normal limits (1,440-1,680g) indicative of  vein  distention. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4729", "text": "In a clinical setting, Bernheim claims that the presence of isolated right ventricular failure clearly came from the presence of  left ventricular hypertrophy  which came secondary resulting to the presence of Bernheims symptom. [ 2 ]  This is especially considered when the heart failure is not due to a weakness in the  myocardium  but in the stenosis of the myocardial wall.  Fluoroscopy  is used to view the blood flow in the heart has also been deemed as a reliable  tool . It would be expected for the left ventricle and right atrium to be enlarged with the other two chambers appearing \"normal\". [ 2 ]  However, it was typical example to only confirm the presence of Bernheim syndrome in the setting of  autopsy . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4730", "text": "In the medical community, however, it is believed that Bernheim syndrome does not actually exist and is only an observed side effect of another condition such as left  ventricular hypertrophy . This is due to the lack of finding regarding sole right ventricle compression, without accompaniment of left ventricular hypertrophy, which is expected to encroach into the right ventricular space. It is claimed that there is no observation of a rightward shift of the ventricular septum as is described by Bernheim. Furthermore, using evidence from right and left  peak systolic pressures , they determined there was no evidence of right ventricular stenosis to begin with. [ 1 ]  When right ventricular heart failure is found without left ventricular heart failure, it was accompanied by  pulmonary embolism  and/or  mitral valve stenosis . [ 4 ]  It is because of these findings that there has been a movement to remove Bernheim syndrome from  medical terminology . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4731", "text": "Brown atrophy of the heart  is  atrophy  of the heart muscle (or  myocardium ) commonly found in the elderly. [ 1 ] [ 2 ]  It is described as brown because fibers become  pigmented  by intracellular deposits (mostly around the  cell nucleus ) of  lipofuscin , [ 1 ]  a type of  lipochrome   granule ."}
{"_id": "WikiPedia_Cardio$$$corpus_4732", "text": "It has no known effect on function, [ 1 ] [ 2 ]  and is described as being expected or normal in aging. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4733", "text": "Ebb Cade  (17 March 1890 \u2013 13 April 1953) was a construction worker at  Clinton Engineer Works  in  Oak Ridge, Tennessee , and was the first person subjected to injection with  plutonium  as an experiment."}
{"_id": "WikiPedia_Cardio$$$corpus_4734", "text": "Cade was born on 17 March 1890 in  Macon County, Georgia , the son of Evens and Carrie Cade. Ebb Cade was married to Ida Cade. At age 63, Cade died as a result of ventricular fibrillation followed by heart failure on 13 April 1953 in  Greensboro, North Carolina . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4735", "text": "On 23 March 1945 Cade was on his way to work at a construction site for the  Manhattan Project  when he was involved in a traffic accident at  Oak Ridge, Tennessee . He was an African-American cement worker for the  J.A. Jones Construction Company . Cade presented at the Oak Ridge Hospital with fractures of right  patella , right  radius  and  ulna  and left  femur . Dr. Hymer Friedell, deputy medical director of the Manhattan Engineer District, determined that as Cade was, as he characterized, a \"well developed..well nourished\" \"colored male\", he was suitable for \"experimentation\" with plutonium injection. Doctors left his fractures untreated for 20 days until after plutonium injections began on 10 April 1945. Cade received the injections at the Oak Ridge Hospital on the  Clinton Engineer Works  reservation without his consent or knowledge. He became known as HP-12 (Human Product-12) and was the first person to be injected with  Plutonium-239 . [ 2 ] [ 3 ]  In order to test the migration of plutonium through his body, subsequently 15 of Cade's teeth were extracted and bone samples taken. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4736", "text": "According to one account, Cade departed suddenly from the hospital on his own initiative; one morning the nurse opened his door, and he was gone. Later it was learned that he moved out of state and died of heart failure in Greensboro. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4737", "text": "From 1945 to 1947, 18 people were part of a series of studies that involved the  injection  of plutonium. In  Rochester, New York  at  Strong Memorial Hospital  11 people were injected. In Chicago, three individuals received injections at  Billings Hospital  of the  University of Chicago . In  San Francisco, California , three people were injected at the University Hospital of the University of California, San Francisco. The first person injected in California was  Albert Stevens . [ 7 ] [ 8 ] [ 9 ] [ 10 ]  Urine and feces samples were collected from the test subjects and forwarded to  Los Alamos National Laboratory  for plutonium analysis. [ 11 ] [ 12 ]  The studies were utilized to formulate mathematical equations necessary to establish plutonium excretion rates. [ 13 ] [ 14 ] [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4738", "text": "Cardiac allograft vasculopathy  (CAV) is a progressive type of  coronary artery disease  in people who have had a  heart transplant . [ 1 ]  As the donor heart has  lost its nerve supply  there is typically no chest pain, and CAV is usually detected on routine testing. [ 2 ]  It may present with symptoms such as tiredness and breathlessness. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4739", "text": "It arises when the  blood vessels  supplying the  transplanted heart  change in structure. [ 3 ]  They gradually  narrow  and  restrict its blood flow , subsequently leading to impairment of the  heart muscle  or sudden death. [ 4 ]  In addition to the same risk factors for coronary artery disease due to the  build up of plaque , CAV is more likely to occur if the  donor  was older or died from  explosive brain death , and if there is  cytomegalovirus infection . [ 2 ]  Its mechanism involves immunological ( innate  and  adaptive ) and nonimmunological factors, with distinct features on  histological  samples of  coronary arteries . [ 2 ]  Other major causes of death following heart transplantation include graft failure, organ rejection and infection. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4740", "text": "Diagnosis is by regular follow-up and monitoring of the transplanted heart for early signs of disease. [ 2 ]  Tests include  coronary angiography ,  intravascular ultrasound ,  dobutamine stress echocardiography ,  positron emission tomography ,  computed tomographic angiography  (CT angiography) and several  biomarkers . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4741", "text": "Statins  and  aspirin  are commenced early after transplantation and on detection of CAV. [ 2 ]  Medications including  sirolimus  and  everolimus  can slow disease progression. [ 2 ]  A repeat heart transplantation may be required. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4742", "text": "CAV affects around half of heart transplant recipients within 10 years. [ 2 ]  It contributes to the death of 11-13% one year from heart transplantation. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4743", "text": "Cardiac allograft vasculopathy is an accelerated type of  coronary artery disease  in people who have had a heart transplantation. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4744", "text": "Unlike the  chest tightness of angina  in those who have not had a heart transplant, people with CAV typically do not experience chest pain because the donor heart has  lost its nerve supply . [ 2 ]  A few regain nerves some years later and may develop unusual chest pain. [ 8 ]  People with CAV may present with a broad spectrum of symptoms including tiredness, nausea, or abdominal discomfort or may have no symptoms at all. [ 2 ]   Shortness of breath  and  arrhythmias  may also occur. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4745", "text": "Similar to  coronary artery disease  in those who have not had a heart transplant, risk factors to CAV include  high blood pressure ,  high cholesterol , and  diabetes mellitus . [ 2 ]  Other risk factors exclusive to CAV include older  donors ,  cytomegalovirus infection  and circulating antibodies after heart transplantation. [ 2 ]  The mechanism of donor brain death, [ 8 ]  particularly  explosive brain death  in the donor has been shown to be a significant factor. It is probably the combination of injuries to the  allograft  that determine the risk of developing CAV. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4746", "text": "Immunological ( innate  and  adaptive ) and nonimmunological factors contribute to the complex  pathogenesis  of CAV. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4747", "text": "In those nontransplanted people who develop coronary artery disease due to atherosclerosis, progression of disease is slow, histological changes are confined mainly to the main coronary arteries and arterial dilatation is observed as a form of compensatory remodelling. [ 8 ]  However, in CAV, histology specimens typically show concentric thickening of the intimal layer of the main coronary arteries on the surface of the heart and in intramyocardial arteries which can become obliterated within a few years. [ 2 ] [ 8 ]  There is  smooth muscle cell  migration,  foamy macrophages  and  lymphocytic  infiltrates. This can be seen to affect the whole length of the  coronary arteries  and often the smaller arteries. [ 2 ]   Calcification  does not always occur in CAV and if it does appear, it happens late. [ 8 ]   The compensatory arterial dilation does not occur in CAV. [ 8 ]  Unlike in nontransplanted people with coronary artery disease due to  atherosclerosis , in CAV occlusion with  thrombus  of the vessel lumen is rare. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4748", "text": "Inflammation and  endothelial  injury can be triggered by the donor  arrest ,  organ procurement , and allograft  ischaemia  and  reperfusion . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4749", "text": "As symptoms are so variable and often absent, diagnosis has been a challenge. Hence, regular follow-up and monitoring of the allograft for early signs of disease is advocated. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4750", "text": "Surveillance is performed by regularly repeating  coronary angiography  in the  cardiac catheterization laboratory , the diagnostic test of choice. [ 2 ]  This is typically performed annually for the first five years after transplantation. [ 8 ]  Angiography in CAV characteristically demonstrates diffuse  stenoses  in large coronary arteries and a reduced number of smaller coronary arteries, also known as \"peripheral pruning\". [ 2 ] [ 6 ]  However, because CAV frequently affects the entire length of the coronary artery, CAV may not be apparent by angiography alone. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4751", "text": "Intravascular ultrasound  (IVUS) is more sensitive at reliably detecting subtle changes in the thickness of the intimal layer of the artery walls and provide measurements of artery lumen. Following transplantation, serial measurements are compared to the baseline. A greater than 0.5  mm  increase in intimal thickness one year after transplantation is predictive of CAV changes on angiography within five years. The paradoxical reduction in the number of blood vessels, can also be detected by intravascular ultrasound. [ 2 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4752", "text": "IVUS, however, tends to be used for research due to its drawbacks of being invasive, requiring the use of contrast material and cost. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4753", "text": "Alternatively,  dobutamine stress echocardiography  (DSE) is commonly performed and has an 85% sensitivity for the presence of CAV. A negative DSE correlates with a good prognosis. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4754", "text": "Other noninvasive diagnostics include  positron emission tomography  and  computed tomographic angiography  (CT angiography). [ 2 ]  In addition,  ECGs  may show atypical features of ischaemia. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4755", "text": "Biomarkers  for increased risk of CAV include  C-reactive protein ,  serum brain natriuretic peptide  and  troponin I  have been suggested. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4756", "text": "The degree of CAV after heart transplantation has been obtained from a variety of sources including The Cardiac Transplant Research Database, the ISHLT registry and The United Network for Organ Sharing registry. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4757", "text": "The  International Society for Heart and Lung Transplantation  (ISHLT) have formulated and standardized a terminology, based on diagnostic findings, to define the presence and severity of CAV, which in turn reflects prognosis. [ 8 ] [ 10 ]  The severity of CAV is defined by the degree of narrowing of the coronary arteries and the presence of restrictive heart disease. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4758", "text": "Prevention of CAV progression is important as once developed, CAV existing treatments are often ineffective. [ 2 ]  Commencing the  statins   pravastatin  and  simvastatin  early after transplantation reduces the incidence and severity of CAV. [ 2 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4759", "text": "When combined with immunosuppressants, the progression of CAV could possibly be slowed by  vitamins C  and  E . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4760", "text": "Since the role of  aspirin  is already established in coronary artery disease in those who have not had a heart transplant, it is usually given after heart transplantation too. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4761", "text": "On detection of CAV, medications including  mTOR inhibitors   sirolimus  and  everolimus  have been shown to slow disease progression. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4762", "text": "Clinically significant CAV may require  percutaneous coronary interventions  for focal disease, but the likelihood of restenosis is high. [ 2 ]  A repeat heart transplantation may be considered. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4763", "text": "Once there is reduced  left ventricular ejection fraction  and symptoms of  heart failure , the outcome is typically poor. [ 2 ]  The risk of  major adverse cardiovascular events  is increased by 3.4 fold if CAV is present on angiography. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4764", "text": "The frequency of CAV after heart transplantation has been obtained from a variety of sources including The Cardiac Transplant Research Database, the ISHLT registry and The United Network for Organ Sharing registry. [ 8 ]  In comparison to between 1994 and 2001, there has been a decline in incidence of CAV between 2001 and 2007. [ 8 ]  ISHLT figures show an incidence of CAV of around 50% at 10 years after heart transplantation. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4765", "text": "CAV is a leading cause of late mortality following heart transplantation. [ 2 ]  Most are not severe but it contributes to the death of 11-13% one year from heart transplantation. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4766", "text": "Unlike  rejection  and infection, CAV in the transplanted heart was not initially a predicted outcome. [ 12 ]  Early survivors of heart transplants soon developed this form of vasculopathy of their coronary arteries, initially identified at post-mortems. [ 12 ]  There were early suggestions that preventing cytomegalovirus (CMV) infection could decrease the prevalence of CAV. [ 12 ]  The impact of CAV has changed over time, with early recipients being younger, having more rejection and cardiovascular risk factors and less use of statins. [ 12 ]  Later recipients used statins routinely and were introduced to the immunosuppressive agent  mycophenolate mofetil  (MMF) and CMV prophylaxis. [ 12 ]  In addition, the later recipients were monitored for antibody-mediated cardiac allograft rejection (AMR). [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4767", "text": "Before 2010 there was no uniform international standards for the nomenclature of CAV. [ 4 ]  A consensus statement on a standard language for CAV was first published in 2010 by the ISHLT. [ 4 ]  This was devised in a similar way to the earlier  acute rejection grading system  by  endomyocardial biopsy . [ 10 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4768", "text": "Antibody-mediated cardiac allograft rejection  (AMR) is a significant factor leading to the rapid progression of CAV. [ 12 ]  Future research directions in this area may include prospective databases that correlate clinical factors with surveillance of the incidence and severity of AMR, the frequency of CMV infection, and the use of immunosuppressants. The role of inducing  immune tolerance  has yet to be established. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4769", "text": "Cardiac amyloidosis  is a subcategory of  amyloidosis  where there is depositing of the protein  amyloid  in the cardiac muscle and surrounding tissues. Amyloid, a misfolded and insoluble protein, can become a deposit in the  heart's atria, valves, or ventricles . These deposits can cause thickening of different sections of the heart, leading to decreased  cardiac function . [ 1 ]  The overall decrease in cardiac function leads to a plethora of symptoms. [ 2 ]  This multisystem disease was often misdiagnosed, with a corrected analysis only during autopsy. Advancements of technologies have increased earlier accuracy of diagnosis. Cardiac amyloidosis has multiple sub-types including  light chain ,  familial , and  senile . [ 3 ]  One of the most studied types is light chain cardiac amyloidosis. [ 2 ]  Prognosis depends on the extent of the deposits in the body and the type of amyloidosis. [ 4 ]  New treatment methods are actively being researched in regards to the treatment of heart failure and specific cardiac amyloidosis problems. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4770", "text": "The multiple subtypes of cardiac amyloidosis have varying epidemiological, diagnostic, and prognostic characteristics. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4771", "text": "This relatively rare form of cardiac amyloidosis occurs in an estimated six to ten cases per 1,000,000 people. [ 4 ]  This sub- type usually affects males over the age of 60 [ 4 ]  and is rapidly progressive. Pathogenesis of this form is due to the aggregation of  immunoglobulin lambda light chains . [ 3 ]  These chains are created by an abnormal expansion of  plasma cells . [ 3 ]  Over time, these light chains deposit into the  interstitial tissue  within the myocardium. [ 4 ]   Diagnostic tests includes serum and urine  electrophoresis , [ 4 ]  laboratory testing for the determination of elevated levels of  troponin  and  BNP , and ECGs showing low QRS voltages. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4772", "text": "This type is caused by mutations of proteins involved in amyloid formation, including  transthyretin  (TTR),  fibrinogen ,  apolipoprotein A1 , or  apolipoprotein A2 . Due to the multiple number of potential genetic causes the incidence of this form is variable. The vast majority of familial cardiac amyloidosis still present after the age of 60. [ 4 ]  A common mutation is the  TTR gene  mutation Val122Ile. [ 2 ]  It is estimated that 3.5\u20134% of African Americans in The United States have the Val 122lle mutation. [ 4 ]  This type of amyloidosis can be identified by  genetic testing  for protein mutation. [ 4 ]  For the diagnosis of familial cardiac amyloidosis to be made a biopsy with histological evaluation must be obtained. [ 7 ]  In this histological evaluation special stains are utilized to visualize the  amyloid deposits . [ 7 ]  One such stain is  Congo Red , which binds specifically to the amyloid deposit and can be characterized by various lighting methods. [ 7 ]  Under polarized light, the amyloid deposits while show pathognomonic apple green birefringence, and under plain light the deposits will appear a light salmon pink color. [ 7 ]  Familial amyloidosis symptoms are centered around neuropathological and cardiac problems. [ 3 ]  Cardiac manifestations of the TTR mutation present more often in The United States. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4773", "text": "This type is considered the wild-type mutation which leads to the development of  TTR deposits . [ 2 ]  It usually affects males over 70 years with the manifestation of  carpal tunnel syndrome . [ 4 ]   Similar to the other subtypes of cardiac amyloidosis, a biopsy is required for diagnosis. [ 4 ]  However, formal diagnosis of Senile cardiac amyloidosis is a diagnosis of exclusion. [ 4 ]  Biopsy with histological evaluation can rule out Light chain and Familial subtypes, leaving the diagnosis of Senile. [ 4 ]  This type is often misdiagnosed. However, greater use of  cardiac magnetic resonance  has increased the rate of diagnosis [ 2 ]  The severity of the disease tends to be less than the Light chain and Familial variants. [ 4 ]   This is due to the amount of time that it takes to accumulate the amyloid depositions being longer in the Senile variant. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4774", "text": "Symptoms of cardiac amyloidosis are a combination of heart failure and amyloid deposition in various other organs. [ 2 ]  Amyloid deposition in the heart causes restrictive diastolic  heart failure  that progresses to systolic heart failure. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4775", "text": "Cardiac manifestations include:"}
{"_id": "WikiPedia_Cardio$$$corpus_4776", "text": "For patients with light-chain amyloidosis, there can be depositions of amyloid into numerous different organs. [ 2 ]  Deposition of amyloid into other organs makes the diagnosis of cardiac amyloidosis difficult as these extracardiac manifestations mask the diagnosis. [ 2 ]  Extracardiac manifestations include:"}
{"_id": "WikiPedia_Cardio$$$corpus_4777", "text": "The general cause of cardiac amyloidosis is the misfolding of a specific protein precursor depending on the amyloidosis type. Protein precursors include immunoglobulin-derived light chains and  transthyretin  mutations. [ 3 ]  The misfolding of the protein causes it to have insoluble beta-pleated sheets, [ 2 ]  creating an amyloid. Amyloid, the aggregation, or clumping, of proteins, is resistant to degradation by the body. Amyloids are mostly  fibrils , while also containing a P component,  apolipoprotein ,  collagen ,  fibronectin , and  laminin . [ 2 ]  The P component, a  pentameric protein , stabilizes the fibrils of the amyloid, which reduces their clearance from the body. [ 1 ]  Deposits of the amyloids can occur throughout the body, including the heart, liver, kidneys, spleen, adrenal glands, and bones. Deposits in the extracellular cardiac space can stiffen the heart, resulting in restriction of the ventricles. [ 3 ]  This restriction in ventricular motion results in a decreased ability for the heart to pump efficiently, leading to the various symptoms associated with cardiac amyloidosis. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4778", "text": "Echocardiography  is a safe and non-invasive method that can be used to assess the structural and functional disease of the heart. [ 4 ]  Amyloidosis presents with ventricle and valvular thickening, biatrial enlargement, [ 4 ]  restrictive filling pattern, with normal to mildly reduced systolic function [ 8 ]  and decreased  diastolic filling . [ 4 ]  An echo can be used to evaluate for prognosis of the disease, measuring the different strains within the heart. [ 4 ]  Cardiac amyloidosis produces specific alterations to the functionality of the heart. Echocardiography can be utilized to detect this specific pattern (relative preservation of the apical myocardium with decreased longitudinal strain in the mid and basal sections), which is 90\u201395% sensitive and 80\u201385% specific for cardiac amyloidosis. [ 4 ]  Echocardiography can be used to help physicians with diagnosis, however, it can only be used for the suggestion of the disease, not the confirmation, unless it is late stage amyloidosis. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4779", "text": "ECGs  of patients with cardiac amyloidosis usually show a low voltage in the limb leads, with an unusual extreme right axis. There is usually a normal  P-wave , however, it can be slightly prolonged. For patients with light-chain amyloidosis, the  QRS complex pattern  is skewed, [ 1 ]  with poor R-waves of the chest leads. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4780", "text": "Holter ECGs  can be used to identify asymptomatic  arrhythmias . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4781", "text": "EKG  changes may be present, showing low voltage and conduction abnormalities like  atrioventricular block  or  sinus node  dysfunction. [ 8 ]  Atrial fibrillation (AF) is observed in up to 70% of patients at the time of diagnosis, and patients typically have controlled ventricular rates caused by concomitant conduction system disease. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4782", "text": "Laboratory tests including  urea  and  creatinine levels ,  liver enzymes , glucose,  thyroid function ,  full blood count , and clotting tests. The analysis of serum and urine for presence of  monoclonal immunoglobulin  is also done through  immunofixation  for detection of the monoclonal band. Presence of the monoclonal band would be consistent with light chain amyloidosis. For light chain amyloidosis,  serum immunoglobulin free light chain assay  can be used for diagnosis and following of the amyloidosis. [ 1 ]  In light-chain amyloidosis, a low  paraprotein level  can be present. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4783", "text": "There are two main cardiac biomarkers used in the assessment of cardiac amyloidosis,  troponin  and  N-terminal proBNP. [ 12 ]  As expected, with cardiac damage and dysfunction, there can be an elevation of these markers in patients with cardiac amyloidosis. These markers have been incorporated into the various staging/scoring systems used by physicians to determine severity of the disease and prognosis. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4784", "text": "Extracardiac biopsies of tissues of the kidney, liver, peripheral nerve, or abdominal fat can be used to confirm the presence of amyloid deposits. Amyloid deposits in biopsy samples are confirmed through the use of  Congo red dye , which produces a green birefringence when viewed under polarized light.  Sirius red staining  or  electron microscopy  examination can also be done.  The determination of the type of amyloid can be done by  immunohisto-labeling  techniques as well as  immunofluorescence  staining. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4785", "text": "For light-chain amyloidosis patients, bone marrow biopsies could be conducted to determine the baseline percentage of plasma cells and to rule out  multiple myeloma . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4786", "text": "Right heart catheterization  is the test used to test for elevated diastolic  ventricular pressures . This test is more invasive and would be performed after inconclusive  endomyocardial biopsy  samples. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4787", "text": "Cardiac magnetic resonance  (CMR) is capable of measuring the thickness of different areas of the heart. This can be used for quantification of the deposits in the heart. [ 1 ]  CMR also shows the characterization of  myocardial tissue  through patterns of  gadolinium  enhancements. [ 2 ]  However, none of the CMR technique is able to differentiate ATTR-CM and AL-CM definitely. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4788", "text": "For AL-CM, 68% of them have symmetrical and concentric  left ventricular hypertrophy . On the other hand, for ATTR-CM, 79% of them have asymmetrical left ventricular hypertrophy and 18% of them have symmetrical and concentric left ventricular hypertrophy. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4789", "text": "In  T1-weighted imaging , edema in the heart can be detected with a high T1 signal. Meanwhile, enlargement of heart cells will reduce the T1 signal. Using T1 signal, Extracellular volume (ECV) is useful to determine the degree of amyloid deposition around the heart cells and detect the regression of amyloid deposits after treatment. ECV is higher in ATTR-CM than in AL-CM. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4790", "text": "In T2-weighted imaging, the T2 signal is increased in acute myocarditis (inflammation of heart muscles), and  myocardial infarction  (heart attack). T2 signal is also increased in AL-CM and ATTR-CM but the signal is greater in AL-CM before starting chemotherapy. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4791", "text": "Late gadolinum enhancement  (LGE) can determine the severity of deposition of amyloid in heart tissue. The higher the LGE signal, the more severe the heart involvement. It can be divided into three stages: no LGE, sub endocardial  LGE, and full-thickness (transmural) LGE. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4792", "text": "Scintigraphy  can be used to measure the extent and distribution of the amyloid throughout the body, including the liver, kidney, spleen, and heart. [ 2 ]  A  radiolabelled  serum amyloid P component can be administered to a patient  intravenously  and the P component pools to the amyloid deposit proportional to the size of the deposit. The labeling of the P component can then be pictured by a  gamma camera . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4793", "text": "Technetium  radionuclide scans can now reliably diagnosis cardiac amyloidosis, with certain scanning methods having greater than 99% sensitivity (but only 91% specific for amyloidosis). [ 14 ]  In this method of imaging, radiolabeled technetium is injected into the body where it binds to cardiac amyloid deposits. [ 14 ]  A subsequent scan is taken to determine where the tracer stays, therefore highlighting the amyloid deposition in the heart. [ 14 ]  This method allows for a noninvasive definitive diagnosis of cardiac amyloidosis (as in the past an endomyocardial biopsy was required) [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4794", "text": "Mass spectrometry  can be used to determine whether the protein is light-chain or familial amyloidosis by identifying the  protein subunit . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4795", "text": "Treatments differ according to the type of amyloidosis present. [ 1 ]  The majority of treatment is aimed at preserving heart function and treating heart failure symptoms. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4796", "text": "Light chain (AL-CM) Treatment:  Since the cause of this subtype of cardiac amyloidosis is the excessive production of free light chains, the major goal of treatment is the reduction in concentration of light chains. [ 5 ]  For light-chain amyloidosis, the use of FLC assays and NT-proBNP levels can be used to monitor the progression of amyloidosis and any response to treatments. [ 1 ]  One of the major routes to decrease the production of these excess light chains is to kill the abnormal cells that are producing them. [ 5 ]  Chemotherapeutic agents such as  melphalan  or  bortezomib  can be used to kill off the abnormal cell line that is producing the free light chains. [ 5 ]  Following chemotherapy, a  bone marrow transplant  can be utilized to restore the normal cell lines. [ 5 ]  There are newer medications ( ixazomib ,  carfilzomib ,  daratumumab ,  elotuzumab ) under research for the treatment of multiple myeloma that can help to decrease the production of free light chains. [ 5 ]  New data suggests that orthotopic heart transplant followed by melphalan and stem cell transplant produces results similar to non cardiac amyloidosis indicated heart transplant. [ 5 ]  To treat complications, medications can be prescribed including  midodrine  for  autonomic neuropathy ,  amiodarone  for patients with  atrial fibrillation  to prevent  arrhythmias , and  warfarin  used after a cardioembolic episode. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4797", "text": "Familial (ATTR m -CM) Treatment:  In recent years there have been developments in the treatment of Familial/Transthyretin cardiac amyloidosis including methods to suppress transthyretin production, stabilize amyloid fibrils, and medications that can destroy already existing fibrils. [ 6 ]  For familial amyloidosis,  ACE-inhibitors  and beta-blockers can be prescribed if there is no autonomic neuropathy. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4798", "text": "The use of  pacemakers  (both right ventricular pacing and biventricular pacing) or  implantable cardioverter defibrillators  remains questionable in cardiac amyloidosis. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4799", "text": "In 2012, Craig Lewis, a 55 year old Texan, presented at the Texas Heart Institute with a severe case of amyloidosis. He was given an experimental continuous-flow artificial heart transplant which saved his life. Lewis died 5 weeks later of liver failure after slipping into a coma due to the amyloidosis. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4800", "text": "Overall prognosis is dependent on the extent of  cardiac dysfunction . Worse outcomes have been seen when echocardiography shows left ventricular wall thickness, poor systolic function and severe diastolic dysfunction. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4801", "text": "Light chain (AL-CM) Prognosis:   For light-chain amyloidosis early detection leads to best possibility of therapies prolonging the period of remission. [ 3 ]  Well treated light chain cardiac amyloidosis has a 4-year survival rate of around 90%. [ 5 ]  In patients that undergo stem cell transplant the average survival time increases to 10 years. [ 5 ]  Staging systems have been developed to stratify severity of the disease, including the Mayo Biomarker Stage, which utilizes various biomarkers such as  troponin I ,  troponin T ,  BNP , and  NT-proBNP , and Free light chain concentrations. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4802", "text": "Familial (ATTR m -CM) Prognosis:  Due to the extensive number of variables involved in this subtype, prognosis varies depending on the specific type of familial cardiac amyloidosis. [ 5 ]  Variables involve mutant vs wild type transthyretin mutation and age of onset of symptoms. [ 5 ]  In comparison to light chain amyloidosis, the familial subtype is slower to progress and has a more favorable prognosis. [ 5 ]  However, the Val 122lle mutation (most common cause of familial cardiac amyloidosis) has a 4-year survival rate of 16% with an average length of 26 months. [ 5 ]  A delay in recognition plays a major factor in this reduced survival rate. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4803", "text": "Cardiac asthma  is the medical condition of intermittent  wheezing , coughing, and  shortness of breath  that is associated with underlying  congestive heart failure  (CHF). [ 1 ]  Symptoms of cardiac asthma are related to the heart's inability to effectively and efficiently pump blood in a CHF patient. [ 2 ]  This can lead to accumulation of fluid in and around the lungs ( pulmonary congestion ), disrupting the lung's ability to oxygenate blood."}
{"_id": "WikiPedia_Cardio$$$corpus_4804", "text": "Cardiac asthma carries similar symptoms to  bronchial asthma , but is differentiated by lacking inflammatory origin. [ 1 ] [ 3 ]  Because of the similarity in symptoms, diagnosis of cardiac versus bronchial asthma relies on full  cardiac workup  and  pulmonary function testing . [ 2 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4805", "text": "Treatment is centered on improving  cardiac function , maintaining  blood oxygen saturation  levels, and stabilizing  total body water  volume and distribution. [ 1 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4806", "text": "The most common findings of cardiac asthma are the presence of wheeze, cough, or shortness of breath (predominantly  occurring at night  or when  lying down ) in a patient that possesses  signs of congestive heart failure . [ 4 ] [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4807", "text": "Additional findings consist of production of frothy or watery  sputum  and presence of  water in the lungs  that can be heard via stethoscope. [ 8 ]  In severe cases, a patient can experience multiple night time episodes of breathlessness,  changes in skin coloration , and episodes of bloody sputum. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4808", "text": "The underlying causes for cardiac asthma stem from the eventual back up of fluid into the pulmonary vasculature as a result of the heart's, particularly left sided, inability to effectively and efficiently pump blood. [ 2 ]  The accumulation of fluid in the heart creates a higher than normal pressure system that places increasing pressure demands on the pulmonary venous system in order for appropriate oxygenation of blood to occur. [ 4 ]  This results in what is called pulmonary venous hypertension (PVH), and results in distention and recruitment of  pulmonary capillaries  to help distribute the increased pressure gradient. [ 2 ] [ 4 ]  At the capillary, there is a microvascular barrier that helps regulate fluid status via molecular pressure forces such as forces that  push outward from vessels  and pressures that  pull or attract into vessels . [ 2 ]  With increasing PVH, pressure outward overcomes pressure inward, and fluid is distributed to the  lung interstitium , preserving oxygen exchange at the capillary. [ 2 ]  Fluid is transported to the  hilum  and  pleural space , and removed via the  lymphatic system . [ 2 ] [ 7 ]  At first, the body is capable of handling excess water. Later, the capillary vasculature is overwhelmed by increased pressure and fluid backs up into the  alveolar sac , resulting in pulmonary edema and decreased oxygenation capability. [ 2 ]  Additionally, increased pressure demands on capillary vasculature result in increases in vascular tone to include remodeling of pre-capillary vessels such as  medial wall hypertrophic changes . [ 2 ]  Over time, the remodeling efforts of the vessels can progress to  hyperplastic  changes of the vessels' wall construction, and results in increased  pulmonary vascular resistance . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4809", "text": "There is ongoing interest into establishing connections of cardiac asthma to abnormalities in  bronchiole  anatomy. [ 1 ] [ 4 ]  Current evaluation has proposed multiple mechanisms for increased airway resistance, and focus is on four alternate explanations:"}
{"_id": "WikiPedia_Cardio$$$corpus_4810", "text": "The diagnosis of cardiac asthma is accomplished through workup of congestive heart failure, complete with:"}
{"_id": "WikiPedia_Cardio$$$corpus_4811", "text": "As well as evaluation of lung function via:"}
{"_id": "WikiPedia_Cardio$$$corpus_4812", "text": "Treatment of asthma symptoms in CHF patients is directed towards optimizing the patient's cardiovascular status and correcting potential oxygen deficit. [ 4 ]  Current recommendations in  acute  asthma symptoms are utilization of diuretics such as  furosemide , venodilators such as  nitroglycerin , and  morphine . [ 1 ]  The initial strategy should focus on decreasing patient fluid retention with diuretic therapy, thereby decreasing  cardiac preload  and overall fluid load in pulmonary circuit ( pulmonary congestion ). [ 1 ]  Next, if aggressive diuresis is not adequately correcting symptoms, venodilators can be used to distribute blood and fluid to the venous system, thereby decreasing cardiac preload and left heart pressures contributing to pulmonary congestion. [ 1 ]  Lastly, morphine can be utilized for assistance in improving ease of breathing through a presumed mechanism similar to venodilation, as well as reducing patient anxiety. [ 1 ]  Additionally, applications of supplemental oxygen and repositioning to upright or standing positions in events of  low blood oxygen saturation  and difficulty breathing can be utilized as needed. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4813", "text": "Chronic  management of cardiac asthma is directed at optimizing therapy of heart failure. Current recommendations can be found at its respective page ( congestive heart failure ). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4814", "text": "There is importance of distinguishing whether asthma is of bronchial or cardiac origin because management of bronchial asthma is primarily centered on utilization of inhalers, such as  bronchodilators  and corticosteroids. At this point in time, there has been limited evidence of improvement of cardiac asthma symptoms with utilization of inhalers. [ 1 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4815", "text": "Cardiac tamponade , also known as  pericardial tamponade  ( / \u02cc t \u00e6 m . p \u0259 \u02c8 n e\u026a d / [ 4 ] ), is a compression of the  heart  due to  pericardial effusion  (the build-up of  pericardial fluid  in the  sac around the heart ). [ 2 ]  Onset may be rapid or gradual. [ 2 ]  Symptoms typically include those of  obstructive shock  including  shortness of breath , weakness,  lightheadedness , and cough. [ 1 ]  Other symptoms may relate to the underlying cause. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4816", "text": "Common causes of cardiac tamponade include  cancer ,  kidney failure ,  chest trauma ,  myocardial infarction , and  pericarditis . [ 2 ] [ 5 ]  Other causes include  connective tissues diseases ,  hypothyroidism ,  aortic rupture ,  autoimmune disease , and complications of  cardiac surgery . [ 2 ] [ 6 ]  In Africa,  tuberculosis  is a relatively common cause. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4817", "text": "Diagnosis may be suspected based on  low blood pressure ,  jugular venous distension , or quiet  heart sounds  (together known as  Beck's triad ). [ 2 ] [ 1 ] [ 7 ]  A  pericardial rub  may be present in cases due to inflammation. [ 2 ]  The diagnosis may be further supported by specific  electrocardiogram  (ECG) changes,  chest X-ray , or an  ultrasound of the heart . [ 2 ]  If fluid increases slowly the pericardial sac can expand to contain more than 2 liters; however, if the increase is rapid, as little as 200 mL can result in tamponade. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4818", "text": "Tamponade is a medical emergency. [ 5 ]  When it results in symptoms, drainage is necessary. [ 8 ]  This can be done by  pericardiocentesis , surgery to create a  pericardial window , or a  pericardiectomy . [ 2 ]  Drainage may also be necessary to rule out infection or cancer. [ 8 ]  Other treatments may include the use of  dobutamine  or in those with  low blood volume ,  intravenous fluids . [ 1 ]  Those with few symptoms and no worrisome features can often be closely followed. [ 2 ]  The frequency of tamponade is unclear. [ 9 ]  One estimate from the United States places it at 2 per 10,000 per year. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4819", "text": "Onset may be rapid (acute) or more gradual (subacute). [ 10 ] [ 2 ]  Signs of cardiac tamponade typically include those of  cardiogenic shock  including  shortness of breath , weakness,  lightheadedness , cough [ 1 ]  and those of  Beck's triad  e.g. jugular vein distention, quiet heart sounds and  hypotension . Other symptoms may relate to the underlying cause. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4820", "text": "Other general signs of shock (such as  fast heart rate ,  shortness of breath  and decreasing  level of consciousness ) may also occur. However, some of these signs may not be present in certain cases. A fast heart rate, although expected, may be absent in people with  uremia  and  hypothyroidism . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4821", "text": "According to Reddy and co-authors, cardiac tamponade and its progression can be described in 3 different phases. [ 11 ]  In phase I, the required filling pressure increases due to the high stiffness of the ventricles. This is because of the accumulation of pericardial fluid in the pericardial cavity. During phase II, the pericardial pressure exceeds the ventricular filling pressure caused by the further accumulation of pericardial fluid. This results in a decrease in cardiac input and output. A further decrease of cardiac input and output is typical in phase III of the progression of cardiac tamponade. This is caused by the equilibration of left ventricular filling and pericardial pressure, leading to \u201csevere deterioration of end-organ perfusion.\u201d [ 11 ]  Some of the symptoms, as a consequence, include abdominal pain due to liver engorgement."}
{"_id": "WikiPedia_Cardio$$$corpus_4822", "text": "Cardiac tamponade is caused by a large or uncontrolled  pericardial effusion , i.e. the buildup of fluid inside the pericardium. [ 12 ]  This commonly occurs as a result of  chest trauma  (both blunt and penetrating), [ 13 ]  but can also be caused by  myocardial infarction ,  myocardial rupture ,  cancer  (most often  Hodgkin lymphoma ),  uremia ,  pericarditis , or cardiac surgery, [ 12 ]  and rarely occurs during retrograde  aortic dissection , [ 14 ]  or while the person is taking anticoagulant therapy. [ 15 ]  The effusion can occur rapidly (as in the case of trauma or myocardial rupture), or over a more gradual period of time (as in cancer). The fluid involved is often  blood , but  pus  is also found in some circumstances. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4823", "text": "One of the most common settings for cardiac tamponade is in the first 7 days after heart surgery. [ 16 ]   After heart surgery,  chest tubes  are placed to drain blood.  These chest tubes, however, are prone to clot formation.  When a chest tube becomes occluded or clogged, the blood that should be drained can accumulate around the heart, leading to tamponade. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4824", "text": "The pericardium, the double-walled sac surrounding the heart, consists of a fibrous pericardium layer on the outside and a double-layered serous pericardium on the inside. [ 18 ]  Between the two layers of the serous pericardium is the pericardial space, which is filled with lubricating serous fluid that prevents friction as the heart contracts. [ 19 ]  The outer layer of the heart is made of fibrous tissue [ 20 ]  which does not easily stretch, so once excess fluid begins to enter the pericardial space, pressure starts to increase. [ 12 ]  Consequently, the heart becomes compressed due to its inability to fully relax. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4825", "text": "If fluid continues to accumulate, each successive diastolic period leads to less blood entering the ventricles. Eventually, increasing pressure on the heart forces the  septum  to bend in towards the  left ventricle , leading to a decrease in  stroke volume . [ 12 ]  This causes the development of  obstructive shock , which if left untreated may lead to  cardiac arrest  (often presenting as  pulseless electrical activity ). [ 22 ]  The decrease in stroke volume can also ultimately lead to a decrease in cardiac output, which could be signaled by tachycardia and hypotension. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4826", "text": "The three classic signs, known as  Beck's triad , are  low blood pressure , jugular-venous distension, and muffled  heart sounds . [ 24 ]  Other signs may include  pulsus paradoxus  (a drop of at least 10 mmHg in arterial blood pressure with inspiration), [ 12 ]  and  ST segment  changes on the  electrocardiogram , [ 24 ]  which may also show low voltage  QRS complexes . [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4827", "text": "Tamponade can often be diagnosed radiographically.  Echocardiography , which is the diagnostic test of choice, often demonstrates an enlarged pericardium or collapsed ventricles. A large cardiac tamponade will show as an enlarged globular-shaped heart on chest x-ray. During inspiration, the negative pressure in the  thoracic cavity  will cause increased pressure into the right ventricle.  This increased pressure in the right ventricle will cause the interventricular septum to bulge towards the left ventricle, leading to decreased filling of the left ventricle. At the same time, right ventricle volume is markedly diminished and sometimes it can collapse. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4828", "text": "Initial diagnosis of cardiac tamponade can be challenging, as there is a broad  differential diagnosis . [ 10 ]  The differential includes possible diagnoses based on symptoms, time course, mechanism of injury, patient history. Rapid onset cardiac tamponade may also appear similar to pleural effusions,  obstructive shock , shock, pulmonary embolism, and  tension pneumothorax . [ 13 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4829", "text": "If symptoms appeared more gradually, the differential diagnosis includes acute  heart failure . [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4830", "text": "In a person with trauma presenting with  pulseless electrical activity  in the absence of hypovolemia and tension pneumothorax, the most likely diagnosis is cardiac tamponade. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4831", "text": "In addition to the diagnostic complications afforded by the wide-ranging differential diagnosis for chest pain, diagnosis can be additionally complicated by the fact that people will often be weak or faint at presentation. For instance, a fast rate of breathing and difficulty breathing on exertion that progresses to air hunger at rest can be a key diagnostic symptom, but it may not be possible to obtain such information from people who are unconscious or who have convulsions at presentation. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4832", "text": "Initial treatment given will usually be supportive in nature, for example administration of  oxygen , and monitoring. There is little care that can be provided pre-hospital other than general treatment for shock. Some teams have performed an emergency  thoracotomy  to release clotting in the  pericardium  caused by a penetrating chest injury. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4833", "text": "Prompt diagnosis and treatment is the key to survival with tamponade.  Some pre-hospital providers will have facilities to provide  pericardiocentesis , which can be life-saving.  If the person has already suffered a  cardiac arrest , pericardiocentesis alone cannot ensure survival, and so rapid evacuation to a hospital is usually the more appropriate course of action. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4834", "text": "Initial management in hospital is by pericardiocentesis. [ 13 ]  This involves the insertion of a needle through the skin and into the pericardium and aspirating fluid under ultrasound guidance preferably. This can be done laterally through the intercostal spaces, usually the fifth, or as a subxiphoid approach. [ 27 ] [ 28 ]  A left parasternal approach begins 3 to 5\u00a0cm left of the sternum to avoid the left internal mammary artery, in the 5th  intercostal space . [ 29 ]  Often, a  cannula  is left in place during resuscitation following initial drainage so that the procedure can be performed again if the need arises. If facilities are available, an emergency  pericardial window  may be performed instead, [ 13 ]  during which the pericardium is cut open to allow fluid to drain. Following stabilization of the person, surgery is provided to seal the source of the bleed and mend the pericardium. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4835", "text": "Following heart surgery, the amount of chest tube drainage is monitored.  If the drainage volume drops off, and the blood pressure goes down, this can suggest a tamponade due to chest tube clogging.  In that case, the person is taken back to the operating room for an emergency reoperation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4836", "text": "If aggressive treatment is offered immediately and no complications arise (shock, AMI or arrhythmia, heart failure, aneurysm, carditis, embolism, or rupture), or they are dealt with quickly and fully contained, then adequate survival is still a distinct possibility. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4837", "text": "The frequency of tamponade is unclear. [ 9 ]  One estimate from the United States places it at 2 per 10,000 per year. [ 3 ]  It is estimated to occur in 2% of those with stab or gunshot wounds to the chest. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4838", "text": "Cardiogenic shock  is a medical emergency resulting from inadequate blood flow to the body's organs due to the dysfunction of the  heart . Signs of inadequate blood flow include low urine production (<30 mL/hour), cool arms and legs, and decreased level of consciousness. People may also have a severely low blood pressure and heart rate."}
{"_id": "WikiPedia_Cardio$$$corpus_4839", "text": "Causes of cardiogenic shock include  cardiomyopathic , arrhythmic, and mechanical. Cardiogenic shock is most commonly precipitated by  a heart attack . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4840", "text": "Treatment of cardiogenic shock depends on the cause with the initial goals to improve blood flow to the body. If cardiogenic shock is due to a heart attack, attempts to  open the heart's arteries  may help. Certain medications, such as dobutamine and milrinone, improve the heart's ability to contract and can also be used. When these measures fail, more advanced options such as mechanical support devices or heart transplantation can be pursued."}
{"_id": "WikiPedia_Cardio$$$corpus_4841", "text": "Cardiogenic shock is a condition that is difficult to fully reverse even with an early diagnosis. [ 4 ]  However, early initiation of treatment may improve outcomes. Care should also be directed to any other organs that are affected by this lack of blood flow (e.g.,  dialysis  for the kidneys, mechanical ventilation for lung dysfunction)."}
{"_id": "WikiPedia_Cardio$$$corpus_4842", "text": "Mortality rates for cardiogenic shock are high but have been decreasing in the United States. This is likely due to its rapid identification and treatment in recent decades. Some studies have suggested that this is possibly related to new treatment advances. Nonetheless, the mortality rates remain high and multi-organ failure in addition to cardiogenic shock is associated with higher rates of mortality. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4843", "text": "The presentation is the following: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4844", "text": "Cardiogenic shock is caused by the failure of the heart to pump effectively.  It is due to damage to the  heart muscle , most often from a heart attack or  myocardial contusion . [ 6 ]  Other causes include  abnormal heart rhythms ,  cardiomyopathy ,  heart valve  problems, ventricular outflow obstruction (i.e. systolic anterior motion in  hypertrophic cardiomyopathy ), or ventriculoseptal defects. It can also be caused by a sudden decompressurization (e.g. in an aircraft), where air bubbles are released into the bloodstream ( Henry's law ), causing  heart failure . [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4845", "text": "An  electrocardiogram  helps to establish the exact diagnosis and guides treatment, it may reveal:"}
{"_id": "WikiPedia_Cardio$$$corpus_4846", "text": "Echocardiography  may show poor ventricular function, signs of PED, [ clarification needed ]  rupture of the  interventricular septum , an obstructed outflow tract or cardiomyopathy. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4847", "text": "The  Swan\u2013Ganz catheter  or pulmonary artery catheter may assist in the diagnosis by providing information on the  hemodynamics . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4848", "text": "When cardiomyopathy is suspected as the cause of cardiogenic shock, a  biopsy  of heart muscle may be needed to make a definite  diagnosis . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4849", "text": "If the  cardiac index  falls acutely below 2.2 L/min/m 2 , the person may be in cardiogenic shock. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4850", "text": "Initial management of cardiogenic shock involves medications to augment the heart's function. Certain medications, such as  dobutamine  or  milrinone , enhance the heart's pumping function and are often used first-line to improve the low blood pressure and delivery of blood to the rest of the body. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4851", "text": "Patients who have cardiogenic shock unresponsive to medication therapy may be candidates for more advanced options such as a mechanical circulatory support device. There are several types of mechanical circulatory support devices, the most common being intra-aortic balloon pumps, left ventricular assist devices, and venous-arterial extra-corporeal membrane oxygenation. It is important to note, however, that none of these devices are permanent solutions but rather are a bridge to a more definitive therapy such as a  heart transplantion ."}
{"_id": "WikiPedia_Cardio$$$corpus_4852", "text": "An intra-aortic balloon pump is a device placed by a cardiac surgeon into the  descending aorta . It consists of a small balloon filled with helium that helps the heart to pump blood by inflating during  diastole  (the resting phase of the cardiac cycle) and deflating during  systole  (the contracting phase of the cardiac cycle). [ 16 ]  Intra-aortic balloon pumps do not directly increase cardiac output, but importantly, they decrease the amount of pressure that the heart has to pump against, thereby allowing for more blood flow and oxygen to be delivered to the heart muscles. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4853", "text": "Intra-aortic balloon pumps have been around for several decades and are most commonly used first-line of the mechanical circulatory support devices. [ 4 ]  However, it is not without its potential complications. Potential complications include injury upon insertion of the device to arteries supplying the spinal cord as well as risks with any procedure such as bleeding and infection. [ 17 ]  Contraindications to intra-aortic balloon pumps include aortic dissection, an abdominal aortic aneurysm, and irregularly fast heart beats. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4854", "text": "There are several types of left ventricular assist devices, with the Impella devices being some of the most common. This device is placed by a cardiac surgeon into the  left ventricle  of the heart and essentially acts as a pump, drawing blood from the left ventricle and pushing it out into the aorta so that it could be delivered to the rest of the body. [ 4 ]  Unlike intra-aortic balloon pumps, the Impella acts independently from the cardiac cycle. [ 17 ]  It can be adjusted to pump at faster rates to take blood out of the left ventricle and into the aorta more quickly, thereby decreasing the amount of work that the left ventricle has to do. [ 4 ]  While the Impella is commonly used in settings of cardiogenic shock, some evidence suggests that it placing an Impella device in an acute cardiogenic shock setting, where the heart fails to pump suddenly, may not necessarily guarantee increased survival. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4855", "text": "Potential complications specific to an Impella device include  hemolysis  (shearing of the blood cells) as well as the formation of lesions on the heart valve, namely the  mitral  or  aortic valves . [ 17 ]  Contraindications to an Impella device insertion include aortic dissection, the presence of a mechanical aortic valve, and the presence of a blood clot in the left ventricle. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4856", "text": "Venous-arterial extra-corporeal membrane oxygenation is a circuit support system that is meant to replace the function of the heart as it heals or awaits a more definitive treatment. [ 17 ]  It consists of a circuit that essentially drains blood from a patient's venous system, runs that blood through a circulator which adds oxygen and removes carbon dioxide, and ultimately returns blood back into the patient's arterial system where the newly oxygenated blood can be delivered to the person's organs. Some evidence suggests that the combination of both an Impella device and Venous-arterial extra-corporeal membrane oxygenation may decrease the heart's  pulmonary capillary wedge pressure , thereby decreasing the amount of stress on the cardiac muscles. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4857", "text": "Because Venous-arterial extra-corporeal membrane oxygenation is a very invasive procedure, it is not usually the first-line chosen device for patients in cardiogenic shock and is often reserved only for patients who have not only cardiogenic shock but also respiratory failure and/or concomitant  cardiac arrest . [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4858", "text": "Complications of venous-arterial extra-corporeal membrane oxygenation include an  air embolism ,  pulmonary edema , and blood clotting in the circuit machine. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4859", "text": "Cardiorenal syndrome (CRS)  is an  umbrella term  used in the medical field that defines disorders of the heart and kidneys whereby \"acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other\". [ 1 ]  When one of these organs fails, the other may subsequently fail. [ 2 ]  The heart and the kidneys are involved in maintaining hemodynamic stability and organ perfusion through an intricate network. Patients who have renal failure first may be hard to determine if  heart failure  is concurrent. [ 3 ]  These two organs communicate with one another through a variety of pathways in an interdependent relationship. In a 2004 report from the  National Heart, Lung and Blood Institute , CRS was defined as a condition where treatment of congestive heart failure is limited by decline in kidney function. [ 4 ]  This definition has since been challenged repeatedly but there still remains little consensus over a universally accepted definition for CRS. At a consensus conference of the Acute Dialysis Quality Initiative (ADQI), the CRS was classified into five subtypes primarily based upon the organ that initiated the insult as well as the acuity of disease. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4860", "text": "Cardiorenal Syndrome is characterized by the dysfunction of both the cardiac and renal systems, resulting in a range of clinical manifestations. Many patients will have volume overload and therefore may show clinical signs such as jugular venous distension, generalized swelling of the abdomen and/or the lower legs, and difficulty breathing. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4861", "text": "Patients with Type 1 CRS, have a rapid worsening of cardiac function leading to  Acute Kidney Injury , which may manifest as oliguria or anuria. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4862", "text": "The following risk factors have been associated with increased incidence of CRS. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4863", "text": "The pathophysiology of CRS can be attributed to two broad categories of \"hemodynamic factors\" such as low cardiac output, elevation of both intra-abdominal and central venous pressures, and non-hemodynamic factors or \"cardiorenal connectors\" such as neurohormonal and inflammatory activation. [ 8 ]  It was previously believed that low cardiac output in heart failure patients results in decreased blood flow to the kidneys which can lead to progressive deterioration of kidney function. As a result, diuresis of these patients will result in  hypovolemia  and pre-renal azotemia. However, several studies did not find an association between kidney dysfunction and cardiac output or other hemodynamic parameters. [ 9 ]  In addition, CRS has been observed in patients with diastolic dysfunction who have normal left ventricular systolic function. [ 5 ]  Therefore, there must be additional mechanisms involved in the progression of CRS. Elevated intra-abdominal pressures resulting from ascites and abdominal wall edema may be associated with worsening kidney functions in heart failure patients. Several studies have shown that as a result of this increased intra-abdominal pressure there is increased central venous pressure and congestion of the kidneys' veins, which can lead to worsening kidney function. [ 5 ]  In addition, many neurohormonal and inflammatory agents are implicated in the progression of CRS. These include increased formation of  reactive oxygen species , endothelin, arginine vasopressin, and excessive sympathetic activity which can result in myocardial hypertrophy and necrosis. [ 10 ]  Other cardiorenal connectors include renin-angiotensin-system activation,  nitric oxide / reactive oxygen species  imbalance, inflammatory factors and abnormal activation of the  sympathetic nervous system , which can cause structural and functional abnormalities in both heart and/or the kidney. There is a close interaction within these cardiorenal connectors as well as between these factors and the hemodynamic factors which makes the study of CRS pathophysiology complicated. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4864", "text": "It is critical to diagnose CRS at an early stage in order to achieve optimal therapeutic efficacy. However, unlike markers of heart damage or stress such as  troponin , creatine kinase, natriuretic peptides, reliable markers for acute kidney injury are lacking. Recently, research has found several biomarkers that can be used for early detection of  acute kidney injury  before serious loss of organ function may occur. Several of these biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-B-D-glucosaminidase (NAG), Cystatin C, and kidney injury molecule-1 (KIM-1) which have been shown to be involved in tubular damage. [ 5 ]  Other biomarkers that have been shown to be useful include BNP, IL-18, and fatty acid binding protein (FABP). [ 5 ]  However, there is great variability in the measurement of these biomarkers and their use in diagnosing CRS must be assessed. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4865", "text": "Ronco et al. first proposed a five-part classification system for CRS in 2008 which was also accepted at ADQI consensus conference in 2010. [ 1 ]  These include:"}
{"_id": "WikiPedia_Cardio$$$corpus_4866", "text": "The distinction between CRS type 2 and CRS type 4 is based on the assumption that, also in advanced and chronic disease, two different pathophysiological mechanisms can be distinguished, whereas both CKD and HF often develop due to a common pathophysiological background, most notably  hypertension  and  diabetes mellitus . Furthermore, the feasibility of the distinction between CRS type 2 and 4 in terms of diagnosis can be questioned. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4867", "text": "Braam et al. argue that classifying the CRS based on the order in which the organs are affected and the timeframe (acute vs chronic) is too simplistic and without a mechanistic classification it is difficult to study CRS. [ 8 ]  They view the cardiorenal syndrome in a more holistic, integrative manner. [ 8 ] [ 13 ]  They defined the cardiorenal syndrome as a pathophysiological condition in which combined heart and kidney dysfunction amplifies progression of failure of the individual organ, by inducing similar pathophysiological mechanisms. Therefore, regardless of which organ fails first, the same neurohormonal systems are activated causing accelerated cardiovascular disease, and progression of damage and failure of both organs. These systems are broken down into two broad categories of \"hemodynamic factors\" and non-hemodynamic factors or \"cardiorenal connectors\". [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4868", "text": "Medical management of patients with CRS is often challenging as focus on treatment of one organ may have worsening outcome on the other. It is known that many of the medications used to treat HF may worsen kidney function. \"As the population ages and the burden of renal disease and cardiovascular disease continue to rise, efforts to better understand the complicated relationship between these two organ systems are greatly needed.\" [ 14 ]  In addition, many trials on HF excluded patients with advanced kidney dysfunction. Therefore, our understanding of CRS management is still limited to this date. [ 15 ]  One study shows how ACE inhibitors and angiotensin II receptor antagonists have been found to prevent nephropathy in patients who have diabetes. [ 16 ]  Patients with kidney failure are less likely to get all guideline-based therapies. Patients who have moderate to severe CKD was seen to have similar care when compared to those patients who had normal kidney function. This helps show how healthcare workers can do more to increase the outcome of those suffering. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4869", "text": "Kidney failure is very common in patients with  congestive heart failure . It was shown that kidney failure complicates one-third of all admissions for heart failure, which is the leading cause of hospitalization in the United States among adults over 65 years old. [ 5 ]   Not only is this the leading cause of hospitalization, it also increases the stays in the ICU. [ 21 ]  These complications led to longer hospital stay, higher mortality, and greater chance for readmission. The inpatient mortality was seen to be much higher for patients with much more sever renal dysfunction. [ 17 ]  The increase of hospital and ICU stays also increases the cost of care in the hospital. Not only are there patients suffering from their disease, they are also suffering financially due to the cost of the hospital stays. [ 21 ]  Another study found that 39% of patients in NYHA class 4 and 31% of patients in NYHA class 3 had severely impaired kidney function. [ 22 ]  Similarly, kidney failure can have deleterious effects on cardiovascular function. It was estimated that about 44% of deaths in patients with  end-stage kidney failure  (ESKF) are due to cardiovascular disease. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4870", "text": "Cardiotoxicity  is the occurrence of heart dysfunction as electric or  muscle damage , resulting in heart toxicity. [ 1 ]  This can cause heart failure, arrhythmia, myocarditis, and cardiomyopathy in patients. [ 2 ]  Some effects are reversible, while in others, permanent damage requiring further treatment may arise. The heart becomes weaker and is not as efficient in pumping blood. Cardiotoxicity may be caused by  chemotherapy  (a usual example is the class of  anthracyclines ) [ 3 ] [ 4 ]  treatment and/or radiotherapy; [ 5 ]  complications from  anorexia nervosa ; adverse effects of  heavy metals  intake; [ 6 ]  the long-term abuse of or ingestion at high doses of certain strong  stimulants  such as  cocaine ; [ 7 ]  or an incorrectly administered drug such as  bupivacaine . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4871", "text": "Many mechanisms have been used to explain cardiotoxicity. While many times, differing etiologies share the same mechanism, it generally depends on the agent inducing cardiac damage. For example, the primary mechanism is thought to be oxidative stress on cardiac myocytes. [ 8 ]  It is thought that reactive oxygen species (ROS) overwhelm the antioxidant defenses of cardiac cells, causing direct cellular damage. This oxidative damage can disrupt mitochondrial function, therefore disrupting energy production in the heart muscle itself, leading to energy depletion via depleted ATP and promoting cell death through apoptosis or necrosis. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4872", "text": "Other mechanisms of cardiotoxicity include inflammatory, [ 10 ]  DNA damaging, and disrupted cell signaling. DNA damage and disrupted cellular signaling are the proposed mechanism for many cardiotoxic chemotherapeutics. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4873", "text": "Regardless of the mechanism, clinical manifestations include heart failure, arrhythmia, myocarditis, and cardiomyopathy that can be permanent. [ 2 ]  These conditions can greatly alter mortality and morbidity in patients meaning careful monitoring is necessary in patients exposed to cardiotoxic agents."}
{"_id": "WikiPedia_Cardio$$$corpus_4874", "text": "The list of inciting agents is vast and involves various classes of medication as well as environmental agents. The effects of the cardiotoxic substances vary and are not all identical."}
{"_id": "WikiPedia_Cardio$$$corpus_4875", "text": "Source: [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4876", "text": "Source: [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4877", "text": "These agents can lead to varying degrees of cardiotoxicity, and their effects may be dose-dependent and influenced by individual factors such as pre-existing cardiovascular disease and genetic predispositions that can foster greater sensitivity to any cardiac damage."}
{"_id": "WikiPedia_Cardio$$$corpus_4878", "text": "The most likely effective treatment is to stop exposure to the inciting agent as soon as possible whether a pharmacologic or environmental agent. While some may fully recover from cardiotoxicity caused from exposure, many are left with permanent damage that may need further management. The management varies on the damage sustained, but generally follows guidelines for each condition such as heart failure, arrhythmias, and myocarditis. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4879", "text": "Patients taking anthracyclines can take Dexrazoxane as a cardioprotective agent to prevent extensive cardiac damage. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4880", "text": "Carditis  (pl.  carditides ) is the  inflammation  of the  heart . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4881", "text": "It is usually studied and treated by specifying it as: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4882", "text": "Coronary artery  aneurysm  is an abnormal dilatation of part of the  coronary artery . This rare disorder occurs in about 0.3\u20134.9% of patients who undergo  coronary angiography . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4883", "text": "The majority of individuals suffering from coronary artery aneurysms do not exhibit any symptoms; the development of complications or concurrent atherosclerotic  coronary artery disease  is what causes clinical manifestations to occur. The most common complications include  coronary spasm , distal  embolization ,  aneurysm  rupture, local  thrombosis , and compression of surrounding structures due to massive enlargement of coronary artery aneurysm. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4884", "text": "Acquired causes include  atherosclerosis  in adults, [ 4 ]   Kawasaki disease  in children [ 5 ]  and  coronary catheterization . With the invention of drug eluting stents, there has been more cases implying stents lead to coronary aneurysms. The pathophysiology, although not completely understood, might be comparable to that of aneurysms of larger vessels. This includes disruption of the arterial media, weakening of the  arterial wall , increased wall strain and slow dilatation of the coronary artery portion. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4885", "text": "It can also be congenital. [ 6 ] [ 7 ]  The following risk factors are thought to be associated with coronary artery aneurysms:"}
{"_id": "WikiPedia_Cardio$$$corpus_4886", "text": "It is often found coincidentally on  coronary angiography . [ 3 ]  Other modalities that can be used to diagnose a coronary artery aneurysm include  echocardiography ,  magnetic resonance imaging  and  computerized tomography . Although coronary  angiography  remains to be the gold standard, the invasive procedure comes with its associated risks, is more expensive than other modalities and the size of the aneurysm might be miscalculated if there is a thrombus in place. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4887", "text": "Treatment for coronary artery aneurysm include medical management, surgery and percutaneous intervention. Underlying coronary artery risk factors should be addressed in patients with  atherosclerosis  and proper guideline-mediated medications should be started. In those with risk for embolism or  thrombosis , anti-platelet or anticoagulation therapy should be contemplated. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4888", "text": "In patients with  Kawasaki disease  prompt administration of intravenous  immunoglobulin (IVIG) therapy  should be given to prevent complication of coronary artery aneurysm. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4889", "text": "Generally, it has a good prognosis. [ 3 ] \nThe prognosis of coronary artery aneurysm is dependent on its diameter. The smaller the aneurysm the better the prognosis. There is less risk for ischemic myocardial damage and mortality with smaller aneurysms. Aneurysms with an internal diameter > 8\u00a0mm have poorer outcomes, since these aneurysms can be occluded and be associated with complications such as  arrhythmias ,  myocardial infarction , or sudden death. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4890", "text": "Coronary artery anomalies  are variations of the  coronary circulation , affecting <1% of the general population. Symptoms include chest pain, shortness of breath and  syncope , although cardiac arrest may be the first clinical presentation. Several varieties are identified, with a different potential to cause  sudden cardiac death ."}
{"_id": "WikiPedia_Cardio$$$corpus_4891", "text": "Coronary arteries  are vessels supplying blood and nutrients to the heart muscle ( myocardium ). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4892", "text": "Coronary arteries arise from ostia, openings of the  aorta  (the largest artery in the human body) at the upper third or middle third of the  sinuses of Valsalva  (the first part of the big pipe coming off the main pumping chamber). The walls of coronary arteries consist of three layers: the  tunica intima  or inner layer (possible site of lipid deposits and fibrosis, during life), the  tunica media  (a smooth muscle layer whose tone is modulated by the nervous system, influencing vessel diameter and resistance) and  adventitia  (where nervous endings are located). Normally, the initial portion of coronary arteries lies onto the external surface of the heart (epicardium) where fat deposits tend to form during life. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4893", "text": "In normal anatomy, three essential coronary arteries are identified:  right coronary artery  (RCA),  left anterior descending artery  (LAD) and  left circumflex artery  (LCx). LAD and LCx usually originate from the bifurcation of a common vessel known as  left main  trunk or left coronary artery (LM or LCA).  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4894", "text": "Coronary arteries are identified according to the myocardial territory they feed: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4895", "text": "1) \u00a0 the LAD supplies the anterior interventricular septum and anterior left ventricular free wall;"}
{"_id": "WikiPedia_Cardio$$$corpus_4896", "text": "2) \u00a0 the LCx supplies the posterolateral left ventricular free wall;"}
{"_id": "WikiPedia_Cardio$$$corpus_4897", "text": "3) \u00a0 the RCA supplies the right ventricular free wall;"}
{"_id": "WikiPedia_Cardio$$$corpus_4898", "text": "In fact, despite a certain degree of variability in coronary artery anatomy among individuals, there is greater consistency in the  regions  of the heart that are supplied by the different coronary arteries. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4899", "text": "The  posterior descending artery , providing blood flow to the infero-posterior wall of the heart, originates from the RCA in 70-90% of individuals (\u201cright coronary dominance\u201d), whereas in 10-15% cases it originates from the LCx (\u201cleft coronary dominance\u201d). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4900", "text": "Coronary vessels diameter progressively decreases proceeding from their origin to the periphery. Besides the LM, LAD, LCx and RCA, arterial vessels that are large enough to be identified by clinical angiography are called \u201cbranches\u201d, while  capillaries  represent the smallest peripheral vessels of the coronary tree that lack muscular tissue (and capacity to cause  spasm ) and are responsible for oxygen and nutrients exchange within the myocardium. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4901", "text": "Regarding coronary artery anatomy, a distinction must be provided when assessing abnormalities: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4902", "text": "- \u00a0 \u00a0 \u00a0 normal : any morphological feature observed in >1% of an unselected population"}
{"_id": "WikiPedia_Cardio$$$corpus_4903", "text": "- \u00a0 \u00a0 \u00a0 normal variant : an alternative, unusual but benign morphological feature identified in >1% of the same population (e.g. left main is absent in 1-2% of the general population with LAD and LCx originating from separate ostia - \u201cabsent left trunk\u201d variant)"}
{"_id": "WikiPedia_Cardio$$$corpus_4904", "text": "- \u00a0 \u00a0 \u00a0 coronary artery anomaly (CAA) : a morphological feature seen in <1% of that population, capable of causing dysfunction"}
{"_id": "WikiPedia_Cardio$$$corpus_4905", "text": "The prevalence of coronary artery anomalies is inconsistent across the scientific literature, but they are considered to affect <1% of the general population. Specifically, recent data came from  MRI  screening of a large population (more than 5000 young children) and provided a precise estimate, suggesting that coronary artery anomalies are present in 0.45% of the US population (approximately 1.300.000 people). [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4906", "text": "Anomalous origin of a coronary artery from the opposite sinus are relevant on a clinical level due to a significant association with sudden cardiac death, if they are accompanied by intramural course. Indeed, the main feature responsible for adverse outcomes is the \u201cintramural\u201d course (sometimes improperly referred to as inter-arterial) characterized by an acute ostial angulation (tangential course), \u201cslit-like\u201d ostium (compressed inside the aortic wall), and a proximal or initial section penetrating into the aortic tunica media (coronary arteries normally take off at a 90 degree angle) with subsequent course reaching the \u201ccorrect\u201d side of the heart. As a consequence, lateral compression of the coronary artery leads to coronary luminal (inside opening) narrowing, with reduced supply of blood and oxygen to the depending myocardial tissue, that is phasic (worse in  systole , the phase of cardiac contraction, and tachycardia). Furthermore, the intramural segment of the ectopic artery, located inside the aorta, is typically but variably \u201c hypoplastic \u201d, smaller in circumference than the distal, extramural segments (it is unable to grow properly either before or after birth). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4907", "text": "Autonomic  and/or  endothelial dysfunction  may occur and induce spasm and/or  thrombosis  at anomalous sites (and critical  ischemia ), although intracoronary clotting has been rarely observed. Therefore,  stenosis  of an intramural proximal segment, lateral compression and spastic hyperreactivity are the mechanisms that have been linked to clinical manifestation. Coronary narrowing is most likely the main process implied in ACAOS, and it may result in symptoms such as chest pain (\u201c angina pectoris \u201d),  dyspnea  (shortness of breath), palpitations, cardiac  arrhythmias  (heart rhythm disorders),  syncope  (fainting). In most cases, however, coronary artery anomalies are silent for many years and the first clinical manifestation of these pathological entities is sudden cardiac death (e.g. due to malignant arrhythmias such as  ventricular fibrillation ) typically after strenuous physical exertion (when arterial compression is more severe, and cardiac work is maximal) such as in young athletes or military recruits. Of note, 19-33% (in different studies) of sudden deaths in young athletes are due to coronary artery anomalies. Clinical manifestations can be found in non-athletic, older individuals and are commonly associated with  hypertension  and aortic dilatation with worsening degree of compression."}
{"_id": "WikiPedia_Cardio$$$corpus_4908", "text": "L-ACAOS-IM  (intramural) is seen in 0.1% of young children and, among coronary anomalies, it has the highest probability of clinical repercussions, being consistently associated with sudden cardiac death following physical exercise."}
{"_id": "WikiPedia_Cardio$$$corpus_4909", "text": "Several more varieties of L-ACAOS are described:"}
{"_id": "WikiPedia_Cardio$$$corpus_4910", "text": "- \u00a0 \u00a0 \u00a0 prepulmonic  (L-ACAOS-PP): origin of the LCA (or only the LAD) from the right sinus of Valsalva (RSV) with an epicardial course (on the surface of the heart) anterior to the pulmonary outflow tract - this does not usually cause stenosis nor requires intervention (benign anomaly, unless spasm occurs);"}
{"_id": "WikiPedia_Cardio$$$corpus_4911", "text": "- \u00a0 \u00a0 \u00a0 subpulmonary, infundibular or intraseptal ( L-ACAOS-SP): the LCA (or only the LAD) originates from the RSV, initially runs inter-arterially (outside the aortic wall) then intramyocardially inside in the ventricular septum and finally epicardially in the anterior interventricular groove - this anomaly is considered benign since it is not associated with significant fixed degree of stenosis (but it could cause spasm);"}
{"_id": "WikiPedia_Cardio$$$corpus_4912", "text": "- \u00a0 \u00a0 \u00a0 retroaortic  (L-ACAOS-RA): origin of the LCA or the only LCx from the RSV or from the RCA, running behind the aortic root and at the central fibrous mitro-aortic septum \u2013 this is considered as a benign anomaly (but it could cause spasm);"}
{"_id": "WikiPedia_Cardio$$$corpus_4913", "text": "- \u00a0 \u00a0 \u00a0 retrocardiac  (L-ACAOS-RC) \u2013 LCA originates from the RCA at the atrioventricular groove - or wrap-around the apex (L-ACAOS-WA) \u2013 generally benign, unless spasm occurs."}
{"_id": "WikiPedia_Cardio$$$corpus_4914", "text": "R-ACAOS-IM [ 3 ]  is observed in a higher percentage of cases (0.35% of adolescents) than L-ACAOS-IM [ 4 ]  but is less likely to be associated with sudden cardiac death in athletes. Varieties of R-ACAOS such as prepulmonic, retroaortic and intraseptal can occur and are considered generally benign."}
{"_id": "WikiPedia_Cardio$$$corpus_4915", "text": "The most frequent symptomatic coronary anomaly in infants and young children is anomalous origin of the left coronary artery from the  pulmonary artery , which may cause acute  myocardial infarction  at neonatal age and requires emergent surgery at the time of diagnosis. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4916", "text": "Anomalies at the mid segments  include  myocardial bridges , affecting >1% of the clinical population, and characterized by an intramyocardial course of coronary arteries within the muscle fibers. This may lead to systolic compression which is usually mild (coronary blood flow is mostly  diastolic ). Significant ischemia is rare in isolated myocardial bridges, and if present this is generally due to localized endothelial dysfunction with a tendency to spasm. Most myocardial bridges are benign and do not require any intervention."}
{"_id": "WikiPedia_Cardio$$$corpus_4917", "text": "Coronary artery  aneurysms  are defined as a > 50% increase of the vessel diameter. Some cases are congenital/idiopathic, but most are secondary to atherosclerosis or  Kawasaki disease  (an immuno-inflammatory disease especially targeting coronary vessels wall). Potential complications include localized thrombosis, distal embolization, rupture, or late lipid deposits."}
{"_id": "WikiPedia_Cardio$$$corpus_4918", "text": "Coronary arteriovenous fistulas  are anomalies at the termination consisting of an anomalous connection of coronary arteries to coronary veins, veins of the pulmonary or systemic circulations, or to any cardiac cavity. Smaller fistulas are usually benign, and only severe cases can be complicated by aneurysmatic dilatation with potential thrombosis and distal embolization, volume overload or \u201cblood steal\u201d from arterial circulation and subsequent ischemia. Treatment is generally not required."}
{"_id": "WikiPedia_Cardio$$$corpus_4919", "text": "There is an open debate about the cost/efficiency of generalized diagnostic  screening  in large populations. Carriers of coronary artery anomalies may receive positive results following stress/imaging tests. However, only in a minority of cases ischemia in the context of coronary artery anomalies is reproducible by stress or imaging testing and is mainly associated with particular conditions such as intense (maximal) exercise, which may lead to confusing results and misdiagnosis by techniques such as treadmill test or nuclear testing."}
{"_id": "WikiPedia_Cardio$$$corpus_4920", "text": "Nonetheless, routine screening of high-risk populations (e.g. individuals participating in competitive sports) should be generally encouraged in clinical practice of sports cardiologists."}
{"_id": "WikiPedia_Cardio$$$corpus_4921", "text": "Various imaging tests have a potential to identify coronary artery anomalies.  Echocardiography  (ultrasound scanning of the heart) is simple, non-invasive and economical. Its use for CAAs screening is limited because its diagnostic sensitivity is highly dependent on the operator's skills and is significantly lower in larger individuals (>40\u00a0kg). The diagnostic power of echocardiography is generally poor in most cases after infancy. \u00a0Especially if clinical suspicion for CAAs is high (e.g. syncope following exertion and/or history of aborted sudden cardiac death).\n Cardiac magnetic resonance  (CMR) is an excellent tool to identify coronary artery anomalies with a significantly higher diagnostic accuracy than standard echocardiography. Compared to CMR,  coronary computed tomographic angiography  (CCTA) provides more precise assessment of coronary anatomy, course and degree of  stenosis , but its clinical use for screening is strongly limited by its cost, the need for ionizing radiation, intravenous contrast and, in many cases, drugs administration. Assessment of severity of stenosis is best achieved by intravascular ultrasound (IVUS) imaging and it should be considered in known carriers of ACAOS-IM or that have symptoms or positive stress test results or are involved in competitive exercises. IVUS consists of cross-sectional imaging of coronary arteries in a  catheterization laboratory  by advancing a thin probe inside the vascular lumen, obtaining precise in-vivo information about degree of area stenosis in different arterial segments, providing a solid basis for treatment strategies."}
{"_id": "WikiPedia_Cardio$$$corpus_4922", "text": "CAAs include a wide spectrum of entities with different severity. We can schematically distinguish anomalies at the ostium, such as congenital ostial atresia or stenosis or anomalous origin of a coronary artery from the opposite sinus [ACAOS] (examples: right coronary artery anomalous origin from the opposite sinus [R-ACAOS] and left coronary artery origin from the opposite sinus [L-ACAOS]); anomalies at the mid segments (such as  myocardial bridge  [MB]); anomalies at the termination (such as coronary arteriovenous fistulas). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4923", "text": "Criteria for intervention in ACAOS-IM are:"}
{"_id": "WikiPedia_Cardio$$$corpus_4924", "text": "- \u00a0 \u00a0 \u00a0symptoms of effort-related chest pain, shortness of breath, syncope or aborted sudden cardiac death (Class I, Level of Evidence A/B) and/or high-risk professional lifestyle."}
{"_id": "WikiPedia_Cardio$$$corpus_4925", "text": "- \u00a0 \u00a0 \u00a0positive treadmill stress test, ideally by nuclear technology, in the correct dependent myocardial territory, in the presence of intramural course (Class I, Level of Evidence B)"}
{"_id": "WikiPedia_Cardio$$$corpus_4926", "text": "For special populations, e.g. athletes, treatment may be indicated with specific advice of medical experts, in the absence of the previously mentioned criteria. Cut-off for stenosis severity requiring intervention is not clear, although narrowing >50% in comparison to the distal normal segment is generally accepted as a marker of severity in L-ACAOS-IM. Decisions on treatment should be guided by the patient's individual characteristics such as age, symptoms, profession and level of engagement in physical activity. Pharmacological treatment and observation may be appropriate in selected, low-risk patients. Importantly, untreated carriers of significant ACAOS should not generally engage in competitive sports or strenuous activities."}
{"_id": "WikiPedia_Cardio$$$corpus_4927", "text": "Treatment options for ACAOS-IM include both catheter-based procedures ( percutaneous coronary intervention  [PCI]) and surgical interventions. PCI consists of stent angioplasty of the proximal, intramural segment by placing a thin metal tube (a stent) in order to keep open the narrowed artery. PCI of R-ACAOS-IM is feasible and quite successful, but further experience is needed in L-ACAOS-IM since few cases have been treated percutaneously, while surgery is the recommended treatment in this subpopulation, at this time. Surgery consists of \u201cunroofing\u201d or denudation of the intramural coronary segment from the aortic wall: this approach is currently the gold standard.  Coronary artery bypass grafting  (CABG) and reimplantation of the ectopic artery are obsolete and not indicated, because of competitive flow in mild resting narrowings. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4928", "text": "Coronary artery disease  ( CAD ), also called  coronary heart disease  ( CHD ), or  ischemic heart disease  ( IHD ), [ 13 ]  is a type of  heart disease  involving  the reduction of blood flow  to the  cardiac muscle  due to a build-up of  atheromatous plaque  in the  arteries of the heart . [ 5 ] [ 6 ] [ 14 ]  It is the most common of the  cardiovascular diseases . [ 15 ]  CAD can cause  stable angina ,  unstable angina , myocardial ischemia, [ 16 ]  and  myocardial infarction . [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4929", "text": "A common symptom is angina, which is  chest pain  or discomfort which may travel into the shoulder, arm, back, neck, or jaw. [ 4 ]  Occasionally it may feel like  heartburn . In  stable angina , symptoms occur with exercise or emotional  stress , last less than a few minutes, and improve with rest. [ 4 ]   Shortness of breath  may also occur and sometimes no symptoms are present. [ 4 ]  In many cases, the first sign is a  heart attack . [ 5 ]  Other complications include  heart failure  or an  abnormal heartbeat . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4930", "text": "Risk factors include  high blood pressure ,  smoking ,  diabetes , lack of exercise,  obesity ,  high blood cholesterol , poor diet,  depression , and excessive  alcohol  consumption. [ 6 ] [ 7 ] [ 18 ]  A number of tests may help with diagnosis including:  electrocardiogram ,  cardiac stress testing ,  coronary computed tomographic angiography , biomarkers ( high-sensitivity cardiac troponins ) and  coronary angiogram , among others. [ 8 ] [ 19 ] \nWays to reduce CAD risk include eating a  healthy diet , regularly  exercising , maintaining a healthy weight, and not smoking. [ 20 ] [ 9 ]  Medications for diabetes, high cholesterol, or high blood pressure are sometimes used. [ 9 ]  There is limited evidence for screening people who are at low risk and do not have symptoms. [ 21 ]  Treatment involves the same measures as prevention. [ 10 ] [ 22 ]  Additional medications such as  antiplatelets  (including  aspirin ),  beta blockers , or  nitroglycerin  may be recommended. [ 10 ]  Procedures such as  percutaneous coronary intervention  (PCI) or  coronary artery bypass surgery  (CABG) may be used in severe disease. [ 10 ] [ 23 ]  In those with stable CAD it is unclear if PCI or CABG in addition to the other treatments improves  life expectancy  or decreases heart attack risk. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4931", "text": "In 2015, CAD affected 110 million people and resulted in 8.9 million deaths. [ 11 ] [ 12 ]  It makes up 15.6% of all deaths, making it the  most common cause of death  globally. [ 12 ]  The risk of death from CAD for a given age decreased between 1980 and 2010, especially in  developed countries . [ 25 ]  The number of cases of CAD for a given age also decreased between 1990 and 2010. [ 26 ]  In the United States in 2010, about 20% of those over 65 had CAD, while it was present in 7% of those 45 to 64, and 1.3% of those 18 to 45; [ 27 ]  rates were higher among males than females of a given age. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4932", "text": "The most common symptom is  chest pain  or discomfort that occurs regularly with activity, after eating, or at other predictable times; this phenomenon is termed stable  angina  and is associated with  narrowing  of the  arteries  of the  heart . Angina also includes chest tightness, heaviness, pressure, numbness, fullness, or squeezing. [ 28 ]  Angina that changes in intensity, character or frequency is termed unstable.  Unstable angina  may precede  myocardial infarction . In adults who go to the emergency department with an unclear cause of pain, about 30% have pain due to coronary artery disease. [ 29 ]  Angina, shortness of breath, sweating, nausea or vomiting, and lightheadedness are signs of a heart attack or myocardial infarction, and immediate emergency medical services are crucial. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4933", "text": "With advanced disease, the narrowing of coronary arteries reduces the supply of oxygen-rich blood flowing to the heart, which becomes more pronounced during strenuous activities during which the heart beats faster and has an increased oxygen demand. [ 30 ]  For some, this causes severe symptoms, while others experience no symptoms at all. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4934", "text": "Symptoms in females can differ from those in males, and the most common symptom reported by females of all races is shortness of breath. [ 31 ]  Other symptoms more commonly reported by females than males are extreme fatigue, sleep disturbances, indigestion, and anxiety. [ 32 ]  However, some females experience irregular heartbeat, dizziness, sweating, and nausea. [ 28 ]  Burning, pain, or pressure in the chest or upper abdomen that can travel to the arm or jaw can also be experienced in females, but females less commonly report it than males. [ 32 ]  Generally, females experience symptoms 10 years later than males. [ 33 ]  Females are less likely to recognize symptoms and seek treatment. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4935", "text": "Coronary artery disease is characterized by heart problems that result from atherosclerosis. [ 34 ]  Atherosclerosis is a type of arteriosclerosis which is the \"chronic inflammation of the arteries which causes them to harden and accumulate cholesterol plaques (atheromatous plaques) on the artery walls\". [ 35 ]  CAD has several well-determined risk factors that contribute to atherosclerosis. These risk factors for CAD include \"smoking, diabetes, high blood pressure (hypertension), abnormal (high) amounts of cholesterol and other fat in the blood (dyslipidemia), type 2 diabetes and being overweight or obese (having excess body fat)\" due to lack of exercise and a poor diet. [ 36 ]  Some other risk factors include  high blood pressure ,  smoking ,  diabetes , lack of exercise,  obesity ,  high blood cholesterol , poor diet,  depression ,  family history ,  psychological stress  and excessive  alcohol . [ 6 ] [ 7 ] [ 18 ]  About half of cases are linked to genetics. [ 37 ]  Smoking and obesity are associated with about 36% and 20% of cases, respectively. [ 38 ]  Smoking just one cigarette per day about doubles the risk of CAD. [ 39 ]  Lack of exercise has been linked to 7\u201312% of cases. [ 38 ] [ 40 ]  Exposure to the  herbicide   Agent Orange  may increase risk. [ 41 ]  Rheumatologic diseases such as  rheumatoid arthritis ,  systemic lupus erythematosus ,  psoriasis , and  psoriatic arthritis  are independent risk factors as well. [ 42 ] [ 43 ] [ 44 ] [ 45 ] [ excessive citations ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4936", "text": "Job stress appears to play a minor role accounting for about 3% of cases. [ 38 ]  In one study, females who were free of stress from work life saw an increase in the diameter of their blood vessels, leading to decreased progression of atherosclerosis. [ 46 ]  In contrast, females who had high levels of work-related stress experienced a decrease in the diameter of their blood vessels and significantly increased disease progression. [ 46 ]  Having a  type A behavior pattern , a group of personality characteristics including time urgency, competitiveness, hostility, and impatience, [ 47 ]  is linked to an increased risk of coronary disease. [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4937", "text": "The consumption of different types of  fats  including  trans fat  (trans unsaturated), and  saturated fat , in a diet \"influences the level of cholesterol that is present in the bloodstream\". [ 49 ]  Unsaturated fats originate from plant sources (such as oils). There are two types of unsaturated fats, cis and trans isomers. Cis unsaturated fats are bent in molecular structure and trans are linear in structure. Saturated fats originate from animal sources (such as animal fats) and are also molecularly linear in structure. [ 50 ]  The linear configurations of unsaturated trans and saturated fats allow them to easily accumulate and stack at the arterial walls when consumed in high amounts (and other positive measures towards physical health are not met)."}
{"_id": "WikiPedia_Cardio$$$corpus_4938", "text": "High levels of cholesterol in the bloodstream lead to atherosclerosis. With increased levels of LDL in the bloodstream, \"LDL particles will form deposits and accumulate within the arterial walls, which will lead to the development of plaques, restricting blood flow\". [ 49 ]  The resultant reduction in the heart's blood supply due to atherosclerosis in coronary arteries \"causes shortness of breath, angina pectoris (chest pains that are usually relieved by rest), and potentially fatal heart attacks (myocardial infarctions)\". [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4939", "text": "The  heritability  of coronary artery disease has been estimated between 40% and 60%. [ 51 ]   Genome-wide association studies  have identified over 160 genetic susceptibility loci for coronary artery disease. [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4940", "text": "Several  RNA Transcripts  associated with CAD -  FoxP1 ,  ICOSLG ,  IKZF4/Eos ,  SMYD3 ,  TRIM28 , and  TCF3/E2A  are likely markers of  regulatory T cells  (Tregs), consistent with known reductions in Tregs in CAD. [ 53 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4941", "text": "The RNA changes are mostly related to ciliary and endocytic transcripts, which in the circulating immune system would be related to the  immune synapse . [ 54 ]  One of the most differentially expressed genes,  fibromodulin  (FMOD), which is increased 2.8-fold in CAD, is found mainly in connective tissue [ 55 ]  and is a modulator of the TGF-beta signaling pathway. However, not all of the RNA changes may be related to the immune synapse. For example,  Nebulette , the most down-regulated transcript (2.4-fold), is found in cardiac muscle; it is a 'cytolinker' that connects actin and desmin to facilitate cytoskeletal function and vesicular movement. The endocytic pathway is further modulated by changes in  tubulin , a key microtubule protein, and  fidgetin , a tubulin-severing enzyme that is a marker for cardiovascular risk identified by  genome-wide association study . Protein recycling would be modulated by changes in the proteasomal regulator  SIAH3 , and the ubiquitin ligase  MARCHF10 . On the ciliary aspect of the immune synapse, several of the modulated transcripts are related to ciliary length and function.  Stereocilin  is a partner to  mesothelin , a related  super-helical  protein, whose transcript is also modulated in CAD.  DCDC2 , a double-cortin protein, is a modulator of ciliary length. In the signaling pathways of the immune synapse, there were numerous transcripts that related directly to T cell function and the control of differentiation.  Butyrophilin  is a co-regulator for T cell activation.  Fibromodulin  is a modulator of the TGF-beta signaling pathway, a primary determinant of Tre differentiation. Further impact on the  TGF-beta  pathway is reflected in concurrent changes in the BMP receptor 1B RNA (BMPR1B), because the bone morphogenic proteins are members of the TGF-beta superfamily, and likewise impact Treg differentiation. Several of the transcripts ( TMEM98 ,  NRCAM ,  SFRP5 ,  SHISA2 ) are elements of the Wnt signaling pathway, which is a major determinant of Treg differentiation."}
{"_id": "WikiPedia_Cardio$$$corpus_4942", "text": "Limitation of blood flow to the heart causes  ischemia  (cell starvation secondary to a lack of oxygen) of the heart's  muscle cells . The heart's muscle cells may die from lack of  oxygen  and this is called a  myocardial infarction  (commonly referred to as a heart attack). It leads to damage, death, and eventual scarring of the heart muscle without regrowth of heart muscle cells. Chronic high-grade  narrowing  of the coronary arteries can induce transient  ischemia  which leads to the induction of a  ventricular arrhythmia , which may terminate into a dangerous heart rhythm known as  ventricular fibrillation , which often leads to death. [ 64 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4943", "text": "Typically, coronary artery disease occurs when part of the smooth, elastic lining inside a  coronary artery  (the arteries that supply blood to the heart muscle) develops  atherosclerosis . With atherosclerosis, the artery's lining becomes hardened, stiffened, and accumulates deposits of calcium, fatty lipids, and abnormal inflammatory  cells  \u2013 to form a  plaque . Calcium phosphate (hydroxyapatite) deposits in the muscular layer of the blood vessels appear to play a significant role in stiffening the arteries and inducing the early phase of coronary  arteriosclerosis . This can be seen in a so-called metastatic mechanism of  calciphylaxis  as it occurs in  chronic kidney disease  and  hemodialysis . [ citation needed ]  Although these people have kidney dysfunction, almost fifty percent of them die due to coronary artery disease. Plaques can be thought of as large \"pimples\" that protrude into the channel of an artery, causing partial obstruction to blood flow. People with coronary artery disease might have just one or two  plaques  or might have dozens distributed throughout their  coronary arteries .  A more severe form is  chronic total occlusion  (CTO) when a coronary artery is completely obstructed for more than 3 months. [ 65 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4944", "text": "Microvascular angina  is a type of  angina pectoris  in which chest pain and chest discomfort occur without signs of blockages in the larger  coronary arteries  of their hearts when an  angiogram  (coronary angiogram) is being performed. [ 66 ] [ 67 ] \nThe exact cause of microvascular angina is unknown. Explanations include  microvascular dysfunction  or  epicardial  atherosclerosis. [ 68 ] [ 69 ]  For reasons that are not well understood, females are more likely than males to have it; however,  hormones  and other risk factors unique to females may play a role. [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4945", "text": "The diagnosis of CAD depends largely on the nature of the symptoms and imaging. The first investigation when CAD is suspected is an  electrocardiogram  (ECG/EKG), both for  stable angina  and acute coronary syndrome. An  X-ray of the chest ,  blood tests  and resting  echocardiography  may be performed. [ 71 ] [ 72 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4946", "text": "For stable symptomatic patients, several non-invasive tests can diagnose CAD depending on pre-assessment of the risk profile. Noninvasive imaging options include;  Computed tomography angiography  (CTA) (anatomical imaging, best test in patients with low-risk profile to \"rule out\" the disease),  positron emission tomography  (PET),  single-photon emission computed tomography (SPECT)/nuclear stress test/myocardial scintigraphy  and  stress echocardiography  (the three latter can be summarized as functional noninvasive methods and are typically better to \"rule in\").  Exercise ECG  or stress test is inferior to non-invasive imaging methods due to the risk of false negative and false positive test results. The use of non-invasive imaging is not recommended on individuals who are exhibiting no symptoms and are otherwise at low risk for developing coronary disease. [ 73 ] [ 74 ]  Invasive testing with  coronary angiography  (ICA) can be used when non-invasive testing is inconclusive or show a high event risk. [ 72 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4947", "text": "The diagnosis of  microvascular angina  (previously known as  cardiac syndrome X  \u2013 the rare coronary artery disease that is more common in females, as mentioned, is a diagnosis of exclusion. Therefore, usually, the same tests are used as in any person suspected of having coronary artery disease: [ 75 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4948", "text": "Stable angina  is the most common manifestation of ischemic heart disease, and is associated with reduced quality of life and increased mortality. It is caused by epicardial coronary stenosis which results in reduced blood flow and oxygen supply to the myocardium. [ 76 ] \nStable angina is short-term chest pain during physical exertion caused by an imbalance between myocardial oxygen supply and metabolic oxygen demand. Various forms of  cardiac stress tests  may be used to induce both symptoms and detect changes by way of electrocardiography (using an ECG),  echocardiography  (using  ultrasound  of the heart) or  scintigraphy  (using uptake of  radionuclide  by the heart muscle). If part of the heart seems to receive an insufficient blood supply,  coronary angiography  may be used to identify  stenosis  of the coronary arteries and suitability for  angioplasty  or  bypass surgery . [ 77 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4949", "text": "In minor to moderate cases, nitroglycerine may be used to alleviate acute symptoms of stable angina or may be used immediately before exertion to prevent the onset of angina. Sublingual nitroglycerine is most commonly used to provide rapid relief for acute angina attacks and as a complement to anti-anginal treatments in patients with refractory and recurrent angina. [ 78 ]  When nitroglycerine enters the bloodstream, it forms free radical nitric oxide, or NO, which activates guanylate cyclase and in turn stimulates the release of cyclic GMP. This molecular signaling stimulates smooth muscle relaxation, ultimately resulting in vasodilation and consequently improved blood flow to regions of the heart affected by atherosclerotic plaque. [ 79 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4950", "text": "Stable coronary artery disease (SCAD) is also often called stable ischemic heart disease (SIHD). [ 80 ]  A 2015 monograph explains that \"Regardless of the nomenclature, stable angina is the chief manifestation of SIHD or SCAD.\" [ 80 ]  There are U.S. and European  clinical practice guidelines  for SIHD/SCAD. [ 81 ] [ 82 ] [ 72 ]  In patients with non-severe asymptomatic  aortic valve stenosis  and no overt coronary artery disease, the increased  troponin T  (above 14 pg/mL) was found associated with an increased 5-year event rate of  ischemic cardiac events  ( myocardial infarction ,  percutaneous coronary intervention , or  coronary artery bypass surgery ). [ 83 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4951", "text": "Diagnosis of  acute coronary syndrome  generally takes place in the  emergency department , where ECGs may be performed sequentially to identify \"evolving changes\" (indicating ongoing damage to the heart muscle). Diagnosis is clear-cut if ECGs show elevation of the \" ST segment \", which in the context of severe typical chest pain is strongly indicative of an acute  myocardial infarction  (MI); this is termed a STEMI (ST-elevation MI) and is treated as an emergency with either urgent  coronary angiography  and  percutaneous coronary intervention  (angioplasty with or without  stent  insertion) or with  thrombolysis  (\"clot buster\" medication), whichever is available. In the absence of ST-segment elevation, heart damage is detected by  cardiac markers  (blood tests that identify heart muscle damage). If there is evidence of damage ( infarction ), the chest pain is attributed to a \"non-ST elevation MI\" (NSTEMI). If there is no evidence of damage, the term \"unstable angina\" is used. This process usually necessitates hospital admission and close observation on a  coronary care unit  for possible complications (such as  cardiac arrhythmias  \u2013 irregularities in the heart rate). Depending on the risk assessment, stress testing or angiography may be used to identify and treat coronary artery disease in patients who have had an NSTEMI or unstable angina. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4952", "text": "There are various risk assessment systems for determining the risk of coronary artery disease, with various emphasis on the different variables above. A notable example is  Framingham Score , used in the  Framingham Heart Study . It is mainly based on age, gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking, and systolic blood pressure. When predicting risk in younger adults (18\u201339 years old), the Framingham Risk Score remains below 10\u201312% for all deciles of baseline-predicted risk. [ 84 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4953", "text": "Polygenic score  is another way of risk assessment. In one study the relative risk of incident coronary events was 91% higher among participants at high genetic risk than among those at low genetic risk. [ 85 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4954", "text": "Up to 90% of cardiovascular disease may be preventable if established risk factors are avoided. [ 86 ] [ 87 ]  Prevention involves adequate physical  exercise , decreasing  obesity , treating  high blood pressure , eating a  healthy diet , decreasing  cholesterol  levels, and  stopping smoking . Medications and exercise are roughly equally effective. [ 88 ]  High levels of physical activity reduce the risk of coronary artery disease by about 25%. [ 89 ]  Life's Essential 8 are the key measures for improving and maintaining cardiovascular health, as defined by the American Heart Association. AHA added sleep as a factor influencing heart health in 2022. [ 90 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4955", "text": "Most guidelines recommend combining these preventive strategies. A 2015 Cochrane Review found some evidence that counseling and education to bring about behavioral change might help in high-risk groups. However, there was insufficient evidence to show an effect on mortality or actual cardiovascular events. [ 91 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4956", "text": "In  diabetes mellitus , there is little evidence that very tight  blood sugar  control improves cardiac risk although improved sugar control appears to decrease other problems such as  kidney failure  and  blindness . [ 92 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4957", "text": "A 2024 study published in  The Lancet Diabetes & Endocrinology  found that the oral glucose tolerance test (OGTT) is more effective than hemoglobin A1c (HbA1c) for detecting dysglycemia in patients with coronary artery disease. [ 93 ]  The study highlighted that 2-hour post-load glucose levels of at least 9 mmol/L were strong predictors of cardiovascular outcomes, while HbA1c levels of at least 5.9% were also significant but not independently associated when combined with OGTT results. [ 94 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4958", "text": "A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death. [ 95 ]   Vegetarians  have a lower risk of heart disease, [ 96 ] [ 97 ]  possibly due to their greater consumption of fruits and vegetables. [ 98 ]  Evidence also suggests that the  Mediterranean diet [ 99 ]  and a  high fiber diet  lower the risk. [ 100 ] [ 101 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4959", "text": "The consumption of  trans fat  (commonly found in  hydrogenated  products such as  margarine ) has been shown to cause a precursor to  atherosclerosis [ 102 ]  and increase the risk of coronary artery disease. [ 103 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4960", "text": "Evidence does not support a beneficial role for  omega-3 fatty acid  supplementation in preventing  cardiovascular disease  (including  myocardial infarction  and  sudden cardiac death ). [ 104 ] [ 105 ]  There is tentative evidence that intake of menaquinone ( Vitamin K 2 ), but not phylloquinone ( Vitamin K 1 ), may reduce the risk of CAD  mortality . [ 106 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4961", "text": "Secondary prevention is preventing further sequelae of already established disease. Effective lifestyle changes include:"}
{"_id": "WikiPedia_Cardio$$$corpus_4962", "text": "Aerobic exercise , like walking, jogging, or swimming, can reduce the risk of mortality from coronary artery disease. [ 109 ]  Aerobic exercise can help decrease blood pressure and the amount of blood cholesterol (LDL) over time. It also increases HDL cholesterol. [ 110 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4963", "text": "Although exercise is beneficial, it is unclear whether doctors should spend time counseling patients to exercise. The  U.S. Preventive Services Task Force  found \"insufficient evidence\" to recommend that doctors counsel patients on exercise but \"it did not review the evidence for the effectiveness of physical activity to reduce chronic disease, morbidity, and mortality\", only the effectiveness of counseling itself. [ 111 ]  The  American Heart Association , based on a non-systematic review, recommends that doctors counsel patients on exercise. [ 112 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4964", "text": "Psychological symptoms are common in people with CHD, and while many psychological treatments may be offered following cardiac events, there is no evidence that they change mortality, the risk of revascularization procedures, or the rate of non-fatal myocardial infarction. [ 108 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4965", "text": "Antibiotics for secondary prevention of coronary heart disease"}
{"_id": "WikiPedia_Cardio$$$corpus_4966", "text": "Early studies suggested that antibiotics might help patients with coronary disease to reduce the risk of heart attacks and strokes. [ 113 ]  However, a 2021 Cochrane meta-analysis found that antibiotics given for secondary prevention of coronary heart disease are harmful for people with increased mortality and occurrence of stroke. [ 113 ]  So, the use of antibiotics is not currently supported for preventing secondary coronary heart disease."}
{"_id": "WikiPedia_Cardio$$$corpus_4967", "text": "A thorough systematic review found that indeed there is a link between a CHD condition and brain dysfunction in females. [ 114 ]  Consequently, since research is showing that cardiovascular diseases, like CHD, can play a role as a precursor for dementia, like Alzheimer's disease, individuals with CHD should have a neuropsychological assessment. [ 115 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4968", "text": "There are a number of treatment options for coronary artery disease: [ 116 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4969", "text": "It is recommended that blood pressure typically be reduced to less than 140/90 mmHg. [ 121 ]  The diastolic blood pressure however should not be lower than 60 mmHg. Beta-blockers are recommended first line for this use. [ 121 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4970", "text": "In those with no previous history of heart disease, aspirin decreases the risk of a myocardial infarction but does not change the overall risk of death. [ 122 ]  Aspirin therapy to prevent heart disease is thus recommended only in adults who are at increased risk for cardiovascular events, which may include  postmenopausal   females, males above 40, and younger people with risk factors for coronary heart disease, including  high blood pressure , a family history of heart disease, or  diabetes . The benefits outweigh the harms most favorably in people at high risk for a cardiovascular event, where high risk is defined as at least a 3% chance over a five-year period, but others with lower risk may still find the potential benefits worth the associated risks. [ 123 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4971", "text": "Clopidogrel  plus aspirin (dual anti-platelet therapy) reduces cardiovascular events more than aspirin alone in those with a  STEMI . In others at high risk but not having an acute event, the evidence is weak. [ 124 ]  Specifically, its use does not change the risk of death in this group. [ 125 ]  In those who have had a stent, more than 12 months of clopidogrel plus aspirin does not affect the risk of death. [ 126 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4972", "text": "Revascularization for  acute coronary syndrome  has a mortality benefit. [ 127 ]  Percutaneous revascularization for  stable  ischaemic heart disease does not appear to have benefits over medical therapy alone. [ 128 ]  In those with disease in more than one artery,  coronary artery bypass grafts  appear better than  percutaneous coronary interventions . [ 129 ]  Newer \"anaortic\" or no-touch off-pump coronary artery revascularization techniques have shown reduced postoperative stroke rates comparable to percutaneous coronary intervention. [ 130 ]  Hybrid coronary revascularization has also been shown to be a safe and feasible procedure that may offer some advantages over conventional CABG though it is more expensive. [ 131 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4973", "text": "As of 2010, CAD was the leading cause of death globally resulting in over 7 million deaths. [ 133 ]  This increased from 5.2 million deaths from CAD worldwide in 1990. [ 133 ]  It may affect individuals at any age but becomes dramatically more common at progressively older ages, with approximately a tripling with each decade of life. [ 134 ]  Males are affected more often than females. [ 134 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4974", "text": "The  World Health Organization  reported that: \"The world's biggest killer is ischemic heart disease, responsible for 13% of the world's total deaths. Since 2000, the largest increase in deaths has been for this disease, rising by 2.7 million to 9.1 million deaths in 2021.\" [ 135 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4975", "text": "It is estimated that 60% of the world's cardiovascular disease burden will occur in the South Asian subcontinent despite only accounting for 20% of the world's population. This may be secondary to a combination of genetic predisposition and environmental factors. Organizations such as the  Indian Heart Association  are working with the  World Heart Federation  to raise awareness about this issue. [ 136 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4976", "text": "Coronary artery disease is the leading cause of death for both males and females and accounts for approximately 600,000 deaths in the United States every year. [ 137 ]  According to present trends in the United States, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old  females. [ 138 ]  It is the most common reason for death of males and females over 20 years of age in the United States. [ 139 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4977", "text": "After analysing data from 2 111 882 patients, the recent meta-analysis revealed that the incidence of coronary artery diseases in breast cancer survivors was 4.29 (95% CI 3.09\u20135.94) per 1000 person-years. [ 140 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4978", "text": "Other terms sometimes used for this condition are \"hardening of the arteries\" and \"narrowing of the arteries\". [ 141 ]  In Latin it is known as  morbus ischaemicus cordis  ( MIC )."}
{"_id": "WikiPedia_Cardio$$$corpus_4979", "text": "The Infarct Combat Project (ICP) is an international  nonprofit organization  founded in 1998 which tries to decrease  ischemic heart diseases  through education and research. [ 142 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4980", "text": "In 2016 research into the archives of the  [ failed verification ] Sugar Association , the  trade association  for the  sugar industry  in the US, had sponsored an influential  literature review  published in 1965 in the  New England Journal of Medicine  that downplayed early findings about the role of a diet heavy in sugar in the development of CAD and emphasized the role of fat; that review influenced decades of research funding and guidance on  healthy eating . [ 143 ] [ 144 ] [ 145 ] [ 146 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4981", "text": "Research efforts are focused on new  angiogenic  treatment modalities and various (adult)  stem-cell therapies . A region on  chromosome 17  was confined to families with multiple cases of myocardial infarction. [ 147 ]  Other genome-wide studies have identified a firm risk variant on  chromosome 9  (9p21.3). [ 148 ]  However, these and other  loci  are found in intergenic segments and need further research in understanding how the  phenotype  is affected. [ 149 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4982", "text": "A more controversial link is that between  Chlamydophila pneumoniae  infection and atherosclerosis. [ 150 ]  While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor. [ 151 ]  Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases. [ 152 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4983", "text": "Myeloperoxidase  has been proposed as a  biomarker . [ 153 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4984", "text": "Plant-based nutrition has been suggested as a way to reverse coronary artery disease, [ 154 ]  but strong evidence is still lacking for claims of potential benefits. [ 155 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4985", "text": "Several immunosuppressive drugs targeting the chronic inflammation in coronary artery disease have been tested. [ 156 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4986", "text": "Spontaneous coronary artery dissection  ( SCAD ) is an uncommon but potentially lethal condition in which one of the  coronary arteries  that supply the heart, spontaneously develops a blood collection, or  hematoma , within the artery wall due to a tear in the wall. SCAD is one of the  arterial dissections  that can occur. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4987", "text": "SCAD is a major cause of  heart attacks  in young, otherwise healthy women who usually lack typical cardiovascular risk factors. While the exact cause is not yet known, SCAD is likely related to changes that occur during and after pregnancy, or possibly genetics, hormonal influences, inflammatory issues or changes due to disease. These changes lead to the dissection of the wall which restricts blood flow to the heart and causes symptoms. SCAD is often diagnosed in the  cath lab  with  angiography , though more advanced confirmatory tests exist. While the risk of death due to SCAD is low, it has a relatively high rate of recurrence leading to further heart attack-like symptoms in the future."}
{"_id": "WikiPedia_Cardio$$$corpus_4988", "text": "SCAD often presents like a  heart attack  in young to middle-aged, healthy women. [ 2 ]  This pattern usually includes chest pain, rapid heartbeat, shortness of breath, sweating, extreme tiredness, nausea, and dizziness. [ 3 ]  A minority of people with SCAD may also present in  cardiogenic shock  (2-5%),  ventricular arrhythmias  (3-11%), or after  sudden cardiac death . [ 4 ]  Pregnancy- and postpartum-associated SCAD generally have worse outcomes compared to other cases. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4989", "text": "Risk factors include pregnancy and the  postpartum  period. Evidence suggests that  estrogen - and  progesterone -related vascular changes affect the coronary arteries during this period, contributing to SCAD. [ 4 ]  Some case reports and case series suggest associations with autoimmune inflammatory diseases, but there have not been larger studies to explore this relationship. [ 4 ]  Underlying heritable conditions such as  fibromuscular dysplasia [ 5 ]  and connective-tissue disorders (e.g.,  Marfan syndrome ,  Ehlers\u2013Danlos syndrome , and  Loeys\u2013Dietz syndrome ) are associated with SCAD, [ 6 ] [ 4 ]  SCAD triggers may include severe physical or emotional stress, but many cases have no obvious cause. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4990", "text": "SCAD symptoms are the result of a restriction in the size of the lumen of the affected coronary artery. A bleed within the wall of the artery ( tunica intima ) originating from the microvessels that perfuse this muscular layer ( vasa vasorum ) leads to a collection of blood, or  hematoma , between the layers of the artery wall. [ 1 ] \nThe hematoma pushes close the lumen, preventing blood from flowing to the heart muscle ( myocardium ). In some cases (~30%) this hematoma (also referred to as an intramural hematoma) is also accompanied by a tear in the inner most layer of the artery - a monolayer of  endothelial cells  called the  tunica intima . It is not clear if this precedes or follows a bleed within the wall of the artery. [ 9 ]  The tracking of blood within the artery wall (both in the presence or absence of an intimal tear) is referred to as a \"false  lumen \". [ 10 ] [ 11 ] [ 12 ]  The restriction of blood flow in the 'true' lumen limits the availability of oxygen and nutrients to the heart muscle, or  myocardium . As a result, the myocardium continues to demand oxygen but is not adequately supplied by the coronary artery. This imbalance leads to  ischemia , damage, and in some cases can lead to death of the myocardium tissue, causing a heart attack ( myocardial infarction )."}
{"_id": "WikiPedia_Cardio$$$corpus_4991", "text": "While the molecular mechanisms that underpin SCAD are still poorly understood, studies have implicated dysfunction of the  vasa vasorum , the microvessels that perfuse the muscular layer of the coronary artery, lead to the bleed. There is an inverse correlation between the amount of  vasa vasorum  present in regions of the  coronary artery  and the likelihood of an area being affected by a SCAD. [ 1 ]  It has been hypothesized that alterations in vessel wall strength, owing to dysfunction in the  TGF-\u03b2  pathway, the  extracellular matrix , and  vascular smooth muscle cell  contractility alter the capacity of the  vasa vasorum  to perfuse the vessel wall, leading  to either (1)  a potential microthrombi and bleed, or (2) an area of hypoxia, which would likely induce new microvessel formation  angiogenesis  of new immature (and thus leaky) vessels. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4992", "text": "It is likely that both genetics and environment play a role in SCAD onset. A number of genetic variants have been linked to an increased the risk of SCAD. As with  dissection (medical)  generally, the genes identified implicate dysfunction in four main cellular molecular pathways: the  TGF-\u03b2  pathway, [ 13 ]   extracellular matrix  pathway,  vascular smooth muscle cell  contractility, and cellular metabolism. [ 1 ] \nVariants in genes including  ALDH18A1, COL3A1, COL4A1, FBN1  and  ACVR1  were implicated in a study of 91 unrelated SCAD cases. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4993", "text": "Given the demographics of SCAD, it is important to maintain a high index of suspicion for the condition in otherwise low-risk women presenting with symptoms of  acute coronary syndrome . Initial evaluation may show  ECG  changes of ST elevation, like heart attacks due to other causes. SCAD comprises 2-4% of all cases of acute coronary syndrome. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4994", "text": "With typically elevated cardiac biomarkers and ECG changes, people will often undergo  coronary angiography  evaluation. [ 4 ] [ 15 ] [ 16 ]  It is important to recognize SCAD through angiography as other confirmatory measures carry increased risks. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4995", "text": "There are 3 types of SCAD based on angiographic and anatomical criteria; with the designations based on the location and extent of the hematoma within the walls of the coronary arteries. [ 18 ]  Type 1 SCAD results from an  intimal  tear of the coronary artery (a tear of the innermost layer of the arterial wall) creating a false  lumen  as blood flows into the new space. [ 18 ]  A type 1 SCAD lesion is seen on angiography or  intravascular imaging  as a  radiolucent  flap separating the two flow channels; separating the false lumen from the true lumen of the coronary artery. [ 18 ]  Type 2 SCAD, the most common type of SCAD lesions, seen in 60-75% of patients, occurs due to an intramural hematoma or a collection of blood in the  muscular layer  of the coronary artery wall with the absence of intimal tearing. [ 18 ]  This is seen on coronary angiography as an abrupt change in coronary caliber with a long segment of a diffusely narrowed artery (typically longer than 20\u00a0mm). [ 18 ]  Type 2 SCAD is subdivided into type 2A where the narrowed segment of the coronary artery is flanked by normal caliber segments and type 2B where the stenosis continues to the terminus of a coronary artery. [ 18 ]  Type 3 SCAD, the least common type, is also due to an intramural hematoma causing coronary stenosis, but the lesions are shorter than as seen in type 2 SCAD, being less than 20\u00a0mm in length. [ 18 ]  Due to the short segment of coronary stenosis in type 3 SCAD, it is often difficult to differentiate type 3 SCAD lesions from coronary stenosis due to atherosclerotic plaques and intra-coronary imaging is often needed to distinguish between the two. [ 18 ]  Some authors have proposed a fourth designation of SCAD, type 4 SCAD, in which there is a complete intraluminal occlusion of the coronary artery due to any of the  previously mentioned types (Type 1\u20133). [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4996", "text": "Intracoronary imaging (ICI), consisting of  intracoronary optical coherence tomography  (OCT) and  intravascular ultrasound  (IVUS) can help distinguish SCAD from an  atherosclerotic lesion  when it is difficult to do so with angiography. [ 19 ]  ICI techniques provide a direct view of the walls of the coronary artery to confirm SCAD, but may actually worsen the dissection as the probes are inserted into the damaged area. [ 4 ]  ICI confers a 3.4% risk of  iatrogenic  dissection in people with SCAD compared to 0.2% risk in the general population. [ 4 ]  Between the two ICI methods, OCT - a newer technique - has superior spatial resolution than IVUS and is the preferred technique if ICI is required, [ 4 ]  but the need to inject extra contrast with OCT poses risk for worsening the dissection. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4997", "text": "Some studies propose  coronary CT angiography  to evaluate SCAD in lower-risk people, with research into the approach ongoing. [ 4 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4998", "text": "Management depends upon the presenting symptoms. In most people who are hemodynamically stable without high-risk coronary involvement, conservative medical management with blood pressure control is recommended. [ 4 ] [ 20 ] [ 21 ]  In these people, especially if angiography demonstrates adequate coronary flow, the most likely course usually leads to spontaneous healing, often within 30 days. [ 22 ]  Anti-coagulation should be discontinued upon diagnosis of SCAD on coronary angiography as continuation of anti-coagulation may lead to hematoma and dissection propagation. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_4999", "text": "In cases involving high-risk coronaries, hemodynamic instability, or a lack of improvement or worsening after initial attempts at treatment, urgent treatment with  coronary stents  or  coronary artery bypass surgery  may be necessary. [ 17 ]  Stents carry the risk of worsening the dissection or have an increased risk of other complications as the vessel walls in SCAD are already weak due to the disease before introducing the stent. [ 4 ]  Large studies into coronary artery bypass surgery are lacking, but this approach is used to redirect blood to the heart around the affected area for cases involving the  left main coronary artery  or when other approaches fail. [ 4 ] [ 23 ] [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5000", "text": "Angina , or chest pain due to coronary insufficiency may persist for months after SCAD, sometimes even when repeat angiography shows vessel healing. Anti-anginal agents such as  nitrates ,  calcium channel blockers  and  ranolazine  are indicated as anti-anginal pharmacologic agents after SCAD. [ 18 ]  Control of hypertension is also indicated after SCAD, with  beta blockers  especially showing a reduction in the recurrence of SCAD. [ 18 ]   Statins  are not recommended in the treatment post-SCAD (in the absence of other indications for statins) as the myocardial infarctions in SCAD are not the result of atherosclerotic plaques. [ 18 ]   Cardiac rehabilitation  is recommended for all patients after myocardial infarction due to SCAD and is associated with a reduction in anginal symptoms increased psychological well-being. [ 18 ]   Dual antiplatelet therapy  should be started after percutaneous coronary intervention (stents) is used to treat SCAD and continued for at least 1 year afterwards. [ 18 ]  Dual antiplatelet therapy during the acute phase and for at least 1 year after medically treated SCAD may be also used, based on expert consensus. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5001", "text": "Physical stress is associated with SCAD recurrence but there are no heart rate, blood pressure or weight exercise parameters that are established in those with SCAD. In general, it is recommended that those with SCAD avoid  isometric exercise , high intensity endurance training, exercising to the point of exhaustion and activities involving a prolonged  Valsalva  to reduce the risk of SCAD recurrence. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5002", "text": "After addressing the SCAD, people are often treated with typical post-heart attack care, though people who are pregnant may need altered therapy due to the possibility of some  teratogenic  cardiac medications affecting  fetal development . [ 17 ]  Depending on the clinical situation, providers may screen for associated connective tissue diseases. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5003", "text": "People with SCAD have a low in-hospital mortality after treatment. However, the lesion may worsen after leaving the hospital within the first month. [ 17 ] [ 25 ]  One study suggested a 1.2% mortality rate following SCAD but a 19.9% risk for either death, heart attacks, or strokes. [ 26 ]  Even afterwards, SCAD has a high recurrence risk at 30% within 10 years, often at a different site than the initial lesion - meaning that stents placed in the location of the first lesion may not protect against a second. [ 17 ]  Given the lack of consensus on the cause of SCAD, prevention of future SCAD may include medical therapy, counseling about becoming pregnant again (for those who had pregnancy-associated SCAD), or avoidance of estrogen therapy. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5004", "text": "Research is currently being carried out to identify what causes SCAD, in an effort to prevent recurrence, or potentially onset in at risk family members of SCAD patients. Australian researchers at the  Victor Chang Cardiac Research Institute , for example, have generated  induced pluripotent stem cell  (iPSC) lines from patients to model SCAD 'in a dish'.  [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5005", "text": "SCAD is the most common cause of  heart attacks  in pregnant and  postpartum  women. Over 90% of people who develop SCAD are women. [ 25 ]  It is especially common among women aged 43\u201352. [ 17 ]  With angiography and improved recognition of the condition, diagnosis of SCAD has improved since the early 2010s. While prior studies had reported a SCAD prevalence of less than 1% in patients presenting with acute coronary syndrome, more recent data suggests the prevalence of SCAD in acute coronary syndrome patients may be between 2-4%. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5006", "text": "SCAD was first described in the year 1931, at postmortem examination, in a 42-year-old woman. [ 29 ] [ 28 ]  Due to a lack of recognition and diagnostic technology though, SCAD literature until the 21st century included only case reports and series. [ 28 ]  With the recent advent of coronary angiography and intracoronary imaging, recognition and diagnosis of SCAD has greatly increased, especially in the 2010s. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5007", "text": "Coronary artery ectasia  is a rare disease that occurs in only 0.3-4.9% of people in North America. Coronary artery ectasia is characterized by the enlargement of a  coronary artery  to 1.5 times or more than its normal diameter. [ 1 ]  The disease is commonly  asymptomatic  and is normally discovered when performing tests for other conditions such as  coronary artery disease ,  stable angina  and other acute coronary syndromes. [ 2 ] [ 3 ]  Coronary artery ectasia occurs 4 times more frequently in males than in females and in people who have risk factors for heart disease such as smokers. [ 1 ] [ 4 ] [ 5 ]   While the disease is commonly found in patients with  atherosclerosis  and coronary artery disease, it can occur by itself and in both cases, it can cause health problems. The disease can cause the heart tissue to be deprived of blood and die due to decreased blood flow, and blockages due to blood clots or spasms of the blood vessel. [ 2 ]  This blood flow disruption can cause permanent damage to the muscle if the deprivation is prolonged. Coronary artery ectasia also increases the chance of developing large weak spots in the affected coronary arteries, or  aneurysms  that can rupture and result in death. [ 1 ]  The damage can result in angina which is pain in the chest and is a common complaint in these patients."}
{"_id": "WikiPedia_Cardio$$$corpus_5008", "text": "Coronary artery ectasia is commonly found in patients with diseases of the connective tissue and an increased inflammatory response such as  Marfan syndrome  and  Kawasaki Disease . [ 6 ]   It can also be found transiently in patients that have undergone stent placement resulting in the stretching of the vessels 1. Coronary artery ectasia is characterized by an increased wall stress of the vessel, thinning of the arterial wall which causes progressive dilation and remodelling of the vessel. [ 2 ]  The permanent dilation of the artery is thought to be mainly caused by inflammation, triggered by disease, chemicals, or physical stress of the vessel. [ 3 ]  A meta-analysis study has shown that The pooled unadjusted OR of CAE in subjects with HTN in comparison by subjects without HTN was estimated 1.44 (95\u00a0% CI, 1.24 to 1.68)  Bahremand, M., Zereshki, E., Matin, B.K. et al. Hypertension and coronary artery ectasia: a systematic review and meta-analysis study. Clin Hypertens 27, 14 (2021). https://doi.org/10.1186/s40885-021-00170-6 .The inflammatory response results in an over expression of  matrix metalloproteinases , cysteine proteinases, and serine proteinases that causes the partial breakdown of the vessel and weakens it. [ 3 ] [ 7 ]   The  inflammation response will also trigger  platelet  activation which increases the risk of blood clots. The risk of blood clots will increase due to the turbulent blood flow of the enlarged vessel which can activate platelets and form clots. [ 8 ]  Inflammation elevated oxidative stress is increased, and antioxidant activity is depressed in coronary artery ectasia. This imbalance can cause damage to the cells and cause them to die, weakening the vessels further. [ 9 ]  The activation of the inflammatory response causes a detectable increase in  C reactive protein ,  interleukin-6 ,  tumor necrosis factor alpha  and  cell adhesion molecules , which can be used as a diagnostic marker,. [ 5 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5009", "text": "To discover the extent and severity of coronary artery ectasia there are a variety of diagnostic tools used. The most common method for discovering the disease is through  angiography . Angiography is the procedure where a contrast dye is entered into the vessels and an x-ray is taken, which will allow the vessels to be seen on the x-ray. [ 10 ]  Using angiography clinicians are able to display the size, location and number of vessels affected by the disease. [ 10 ]  Is can also be analyzed through other methods such as  intravascular ultrasound , and  magnetic resonance imaging . [ 10 ]  Using these diagnostic methods, it has been discovered that the disease normally occurs most often in the  right coronary artery , followed by the  left anterior descending artery , and finally the  left anterior circumflex artery . [ 11 ]  Using these methods Coronary artery ectasia can be divided into four different types: Type 1\u00ac\u2192diffuse ectasia in 2-3 different vessels, Type 2\u00ac\u2192 diffuse disease in 1 vessel and local disease in another, Type 3\u00ac\u2192 diffuse disease in one vessel and Type 4\u00ac\u2192 localized or segmental ectasia. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5010", "text": "There are currently no cardiovascular society guidelines or recommendations for the treatment of coronary artery ectasia. Experts in the field urge clinicians to consider anti-platelet therapy, such as Aspirin, to reduce thrombus formation in pocket vortices associated with turbulent blood flow. Dual anti-platelet therapy and full anticoagulation are currently under investigation. The primary etiology of coronary ectasia in adults is atherosclerosis, thus treatment with statin therapy should be considered. Statin therapy may also reduce inflammation and matrix metalloproteinase activation which may reduce the progression of vessel ectasia. Some studies have also suggested the use of  angiotensin converting enzyme inhibitors , as ACE gene polymorphisms have been implicated in disease progression. Risk factor modification is recommended; including tobacco cessation, blood pressure control and avoidance of illicit substance use, specifically cocaine. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5011", "text": "A  coronary occlusion , or  coronary artery disease , is the partial or complete  obstruction  of blood flow in a  coronary artery . This condition was first discussed in 1910 by  Sir William Osler . [ 1 ]  This condition slows or blocks the supply of oxygen-rich blood to the  heart . [ 2 ]  This condition can lead to  myocardial ischemia [ 2 ]  and if untreated, may cause a  heart attack  and heart failure. [ 3 ]  It is the most common form of  cardiovascular disease , and is the leading cause of death in the United States, affecting 18 million adults. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5012", "text": "A coronary occlusion can be caused by smoking, having other heart or blood conditions, or being physically inactive. It is also  hereditary . [ 4 ]  Symptoms include chest pain, shortness of breath, pain in upper body, fatigue, nausea, an irregular heartbeat, and drowsiness. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5013", "text": "To diagnose a coronary occlusion, a doctor may view a patient's medical history, or perform a coronary angiography; a doctor will stick a  catheter  into the wrist or groin, lead it to the heart, and inject a liquid for X-ray imaging. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5014", "text": "To treat a coronary occlusion, medication may be used to relieve symptoms.  Percutaneous coronary intervention  or  coronary artery bypass surgery  may also be used. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5015", "text": "Symptoms include chest pain or  angina ,  shortness of breath , and  fatigue . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5016", "text": "A completely blocked coronary artery will cause a heart attack. [ 6 ]  Common heart attack symptoms include chest pain or  angina , pain or discomfort that spreads to the shoulder, arm, back, neck jaw, teeth or the upper belly, cold sweats, fatigue,  heartburn ,  nausea ,  shortness of breath , or  lightheadedness . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5017", "text": "Coronary occlusion is caused by the buildup of  fats ,  cholesterol  and other substances in and on the walls of the hearts  arteries . [ 6 ]  As plaque builds up, the arteries narrow. [ 7 ]  Plaque often starts building up during childhood and is heavily influence by genetics, but also lifestyle and high blood cholesterol. [ 7 ]  This condition is referred to as  atherosclerosis . [ 6 ]  The buildup on the walls of the hearts arteries is referred to as plaque. Plaque causes arteries to narrow and block blood flow. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5018", "text": "Conditions that aid in the development of coronary artery disease are  diabetes  or  insulin resistance ,  high blood pressure ,  sedentary lifestyle , and  smoking  or  tobacco  use. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5019", "text": "Risk Factors that are not controllable are age,  birth sex , and  family history . [ 6 ]  Getting older increases the risk of damaged and narrowed arteries. [ 6 ]  Men are at a greater risk of coronary artery disease, with women's risk increasing after menopause. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5020", "text": "Coronary occlusion is caused by plaque inside of the blood vessels that direct oxygen rich blood to the heart. [ 8 ]  Plaque is caused by fatty deposits and scar tissue that cling to the walls of coronary arteries. [ 9 ]  The development of plaque takes years and leads to  stenosis  of the  coronary arteries  and progressively reduces blood flow. [ 8 ]  Due to the slower development of this condition, the body will adapt and create small blood vessels that circumvent the blockage. [ 8 ]  The small  blood vessels  form a natural bypass of the blockage, but often do not supply enough blood to meet an increased demand when stressors are applied like  exercise . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5021", "text": "When a plaque has a greater than 50% diameter stenosis, the reduced blood flow through the coronary artery during exertion may lead to  angina . [ 10 ]  Acute coronary events occur when a  thrombus  forms due to disruption of a plaque. [ 10 ]  In acute heart attack, occlusion is greater than in  unstable angina , where arterial occlusion is not full blockage. Downstream embolism of thrombus may also produce  microinfarcts . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5022", "text": "Heart disease is often undiagnosed until a serious problem occurs, such as  heart attack  or  cardiac arrest . [ 11 ]  Regular checkups can lead to an early diagnosis and  preventative treatment . [ 11 ]  Screening tests and risk assessments should begin around age 20 if one does not have any risk factors. [ 11 ]  Screenings should begin in childhood if one has risk factors such as  obesity , sedentary lifestyle, or a family history of  heart conditions . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5023", "text": "Healthcare providers will run blood tests to check for  cholesterol ,  triglycerides ,  lipoproteins ,  sugar , or  proteins  that are a sign of  inflammation . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5024", "text": "To assist in a diagnosis, healthcare providers may also order a  electrocardiogram  (ECG or EKG),  coronary calcium scan,   stress test ,  cardiac magnetic resonance imaging  (MRI),  cardiac positron emission tomography ( PET), invasive  coronary angiography,  and/or  coronary CT angiography . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5025", "text": "Healthcare providers may recommend lifelong  heart-healthy  lifestyle choices. [ 12 ]  These choices included a  heart-healthy eating plan , physical activity, quitting smoking, improved  sleep hygiene ,  weight loss ,  blood pressure control ,  cholesterol  control, blood  pressure  control, and  stress management . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5026", "text": "Some medications may be prescribed to allow the blood vessels to widen and help the heart pump include  ACE inhibitors ,  beta blockers ,  calcium channel blockers ,  nitrates , and  Ranolazine . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5027", "text": "Some medications may be prescribed to manage cholesterol include  statins , nonstatins, and  fribrates . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5028", "text": "Some medications may be prescribed for other risk factors for heart disease like blood sugar and obesity such as  empagliflozin ,  canagliflozin ,  metformin ,  liraglutide ,  orlistat , and  semaglutide . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5029", "text": "Heart surgery  may be needed to treat this condition. Some procedures include  percutaneous coronary intervention  (PCI),  coronary artery bypass grafting  (CABG), and  transmyocardial laser revascularization  ( coronary endarterectomy ). [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5030", "text": "Preventative procedures like  bariatric surgery  can help lower coronary heart disease risk. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5031", "text": "Coronary artery disease cannot be reversed.  [ 3 ]  To reduce future problems, a patient may be referred to get exercise-based  cardiac rehabilitation . [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5032", "text": "Patients with coronary artery disease over 15-year period based off expectations in a 1-year follow up saw a  mortality  rate of those in the highest  quartiles  of expectations are 28-30 deaths per 100 patients. [ 14 ]  The lowest  quartile  of expectations are 50-57 deaths per 100 patients. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5033", "text": "Prognosis for heart attacks when people reach emergency care promptly improve dramatically, though many people still die before reaching the hospital. [ 15 ]  One out of every 10 patients who have a heart attack die within the first three to four months. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5034", "text": "Coronary artery disease is the leading cause of death in men and women. [ 16 ]  This condition is the cause of one third of all deaths, which is especially worse in areas with lower  socioeconomic  status. [ 16 ]  Mortality is nearly five times higher in men than women, but mortality difference narrows with age. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5035", "text": "Black women are more likely than white women to have a heart attack. Black adults have a higher mortality rate than white adults from heart attack.  [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5036", "text": "Asian adults have the least incidence of  coronary artery disease . Asian Indian men, Filipino men and Filipino women have a higher risk than white people. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5037", "text": "Young Hispanic women who have a heart attack have a higher mortality rate than young Hispanic men. They have a higher mortality rate than young Black adults and young white adults. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5038", "text": "Recent studies focus on advanced imagining techniques, pharmacological advancements, and  regenerative therapies . A new heart disease diagnosis approach has led to a 99.1% accuracy in diagnosing heart disease. [ 18 ]  This new diagnosis approach uses  CT-scan  imagery to focus on coronary artery diseases and blockages in contrast to  angiography . [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5039", "text": "Further research directions in preventing and treating coronary artery disease include: [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5040", "text": "Coronary occlusion was first discussed in 1910 by  Sir William Osler  who discussed coronary occlusion during the  Lumleian Lectures . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5041", "text": "In 1912,  James Herrick  published an article in  JAMA  documenting his findings on coronary occlusion in animals. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5042", "text": "According to  Robert K. Massie 's  Nicholas and Alexandra: The Fall of the Romanov Dynasty ,  Tsar Nicholas II  may have suffered a coronary occlusion right before he was toppled from his throne during the Russian Revolution in 1917. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5043", "text": "Coroners cited a coronary occlusion as the cause of death for  Mongomery Clift ."}
{"_id": "WikiPedia_Cardio$$$corpus_5044", "text": "Coronary steal  (with its  symptoms  termed  coronary steal syndrome  or  cardiac steal syndrome ) is a phenomenon where an alteration of  circulation  patterns leads to a reduction in the blood flow directed to the  coronary circulation . [ 1 ]  It is caused when there is narrowing of the  coronary arteries  and a coronary vasodilator [ 2 ]  is used \u2013 \"stealing\" blood away from those parts of the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_5045", "text": "This happens as a result of the narrowed coronary arteries being always maximally dilated to compensate for the decreased upstream blood supply. Thus, dilating the  resistance vessels  in the coronary circulation causes blood to be shunted away from the coronary vessels supplying the  ischemic zones , creating more  ischemia ."}
{"_id": "WikiPedia_Cardio$$$corpus_5046", "text": "Mild coronary steal may occur without any symptoms, but as the syndrome progresses, chest pain is usually the first obvious symptom. In worse cases, symptoms can include dizziness, flushing, headaches, nausea, and shortness of breath. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5047", "text": "It is associated with  dipyridamole . Dipyridamole is thus a pharmacological success diagnostically, but a therapeutic failure because of the coronary steal phenomenon. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5048", "text": "Coronary steal is also the mechanism in most drug-based  cardiac stress tests ; When a patient is incapable of doing physical activity they are given a vasodilator that produces a \"cardiac steal syndrome\" as a diagnostic procedure. The test result is positive if the patient's symptoms reappear or if ECG alterations are seen. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5049", "text": "Hydralazine can potentially cause this condition as well, as it is a direct arteriolar vasodilator. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5050", "text": "It has been associated with  nitroprusside . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5051", "text": "Coronary arteriovenous fistula between coronary artery and another cardiac chamber, like, the coronary sinus, right atrium, or right ventricle may cause steal syndrome under conditions like myocardial infarction and possible angina or ventricular arrhythmias, if the shunt is large in magnitude. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5052", "text": "It can also be associated with new patterns of blood vessel growth. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5053", "text": "Coronary steal syndrome can be diagnosed by:"}
{"_id": "WikiPedia_Cardio$$$corpus_5054", "text": "Coronary steal is sometimes treated by surgery. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5055", "text": "Coronary thrombosis  is defined as the formation of a blood clot inside a blood vessel of the heart. This blood clot may then restrict  blood flow within the heart , leading to heart tissue damage, or a  myocardial infarction , also known as a heart attack. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5056", "text": "Coronary thrombosis is most commonly caused as a downstream effect of  atherosclerosis , a buildup of  cholesterol  and fats in the artery walls. The smaller vessel diameter allows less blood to flow and facilitates progression to a  myocardial infarction . Leading risk factors for coronary thrombosis are high  low-density lipoprotein cholesterol , smoking,  sedentary lifestyle , and  hypertension . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5057", "text": "Symptoms of coronary thrombosis are not always evident at the start. Symptoms include chest pain, shortness of breath, and discomfort in the upper body."}
{"_id": "WikiPedia_Cardio$$$corpus_5058", "text": "A coronary thrombosis is a medical emergency (life threatening) and requires urgent care at a hospital."}
{"_id": "WikiPedia_Cardio$$$corpus_5059", "text": "A coronary thrombus is  asymptomatic  until it causes significant obstruction, leading to various forms of  angina  or eventually a  myocardial infarction . Common warning symptoms are crushing chest pain, shortness of breath, and upper body discomfort. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5060", "text": "Coronary thrombosis and  myocardial infarction  are sometimes used as synonyms, although this is technically inaccurate as the thrombosis refers to the  blocking of blood vessels  with a thrombus, while myocardial infarction refers to heart  tissue death  due to the consequent loss of  blood flow  to the heart. Due to extensive  collateral circulation , a coronary thrombus does not necessarily cause tissue death and may be asymptomatic. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5061", "text": "The formation of coronary thrombosis generally follows the same mechanism as other blood clots in the body, the  coagulation cascade . Also applicable is the  Virchow's triad  of blood stasis,  endothelial  injury, and  hypercoagulable state .  Atherosclerosis  contributes to coronary thrombosis formation by facilitating blood stasis as well as causing local endothelial injury. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5062", "text": "Due to the large number of cases of myocardial infarction leading to death and disease in the world, there has been extensive study towards the generation of clots specifically in the  coronary arteries . [ citation needed ]  Some areas of focus:"}
{"_id": "WikiPedia_Cardio$$$corpus_5063", "text": "Clinical signs of myocardial infarction (heart attack) or  angina  if coronary thrombus is symptomatic:"}
{"_id": "WikiPedia_Cardio$$$corpus_5064", "text": "Imaging modalities used to evaluate the presence of coronary thrombi: [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5065", "text": "Postmortem examiners may look for  Lines of Zahn , to determine whether blood clotted in the heart vessels before or after death. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5066", "text": "Management of symptomatic coronary thrombosis follows established treatment algorithms for myocardial infarction. Treatment options include: [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5067", "text": "To address the possibility of identifying and treating asymptomatic coronary artery disease to prevent development of coronary thrombosis, a study published 2018 determined that preemptive treatment with  percutaneous coronary intervention  did not lead to a difference in death or myocardial infarction over a 15-year period. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5068", "text": "There are numerous treatments currently being studied for management and prevention of coronary thrombosis.  Statin  drugs, in addition to their primary  cholesterol -lowering mechanisms of action, have been studied to target a number of pathways that may decrease coronary  inflammation  and subsequent thrombosis. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5069", "text": "Another realm of potential treatments in early stages of adoption is in therapeutic use of contrast  ultrasound  on thrombus dissolution. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5070", "text": "Thrombosis  is defined as the formation of a  thrombus (blood clot)  inside a  blood vessel , leading to obstruction of blood flow within the  circulatory system . Coronary thrombosis refers to the formation and presence of thrombi in the coronary arteries of the heart. The heart does not contain veins, but rather  coronary sinuses  that serve the purpose of returning  de-oxygenated blood  from the heart muscle. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5071", "text": "A thrombus is a type of  embolism , a more general term for any material that partially or fully blocks a blood vessel. An  atheroembolism , or cholesterol embolism, is when an  atherosclerotic  plaque ruptures and becomes an embolism.  Atherosclerosis  is the progressive thickening of blood vessels and plaque formation that eventually can lead to  coronary artery disease . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5072", "text": "Coronary vasospasm  refers to when a  coronary artery  suddenly undergoes either complete or sub-total temporary occlusion. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5073", "text": "In 1959, Prinzmetal et al. described a type of chest pain resulting from coronary vasospasm, referring to it as a variant form of classical  angina pectoris . [ 2 ]  Consequently, this angina has come to be reported and referred to in the literature as  Prinzmetal angina . [ 3 ]  A subsequent study distinguished this type of angina from classical angina pectoris further by showing normal coronary arteries on  cardiac catheterization . This finding is unlike the typical findings in classical angina pectoris, which usually shows  atherosclerotic  plaques on cardiac catheterization. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5074", "text": "When coronary vasospasm occurs, the occlusion temporarily produces  ischemia . A wide array of symptoms or presentations can follow: ranging from asymptomatic myocardial ischemia, sometimes referred to as silent ischemia, to  myocardial infarction  and even sudden  cardiac death . [ 4 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5075", "text": "Coronary vasospasm classically produces chest pain at rest, also known as  variant angina  (vasospastic angina or Prinzmetal's angina). [ 5 ]  Chest pain is more common at certain times of the day, usually from late night to early morning. [ 6 ]  These episodes can be accompanied by nausea, vomiting, cold sweating, and even syncope. [ 7 ] [ 8 ]  Coronary vasospasm is also associated with symptoms of fatigue and tiredness, dyspnea, and palpitations. [ 5 ]  These can sometimes be the primary presenting symptoms, but they can also occur in conjunction with chest pain. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5076", "text": "There are cases of coronary vasospasm that occur without any symptoms at all, leading to episodes of silent or asymptomatic myocardial ischemia. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5077", "text": "Depending on how long the occlusion lasts, a spectrum of different myocardial ischemic syndromes can occur. Shorter episodes of occlusion can lead to what is referred to as silent myocardial ischemia due to its asymptomatic nature. [ 1 ]  These episodes can also be accompanied by arrhythmias. [ 1 ]  Longer episodes of occlusion can lead to stable or unstable angina, myocardial infarction, and sudden cardiac death. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5078", "text": "Unlike classical  angina pectoris , traditional cardiovascular risk factors are not thought to be significantly associated with coronary vasospasm. [ 9 ]  The exception to this is with smoking, which is known to be a modifiable risk factor for vasospastic angina. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5079", "text": "There are several risk factors that are thought to precipitate, or trigger, episodes of coronary vasospasm. Many of these factors work by exerting effects on the autonomic nervous system. One of the mechanisms through which this occurs is via increasing sympathetic nervous system activity. The resulting increased sympathetic outflow leads to vasoconstrictive effects on blood vessels. [ 9 ]  For example, cocaine use can trigger vasospasm in coronary arteries through its actions on adrenergic receptors causing vasoconstriction. [ 11 ]  Exercise, cold weather, physical activity or exertion, mental stress, hyperventilation are additional precipitating factors. [ 9 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5080", "text": "The exact pathophysiology behind coronary vasospasm has not been elucidated. Instead, a combination of different factors has been proposed to contribute to coronary vasospasm. [ 12 ]  In general, it is thought that an abnormality within a coronary artery causes it to become hyperreactive to vasoconstrictor stimuli. This abnormality can be located in one segment of the coronary artery, or it may be diffuse and present throughout the entire artery. If and when vasoconstrictor stimuli act upon the hyperreactive segment of the artery, then vasospasm can result. [ 9 ]  Ultimately, when large coronary arteries undergo vasospasm, this can lead to either complete or transient occlusion of blood flow within the artery. As a result, ischemia to the tissues served by the artery can occur. Symptoms due to ischemia can follow. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5081", "text": "Some of the factors that have been proposed to contribute to coronary vasospasm include the following: [ 1 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5082", "text": "There are no set criteria to diagnose coronary vasospasm. Thorough history taking by a clinician can assist in the diagnosis of coronary vasospasm. In cases where symptoms of chest pain are present, identifying features that distinguish episodes of vasospastic angina from traditional angina can aid in the diagnosis. [ 6 ]  Features such as chest pain at rest, a diurnal variation in tolerance for exercise with a reduction in tolerance for exercise in the morning, and responsiveness of chest pain to  calcium channel blockers  as opposed to  beta blockers  can be important clues. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5083", "text": "EKG can occasionally be used to diagnose episodes of coronary vasospasm. However, relying on EKG is not always possible due to the transient nature of coronary vasospasm episodes. [ 6 ] [ 19 ]  Due to the challenge of capturing episodes of coronary vasospasm spontaneously, provocative testing to induce coronary vasospasm during coronary catheterization can be used to make the diagnosis. [ 19 ]  Provocative testing relies upon the use of pharmacological agents that promote or trigger episodes of vasospasm. Agents commonly administered include ergonovine and  acetylcholine . Both pharmacological agents have vasoconstrictive effects on coronary arteries. [ 19 ]  However, in the clinical setting, provocative testing is not routinely performed. [ 20 ]  The reason for this is due to the adverse effects of these pharmacological agents. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5084", "text": "When coronary vasospasm causes an artery to undergo complete occlusion, an EKG might show evidence of ST-segment elevation in the leads indicative of that artery's territory. Transient ST-segment depression can also occur, usually in the setting of sub-total occlusion of an artery. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5085", "text": "Additional EKG findings in coronary vasospasm include evidence of arrhythmias that might be induced by ischemia: ventricular premature contractions, ventricular tachycardia, ventricular fibrillation, and more. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5086", "text": "Chest pain due to coronary vasospasm was described in the medical literature by Prinzmetal et al. in 1959. [ 2 ]  This discovery led to this type of angina being referred to in the literature as Prinzmetal angina. [ 3 ] [ 20 ]  A following study further distinguished this angina from classical angina pectoris due to the fact that the results showed that the patients with chest pain due to coronary vasospasm lacked evidence of atherosclerosis on cardiac catheterization. [ 3 ] [ 20 ]  Angina due to coronary vasospasm is also known as variant angina. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5087", "text": "During the 70\u2019s and 80\u2019s, intense research [ 21 ]  headed by Dr. Robert A. Chahine resulted in the delineation of Spasm's role in Prinzmetal's angina, allowing for easy identification and effective treatment. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5088", "text": "C\u0153ur en sabot  (French for \"clog-shaped heart\" or \"boot-shaped heart\" [ 1 ] ) is a  radiological sign  seen most commonly in patients with  tetralogy of Fallot , [ 2 ]  a cyanotic congenital heart disease. It is a radiological term to describe the following findings in the x-ray: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5089", "text": "Echocardiography  has been used for confirmation and differentiation of congenital heart diseases. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5090", "text": "Coxsackieviruses -induced cardiomyopathy  are  positive-stranded  RNA viruses in  picornavirus  family and the genus  enterovirus , acute  enterovirus infections  such as Coxsackievirus B3 have been identified as the cause of  virally induced   acute myocarditis , resulting in  dilated cardiomyopathy . [ 1 ]   Dilated cardiomyopathy in humans can be caused by multiple factors including hereditary defects in the cytoskeletal protein  dystrophin  in  Duchenne muscular dystrophy (DMD)  patients). A heart that undergoes dilated cardiomyopathy shows unique enlargement of ventricles, and thinning of the ventricular wall that may lead to heart failure.  In addition to the genetic defects in dystrophin or other cytoskeletal proteins, a subset of dilated cardiomyopathy is linked to enteroviral infection in the heart, especially coxsackievirus B. Enterovirus infections are responsible for about 30% of the cases of acquired dilated cardiomyopathy in humans. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5091", "text": "Coxsackievirus shows a cardiac tropism partly due to the high expression of coxsackievirus and adenovirus receptors (CAR) in cardiomyocytes. [ 3 ]  Coxsackievirus B genome is approximately 7.4 Kb and translated as a  polycistronic  polyprotein. Upon translation, the  polyprotein  is cleaved by two essential viral proteases, 2A and 3C. The viral protease 2A cleaves the proteins in a sequence specific manner. These viral proteases can also act on host proteins exerting negative effects on the residing cell. Enteroviral protease 2A can cleave the cytoskeletal dystrophin protein in cardiomyocytes disrupting the dystrophin glycoprotein (DCG) complex. The cleavage site of dystrophin by protease 2A occurs in the hinge 3 region of the protein resulting a disruption of DCG complex and loss of  sarcolemma  integrity and increasing myocyte permeability. This eventually results in similar cardiac deformities observed in dilated cardiomyopathy caused by hereditary defects in dystrophin in DMD patients. Additionally, dystrophin deficiency has been shown to increase the severity in dilated cardiomyopathy in a mouse model for DMD. The increased susceptibility of dystrophin deficient heart to coxsackievirus-induced dilated cardiomyopathy is attributed to more efficient release of the virus from infected cells resulting an increase in viral-mediated cytopathic effects. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5092", "text": "Viral-induced dilated cardiomyopathy can be characterized using different methods. A 2011 study showed in coxsackievirus infected heart  proteome , increased levels of fibrotic  extracellular matrix  proteins and reduced amounts of energy-producing enzymes can be observed suggesting they could be characteristic in enteroviral cardiomyopathy. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5093", "text": "There are notable differences between the hereditary dilated cardiomyopathy in DMD and acute coxsackieviral-mediated cardiomyopathy. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5094", "text": "A wide variety of treatment modalities are currently recommended including  Immunosuppressive agents ,  intravenous immunoglobulins (IVIG) , and  antiviral agents  although the effectiveness of these treatments are not well established and no specific treatment is available. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5095", "text": "Duroziez's disease  is a  congenital  variant of  mitral stenosis . It was described in 1877 by  Paul Louis Duroziez . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5096", "text": "Eisenmenger syndrome  or  Eisenmenger's syndrome  is defined as the process in which a long-standing left-to-right  cardiac shunt  caused by a  congenital heart defect  (typically by a  ventricular septal defect ,  atrial septal defect , or less commonly,  patent ductus arteriosus ) causes  pulmonary hypertension [ 1 ] [ 2 ]  and  eventual reversal of the shunt into a  cyanotic   right-to-left shunt . Because of the advent of fetal screening with  echocardiography  early in life, the incidence of heart defects progressing to Eisenmenger syndrome has decreased."}
{"_id": "WikiPedia_Cardio$$$corpus_5097", "text": "Eisenmenger syndrome in a  pregnant  mother can cause serious complications, [ 3 ]  though successful delivery has been reported. [ 4 ]  Maternal mortality ranges from 30% to 60%, and may be attributed to  fainting spells ,  blood clots forming in the veins and traveling to distant sites , hypovolemia,  coughing up blood  or  preeclampsia . Most deaths occur either during or within the first weeks after delivery. [ 5 ]  Pregnant women with Eisenmenger syndrome should be hospitalized after the 20th week of pregnancy, or earlier if clinical deterioration occurs."}
{"_id": "WikiPedia_Cardio$$$corpus_5098", "text": "Signs and symptoms of Eisenmenger syndrome include the following: [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5099", "text": "One of the most severe and common complications of Eisenmenger syndrome is cardiac arrhythmia, especially  supraventricular arrhythmias . Approximately 40% of patients diagnosed with Eisenmenger syndrome were also found to have these arrhythmias during routine  ECG  screenings. These arrhythmias have worse  prognosis  in patients with Eisenmenger syndrome, compared to the general population, and can be a source of  sudden cardiac death . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5100", "text": "A number of congenital heart defects can cause Eisenmenger syndrome, including  atrial septal defects ,  ventricular septal defects ,  patent ductus arteriosus , and more complex types of acyanotic  heart disease . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5101", "text": "Diagnosis of Eisenmenger syndrome is typically conducted via  transthoracic echocardiography , which facilitates the identification and evaluation of shunts, anatomical defects, and ventricular function. Following diagnosis, or in some cases of inconclusive diagnosis, a  cardiac catheter  may be used to both confirm the diagnosis and to assess the patient's pulmonary arterial pressure, an important predictive value for prognosis and treatment. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5102", "text": "If the inciting defect in the heart is identified  before  it causes significant pulmonary hypertension, it can normally be repaired through surgery, preventing the disease. [ 10 ]  After  pulmonary hypertension  is sufficient to reverse the blood flow through the defect, however, the maladaptation is considered irreversible, and a  heart\u2013lung transplant  or a  lung transplant  with repair of the heart is the only curative option.\nTransplantation is the final therapeutic option and only for patients with poor prognosis and quality of life. Timing and appropriateness of transplantation remain difficult decisions. [ 5 ]  5-year and 10-year survival ranges between 70% and 80%, 50% and 70%, 30% and 50%, respectively. [ 11 ] [ 12 ] [ 13 ]  Since the average life expectancy of patients after lung transplantation is as low as 30% at 5 years, patients with  reasonable functional status  related to Eisenmenger syndrome have  improved survival with conservative medical care  compared with transplantation. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5103", "text": "Various medicines and therapies for pulmonary hypertension are under investigation for treatment of the symptoms. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5104", "text": "Antiarrhythmic drugs  are important for many patients with Eisenmenger syndrome, as evidence suggests that arrhythmia-induced sudden cardiac death may be the leading cause of death among patients with the disease. These therapies generally aim to restore and maintain sinus rhythm, but the specific interventions chosen will depend on the nature of the patient's arrhythmia. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5105", "text": "Eisenmenger syndrome was  named [ 16 ]  by Paul Wood after  Victor Eisenmenger , who first described [ 17 ]  the condition in 1897. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5106", "text": "Embryocardia  is a condition in which  S 1  and  S 2  ( the two  heart sounds  that produce the typical \" lubb-dubb \" sound of the heart) become indistinguishable and equally spaced. [ 1 ]  Thus the normal \"lubb-dubb\" rhythm of the heart becomes a \"tic-toc\" rhythm resembling the heart sounds of a  fetus . This indicates a serious loss of natural fluctuation and often precedes a fatal collapse. [ 2 ] [ 3 ]  This condition is observed in  myocarditis . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5107", "text": "Endocardial fibroelastosis  ( EFE ) is a rare  heart  disorder usually occurring in children two years old and younger. [ 1 ]  It may also be considered a reaction to stress, not necessarily a specific disease. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5108", "text": "It should not be confused with  endomyocardial fibrosis . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5109", "text": "EFE is characterized by a thickening of the innermost lining of the heart chambers (the  endocardium ) due to an increase in the amount of supporting connective tissue and elastic fibres. It is an uncommon cause of unexplained  heart failure  in infants and children, and is one component of  HEC syndrome . Fibroelastosis is strongly seen as a primary cause of  restrictive cardiomyopathy  in children, along with  cardiac amyloidosis , which is more commonly seen in progressive multiple myeloma patients and the elderly. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5110", "text": "A review cites references to 31 different diseases and other stresses associated with the EFE reaction. [ 2 ]  These include infections, cardiomyopathies, immunologic diseases, congenital malformations, even electrocution by lightning strike. EFE has two distinct  genetic  forms, each having a different mode of  inheritance . An  X-linked recessive  form, [ 3 ]  and an  autosomal   recessive  form [ 4 ]  have both been observed."}
{"_id": "WikiPedia_Cardio$$$corpus_5111", "text": "A Cardiac MRI can show eccentric patchy thickening of  endocardium which is a non-specific finding. Myocardial biopsy is a definitive test. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5112", "text": "The cause should be identified and, where possible, the treatment should be directed to that cause. A last resort form of treatment is  heart transplant . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5113", "text": "An infant with dilated, failing heart was no rarity on the pediatric wards of hospitals in the mid-twentieth century. On autopsy, most of these patients' hearts showed the thickened endocardial layer noted above. This was thought to be a disease affecting both the heart muscle and the endocardium and it was given various names such as: idiopathic hypertrophy of the heart, endocardial sclerosis, cardiac enlargement of unknown cause, etc. Some of these hearts also had overt congenital anomalies, especially aortic stenosis and coarctation of the aorta. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5114", "text": "The term \"endocardial fibroelastosis\" was introduced by Weinberg and Himmelfarb in 1943. [ 6 ]  In their pathology laboratory they noted that usually the  endocardium  was pearly white or opaque instead of normally thin and transparent and microscopically showed a systematic layering of collagenous and  elastic fibers . They felt their new term was more adequately descriptive, and, indeed it was quickly and widely adopted. Clinicians began applying it to any infant with a dilated, failing heart, in spite of the fact that the only way to definitively establish the presence of EFE was to see it at autopsy. EFE had quickly become the name of a disease, and it continues to be used by many physicians in this way, though many patients with identical symptoms do not have the endocardial reaction of EFE. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5115", "text": "In the latter decades of the twentieth century, new discoveries and new thinking about heart muscle disease gave rise to the term \"cardiomyopathy\". Many of the cases of infantile cardiac failure were accordingly called \"primary cardiomyopathy\" as well as \"primary EFE\", while those with identifiable congenital anomalies stressing the heart were called \"secondary EFE\". In 1957 Black-Schaffer proposed a unitary explanation that stress on the ventricle, of any kind, may trigger the endocardial reaction, so that all EFE could be thought of as secondary. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5116", "text": "Evidence gradually accumulated as to the role of infection as one such type of stress. The studies of Fruhling and colleagues in 1962 were critical. [ 8 ]  They followed a series of epidemics of  Coxsackie virus  infection in their part of France. After each epidemic there were increased numbers of cases with EFE coming to autopsy. On closer study there were cases of pure acute myocarditis, cases of mixed myocarditis and EFE, and cases where myocarditis had healed, leaving just EFE. They were able to culture Coxsackie virus from the tissues of many of the cases at all stages  of this apparent progression. A similar progression from myocarditis to EFE was later observed at Johns Hopkins but no virology was done. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5117", "text": "Noren and colleagues at the  University of Minnesota , acting on an idea floated at a pediatric meeting, were able to show a relation between exposure to maternal  mumps  in fetal life, EFE, and a positive skin test for mumps in infants. [ 10 ]  This brought on a large ongoing controversy and finally prompted a virologist colleague of theirs to inject embryonated eggs with  mumps virus . [ 11 ]  The chicks at first showed the changes of myocarditis, about a year later, typical EFE, and transitional changes in between. Despite this, the controversy about the role of mumps continued as the actual incidence of EFE plummeted. The proponents of mumps as a cause pointed to this as the effect of the recent implementation of widespread mumps immunization. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5118", "text": "Evidence that  viral  infection may play a role as a cause or trigger of EFE was greatly reinforced by the study directed by Towbin in the virus laboratory of  Texas Children's Hospital . [ 12 ]  They applied the methods of today's genetics to old preserved specimens from autopsies of patients with EFE done well before mumps immunization began and found mumps genome in the tissues of over 80% of these patients. It seems undeniable that transplacental mumps infection had been in the past the major cause of EFE, and that immunization was indeed the cause of EFE having become rare. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5119", "text": "Non-infectious causes of EFE have also been studied, spurred by the opening of new avenues of genetics research. Now there are specific named genes associated with certain cardiomyopathies, some of which show the characteristic reaction of EFE. A typical example is Barth syndrome and the responsible gene, tafazzin. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5120", "text": "Developments in echocardiography, both the technology of the machines and the skill of the operators, have made it no longer necessary to see the endocardium at autopsy. EFE can now be found non-invasively by the recording of increased endocardial echos.  Fetal echocardiography has shown that EFE can begin to accumulate as early as 14 weeks of gestation, and increase with incredible rapidity [ 14 ]  and even that it can be reversed if the stress can be removed early in fetal life. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5121", "text": "The North American Pediatric Cardiomyopathy Registry was founded in 2000 and has been supported since by the National Heart, Lung and Blood Institute. Because of the logic of the diagnostic tree, where EFE applies to many branches of the tree and thus cannot occupy a branch, it is not listed by the Registry as a cause but rather, \"with EFE\" is a modifier that can be applied to any cause. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5122", "text": "Thus, the past half-century has seen EFE evolve from a mysterious but frequently observed disease to a rare but much better understood reaction to many diseases and other stresses. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5123", "text": "Eosinophilic myocarditis  is  inflammation  in the  heart muscle  that is caused by the infiltration and destructive activity of a type of  white blood cell , the  eosinophil . Typically, the disorder is associated with  hypereosinophilia , i.e. an eosinophil blood cell count greater than 1,500 per microliter (normal 100 to 400 per microliter). It is distinguished from non-eosinophilic  myocarditis , which is heart inflammation caused by other types of white blood cells, i.e.  lymphocytes  and  monocytes , as well as the respective descendants of these cells,  NK cells  and  macrophages . This distinction is important because the eosinophil-based disorder is due to a particular set of underlying diseases and its preferred treatments differ from those for non-eosinophilic myocarditis. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5124", "text": "Eosinophilic myocarditis is often viewed as a disorder that has three progressive stages. The first stage of eosinophilic myocarditis involves acute inflammation and cardiac cell  necrosis  (i.e. areas of dead cells); it is dominated by symptoms characterized as the  acute coronary syndrome  such as  angina ,  heart attack  and/or  congestive heart failure . The second stage is a thrombotic stage wherein the  endocardium  (i.e. interior wall) of the diseased heart forms  blood clots  which  break off, travel in, and block blood  through  systemic  or  pulmonary  arteries; this stage may dominate the initial presentation in some individuals. The third stage is a fibrotic stage wherein  scarring  replaces damaged heart muscle tissue to cause a clinical presentation dominated by a poorly contracting heart and  cardiac valve disease . [ 3 ] [ 4 ] [ 5 ]  Perhaps less commonly, eosinophilic myocarditis, eosinophilic thrombotic myocarditis, and eosinophilic fibrotic myocarditis are viewed as three separate but sequentially linked disorders in a spectrum of disorders termed eosinophilic cardiac diseases. [ 1 ]  The focus here is on eosinophilic myocarditis as a distinct disorder separate from its thrombotic and fibrotic sequelae."}
{"_id": "WikiPedia_Cardio$$$corpus_5125", "text": "Eosinophilic myocarditis is a rare disorder. It is usually associated with, and considered secondary to, an underlying cause for the pathological behavior of the eosinophils such a  toxic reaction to a drug  (one of its more common causes in developed nations), the consequence of certain types of  parasite  and  protozoan   infections  (a more common cause of the disorder in areas with these infestations), or the result of  excessively high levels of activated blood eosinophils  due to a wide range of other causes. [ 6 ]  The specific treatment (i.e. treatment other than measures to support the cardiovascular system) of eosinophilic myocarditis differs from the specific treatment of other forms of myocarditis in that it is focused on relieving the underlying reason for the excessively high numbers and hyperactivity of eosinophils as well as on inhibiting the pathological actions of these cells. [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5126", "text": "Symptoms in eosinophilic myocarditis are highly variable. They tend to reflect the many underlying disorders causing eosinophil dysfunction as well as the widely differing progression rates of cardiac damage. Before cardiac symptoms are detected, some 66% of cases have symptoms of a common cold and 33% have symptoms of  asthma ,  rhinitis ,  urticarial , or other allergic disorder. Cardiac manifestations of eosinophilic myocarditis range from none to life-threatening conditions such as  cardiogenic shock  or sudden death due to abnormal  heart rhythms . More commonly the presenting cardiac symptoms of the disorder are the same as those seen in other forms of heart disease:  chest pain , shortness of breath, fatigue, chest  palpitations , light headedness, and  syncope . [ 7 ]  In its most extreme form, however, eosinophilic myocarditis can present as acute necrotizing eosinophilic myocarditis, i.e. with symptoms of chaotic and potentially lethal  heart failure  and  heart arrhythmias . This rarest form of the disorder reflects a rapidly progressive and extensive eosinophilic infiltration of the heart that is accompanied by massive  myocardial  cell  necrosis . [ 1 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5127", "text": "Hypereosinophilia  (i.e. blood eosinophil counts at or above 1,500 per microliter) or, less commonly,  eosinophilia  (counts above 500 but below 1,500 per microliter) are found in the vast majority of cases of eosinophilic myocarditis and are valuable clues that point to this rather than other types of myocarditis or myocardial injuries. However, elevated blood eosinophil counts may not occur during the early phase of the disorder. Other, less specific laboratory findings implicate a cardiac disorder but not necessarily eosinophilic myocarditis. These include elevations in blood markers for systemic inflammation (e.g.  C reactive protein ,  erythrocyte sedimentation rate ), elevations in blood markers for cardiac injury (e.g.  creatine kinase ,  troponins ); and abnormal  electrocardiograms  ( mostly  ST segment - T wave  abnormalities). [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5128", "text": "There are many  causes of eosinophilia  that may underlie eosinophilic myocarditis. These causes are classified as primary (i.e. a defect intrinsic to the eosinophil cell line), secondary (induced by an underlying disorder that stimulates the proliferation and activation of eosinophils), or  idiopathic  (i.e. unknown cause). Non-idiopathic causes of the disorder are sub-classified into various forms of  allergic ,  autoimmune ,  infectious , or  malignant  diseases and  hypersensitivity reactions  to drugs, vaccines, or transplanted hearts. While virtually any cause for the elevation and activation of blood eosinophils must be considered as a potential cause for eosinophilic myocarditis,  the following list gives the principal types of eosinophilia known or thought to underlie the disorder. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5129", "text": "Primary conditions that may lead to eosinophilic myocarditis are:"}
{"_id": "WikiPedia_Cardio$$$corpus_5130", "text": "Secondary conditions that may lead to eosinophilic myocarditis are:"}
{"_id": "WikiPedia_Cardio$$$corpus_5131", "text": "The DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe immunological  drug reaction . It differs from other drug reactions in that it:  a)  is caused by a particular set of drugs;  b)  typically occurs after a delay of 2 to 8 weeks following intake of an offending drug;  c)  presents with a specific set of signs and symptoms (i.e.  modest  or  extreme  elevations in blood  eosinophil  and  atypical lymphocyte  counts; acute onset of a skin rash;  lymphadenopathy ; fever;  neuralgia ; and involvement of at least one internal organ such as the liver, lung, or heart;  d)  develops in individuals with particular genetic predispositions; and  e)  involves reactivation of  latent viruses , most commonly  human herpesvirus 6  or more rarely  human herpes virus 5  (i.e. human cytomegalovirus),  human herpesvirus 7 , and  human herpesvirus 4  (i.e. Epstein\u2013Barr virus). These viruses usually become dormant after infecting humans but under special circumstances, such as drug intake, are reactivated and may contribute to serious diseases such as the DRESS syndrome. [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5132", "text": "Eosinophils normally function to neutralize invading microbes, primarily  parasites  but also certain types of fungi and viruses. In conducting these functions, eosinophils normally occupy the gastrointestinal tract, respiratory tract, and skin where they produce and release on demand a range of toxic reactive oxygen species (e.g.  hypobromite ,  hypobromous acid ,  superoxide , and  peroxide ) and also release on demand a preformed armamentarium of chemical signals including  cytokines ,  chemokines ,  growth factors , lipid mediators (e.g.  leukotrienes ,  prostaglandins ,  platelet activating factor ,  5-oxo-eicosatetraenoic acid ), and toxic proteins (e.g.  metalloproteinases ,  major basic protein ,  eosinophil cationic protein ,  eosinophil peroxidase , and  eosinophil-derived neurotoxin ). These agents serve to orchestrate robust  inflammatory responses  that destroy invading  microorganisms . Eosinophils also participate in  transplant rejection ,  Graft-versus-host disease , the destruction or walling off of foreign objects, and the killing of  cancer cells . In conducting these functions, eosinophils enter tissues that they do not normally occupy. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5133", "text": "When overproduced and over-activated, such as in cases of eosinophilic myocarditis, eosinophils behave as though they were attacking a foreign or malignant tissue: they enter a seemingly normal organ such as the heart, misdirect their reactive oxygen species and armamentarium of preformed molecules toward seemingly normal tissue such as heart muscle, and thereby produce serious damage such as heart failure. [ 1 ] [ 22 ] [ 23 ] [ 24 ]  Animal model studies suggest reasons why eosinophils are directed to and injure the heart muscle. Mice made hypereosinophilic by the forced overexpression of an interleukin-5 transgene ( interleukin 5  stimulates eosinophil proliferation, activation, and migration) develop eosinophilic myocarditis. A similar eosinophilic endocarditis occurs in mice immunized with the cardiac muscle protein, mouse myosin. In the latter model, endocarditis is reduced by inhibiting the cytokine  interleukin-4  or eosinophils and is exacerbated by concurrently blocking two cytokines,  interferon gamma  and  interleukin-17A . Finally, certain eosinophil- attracting  agents, viz.,  eotaxins , are elevated in the cardiac tissue of myosin-immunized mice that are concurrently depleted of interferon-gamma and interleukin-17A. Eotaxins are also elevated in the cardiac muscle biopsy specimens of individuals with eosinophilic myocarditis compared to their levels in non-eosinophilic myocarditis. These findings suggest that eosinophilic myocarditis is caused by the abnormal proliferation and activation of eosinophils and that their directional migration into the heart is evoked by a set of cytokines and chemoattractants in mice and possibly humans. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5134", "text": "In eosinophilic myocarditis,  echocardiography  typically gives non-specific and only occasional findings of  endocardium  thickening,  left ventricular hypertrophy , left ventricle dilation, and involvement of the  mitral  and/or  tricuspid valves . However, in acute necrotizing eosinophilic myocarditis, echocardiography usually gives diagnostically helpful evidence of a non-enlarged heart with a thickened and poorly contracting  left ventricle .  Gadolinium -based  cardiac magnetic resonance  imaging is the most useful  non-invasive procedure  for diagnosing eosinophilic myocarditis. It supports this diagnosis if it shows at least two of the following abnormalities:  a)  an increased signal in  T2-weighted images ;  b)  an increased global myocardial early enhancement ratio between myocardial and  skeletal muscle  in enhanced  T1 images  and  c)  one or more focal enhancements distributed in a non-vascular pattern in late enhanced T1-weighted images. Additionally, and unlike in other forms of myocarditis, eosinophilic myocarditis may also show enhanced gadolinium uptake in the sub-endocardium. [ 1 ] [ 7 ]  However, the only definitive test for eosinophilic myocarditis is cardiac muscle biopsy showing the presence of eosinophilic infiltration. Since the disorder may be patchy, multiple tissue samples taken during the procedure improve the chances of uncovering the pathology but in any case, negative results do not exclude the diagnosis. [ 5 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5135", "text": "Eosinophilic coronary periarteritis is an extremely rare heart disorder caused by extensive eosinophilic infiltration of the  adventitia  and periadventitia, i.e. the soft tissues, surrounding the  coronary arteries . The  intima ,  tunica media , and  tunica intima  layers of these arteries remain intact and are generally unaffected. Thus, this disorder is characterized by episodes of  angina , particularly  Prinzmetal's angina , and chaotic heart  arrhythmias  which may lead to sudden death. The disorder is considered distinct from eosinophilic myocarditis as well as other forms of  inflammatory arterial disorders  in that it is limited to the coronary artery system. [ 1 ] [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5136", "text": "Due to its rarity, no comprehensive treatment studies on eosinophilic myocarditis have been conducted. Small studies and  case reports  have directed efforts towards:  a)  supporting cardiac function by relieving heart failure and suppressing life-threatening  abnormal heart rhythms ;  b)  suppressing eosinophil-based cardiac inflammation; and  c)  treating the underlying disorder. In all cases of symptomatic eosinophilic myocarditis that lack specific treatment regimens for the underlying disorder, available studies recommend treating the inflammatory component of this disorder with non-specific  immunosuppressive drugs , principally high-dosage followed by slowly tapering to a low-dosage maintenance  corticosteroid  regimens. It is recommended that affected individuals who fail this regimen or present with  cardiogenic shock  be treated with other non-specific immunosuppressive drugs viz.,  azathioprine  or  cyclophosphamide , as adjuncts to, or replacements for, corticosteroids. However, individuals with an underlying therapeutically accessible disease should be treated for this disease; in seriously symptomatic cases, such individuals may be treated concurrently with a corticosteroid regimen. Examples of diseases underlying eosinophilic myocarditis that are recommended for treatments directed at the underlying disease include  [ 6 ] [ 7 ] [ 12 ] [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5137", "text": "The prognosis of eosinophilic myocarditis is anywhere from rapidly fatal to extremely chronic or non-fatal. Progression at a moderate rate over many months to years is the most common prognosis. [ 1 ] [ 9 ]  In addition to the speed of inflammation-based heart muscle injury, the prognosis of eosinophilic myocarditis may be dominated by that of its underlying cause. For example, an underlying malignant cause for eosinophilia may be survival-limiting. [ 6 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5138", "text": "In 1936, the famed Swiss physician  Wilhem L\u00f6ffler  first described heart damage that appeared due to massive cardiac eosinophil infiltrations and was associated with excessively high levels of blood eosinophils. Subsequent cases of this disorder, termed  Loeffler endocarditis , were found to occur in about 20% of individuals diagnosed with the  hypereosinophilic syndrome . Loeffler's and the latter cases had pathological features of eosinophil infiltrations not only into the heart's  myocardium  but also its  epicardium  (i.e. lining of the heart chambers). Although eosinophilic myocarditis due to other underlying causes may show little or no eosinophil infiltrations into the endocardium, Loeffler endocarditis is considered an important form of the disorder. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5139", "text": "Heart failure  ( HF ), also known as  congestive heart failure  ( CHF ), is a  syndrome  caused by an impairment in the  heart 's ability to  fill with and pump   blood ."}
{"_id": "WikiPedia_Cardio$$$corpus_5140", "text": "Although symptoms vary based on which side of the heart is affected, HF typically presents with  shortness of breath ,  excessive fatigue , and bilateral  leg swelling . [ 3 ]  The severity of the heart failure is mainly decided based on  ejection fraction  and also measured by the severity of symptoms. [ 7 ]  Other conditions that have symptoms similar to heart failure include  obesity ,  kidney failure ,  liver disease ,  anemia , and  thyroid disease . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5141", "text": "Common causes of heart failure include  coronary artery disease ,  heart attack ,  high blood pressure ,  atrial fibrillation ,  valvular heart disease ,  excessive alcohol consumption ,  infection , and  cardiomyopathy . [ 4 ] [ 6 ]  These cause heart failure by altering the structure or the function of the heart or in some cases both. [ 6 ]  There are different types of heart failure:  right-sided heart failure , which affects the  right heart ,  left-sided heart failure , which affects the  left heart , and biventricular heart failure, which affects both sides of the heart. [ 11 ]  Left-sided heart failure may be present with a reduced  ejection fraction  or with a  preserved ejection fraction . [ 10 ]  Heart failure is not the same as  cardiac arrest , in which blood flow stops completely due to the failure of the heart to pump. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5142", "text": "Diagnosis is based on symptoms, physical findings, and  echocardiography . [ 6 ]   Blood tests , and a  chest x-ray  may be useful to determine the underlying cause. [ 14 ]  Treatment depends on severity and case. [ 15 ]  For people with chronic, stable, or mild heart failure, treatment usually consists of lifestyle changes, such as  not smoking ,  physical exercise , and dietary changes, as well as medications. [ 16 ] [ 17 ] [ 18 ]  In heart failure due to left ventricular dysfunction,  angiotensin-converting-enzyme inhibitors ,  angiotensin II receptor blockers  (ARBs), or  angiotensin receptor-neprilysin inhibitors , along with  beta blockers ,  mineralocorticoid receptor antagonists  and  SGLT2 inhibitors  are recommended. [ 6 ]   Diuretics  may also be prescribed to prevent fluid retention and the resulting shortness of breath. [ 19 ]  Depending on the case, an implanted device such as a  pacemaker  or  implantable cardiac defibrillator   may sometimes be recommended. [ 15 ]  In some moderate or more severe cases,  cardiac resynchronization therapy  (CRT) [ 20 ]  or  cardiac contractility modulation  may be beneficial. [ 21 ]  In severe disease that persists despite all other measures, a cardiac assist device  ventricular assist device , or, occasionally,  heart transplantation  may be recommended. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5143", "text": "Heart failure is a common, costly, and potentially fatal condition, [ 22 ]  and is the leading cause of hospitalization and readmission in older adults. [ 23 ] [ 24 ]  Heart failure often leads to more drastic health impairments than the failure of other, similarly complex  organs  such as the kidneys or liver. [ 25 ]  In 2015, it affected about 40 million people worldwide. [ 8 ]  Overall, heart failure affects about 2% of adults, [ 22 ]  and more than 10% of those over the age of 70. [ 6 ]  Rates are predicted to increase. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5144", "text": "The risk of  death  in the first year after diagnosis is about 35%, while the risk of death in the second year is less than 10% in those still alive. [ 10 ]  The risk of death is comparable to that of some cancers. [ 10 ]  In the United Kingdom, the disease is the reason for 5% of emergency hospital admissions. [ 10 ]  Heart failure has been known since ancient times in  Egypt ; it is mentioned in the  Ebers Papyrus  around 1550 BCE. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5145", "text": "When the heart functions poorly as a pump and does not circulate blood adequately via the  circulatory system  to meet the demands of the body the term cardiovascular insufficiency is sometimes used. This generally leads to the syndrome of heart failure, a combination of  signs and symptoms [ 6 ] :\u200a3612\u200a [ 3 ]  It develops when the heart fails to properly fill with blood during  diastole , resulting in a decrease in  intracardiac pressures  or in ejection during  systole , reducing cardiac output to the rest of the body. [ 6 ] :\u200a3612\u200a [ 4 ] :\u200ae272\u200a  The filling failure and high intracardiac pressure can lead to fluid accumulation in ventricles of the heart. This manifests as water retention and swelling due to fluid accumulation ( edema ) called  congestion . Impaired ejection can lead to inadequate blood flow to the body tissues, resulting in  ischemia . [ 27 ] [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5146", "text": "Congestive heart failure is a  pathophysiological  condition in which the  heart's output  is insufficient to meet the needs of the body and lungs. [ 10 ]  The term \"congestive heart failure\" is often used because one of the most common symptoms is  congestion  or fluid accumulation in the tissues and veins of the lungs or other parts of a person's body. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5147", "text": "Congestion manifests itself particularly in the form of  fluid accumulation and swelling (edema) , in the form of  peripheral edema  (causing swollen limbs and feet) and  pulmonary edema  (causing difficulty breathing) and  ascites  (swollen abdomen). [ 28 ]   Pulse pressure , which is the difference between the systolic (\"top number\") and diastolic (\"bottom number\") blood pressures, is often low/narrow (i.e. 25% or less of the level of the systolic) in people with heart failure, and this can be an early warning sign. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5148", "text": "Symptoms of heart failure are traditionally divided into left-sided and right-sided because the left and right ventricles supply different parts of the circulation. In biventricular heart failure, both sides of the heart are affected. Left-sided heart failure is the more common. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5149", "text": "The left side of the heart takes oxygen-rich blood from the lungs and pumps it to the rest of the  circulatory system  in the body (except for the  pulmonary circulation ). Failure of the left side of the heart causes blood to back up into the lungs, causing breathing difficulties and fatigue due to an insufficient supply of oxygenated blood. Common respiratory signs include  increased respiratory rate  and labored breathing (nonspecific signs of shortness of breath).  Rales  or crackles are heard initially in the lung bases and when severe in all  lung fields  indicate the development of  pulmonary edema  (fluid in the  alveoli ).  Cyanosis , indicates  deficiency of oxygen in the blood , is a late sign of extremely severe pulmonary edema. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5150", "text": "Other signs of left ventricular failure include a laterally displaced  apex beat  (which occurs when the heart is enlarged) and a  gallop rhythm  (additional heart sounds), which may be heard as a sign of increased blood flow or increased intracardiac pressure.  Heart murmurs  may indicate the presence of valvular heart disease, either as a cause (e.g.,  aortic stenosis ) or as a consequence (e.g.,  mitral regurgitation ) of heart failure. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5151", "text": "Reverse  insufficiency of the left ventricle causes congestion in the blood vessels of the lungs so that symptoms are predominantly respiratory. Reverse insufficiency can be divided into the failure of the left atrium, the left ventricle, or both within the left circuit. Patients will experience  shortness of breath (dyspnea)  on exertion and, in severe cases, dyspnea at rest. Increasing breathlessness while lying down, called  orthopnea , also occurs. It can be measured by the number of pillows required to lie comfortably, with extreme cases of orthopnea forcing the patient to sleep sitting up. Another symptom of heart failure is  paroxysmal nocturnal dyspnea : a sudden nocturnal attack of severe shortness of breath, usually occurring several hours after falling asleep. [ 33 ]  There may be \" cardiac asthma \" or  wheezing . Impaired left ventricular  forward  function can lead to symptoms of poor systemic perfusion such as  dizziness ,  confusion , and cool extremities at rest. Loss of consciousness may also occur due to loss of blood supply to the brain. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5152", "text": "Right-sided heart failure is often caused by  pulmonary heart disease  (cor pulmonale), which is typically caused by issues with  pulmonary circulation  such as  pulmonary hypertension  or  pulmonic stenosis . Physical examination may reveal pitting peripheral edema, ascites,  liver enlargement , and  spleen enlargement .  Jugular venous pressure  is frequently assessed as a marker of fluid status, which can be accentuated by testing  hepatojugular reflux . If the right ventricular pressure is increased, a  parasternal heave  which causes the compensatory increase in contraction strength may be present. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5153", "text": "Backward  failure of the right ventricle leads to congestion of systemic capillaries. This generates excess fluid accumulation in the body. This causes swelling under the skin ( peripheral edema  or  anasarca ) and usually affects the dependent parts of the body first, causing foot and ankle swelling in people who are standing up and  sacral  edema in people who are predominantly lying down.  Nocturia  (frequent night-time urination) may occur when fluid from the legs is returned to the bloodstream while lying down at night. In progressively severe cases, ascites (fluid accumulation in the abdominal cavity causing swelling) and liver enlargement may develop. Significant liver congestion may result in impaired liver function ( congestive hepatopathy ), jaundice, and  coagulopathy  (problems of decreased or increased blood clotting). [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5154", "text": "Dullness of the lung fields when  percussed  and reduced breath sounds at the base of the lungs may suggest the development of a  pleural effusion  (fluid collection  between the lung and the chest wall ). Though it can occur in isolated left- or right-sided heart failure, it is more common in biventricular failure because pleural veins drain into both the systemic and pulmonary venous systems. When unilateral, effusions are often right-sided. [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5155", "text": "If a person with a failure of one ventricle lives long enough, it will tend to progress to failure of both ventricles. For example, left ventricular failure allows pulmonary edema and pulmonary hypertension to occur, which increases stress on the right ventricle. Though still harmful, right ventricular failure is not as deleterious to the left side. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5156", "text": "Since heart failure is a  syndrome  and not a disease, establishing the underlying cause is vital to diagnosis and treatment. [ 39 ] [ 30 ]  In heart failure, the structure or the function of the heart or in some cases both are altered. [ 6 ] :\u200a3612\u200a  Heart failure is the potential end stage of all heart diseases. [ 40 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5157", "text": "Common causes of heart failure include  coronary artery disease , including a previous  myocardial infarction  (heart attack),  high blood pressure ,  atrial fibrillation ,  valvular heart disease ,  excess alcohol use ,  infection , and  cardiomyopathy  of an unknown cause. [ 9 ] [ 4 ] :\u200ae279\u200a [ 6 ] :\u200aTable 5\u200a  In addition, viral infection and subsequent inflammation of the heart's myocardial tissue (termed  myocarditis ) can similarly contribute to the development of heart failure. Genetic predisposition plays an important role. If more than one cause is present, progression is more likely and prognosis is worse. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5158", "text": "Heart damage  can predispose a person to develop heart failure later in life and has many causes including systemic viral infections (e.g.,  HIV ),  chemotherapeutic agents  such as  daunorubicin ,  cyclophosphamide ,  trastuzumab  and  substance use disorders  of substances such as  alcohol ,  cocaine , and  methamphetamine . An uncommon cause is exposure to certain toxins such as  lead  and  cobalt . Additionally, infiltrative disorders such as  amyloidosis  and  connective tissue diseases  such as  systemic lupus erythematosus  have similar consequences.  Obstructive sleep apnea  (a condition of sleep wherein disordered breathing overlaps with obesity, hypertension, and/or diabetes) is regarded as an independent cause of heart failure. [ 42 ]  Recent reports from  clinical trials  have also linked variation in blood pressure to heart failure [ 43 ] [ 44 ]  and cardiac changes that may give rise to heart failure. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5159", "text": "High-output heart failure  happens when the amount of blood pumped out is more than typical and the heart cannot keep up. [ 46 ]  This can occur in  overload  situations such as blood or serum infusions, kidney diseases, chronic severe  anemia ,  beriberi  (vitamin B 1 / thiamine  deficiency),  hyperthyroidism ,  cirrhosis ,  Paget's disease ,  multiple myeloma ,  arteriovenous fistulae , or  arteriovenous malformations . [ 47 ] [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5160", "text": "Chronic stable heart failure may easily  decompensate  (fail to meet the body's metabolic needs). This most commonly results from a concurrent illness (such as  myocardial infarction  (a heart attack) or  pneumonia ),  abnormal heart rhythms , uncontrolled  hypertension , or a person's failure to maintain a fluid restriction, diet, or medication. [ 49 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5161", "text": "Other factors that may worsen CHF include: anemia, hyperthyroidism, excessive fluid or salt intake, and medication such as  NSAIDs  and  thiazolidinediones . [ 50 ]  NSAIDs increase the risk twofold. [ 51 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5162", "text": "A number of medications may cause or worsen the disease. This includes  NSAIDs ,  COX-2 inhibitors , a number of  anesthetic  agents such as  ketamine , thiazolidinediones, some  cancer medications , several  antiarrhythmic medications ,  pregabalin ,  alpha-2 adrenergic receptor agonists ,  minoxidil ,  itraconazole ,  cilostazol ,  anagrelide ,  stimulants  (e.g.,  methylphenidate ),  tricyclic antidepressants ,  lithium ,  antipsychotics ,  dopamine agonists ,  TNF inhibitors ,  calcium channel blockers  (especially  verapamil  and  diltiazem [ 52 ] [ 53 ] ),  salbutamol , and  tamsulosin . [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5163", "text": "By inhibiting the formation of  prostaglandins , NSAIDs may exacerbate heart failure through several mechanisms, including promotion of fluid retention, increasing  blood pressure , and decreasing a person's response to diuretic medications. [ 54 ]  Similarly, the ACC/AHA recommends against using COX-2 inhibitor medications in people with heart failure. [ 54 ]  Thiazolidinediones have been strongly linked to new cases of heart failure and worsening of pre-existing congestive heart failure due to their association with weight gain and fluid retention. [ 54 ]  Certain calcium channel blockers, such as  diltiazem  and  verapamil , are known to  decrease the force with which the heart ejects blood , thus are not recommended in people with heart failure with a reduced ejection fraction. [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5164", "text": "Breast cancer patients are at high risk of heart failure due to several factors. [ 55 ]  After analyzing data from 26 studies (836,301 patients), the recent meta-analysis found that breast cancer survivors demonstrated a higher risk heart failure within first ten years after diagnosis (hazard ratio = 1.21; 95% CI: 1.1, 1.33). [ 56 ]  The pooled incidence of heart failure in breast cancer survivors was 4.44 (95% CI 3.33-5.92) per 1000 person-years of follow-up. [ 56 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5165", "text": "Certain  alternative medicines  carry a risk of exacerbating existing heart failure, and are not recommended. [ 54 ]  This includes  aconite ,  ginseng ,  gossypol ,  gynura ,  licorice ,  lily of the valley ,  tetrandrine , and  yohimbine . [ 54 ]  Aconite can cause abnormally slow heart rates and abnormal heart rhythms such as ventricular tachycardia. [ 54 ]  Ginseng can cause abnormally low or high blood pressure and may interfere with the effects of diuretic medications. Gossypol can increase the effects of diuretics, leading to toxicity."}
{"_id": "WikiPedia_Cardio$$$corpus_5166", "text": "Gynura can cause low blood pressure. Licorice can worsen heart failure by increasing blood pressure and promoting fluid retention. [ 54 ]  Lily of the Valley can cause abnormally slow heart rates with mechanisms similar to those of digoxin. Tetrandrine can lower blood pressure by inhibiting  L-type calcium channels . Yohimbine can exacerbate heart failure by increasing blood pressure through alpha-2 adrenergic receptor antagonism. [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5167", "text": "Heart failure is caused by any condition that reduces the efficiency of the heart muscle, through damage or  overloading . Over time, these increases in workload, which are mediated by long-term activation of neurohormonal systems such as the  renin\u2013angiotensin system  and the sympathoadrenal system, lead to  fibrosis , dilation, and structural changes in the shape of the left ventricle from elliptical to spherical. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5168", "text": "The heart of a person with heart failure may have a reduced force of contraction due to overloading of the  ventricle . In a normal heart, increased filling of the ventricle results in increased contraction force by the  Frank\u2013Starling law of the heart , and thus a rise in  cardiac output . In heart failure, this mechanism fails, as the ventricle is loaded with blood to the point where heart muscle contraction becomes less efficient. This is due to the reduced ability to cross-link  actin  and  myosin   myofilaments  in over-stretched heart muscle. [ 57 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5169", "text": "No diagnostic criteria have been agreed on as the  gold standard  for heart failure, especially  heart failure with preserved ejection fraction  (HFpEF)."}
{"_id": "WikiPedia_Cardio$$$corpus_5170", "text": "In the  UK , the  National Institute for Health and Care Excellence  recommends measuring  N-terminal pro-BNP (NT-proBNP)  followed by an  ultrasound of the heart  if positive. [ 14 ]  In  Europe , the  European Society of Cardiology , and in the United States, the  AHA / ACC / HFSA , recommend measuring NT-proBNP or BNP followed by an  ultrasound of the heart  if positive. [ 6 ] [ 4 ]  This is recommended in those with symptoms consistent with heart failure such as  shortness of breath . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5171", "text": "The  European Society of Cardiology  defines the diagnosis of heart failure as symptoms and signs consistent with heart failure in combination with \"objective evidence of cardiac structural or functional abnormalities\". [ 6 ]  This definition is consistent with an international 2021 report termed \"Universal Definition of Heart Failure\". [ 6 ] :\u200a3613\u200a  Score-based algorithms have been developed to help in the diagnosis of  HFpEF , which can be challenging for physicians to diagnose. [ 6 ] :\u200a3630\u200a  The  AHA / ACC / HFSA  defines heart failure as symptoms and signs consistent with heart failure in combination with shown \"structural and functional alterations of the heart as the underlying cause for the clinical presentation\", for HFmrEF and HFpEF specifically requiring \"evidence of spontaneous or provokable increased left ventricle filling pressures\". [ 4 ] :\u200ae276\u2013e277"}
{"_id": "WikiPedia_Cardio$$$corpus_5172", "text": "The  European Society of Cardiology  has developed a diagnostic algorithm for  HFpEF , named HFA-PEFF. [ 6 ] :\u200a3630\u200a [ 58 ]  HFA-PEFF considers symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes, elderly, atrial fibrillation), and diagnostic laboratory tests, ECG, and echocardiography. [ 4 ] :\u200ae277\u200a [ 58 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5173", "text": "One historical method of categorizing heart failure is by the side of the heart involved (left heart failure versus right heart failure). Right heart failure was thought to compromise blood flow to the lungs compared to left heart failure compromising blood flow to the  aorta  and consequently to the brain and the remainder of the body's systemic circulation. However, mixed presentations are common, and left heart failure is a common cause of right heart failure. [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5174", "text": "A more accurate classification of heart failure type is made by measuring  ejection fraction , or the proportion of blood pumped out of the heart during a single contraction. [ 60 ]  Ejection fraction is given as a percentage with the normal range being between 50 and 75%. [ 60 ]  The types are:"}
{"_id": "WikiPedia_Cardio$$$corpus_5175", "text": "Heart failure may also be classified as acute or chronic. Chronic heart failure is a long-term condition, usually kept stable by the treatment of symptoms.  Acute decompensated heart failure  is a worsening of chronic heart failure symptoms, which can result in  acute respiratory distress . [ 66 ]   High-output heart failure  can occur when there is increased cardiac demand that results in increased left ventricular diastolic pressure which can develop into pulmonary congestion (pulmonary edema). [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5176", "text": "Several terms are closely related to heart failure and may be the cause of heart failure, but should not be confused with it.  Cardiac arrest  and  asystole  refer to situations in which no cardiac output occurs at all. Without urgent treatment, these events result in sudden death. Myocardial infarction (\"Heart attack\") refers to heart muscle damage due to insufficient blood supply, usually as a result of a blocked  coronary artery . Cardiomyopathy refers specifically to problems within the heart muscle, and these problems can result in heart failure. [ 67 ]  Ischemic cardiomyopathy implies that the cause of muscle damage is coronary artery disease.  Dilated cardiomyopathy  implies that the muscle damage has resulted in enlargement of the heart. [ 68 ]   Hypertrophic cardiomyopathy  involves enlargement and  thickening  of the heart muscle. [ 69 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5177", "text": "An  echocardiogram  ( ultrasound  of the heart) is commonly used to support a clinical diagnosis of heart failure. This can determine the  stroke volume  (SV, the amount of blood in the heart that exits the ventricles with each beat), the  end-diastolic volume  (EDV, the total amount of blood at the end of diastole), and the SV in proportion to the EDV, a value known as the  ejection fraction  (EF). In pediatrics, the  shortening fraction  is the preferred measure of systolic function. Normally, the EF should be between 50 and 70%; in systolic heart failure, it drops below 40%. Echocardiography can also identify valvular heart disease and assess the state of the  pericardium  (the connective tissue sac surrounding the heart). Echocardiography may also aid in deciding specific treatments, such as medication, insertion of an  implantable cardioverter-defibrillator , or  cardiac resynchronization therapy . Echocardiography can also help determine if acute myocardial ischemia is the precipitating cause, and may manifest as regional wall motion abnormalities on echo. [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5178", "text": "Chest X-rays  are frequently used to aid in the diagnosis of CHF. In a person who is compensated, this may show  cardiomegaly  (visible enlargement of the heart), quantified as the  cardiothoracic ratio  (proportion of the heart size to the chest). In left ventricular failure, evidence may exist of vascular redistribution (upper lobe blood diversion or cephalization),  Kerley lines ,  cuffing of the areas around  the  bronchi , and interstitial edema. Ultrasound of the lung may also detect Kerley lines. [ 72 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5179", "text": "An  electrocardiogram  (ECG or EKG) may be used to identify  arrhythmias ,  ischemic heart disease ,  right  and  left ventricular hypertrophy , and presence of conduction delay or abnormalities (e.g.  left bundle branch block ). Although these findings are not specific to the diagnosis of heart failure, a normal ECG virtually excludes left ventricular systolic dysfunction. [ 73 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5180", "text": "N-terminal pro-BNP (NT-proBNP)  is the favored biomarker for the diagnosis of heart failure, according to guidelines published 2018 by  NICE  in the  UK . [ 3 ]   Brain natriuretic peptide 32  (BNP) is another biomarker commonly tested for heart failure. [ 74 ] [ 6 ] [ 75 ]  An elevated NT-proBNP or BNP is a specific test indicative of heart failure. Additionally, NT-proBNP or BNP can be used to differentiate between causes of dyspnea due to heart failure from other causes of dyspnea. If a myocardial infarction is suspected, various  cardiac markers  may be used."}
{"_id": "WikiPedia_Cardio$$$corpus_5181", "text": "Blood tests  routinely performed include  electrolytes  ( sodium ,  potassium ), measures of  kidney function ,  liver function tests ,  thyroid function tests , a  complete blood count , and often  C-reactive protein  if infection is suspected."}
{"_id": "WikiPedia_Cardio$$$corpus_5182", "text": "Hyponatremia  (low serum sodium concentration) is common in heart failure.  Vasopressin  levels are usually increased, along with renin, angiotensin II, and catecholamines to compensate for reduced circulating volume due to inadequate cardiac output. This leads to increased fluid and sodium retention in the body; the rate of fluid retention is higher than the rate of sodium retention in the body, this phenomenon causes hypervolemic hyponatremia (low sodium concentration due to high body fluid retention). This phenomenon is more common in older women with low body mass. Severe hyponatremia can result in accumulation of fluid in the brain, causing  cerebral edema  and  intracranial hemorrhage . [ 76 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5183", "text": "Angiography  is the  X-ray  imaging of  blood vessels , which is done by injecting contrast agents into the  bloodstream  through a thin plastic tube ( catheter ), which is placed directly in the blood vessel. X-ray images are called angiograms. [ 77 ]  Heart failure may be the result of coronary artery disease, and its prognosis depends in part on the ability of the  coronary arteries  to supply blood to the  myocardium  (heart muscle). As a result,  coronary catheterization  may be used to identify possibilities for revascularisation through  percutaneous coronary intervention  or  bypass surgery ."}
{"_id": "WikiPedia_Cardio$$$corpus_5184", "text": "Heart failure is commonly stratified by the degree of functional impairment conferred by the severity of the heart failure, as reflected in the  New York Heart Association (NYHA) functional classification . [ 78 ]  The NYHA functional classes (I\u2013IV) begin with class I, which is defined as a person who experiences no limitation in any activities and has no symptoms from ordinary activities. People with NYHA class II heart failure have slight, mild limitations with everyday activities; the person is comfortable at rest or with mild exertion. With NYHA class III heart failure, a marked limitation occurs with any activity; the person is comfortable only at rest. A person with NYHA class IV heart failure is symptomatic at rest and becomes quite uncomfortable with any physical activity. This score documents the severity of symptoms and can be used to assess response to treatment. While its use is widespread, the NYHA score is not very reproducible and does not reliably predict walking distance or exercise tolerance on formal testing. [ 79 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5185", "text": "In its 2001 guidelines, the  American College of Cardiology / American Heart Association  working group introduced four stages of heart failure: [ 80 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5186", "text": "The ACC staging system is useful since stage A encompasses \"pre-heart failure\" \u2013 a stage where intervention with treatment can presumably prevent progression to overt symptoms. ACC stage A does not have a corresponding NYHA class. ACC stage B would correspond to NYHA class I. ACC stage C corresponds to NYHA class II and III, while ACC stage D overlaps with NYHA class IV."}
{"_id": "WikiPedia_Cardio$$$corpus_5187", "text": "Histopathology  can diagnose heart failure in  autopsies . The presence of  siderophages  indicates chronic left-sided heart failure, but is not  specific  for it. [ 81 ]  It is also indicated by congestion of the pulmonary circulation."}
{"_id": "WikiPedia_Cardio$$$corpus_5188", "text": "A person's risk of developing heart failure is inversely related to the level of  physical activity . Those who achieved at least 500  MET-minutes/week  (the recommended minimum by U.S. guidelines) had lower heart failure risk than individuals who did not report exercising during their free time; the reduction in heart failure risk was even greater in those who engaged in higher levels of physical activity than the recommended minimum. [ 82 ] \nHeart failure can also be prevented by lowering high blood pressure and high blood cholesterol, and by controlling diabetes. Maintaining a healthy weight, and decreasing sodium, alcohol, and sugar intake, may help. Additionally, avoiding tobacco use has been shown to lower the risk of heart failure. [ 83 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5189", "text": "According to  Johns Hopkins  and the  American Heart Association  there are a few ways to help prevent a cardiac event. Johns Hopkins states that stopping tobacco use, reducing high blood pressure, physical activity, and nutrition can drastically affect the chances of developing heart disease. High blood pressure accounts for most cardiovascular deaths. High blood pressure can be lowered into the normal range by making dietary decisions such as consuming less salt. Exercise also helps to bring blood pressure back down. One of the best ways to help avoid heart failure is to promote healthier eating habits like eating more vegetables, fruits, grains, and lean protein. [ 84 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5190", "text": "Diabetes is a major risk factor for heart failure. For women with Coronary Heart disease (CHD), diabetes was the strongest risk factor for heart failure. [ 85 ]  Diabetic women with depressed creatinine clearance or elevated BMI were at the highest risk of heart failure. While the annual incidence rate of heart failure for non-diabetic women with no risk factors is 0.4%, the annual incidence rate for diabetic women with elevated body mass index (BMI) and depressed creatinine clearance was 7% and 13%, respectively. [ 86 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5191", "text": "Treatment focuses on improving the symptoms and preventing the progression of the disease. Reversible causes of heart failure also need to be addressed (e.g.  infection , alcohol ingestion, anemia,  thyrotoxicosis ,  arrhythmia , and hypertension). Treatments include lifestyle and pharmacological modalities, and occasionally various forms of device therapy. Rarely, cardiac transplantation is used as an effective treatment when heart failure has reached the end stage. [ 87 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5192", "text": "In  acute decompensated heart failure , the immediate goal is to re-establish adequate perfusion and oxygen delivery to end organs. This entails ensuring that  airway, breathing, and circulation  are adequate. Immediate treatments usually involve some combination of vasodilators such as  nitroglycerin , diuretics such as  furosemide , and possibly  noninvasive positive pressure ventilation .  Supplemental oxygen  is indicated in those with oxygen saturation levels below 90%, but is not recommended in those with normal oxygen levels in the normal atmosphere. [ 88 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5193", "text": "The goals of treatment for people with chronic heart failure are prolonging life, preventing acute decompensation, and reducing symptoms, allowing for greater activity."}
{"_id": "WikiPedia_Cardio$$$corpus_5194", "text": "Heart failure can result from a variety of conditions. In considering therapeutic options, excluding reversible causes is of primary importance, including  thyroid disease ,  anemia , chronic  tachycardia ,  alcohol use disorder ,  hypertension , and dysfunction of one or more  heart valves . Treatment of the underlying cause is usually the first approach to treating heart failure. In most cases, though, either no primary cause is found or treatment of the primary cause does not restore normal heart function. In these cases,  behavioral ,  medical  and  device  treatment strategies exist that can provide a significant improvement in outcomes, including the relief of symptoms, exercise tolerance, and a decrease in the likelihood of  hospitalization  or death. Breathlessness rehabilitation for  chronic obstructive pulmonary disease  and heart failure has been proposed with exercise training as a core component. Rehabilitation should also include other interventions to address shortness of breath including the psychological and educational needs of people and the needs of caregivers. [ 89 ]   Iron supplementation  appears to reduce hospitalization but not all-cause mortality in patients with iron deficiency and heart\nfailure. [ 90 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5195", "text": "The latest evidence indicates that advance care planning (ACP) may help to increase documentation by medical staff regarding discussions with participants and improve an individual's depression. [ 91 ]  This involves discussing an individual's future care plan, preferences, and values. The findings are, however, based on low-quality evidence. [ 91 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5196", "text": "The various measures often used to assess the progress of people being treated for heart failure include  fluid balance  (calculation of fluid intake and excretion) and monitoring  body weight  (which in the shorter term reflects fluid shifts). [ 92 ]  Remote monitoring can be effective to reduce complications for people with heart failure. [ 93 ] [ 94 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5197", "text": "Behavior modification is a primary consideration in chronic heart failure management programs, with  dietary guidelines  regarding  fluid  and  salt  intake. [ 95 ]  Fluid restriction is important to reduce fluid retention in the body and to correct the hyponatremic status of the body. [ 76 ]  The evidence of the benefit of reducing salt, however, is poor as of 2018. [ 96 ]  Thirst is a common and burdensome symptom for patients to cope with.  Chewing gum  is an effective intervention to relieve thirst in patients experiencing heart failure, although patient acceptability remains an issue."}
{"_id": "WikiPedia_Cardio$$$corpus_5198", "text": "Exercise should be encouraged and tailored to suit an individual's capabilities. A meta-analysis found that center-based group interventions delivered by a physiotherapist help promote physical activity in HF. [ 97 ]  There is a need for additional training for physiotherapists in delivering behavior change intervention alongside an exercise program. An intervention is expected to be more efficacious in encouraging physical activity than the usual care if it includes  Prompts and cues  to walk or exercise, like a phone call or a text message. It is helpful if a trusted clinician provides explicit advice to engage in physical activity ( Credible source ). Another highly effective strategy is to place objects that will serve as a cue to engage in physical activity in the person's everyday environment ( Adding object to the environment ; e.g., exercise step or treadmill). Encouragement to walk or exercise in various settings beyond CR (e.g., home, neighborhood, parks) is also promising ( Generalisation of target behavior ). Additional promising strategies are  Graded tasks  (e.g., gradual increase in intensity and duration of exercise training),  Self-monitoring ,  Monitoring of physical activity by others without feedback ,  Action planning , and  Goal-setting . [ 98 ]  The inclusion of regular physical conditioning as part of a cardiac rehabilitation program can significantly improve  quality of life  and reduce the risk of hospital admission for worsening symptoms, but no evidence shows a reduction in mortality rates as a result of exercise."}
{"_id": "WikiPedia_Cardio$$$corpus_5199", "text": "Home visits and regular monitoring at heart-failure clinics reduce the need for hospitalization and improve  life expectancy . [ 99 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5200", "text": "Quadruple medical therapy using a combination of  angiotensin receptor-neprilysin inhibitors (ARNI) ,  beta blockers ,  mineralocorticoid receptor antagonists (MRA) , and  sodium/glucose cotransporter 2 inhibitors (SGLT2 inhibitors)  is the standard of care as of 2021 for heart failure with reduced ejection fraction (HFrEF). [ 100 ] [ 101 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5201", "text": "There is no convincing evidence for pharmacological treatment of heart failure with preserved ejection fraction (HFpEF). [ 6 ]  Medication for HFpEF is symptomatic treatment with diuretics to treat congestion. [ 6 ]  Managing risk factors and comorbidities such as  hypertension  is recommended in HFpEF. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5202", "text": "Inhibitors of the  renin\u2013angiotensin system  (RAS) are recommended for heart failure. The  angiotensin receptor-neprilysin inhibitors (ARNI) sacubitril/valsartan  is recommended as the first choice of RAS inhibitors in American guidelines published by AHA/ACC in 2022. [ 4 ]  Use of  ACE inhibitor , or  angiotensin receptor blockers  (ARBs) if the person develops a long-term cough as a side effect of the ACE-I, [ 102 ]  is associated with improved survival, fewer hospitalizations for heart failure exacerbations, and improved quality of life in people with heart failure. [ 103 ]  European guidelines published by ESC in 2021 recommends that  ARNI  should be used in those who still have symptoms while on an  ACE-I  or  ARB ,  beta blocker , and a  mineralocorticoid receptor antagonist . Use of the combination agent ARNI requires the cessation of ACE-I or ARB therapy at least 36 hours before its initiation. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5203", "text": "Beta-adrenergic blocking agents (beta blockers)  add to the improvement in symptoms and  mortality  provided by ACE-I/ARB. [ 103 ] [ 104 ]  The mortality benefits of beta blockers in people with systolic dysfunction who also have  atrial fibrillation  is more limited than in those who do not have it. [ 105 ]  If the ejection fraction is not diminished (HFpEF), the benefits of beta blockers are more modest; a decrease in mortality has been observed, but reduction in hospital admission for uncontrolled symptoms has not been observed. [ 106 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5204", "text": "In people who are intolerant of ACE-I and ARB or who have significant kidney dysfunction, the use of combined  hydralazine  and a long-acting nitrate, such as  isosorbide dinitrate , is an effective alternate strategy. This regimen has been shown to reduce mortality in people with moderate heart failure. [ 107 ]  It is especially beneficial in the black population. [ a ] [ 107 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5205", "text": "Use of a  mineralocorticoid antagonist , such as  spironolactone  or  eplerenone , in addition to beta blockers and ACE-I, can improve symptoms and reduce mortality in people with symptomatic heart failure with reduced ejection fraction (HFrEF). [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5206", "text": "SGLT2 inhibitors  are used for heart failure with reduced ejection fraction as they have demonstrated benefits in reducing hospitalizations and mortality, regardless of whether an individual has comorbid Type 2 Diabetes or not. [ 4 ] [ 108 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5207", "text": "Second-line medications for CHF do not confer a mortality benefit.  Digoxin  is one such medication. Its narrow therapeutic window, a high degree of toxicity, and the failure of multiple trials to show a mortality benefit have reduced its role in clinical practice. It is now used in only a small number of people with refractory symptoms, who are in atrial fibrillation, and/or who have chronic hypotension. [ 109 ] [ 110 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5208", "text": "Diuretics have been a mainstay of treatment against symptoms of fluid accumulation, and include diuretics classes such as  loop diuretics  (such as  furosemide ),  thiazide-like diuretics , and  potassium-sparing diuretics . Although widely used, evidence on their efficacy and safety is limited, except for  mineralocorticoid antagonists  such as  spironolactone . [ 16 ] [ 111 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5209", "text": "Anemia is an independent factor in mortality in people with chronic heart failure. Treatment of anemia significantly improves the quality of life for those with heart failure, often with a reduction in severity of the NYHA classification, and also improves mortality rates. [ 112 ] [ 113 ]  The  European Society of Cardiology  recommends screening for iron deficiency and treating with  intravenous iron  if deficiency is found. [ 6 ] :\u200a3668\u20133669"}
{"_id": "WikiPedia_Cardio$$$corpus_5210", "text": "The decision to anticoagulate people with HF, typically with left ventricular ejection fractions <35% is debated, but generally, people with coexisting atrial fibrillation, a prior embolic event, or conditions that increase the risk of an embolic event such as amyloidosis, left ventricular noncompaction, familial dilated cardiomyopathy, or a thromboembolic event in a first-degree relative. [ 80 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5211", "text": "Vasopressin receptor antagonists  can also treat heart failure.  Conivaptan  is the first medication approved by the US  Food and Drug Administration  for the treatment of euvolemic hyponatremia in those with heart failure. [ 76 ]  In rare cases hypertonic 3% saline together with diuretics may be used to correct hyponatremia. [ 76 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5212", "text": "Ivabradine  is recommended for people with symptomatic heart failure with reduced left ventricular ejection fraction who are receiving optimized guideline-directed therapy (as above) including the maximum tolerated dose of beta-blocker, have a normal heart rhythm and continue to have a resting heart rate above 70 beats per minute. [ 114 ]  Ivabradine has been found to reduce the risk of hospitalization for heart failure exacerbations in this subgroup of people with heart failure. [ 114 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5213", "text": "In people with severe cardiomyopathy (left ventricular ejection fraction below 35%), or in those with recurrent VT or malignant arrhythmias, treatment with an automatic implantable cardioverter-defibrillator (AICD) is indicated to reduce the risk of severe life-threatening arrhythmias. The AICD does not improve symptoms or reduce the incidence of malignant arrhythmias but does reduce mortality from those arrhythmias, often in conjunction with antiarrhythmic medications. In people with left ventricular ejection (LVEF) below 35%, the incidence of  ventricular tachycardia  or  sudden cardiac death  is high enough to warrant AICD placement. Its use is therefore recommended in  AHA / ACC  guidelines. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5214", "text": "Cardiac contractility modulation  (CCM) is a  treatment  for people with moderate to severe  left ventricular  systolic heart failure (NYHA classes II\u2013IV), which enhances both the strength of ventricular  contraction  and the heart's pumping capacity. The CCM mechanism is based on stimulation of the cardiac muscle by  nonexcitatory electrical signals , which are delivered by a  pacemaker -like device. CCM is particularly suitable for the treatment of heart failure with normal  QRS complex  duration (120 ms or less) and has been demonstrated to improve the symptoms, quality of life, and exercise tolerance. [ 21 ] [ 115 ] [ 116 ] [ 117 ] [ 118 ]  CCM is approved for use in Europe, and was approved by the Food and Drug Administration for use in the United States in 2019. [ 119 ] [ 120 ] [ 121 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5215", "text": "About one-third of people with an  LVEF  below 35% have markedly altered conduction to the ventricles, resulting in dyssynchronous depolarization of the right and left ventricles. This is especially problematic in people with left bundle branch block (blockage of one of the two primary conducting fiber bundles that originate at the base of the heart and carry depolarizing impulses to the left ventricle). Using a special pacing algorithm, biventricular  cardiac resynchronization therapy  (CRT) can initiate a normal sequence of ventricular depolarization. In people with LVEF below 35% and prolonged QRS duration on ECG (LBBB or QRS of 150 ms or more), an improvement in symptoms and mortality occurs when CRT is added to standard medical therapy. [ 122 ]  However, in the two-thirds of people without prolonged QRS duration, CRT may be harmful. [ 20 ] [ 21 ] [ 123 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5216", "text": "People with the most severe heart failure may be candidates for  ventricular assist devices , which have commonly been used as a bridge to heart transplantation but have been used more recently as a destination treatment for advanced heart failure. [ 124 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5217", "text": "In select cases, heart transplantation can be considered. While this may resolve the problems associated with heart failure, the person must generally remain on an immunosuppressive regimen to prevent rejection, which has its own significant downsides. [ 125 ]  A major limitation of this treatment option is the scarcity of hearts available for transplantation."}
{"_id": "WikiPedia_Cardio$$$corpus_5218", "text": "People with heart failure often have significant symptoms, such as shortness of breath and chest pain. Palliative care should be initiated early in the HF trajectory, and should not be an option of last resort. [ 126 ]  Palliative care can not only provide symptom management, but also assist with advanced care planning, goals of care in the case of a significant decline, and making sure the person has a medical  power of attorney  and discussed his or her wishes with this individual. [ 127 ]  A 2016 and 2017 review found that palliative care is associated with improved outcomes, such as quality of life, symptom burden, and satisfaction with care. [ 126 ] [ 128 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5219", "text": "Without transplantation, heart failure may not be reversible and heart function typically deteriorates with time. The growing number of people with stage IV heart failure (intractable symptoms of fatigue, shortness of breath, or chest pain at rest despite optimal medical therapy) should be considered for palliative care or  hospice , according to American College of Cardiology/American Heart Association guidelines. [ 127 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5220", "text": "Prognosis in heart failure can be assessed in multiple ways, including clinical prediction rules and cardiopulmonary exercise testing. Clinical prediction rules use a composite of clinical factors such as laboratory tests and blood pressure to estimate prognosis. Among several  clinical prediction rules  for prognosticating acute heart failure, the 'EFFECT rule' slightly outperformed other rules in stratifying people and identifying those at low risk of death during hospitalization or within 30 days. [ 129 ]  Easy methods for identifying people that are low-risk are:"}
{"_id": "WikiPedia_Cardio$$$corpus_5221", "text": "A crucial method for assessing prognosis in people with advanced heart failure is cardiopulmonary exercise testing (CPX testing). CPX testing is usually required before heart transplantation as an indicator of prognosis. CPX testing involves the measurement of exhaled oxygen and carbon dioxide during exercise. The peak oxygen consumption ( VO 2  max ) is used as an indicator of prognosis. As a general rule, a VO 2  max less than 12\u201314 cc/kg/min indicates poor survival and suggests that the person may be a candidate for a heart transplant. People with a VO 2  max <10 cc/kg/min have a poorer prognosis. The most recent International Society for Heart and Lung Transplantation guidelines [ 130 ]  also suggest two other parameters that can be used for evaluation of prognosis in advanced heart failure, the heart failure survival score and the use of a criterion of VE/VCO 2  slope > 35 from the CPX test. The heart failure survival score is calculated using a combination of clinical predictors and the VO 2  max from the CPX test."}
{"_id": "WikiPedia_Cardio$$$corpus_5222", "text": "Heart failure is associated with significantly reduced physical and mental health, resulting in a markedly decreased quality of life. [ 131 ] [ 132 ]  With the exception of heart failure caused by reversible conditions, the condition usually worsens with time. Although some people survive many years, progressive disease is associated with an overall annual mortality rate of 10%. [ 133 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5223", "text": "Around 18 of every 1000 persons will experience an ischemic stroke during the first year after diagnosis of HF. As the duration of follow-up increases, the stroke rate rises to nearly 50 strokes per 1000 cases of HF by 5 years. [ 134 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5224", "text": "In 2022, heart failure affected about 64 million people globally. [ 135 ]  Overall, around 2% of adults have heart failure. [ 22 ]  In those over the age of 75, rates are greater than 10%. [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5225", "text": "Rates are predicted to increase. [ 22 ]  Increasing rates are mostly because of increasing lifespan, but also because of increased risk factors (hypertension, diabetes, dyslipidemia, and obesity) and improved survival rates from other types of cardiovascular disease (myocardial infarction, valvular disease, and arrhythmias). [ 136 ] [ 137 ] [ 138 ]  Heart failure is the leading cause of hospitalization in people older than 65. [ 139 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5226", "text": "In the United States, heart failure affects 5.8 million people, and each year 550,000 new cases are diagnosed. [ 140 ]  In 2011, heart failure was the most common reason for hospitalization for adults aged 85 years and older, and the second-most common for adults aged 65\u201384 years. [ 141 ]  An estimated one in five adults at age 40 will develop heart failure during their remaining lifetimes and about half of people who develop heart failure die within 5 years of diagnosis. [ 142 ]  Heart failure \u2013 much higher in African Americans, Hispanics, Native Americans, and recent immigrants from Eastern Europe countries \u2013 has been linked in these ethnic minority populations to the high incidence of diabetes and hypertension. [ 143 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5227", "text": "Nearly one of every four people (24.7%) hospitalized in the U.S. with congestive heart failure is readmitted within 30 days. [ 144 ]  Additionally, more than 50% of people seek readmission within 6 months after treatment and the average duration of hospital stay is 6 days. Heart failure is a leading cause of hospital readmissions in the U.S. People aged 65 and older were readmitted at a rate of 24.5 per 100 admissions in 2011. In the same year, heart failure patients under Medicaid were readmitted at a rate of 30.4 per 100 admissions, and uninsured people were readmitted at a rate of 16.8 per 100 admissions. These are the highest readmission rates for both categories. Notably, heart failure was not among the top-10 conditions with the most 30-day readmissions among the privately insured. [ 145 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5228", "text": "In the UK, despite moderate improvements in prevention, heart failure rates have increased due to population growth and aging. [ 146 ]  Overall heart failure rates are similar to the four most common causes of cancer (breast, lung, prostate, and colon) combined. [ 146 ]  People from deprived backgrounds are more likely to be diagnosed with heart failure at a younger age. [ 146 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5229", "text": "In tropical countries, the most common cause of heart failure is valvular heart disease or some type of cardiomyopathy. As underdeveloped countries have become more affluent, the incidences of  diabetes ,  hypertension , and  obesity  have increased, which have in turn raised the incidence of heart failure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5230", "text": "Men have a higher incidence of heart failure, but the overall prevalence rate is similar in both sexes since women survive longer after the onset of heart failure. [ 147 ]  Women tend to be older when diagnosed with heart failure (after  menopause ), they are more likely than men to have diastolic dysfunction, and seem to experience a lower overall quality of life than men after diagnosis. [ 147 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5231", "text": "Some sources state that people of  Asian  descent are at a higher risk of heart failure than other ethnic groups. [ 148 ]  Other sources however have found that rates of heart failure are similar to rates found in other ethnic groups. [ 149 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5232", "text": "For centuries, the disease entity which would include many cases of what today would be called heart failure was  dropsy ; the term denotes generalized edema, a major manifestation of a failing heart, though also caused by other diseases. Writings of ancient civilizations include evidence of their acquaintance with dropsy and heart failure: Egyptians were the first to use  bloodletting  to relieve fluid accumulation and shortage of breath, and provided what may have been the first documented observations on heart failure in the  Ebers papyrus  (around 1500 BCE). [ 150 ]  Greeks described cases of dyspnea, fluid retention and fatigue compatible with heart failure. [ 151 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5233", "text": "Romans used the flowering plant  Drimia maritima  (sea squill), which contains  cardiac glycosides , for the treatment of dropsy; [ 152 ]  descriptions pertaining to heart failure are also known in the civilizations of ancient India and China. [ 153 ]  However, the manifestations of failing heart were understood in the context of these peoples' medical theories \u2013 including ancient Egyptian religion,  Hippocratic   theory of humours , or ancient  Indian  and  Chinese medicine , and the current concept of heart failure had not developed yet. [ 151 ] [ 153 ]  Although shortage of breath had been connected to heart disease by  Avicenna  round 1000 CE, [ 154 ]  decisive for modern understanding of the nature of the condition were the description of  pulmonary circulation  by  Ibn al-Nafis  in the 13th century, and of  systemic circulation  by  William Harvey  in 1628. [ 151 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5234", "text": "The role of the heart in fluid retention began to be better appreciated, as  dropsy of the chest  (fluid accumulation in and around the lungs causing shortness of breath) became more familiar and the current concept of heart failure, which brings together swelling and shortage of breath due to fluid retention, began to be accepted, in the 17th and especially in the 18th century:  Richard Lower  linked dyspnea and foot swelling in 1679, and  Giovanni Maria Lancisi  connected jugular vein distention with right ventricular failure in 1728. [ 154 ]  Dropsy attributable to other causes, e.g. kidney failure, was differentiated in the 19th century. [ 155 ] [ 156 ] [ 157 ]  The stethoscope, invented by  Ren\u00e9 Laennec  in 1819,  x-rays , discovered by  Wilhelm R\u00f6ntgen  in 1895, and  electrocardiography , described by  Willem Einthoven  in 1903, facilitated the investigation of heart failure. [ 40 ] [ 157 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5235", "text": "The 19th century also saw experimental and conceptual advances in the physiology of heart contraction, which led to the formulation of the  Frank-Starling law  of the heart (named after physiologists  Otto Frank  and  Ernest Starling ), a remarkable advance in understanding mechanisms of heart failure. [ 158 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5236", "text": "One of the earliest treatments of heart failure, relief of swelling by bloodletting with various methods, including  leeches , continued through the centuries. [ 159 ]  Along with bloodletting,  Jean-Baptiste de S\u00e9nac  in 1749 recommended  opiates  for acute shortage of breath due to heart failure. [ 157 ]  In 1785,  William Withering  described the therapeutic uses of the  foxglove  genus of plants in the treatment of edema; their extract contains  cardiac glycosides , including digoxin, still used today in the treatment of heart failure. [ 152 ]  The  diuretic effects of inorganic mercury salts , which were used to treat  syphilis , had already been noted in the 16th century by  Paracelsus ; [ 160 ]  in the 19th century they were used by noted physicians like  John Blackall  and  William Stokes . [ 161 ]  In the meantime,  cannulae  (tubes) invented by English physician  Reginald Southey  in 1877 was another method of removing excess fluid by directly inserting into swollen limbs. [ 159 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5237", "text": "Use of organic mercury compounds as diuretics, beyond their role in syphilis treatment, started in 1920, though it was limited by their  parenteral  route of administration and their side-effects. [ 161 ] [ 162 ]  Oral mercurial diuretics were introduced in the 1950s; so were thiazide diuretics, which caused less toxicity, and are still used. [ 40 ] [ 161 ]  Around the same time, the invention of echocardiography by  Inge Edler  and  Hellmuth Hertz  in 1954 marked a new era in the evaluation of heart failure. [ 40 ]  In the 1960s,  loop diuretics  were added to available treatments of fluid retention, while a patient with heart failure received the first  heart transplant  by  Christiaan Barnard . [ 40 ] [ 161 ]  Over the following decades, new drug classes found their place in heart failure therapeutics, including  vasodilators  like  hydralazine ;  renin-angiotensin system  inhibitors; and  beta-blockers . [ 163 ] [ 164 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5238", "text": "In 2011, nonhypertensive heart failure was one of the 10 most expensive conditions seen during inpatient hospitalizations in the U.S., with aggregate inpatient hospital costs more than $10.5 billion. [ 165 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5239", "text": "Heart failure is associated with a high health expenditure, mostly because of the cost of hospitalizations; costs have been estimated to amount to 2% of the total budget of the  National Health Service  in the United Kingdom, and more than $35 billion in the United States. [ 166 ] [ 167 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5240", "text": "Some research indicates that  stem cell therapy  may help. [ 168 ]  Although this research indicated benefits of stem cell therapy, other research does not indicate benefit. [ 169 ]  There is tentative evidence of longer life expectancy and improved left ventricular ejection fraction in persons treated with bone marrow-derived stem cells. [ 168 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5241", "text": "The maintenance of heart function depends on appropriate  gene expression  that is regulated at multiple levels by  epignetic mechanisms  including  DNA methylation  and  histone post-translational modification . [ 170 ] [ 171 ]   Currently, an increasing body of research is directed at understanding the role of perturbations of epigenetic processes in  cardiac hypertrophy  and  fibrotic scarring . [ 170 ] [ 171 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5242", "text": "Heart failure with preserved ejection fraction  ( HFpEF ) is a form of  heart failure  in which the  ejection fraction  \u2013 the percentage of the volume of blood ejected from the left ventricle with each heartbeat divided by the volume of blood when the left ventricle is maximally filled \u2013 is normal, defined as greater than 50%; [ 1 ]  this may be measured by  echocardiography  or  cardiac catheterization . Approximately half of people with heart failure have preserved ejection fraction, while the other half have a reduction in ejection fraction, called  heart failure with reduced ejection fraction  (HFrEF). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5243", "text": "Risk factors for HFpEF include  hypertension ,  hyperlipidemia ,  diabetes ,  smoking , and  obstructive sleep apnea ."}
{"_id": "WikiPedia_Cardio$$$corpus_5244", "text": "HFpEF is characterized by abnormal  diastolic  function: there is an increase in the stiffness of the  left ventricle , which causes a decrease in left ventricular relaxation during diastole, with resultant increased pressure and/or impaired filling. [ 2 ]   There is an increased risk for  atrial fibrillation  and  pulmonary hypertension ."}
{"_id": "WikiPedia_Cardio$$$corpus_5245", "text": "There is controversy regarding the relationship between  diastolic heart failure  and HFpEF. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5246", "text": "Clinical manifestations of HFpEF are similar to those observed in HFrEF and include shortness of breath including exercise induced  dyspnea ,  paroxysmal nocturnal dyspnea  and  orthopnea , exercise intolerance, fatigue, elevated  jugular venous pressure , and  edema . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5247", "text": "Patients with HFpEF poorly tolerate stress, particularly hemodynamic alterations of ventricular loading or increased diastolic pressures. Often there is a more dramatic elevation in systolic blood pressure in HFpEF than is typical of HFrEF. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5248", "text": "Diverse mechanisms contribute to the development of HFpEF, many of which are under-investigated and remain obscure. Despite this, there are clear risk factors that contribute to the development of HFpEF. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5249", "text": "Hypertension ,  obesity ,  metabolic syndrome , and sedentary lifestyle have been identified as important risk factors for diverse types of heart disease including HFpEF. There is mechanistic and epidemiological evidence for a link between  insulin resistance  and HFpEF. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5250", "text": "This pro-inflammatory state may also induce changes in the vascular  endothelium  of the heart. Specifically, by reducing availability of  nitric oxide , an important  vasodilator  and regulator of  protein kinase G  activity. As protein kinase G activity diminishes, cardiomyocytes undergo hypertrophic changes. Endothelial cells also are responsible for the production of  E-selectin , which recruits  lymphocytes  into the tissue beneath the endothelium that subsequently release  transforming growth factor beta , encouraging  fibrosis  and thus ventricular stiffening. Cardiac macrophages are thought to play an important role in the development of fibrosis as they are increased in HFpEF and release pro-fibrotic  cytokines , such as IL-10. [ 9 ] [ 10 ]  Further investigation of the role of inflammation in HFpEF is needed. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5251", "text": "Conditions, such as hypertension, that encourage increased left ventricular  afterload  can lead to structural changes in the heart on a  gross , as well as a microscopic level. It is thought that increased pressure, in concert with a pro-inflammatory state (insulin resistance, obesity), encourage ventricular stiffening and remodeling that lead to poor cardiac output seen in HFpEF. There changes are a result of left ventricular muscle  hypertrophy  caused by the high pressure, leading to the left ventricle becoming stiff. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5252", "text": "Ischemia , or inadequate oxygenation of the myocardium, is observed in a high proportion of HFpEF patients. This ischemia may be secondary to  coronary artery disease , or a result of the previously described changes in  microvasculature . [ 12 ] \nIschemia can result in impaired relaxation of the heart; when myocytes fail to relax appropriately,  myosin cross bridges  remain intact and generate tension throughout diastole and thus increase stress on the heart. This is termed partial persistent  systole . Ischemia may manifest in distinct ways, either as a result of increasing tissue oxygen demand, or diminished ability of the heart to supply oxygen to the tissue. The former is the result of stress, such as exercise, while the latter is the result of reduced  coronary  flow. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5253", "text": "Cardiac  senescence , or cellular deterioration that occurs as part of normal aging, closely resembles the manifestations of HFpEF. Specifically, loss of  cardiac reserve , diminished  vascular compliance , and diastolic dysfunction are characteristic of both processes. It has been suggested [ 13 ] [ 14 ]  that HFpEF merely represents an acceleration of a normal aging process."}
{"_id": "WikiPedia_Cardio$$$corpus_5254", "text": "Senile systemic amyloidosis , resulting from accumulation of aggregated wild-type  transthyretin  as part of the  degenerative aging  process, is emerging as an important and underdiagnosed contributor to HFpEF with age. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5255", "text": "The decline in  estrogen  levels that occurs with  menopause  has been hypothesized to contribute to the increase in HFpEF observed amongst post-menopausal women. [ 17 ]  Animal studies show that even at a young age, a decline in estrogen leads to changes in expression of  fibrosis  related genes in the heart. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5256", "text": "Any condition or process that leads to stiffening of the left ventricle can lead to diastolic dysfunction. Other causes of left ventricular stiffening include: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5257", "text": "Causes of isolated right ventricular diastolic failure are uncommon. These causes include: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5258", "text": "Structural changes that occur with HFpEF are often radically different from those associated with heart failure with reduced  ejection fraction  (HFrEF). [ 19 ]  Many patients experience increased thickening of the ventricular wall in comparison to chamber size, termed  concentric hypertrophy . This leads to increased left ventricular mass and is typically accompanied by a normal, or slightly reduced, end diastolic filling volume. Conversely, HFrEF is typically associated with  eccentric hypertrophy , characterized by an increase in cardiac chamber size without an accompanying increase in wall thickness. This leads to a corresponding increase in left ventricular end diastolic volume. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5259", "text": "Cellular changes generally underlie alterations in cardiac structure. In HFpEF  cardiomyocytes  have been demonstrated to show increased diameter without an increase in length; this is consistent with observed concentric ventricular hypertrophy and increased left ventricular mass. HFrEF cardiomyocytes exhibit the opposite morphology; increased length without increased cellular diameter. This too is consistent with eccentric hypertrophy seen in this condition. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5260", "text": "Changes in the  extracellular  environment are of significant importance in heart disease. [ 21 ] [ 22 ]  Particularly, regulation of genes that alter  fibrosis  contribute to the development and progression of HFrEF. This regulation is dynamic and involves changes in  fibrillar collagens  through increased deposition as well as inhibition of enzymes that break down extracellular matrix components (matrix  metalloproteinases ,  collagenases ). While early stage HFrEF is associated with a significant disruption of extracellular matrix proteins initially, as it progresses fibrotic replacement of  myocardium  may occur, leading to scarring and increased interstitial collagen. [ 23 ]  Fibrotic changes in HFpEF are more variable. Though there is typically an increased amount of collagen observed in these patients it is usually not dramatically different from healthy individuals. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5261", "text": "Diastolic  alterations in HFpEF are the predominating factor in impaired cardiac function and subsequent clinical presentation. [ 25 ]  Diastolic dysfunction is multifaceted, and a given patient may express diverse combinations of the following: incomplete myocardial relaxation, impaired rate of ventricular filling, increased left atrial pressure in filling, increased passive stiffness and decreased distensibility of the ventricle, limited ability to exploit the  Frank-Starling mechanism  with increased  output  demands, increased diastolic left heart or pulmonary venous pressure. [ 25 ] [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5262", "text": "Diastolic failure appears when the ventricle cannot be filled properly because it cannot relax because its wall is thick or rigid. This situation presents usually a  concentric hypertrophy . In contrast, systolic heart failure has usually an  eccentric hypertrophy . [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5263", "text": "Diastolic failure is characterized by an elevated diastolic pressure in the left ventricle, despite an essentially normal/physiologic end diastolic volume (EDV). Histological evidence supporting diastolic dysfunction demonstrates  ventricular hypertrophy , increased interstitial  collagen  deposition and infiltration of the myocardium. These influences collectively lead to a decrease in distensibility and elasticity (ability to stretch) of the myocardium. As a consequence, cardiac output becomes diminished. When the left ventricular diastolic pressure is elevated, venous pressure in lungs must also become elevated too: left ventricular stiffness makes it more difficult for blood to enter it from the left atrium. As a result, pressure rises in the atrium and is transmitted back to the pulmonary venous system, thereby increasing its  hydrostatic pressure  and promoting  pulmonary edema . [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5264", "text": "It may be misguided to classify the volume-overloaded heart as having diastolic dysfunction if it is behaving in a stiff and non-compliant manner. The term diastolic dysfunction should not be applied to the dilated heart. Dilated (\"remodeled\") hearts have increased volume relative to the amount of diastolic pressure, and therefore have increased ( not  decreased) distensibility. The term diastolic dysfunction is sometimes erroneously applied in this circumstance, when increased fluid volume retention causes the heart to be over-filled ( high output cardiac failure ). [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5265", "text": "Although the term diastolic heart failure is often used when there are signs and symptoms of heart failure with normal left ventricular systolic function, this is not always appropriate. Diastolic function is determined by the relative end diastolic volume in relation to end diastolic pressure, and is therefore independent of left ventricular systolic function. A leftward shift of the end-diastolic pressure-volume relationship (i.e. decreased left ventricular distensibility) can occur both in those with normal and those with decreased left ventricular systolic function. Likewise, heart failure may occur in those with dilated left ventricular and normal systolic function. This is often seen in valvular heart disease and high-output heart failure. Neither of these situations constitutes a diastolic heart failure. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5266", "text": "Stiffening of the left ventricle contributes to heart failure with preserved ejection fraction, a condition that can be prevented by four exercise sessions/week or more (more than casual exercise) throughout adulthood. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5267", "text": "In diastolic heart failure, the volume of blood contained in the ventricles during diastole is lower than it should be, and the pressure of the blood within the chambers is elevated. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5268", "text": "During diastole, the ventricular pressure falls from the peak reached at the end of  systole . When this pressure falls below the atrial pressure, atrio-ventricular valves open ( mitral valve  at left side and  tricuspid valve  at right side) and the blood passes from the atria into the ventricles. First, ventricles are filled by a pressure gradient but near the end, atria contract (atrial kick) and force more blood to pass into ventricles. Atrial contraction is responsible for around 20% of the total filling blood volume. (In atrial fibrillation, this additional 20% filling volume is lost and the patient may experience systolic heart failure symptoms). [ 32 ]  Complete left ventricular filling is essential to maintain maximum cardiac output. Left ventricular filling is dependent upon  ventricular relaxation  and  compliance , mitral valve area, atrio-ventricular gradient, atrial contraction and end-systolic volume. Diastole has four phases: isovolumetric relaxation, rapid filling, diastasis and atrial contraction. All of these phases can be evaluated by  Doppler echocardiography . [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5269", "text": "Though HFpEF is characterized by a normal ejection fraction, this parameter is a rather poor index of the heart's contractile function. [ 33 ]  Some studies have shown that metrics of load independent contractility (such as left ventricular stiffness) reveal diminished systolic function in HFpEF patients compared to healthy controls, [ 20 ]  and are corroborated by tissue Doppler findings that reveal changes in longitudinal contraction and motion abnormalities. [ 34 ]  While these systolic impairments may be minimal at rest, they become more exaggerated with increased demand, as seen in exercise. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5270", "text": "Most HFpEF patients exhibit  pulmonary hypertension  which is significantly associated with increased morbidity and mortality. [ 36 ]  Left atrial and pulmonary venous pressure increases in HFpEF due to diastolic insufficiency thus increasing pulmonary artery pressure. In patients with advanced HFpEF changes in the pulmonary vasculature may develop, leading to pre-capillary pulmonary hypertension. [ 37 ]  Right ventricular dysfunction is also common in HFpEF patients, occurring in 20-35% of patients. This right ventricular dysfunction is more common in patients with more advanced HFpEF as well as those with pulmonary hypertension and lower ejection fractions. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5271", "text": "Cardiac output is dependent on  stroke volume  and  heart rate . A significant portion (55-77%) of HFpEF patients are unable to increase heart rate to compensate for increased output demand (as in the setting of exercise); this is termed  chronotropic  incompetence. [ 39 ]  Combined with the characteristic deficit in stroke volume observed in HFpEF patients, many individuals display poor exercise tolerance. [ 40 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5272", "text": "Non-simultaneous contraction of the left and right ventricle,  dyssychrony , is present in up to 58% of HFpEF patients. [ 41 ]  However, dyssynchrony is also common in HFrEF and its role in HFpEF in particular remains obscure. While therapies for dyssynchrony, such as  biventricular pacing  provide benefits to HFrEF patients, no benefit is appreciable in HFpEF patients at this time. [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5273", "text": "Patients with HFpEF, in addition to cardiac abnormalities, display changes in (endothelial)  microvascular function , skeletal muscle metabolism and in fat distribution and character throughout the body. [ 43 ]  The importance of these changes is demonstrated in that stable, non-decompensated patients seem to benefit from exercise; specifically increased  VO2 max  and exercise tolerance. However, this benefit appears to be derived from changes in muscle and vasculature as opposed to directly on the heart, which displays minimal change in output following exercise training. [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5274", "text": "HFpEF is typically diagnosed with  echocardiography . Techniques such as  catheterization  are invasive procedures and thus reserved for patients with  co-morbid  conditions or those who are suspected to have HFpEF but lack clear non-invasive findings. Catheterization does represent are more definitive diagnostic assessment as pressure and volume measurements are taken simultaneously and directly. In either technique, the heart is evaluated for left ventricular diastolic function. Important parameters include, rate of  isovolumic  relaxation, rate of ventricular filling, and stiffness. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5275", "text": "Frequently patients are subjected to stress echocardiography, which involves the above assessment of  diastolic  function during exercise. [ 45 ]  This is undertaken because perturbations in diastole are exaggerated during the increased demands of exercise. Exercise requires increased left ventricular filling and subsequent output. Typically the heart responds by increasing heart rate and relaxation time. [ 35 ]  However, in patients with HFpEF both responses are diminished due to increased ventricular stiffness. Testing during this demanding state may reveal abnormalities that are not as discernible at rest. [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5276", "text": "Diastolic dysfunction must be differentiated from diastolic heart failure. Diastolic dysfunction can be found in elderly and apparently quite healthy patients. If diastolic dysfunction describes an abnormal mechanical property, diastolic heart failure describes a clinical syndrome. Mathematics describing the relationship between the ratio of Systole to Diastole in accepted terms of End Systolic Volume to End Diastolic Volume implies many mathematical solutions to forward and backward heart failure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5277", "text": "Criteria for diagnosis of diastolic dysfunction or diastolic heart failure remain imprecise. This has made it difficult to conduct valid clinical trials of treatments for diastolic heart failure. The problem is compounded by systolic and diastolic heart failure commonly coexisting when patients present with many ischemic and nonischemic etiologies of heart failure. Narrowly defined, diastolic failure has often been defined as \"heart failure with normal systolic function\" (i.e. left ventricular ejection fraction of 60% or more).  Chagasic heart disease  may represent an optimal academic model of diastolic heart failure that spares systolic function. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5278", "text": "A patient is said to have diastolic dysfunction if they have signs and symptoms of heart failure but the left ventricular ejection fraction is normal. A second approach is to use an elevated  BNP  level in the presence of normal ejection fraction to diagnose diastolic heart failure. Concordance of both volumetric and biochemical measurements and markers lends to even stronger terminology regarding scientific/mathematical expression of diastolic heart failure. These are both probably too broad a definition for diastolic heart failure, and this group of patients is more precisely described as having heart failure with normal systolic function. Echocardiography can be used to diagnose diastolic dysfunction but is a limited modality unless it is supplemented by  stress imaging .  MUGA  imaging is an earlier mathematical attempt to distinguish systolic from diastolic heart failure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5279", "text": "No single echocardiographic parameter can confirm a diagnosis of diastolic heart failure. Multiple echocardiographic parameters have been proposed as sufficiently sensitive and specific, including mitral inflow velocity patterns, pulmonary vein flow patterns, E/A reversal, tissue Doppler measurements, and M-mode echo measurements (i.e. of left atrial size). Algorithms have also been developed which combine multiple echocardiographic parameters to diagnose diastolic heart failure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5280", "text": "There are four basic echocardiographic patterns of diastolic heart failure, which are graded I to IV. [ citation needed ]  Grade III and IV diastolic dysfunction are called \"restrictive filling dynamics\"; they are both severe forms of diastolic dysfunction, and patients tend to have advanced heart failure symptoms. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5281", "text": "The presence of either class [ clarification needed ]  III and IV diastolic dysfunction is associated with a significantly worse prognosis. These patients will have left atrial enlargement, and many will have a reduced left ventricular ejection fraction that indicates a combination of systolic and diastolic dysfunction. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5282", "text": "Imaged volumetric definition of systolic heart performance is commonly accepted as  ejection fraction . Volumetric definition of the heart in  systole  was first described by  Adolph Fick  as  cardiac output . Fick may be [ clarification needed ]  readily and inexpensively inverted to cardiac output and ejection fraction to mathematically describe  diastole .  Decline of ejection fraction paired with decline of E/A ratio seems a stronger argument in support of a mathematical definition of diastolic heart failure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5283", "text": "Another parameter to assess diastolic function is the  E/E' ratio , which is the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E'). Diastolic dysfunction is assumed when the E/E' ratio exceed 15. [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5284", "text": "Newer echocardiographic techniques such as speckle tracking for strain measurement, particularly for the left atrium, [ 48 ]  are becoming increasingly utilised for the diagnosis of HFpEF."}
{"_id": "WikiPedia_Cardio$$$corpus_5285", "text": "Despite increasing incidence of HFpEF effective inroads to therapeutics have been largely unsuccessful. [ 49 ]  Currently [ when? ] , recommendations for treatment are directed at symptom relief and co-morbid conditions. Frequently this involves administration of  diuretics  to relieve complications associated with volume overload, such as  leg swelling  and high blood pressure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5286", "text": "Commonly encountered conditions that must be treated for and have independent recommendations for  standard of care  include  atrial fibrillation , coronary artery disease, hypertension, and hyperlipidemia. There are particular factors unique to HFpEF that must be accounted for with therapy. Randomized clinical trials addressing the therapeutic adventure for these conditions in HFpEF have found conflicting or limited evidence. [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5287", "text": "Specific aspects of therapeutics should be avoided in HFpEF to prevent the deterioration of the condition. Considerations that are generalizable to heart failure include avoidance of a fast heart rate, elevations in blood pressure, development of ischemia, and atrial fibrillation. Considerations more specific to HFpEF include avoidance of  preload  reduction. As patients display normal ejection fraction but reduced cardiac output they are especially sensitive to changes in preloading and may rapidly display signs of output failure. This means administration of diuretics and vasodilators must be monitored carefully. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5288", "text": "HFrEF and HFpEF represent distinct entities in terms of development and effective therapeutic management. Specifically, cardiac resynchronization, administration of  beta blockers  and  angiotensin converting enzyme inhibitors  are applied to good effect in HFrEF but are largely ineffective at reducing morbidity and mortality in HFpEF. [ 49 ] [ 51 ]  Many of these therapies are effective in reducing the extent of cardiac dilation and increasing ejection fraction in HFrEF patients. It is unsurprising they fail to effect improvement in HFpEF patients, given their un-dilated phenotype and relative normal ejection fraction. Understanding and targeting mechanisms unique to HFpEF are thus essential to the development of therapeutics. [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5289", "text": "Randomized studies on HFpEF patients have shown that exercise improves  left ventricular diastolic function , the heart's  ability to relax , and is associated with improved  aerobic exercise capacity . [ 53 ]  The benefit patients seem to derive from exercise does not seem to be a direct cardiac effect, but rather is due to changes in peripheral vasculature and skeletal muscle, which show abnormalities in HFpEF patients. [ citation needed ]  A two-year exercise trial on otherwise-healthy middle-aged adults having HFpEF showed improved cardiac function, and regular exercise was recommended to prevent future risk of HFpEF. [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5290", "text": "Regularly assessment of patients allows determination of progression of the condition, response to interventions, and need for alteration of therapy. Ability to perform daily tasks, hemodynamic status, kidney function,  electrolyte  balance, and serum  natriuretic peptide  levels are important parameters. Behavioral management is important in these patients and it is recommended that individuals with HFpEF avoid alcohol, smoking, and high sodium intake. [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5291", "text": "Management of HFpEF is primarily dependent on the treatment of symptoms and exacerbating conditions. The role of specific treatments for diastolic dysfunction  per se  is as yet unclear. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5292", "text": "Currently treatment with ACE inhibitors, calcium channel blockers, beta blockers, and  angiotensin receptor blockers  is employed, but does not have a proven benefit in HFpEF patients. Caution is required with use of diuretics or other therapies that can alter loading conditions or blood pressure. It is not recommended that patients be treated with  phosphodiesterase-5-inhibitors  or  digoxin . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5293", "text": "MRAs ( spironolactone ,  finerenone ) are recommended for appropriately selected patients with symptomatic HFpEF (LVEF >= 45%, elevated  BNP  level or heart failure admission within 1 year, eGFR > 30 mL/min/1.73 m2, creatinine < 2.5 ml/dL, potassium < 5.0 mEq/L). [ 56 ]  Monitoring of serum potassium levels and kidney function, specifically  glomerular filtration rate , during treatment is necessary."}
{"_id": "WikiPedia_Cardio$$$corpus_5294", "text": "Beta blockers  play a rather obscure role in HFpEF treatment, though there is suggestion of a beneficial role in patient management. [ 57 ]  Evidence from a meta-analysis demonstrated significant reductions in all-cause mortality with beta-blocker therapy, though overall effects were driven largely by small, older trials of patients post-myocardial infarction. [ 49 ]  Some evidence suggests that vasodilating beta blockers, such as  nebivolol , can provide a benefit for patients with heart failure regardless of ejection fraction. [ 58 ]  Additionally, because of the  chronotropic  perturbation and diminished LV filling seen in HFpEF the  bradycardic  effect of beta blockers may enable improved filling, reduce myocardial oxygen demand, and lower blood pressure. However, this effect also can contribute to diminished response to exercise demands and can result in an excessive reduction in heart rate. [ 59 ] [ 60 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5295", "text": "Beta-blockers are the first-line therapy: they lower the heart rate and thus give more time for ventricles to fill. They may also improve survival. [ 49 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5296", "text": "Likewise, treatment with  angiotensin converting enzyme inhibitors , such as  enalapril ,  ramipril , and many others, may be of benefit due to their effect on preventing  ventricular remodeling  but under control to avoid hypotension. [ 61 ] \nACE inhibitors do not appear to improve morbidity or mortality associated with HFpEF alone. [ 60 ]  However, they are important in the management of  hypertension , a significant player in the pathophysiology of HFpEF. [ 62 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5297", "text": "ARB treatment results in an improvement in diastolic dysfunction and hypertension that is comparable to other anti-hypertensive medication. [ 63 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5298", "text": "There is some evidence that  calcium channel blockers  may be of benefit in reducing ventricular stiffness. In some cases, ( verapamil  has the benefit lowering the heart rate) [ clarification needed ] ."}
{"_id": "WikiPedia_Cardio$$$corpus_5299", "text": "Diuretics can be useful if significant congestion develops, but patients must be monitored because they frequently develop  low blood pressure . [ 61 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5300", "text": "In patients with HFpEF, SGLT2 inhibitors carry a class 2a recommendation according to the 2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure as a potentially beneficial treatment for reducing HF hospitalizations and CV mortality. [ 64 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5301", "text": "The use of a self-expanding device that attaches to the external surface of the left ventricle has been suggested. When the heart muscle squeezes, energy is loaded into the device, which absorbs the energy and releases it to the left ventricle in the diastolic phase. This helps retain muscle elasticity. This had not been approved by the  FDA  as of 2008 [update] . [ 65 ]  Trials were in progress of the ImCardia (implanted at the level of the pericardium) and the CORolla transapical approach device (CORolla TAA; implanted at the level of the endocardium) as of 2023 [update] [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5302", "text": "The progression of HFpEF and its clinical course is poorly understood in comparison to HFrEF.  Despite this, patients with HFrEF and HFpEF appear to have comparable outcomes in terms of hospitalization and mortality. [ 1 ] [ 67 ]  Causes of death in patients vary substantially. However, among patients in more  advanced heart failure  (NYHA classes II-IV), cardiovascular death, including  heart attacks  and  sudden cardiac death , was the predominant cause in population-based studies. [ 68 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5303", "text": "Until recently, it was generally assumed that the prognosis for individuals with diastolic dysfunction and associated intermittent pulmonary edema was better than those with systolic dysfunction. However, in two studies in the  New England Journal of Medicine  in 2006, evidence was presented to suggest that the prognosis in diastolic dysfunction is the same as that in  systolic dysfunction . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5304", "text": "Heart failure with reduced ejection fraction  ( HFrEF ,  hef- REF ) is a form of  heart failure  in which the  ejection fraction  is reduced. [ 1 ]  This is defined as a  left ventricular   ejection fraction  (LVEF) of 40% or less. About half of heart failure patients have a reduced ejection fraction. [ 2 ]  Other types of heart failure are  heart failure with mildly reduced ejection fraction  (LVEF\u00a0between 40% and 50%) and  heart failure with preserved ejection fraction  (LVEF 50% or higher). [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5305", "text": "Heart to Heart  is a 1949 American  short   documentary film  about  heart disease  directed by  Gunther von Fritsch . It was nominated for an  Academy Award  for  Best Documentary Short . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5306", "text": "This article about a scientific  documentary  film is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_5307", "text": "This article about a short documentary film is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_5308", "text": "High-output heart failure  is a heart condition that occurs when the  cardiac output  is higher than normal because of increased peripheral demand. There is a circulatory overload which may lead to pulmonary edema secondary to an elevated  diastolic pressure  in the  left ventricle . These individuals usually have a normal systolic function but symptoms are those of  heart failure . With time, this overload causes systolic failure. Ultimately  cardiac output  can be reduced to very low levels. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5309", "text": "It may occur in situations with an increased  blood volume , morbid obesity,  from excess of water and salt (kidney pathology, excess of fluid or blood administration, treatment with retaining water steroids), chronic and severe  anemia , large  arteriovenous fistula  or multiple small arteriovenous shunts as in  HHT  or  Paget's disease of bone , some forms of severe liver or kidney disorders,  hyperthyroidism , and wet  beriberi , [ 2 ]  and acutely in  septic shock , especially caused by  Gram-negative bacteria . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5310", "text": "(redirect from  hyperactive precordium )"}
{"_id": "WikiPedia_Cardio$$$corpus_5311", "text": "Hyperdynamic precordium  is a condition where the  precordium  (the area of the chest over the heart) moves too much (is  hyper dynamic ) due to some  pathology  of the  heart .  That means a forceful and hyperdynamic impulse ( large amplitude that terminates quickly) can be palpated during physical examination. [ 1 ]  Hyperdynamic precordium is a physical finding which can be normal or pathological. Some possible etiologies are as followings: [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5312", "text": "In addition,  hyperactive precordium  indicates this physical finding with a pathologic cause which is noted by a clinician. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5313", "text": "This problem (hyperdynamic precorrdium) can be  hypertrophy  of the ventricles,  tachycardia , or some other heart problem. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5314", "text": "Compared with  forceful and hyperdynamic  impulse finding, another abnormal finding is \" forceful and sustained\"  impulse, which sustained through the systolic phase. The former means the ventricle is doing \" volume \" work, and the latter with \" pressure\"  work (high pressure within left ventricle; some may transmit to the aorta, some may not). The latter can be seen in cases with left ventricle hypertrophy or outflow obstruction. Another possible cause of sustained impulse is heart failure with reduced ejection fraction. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5315", "text": "Hyperdynamic precordium can also be due to  hyperthyroidism , and thus indicates an increased  cardiac contractility , with  systolic hypertension . It may also be due to  aortic coarctation , and most other  congenital  heart malformations. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5316", "text": "Palpation  of the chest wall can be done to assess volume changes within the heart. A hyperdynamic precordium reflects a large volume change. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5317", "text": "Idiopathic giant-cell myocarditis  ( IGCM ) is a cardiovascular disease of the muscle of the heart ( myocardium )."}
{"_id": "WikiPedia_Cardio$$$corpus_5318", "text": "The condition is rare; [ 2 ]  however, it is often fatal and there is no proven cure because of the unknown nature of the disorder."}
{"_id": "WikiPedia_Cardio$$$corpus_5319", "text": "IGCM frequently leads to death with a high rate of about 70% in first year. A patient with IGCM typically presents with symptoms of  heart failure , although some may present initially with  ventricular arrhythmia  or  heart block . Median age from the time the disease is diagnosed to the time of death is approximately 6 months. 90% of patients are either deceased by the end of 1 year or have received a heart transplant. Diagnosis is made by  endomyocardial  biopsy during  heart catheterization . Biopsy shows  multinucleated giant cells  and thus the name. While previously cases universally required heart transplantation, recent studies show that two-thirds of patients can survive past one year with high doses of immunosuppressants such as prednisone and cyclosporine. The transplanted heart has a high chance of disease recurrence. Compared to lymphocytic (presumed  viral ) myocarditis, giant cell myocarditis is much more severe with much more rapid progression."}
{"_id": "WikiPedia_Cardio$$$corpus_5320", "text": "It is suggested to be caused by  T-lymphocytes ."}
{"_id": "WikiPedia_Cardio$$$corpus_5321", "text": "Isolated atrial amyloidosis  is a form of  amyloidosis  affecting the  atria  of the heart. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5322", "text": "It is associated with accumulation of the protein  atrial natriuretic factor . [ 1 ]  It may cause  abnormal heart rhythms ."}
{"_id": "WikiPedia_Cardio$$$corpus_5323", "text": "Keshan disease  is a congestive  cardiomyopathy  caused by a combination of  dietary deficiency of selenium  and the presence of a mutated strain of  Coxsackievirus , named after  Keshan County  of  Heilongjiang  province, Northeast China, where symptoms were first noted. These symptoms were later found prevalent in a wide belt extending from northeast to  southwest China , all due to  selenium -deficient soil. The disease peaked in 1960\u20131970, killing thousands of people. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5324", "text": "Often fatal, the disease affects children and women of child-bearing age, characterized by  heart failure  and  pulmonary edema . Over decades, supplementation with selenium reduced this condition. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5325", "text": "It had been linked to the  coxsackie B  virus. Current research suggests that the lack of selenium results in a more virulent strain of the coxsackievirus becoming the dominant  viral species  present in the population of virus, but the mechanism of this selection event is unclear. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5326", "text": "Keshan disease can also lead to higher rates of cancer, cardiovascular disease, hypertension, and strokes. In addition, an individual can experience eczema, psoriasis, arthritis, cataracts, alcoholism, and infections. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5327", "text": "There are four main types of Keshan disease: acute, subacute, chronic, and latent."}
{"_id": "WikiPedia_Cardio$$$corpus_5328", "text": "Some signs and symptoms of acute Keshan disease include dizziness,  malaise , nausea, chills, loss of appetite, projectile vomiting, pallor, low arterial blood pressure (less than 80/60 mmHg),  dyspnea , precardiac (anterior to the heart) or substernal (behind or below the sternum) discomfort,  cardiogenic shock , and constricted veins in one's extremities."}
{"_id": "WikiPedia_Cardio$$$corpus_5329", "text": "Some signs and symptoms of subacute Keshan disease include malaise, restlessness,  gallop rhythm , facial  edema , heart dilation, and cardiac shock."}
{"_id": "WikiPedia_Cardio$$$corpus_5330", "text": "Some signs and symptoms of chronic Keshan disease include palpitations, dyspnea, cough (with blood), pain in one's right upper quadrant, edema,  oliguria , enlargement of the heart, systolic murmur, gallop rhythm, and  hepatomegaly ."}
{"_id": "WikiPedia_Cardio$$$corpus_5331", "text": "Some signs and symptoms of latent Keshan disease include dizziness, fatigue, palpitations, and mild enlargement of the heart. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5332", "text": "The treatment for Keshan disease is selenium supplementation. The recommended amounts are fifty-five micrograms of selenium per day for adult men and women, sixty micrograms a day for women during pregnancy and seventy micrograms per day for women after pregnancy. A doctor may insist that if a man is sexually active, he may have to take up to seventy micrograms of selenium per day. A doctor may also recommend that the individual take vitamin E; selenium and  vitamin E  are medically linked and seem to work together. An individual will also be advised to have a diet that includes seafood, meats such as kidney, and liver, and some grains and seeds; all of these are high in selenium.  Brewer's yeast  and  wheat germ  both contain high levels of selenium. Garlic, onions, mushroom, broccoli, tomatoes, radishes, and Swiss chard may be good sources of selenium if the soil in which they are grown contains it. An individual will have to be monitored once they begin to take the selenium supplements, due to the fact that too much of it can cause balding, intestinal distress, weakness, and slow mental functioning. Individuals in China with the disease treat it with a herb called  Astragalus , which accumulates selenium from the soil. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5333", "text": "An individual will most likely be prescribed selenium supplements (in the form of  selenomethionine ) or have injections of this mineral.  Other recommendations for managing Keshan disease are to increase consumption of foods rich in selenium in addition to supplements, avoid alcohol, monitor side effects to medications, and increase sleep.  Cardiac surgery (implants, stents or full heart transplant) may be advised. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5334", "text": "Loeffler endocarditis  is a form of heart disease characterized by a  stiffened, poorly-functioning heart  caused by infiltration of the heart by  white blood cells  known as  eosinophils . [ 1 ]  Restrictive cardiomyopathy is a disease of the heart muscle which results in impaired  diastolic  filling of the  heart ventricles , i.e. the large heart chambers which pump blood into the  pulmonary  or  systemic circulation . Diastole is the part of the  cardiac contraction-relaxation cycle  in which the heart fills with venous blood after the emptying done during its previous  systole  (i.e. contraction). [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5335", "text": "An eosinophil-based specific type of heart damage was first described by the Swiss doctor,  Wilhelm Loeffler , in 1936. [ 3 ] [ 4 ]  As initially described, the disorder manifests as a restrictive cardiomyopathy, i.e. a poorly expanding and contracting rigid heart that was infiltrated with eosinophils and showed replacement of heart cells by stiff fibrotic  connective tissue . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5336", "text": "Loeffler endocarditis is now regarded as a manifestation of  eosinophilic myocarditis , a disorder that involves the infiltration of the heart's muscular layer by eosinophils that leads to three progressive clinical stages. The first stage involves acute  inflammation  and subsequent  death  of  heart muscle cells . This stage is dominated by signs and symptoms of the  acute coronary syndrome  such as  angina ,  heart attack , and  congestive heart failure . In the second stage, the  endocardium  (i.e. interior wall) of the heart forms  blood clots  which  break off  and then travel through and block various arteries; this clotting stage may dominate the initial presentation in some individuals. The third stage is a fibrotic stage, i.e. Loeffler endocarditis, wherein  scarring  replaces damaged heart muscle tissue to cause a poorly contracting heart and/or  heart valve disease . Recent publications commonly refer to Loeffler endocarditis as a historical term for the third stage of eosinophilic myocarditis. [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5337", "text": "The signs and symptoms of Loeffler endocarditis tend to reflect the many underlying disorders causing eosinophil dysfunction as well as the widely differing progression rates of cardiac damage. Before cardiac symptoms are detected, individuals may suffer symptoms of a common cold,  asthma ,  rhinitis ,  urticarial , or other allergic disorder. Cardiac manifestations include life-threatening conditions such as  cardiogenic shock  or sudden death due to abnormal  heart rhythms . More commonly, however, the presenting cardiac signs and symptoms of the disorder are the same as those seen in other forms of cardiomyopathy: the  heart arrhythmia  of  ventricular fibrillation  seen as an irregular pulse and heart rate, other  cardiac arrhythmias , symptoms of these arrhythmias such as chest  palpitations , dizziness, light headedness, and fainting; and symptoms of a heart failure such as fatigue,  edema , i.e. swelling, of the lower extremities, and  shortness of breath . [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5338", "text": "Hypereosinophilia  (i.e. blood eosinophil counts at or above 1,500 per microliter) or, less commonly,  eosinophilia  (counts above 500 but below 1,500 per microliter) are found in the vast majority of cases and are valuable clues pointing to this rather than other types of cardiomyopathies. However, elevated blood eosinophil counts may not occur during the early phase of the disorder. Other, less specific laboratory findings implicate a cardiac disorder but not necessarily eosinophilic myocarditis. These include elevations in blood markers for systemic inflammation (e.g.  C reactive protein ,  erythrocyte sedimentation rate ) and cardiac injury (e.g.  creatine kinase ,  troponins ); and abnormal  electrocardiograms  ( mostly  ST segment - T wave  abnormalities). [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5339", "text": "Eosinophilic states that may occur in and underlie Loeffler endocarditis (as well as the other stages of eosinophilic myocarditis) include primary and secondary  eosinophilias  or  hypereosinophilias . Primary eosinophilias or hypereosinophilias (i.e. disorders in which the eosinophil appears to be intrinsically diseased) that lead to Loeffler endocarditis are  clonal hypereosinophilia ,  chronic eosinophilic leukemia  and the  hypereosinophilic syndrome . [ 5 ] [ 8 ] [ 10 ] [ 11 ]  Secondary causes (i.e. disorders in which other diseases cause the eosinophil to become dysfunctional) include  allergic  and  autoimmune diseases ; infections due to certain  parasitic worms ,  protozoa , and  viruses ; malignant and premalignant hematologic disorders commonly associated with eosinophilia or hypereosinophilia; and adverse reactions to various drugs. [ 1 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5340", "text": "The disorder develops because of  eosinophilic  penetration into the cardiac tissues. This leads to a fibrotic thickening of portions of the heart (similar to that of  endomyocardial fibrosis ) and heart valves. In consequence, the heart becomes rigid and poorly contractile while the heart valves may become  stenotic or insufficient , i.e. reduced in ability to open or close, respectively. The damaged heart may also develop mural  thrombi , i.e. clots which lay against ventricle walls, tend to break off, and flow through and block arteries; this condition often precedes the fibrotic stage of eosinophilic myocarditis and is termed the thrombotic stage. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5341", "text": "The diagnosis of Loeffler endocarditis should be considered in individuals exhibiting signs and symptoms of poor heart contractility and/or valve disease in the presence of significant increases in blood eosinophil counts. Ancillary tests may help in the diagnosis.  Echocardiography  typically gives non-specific and only occasional findings of  endocardium  thickening,  left ventricular hypertrophy , left ventricle dilation, and involvement of the  mitral  and/or  tricuspid valves .  Gadolinium -based  cardiac magnetic resonance  imaging is the most useful  non-invasive procedure  for diagnosing eosinophilic myocarditis. It supports this diagnosis if it shows at least two of the following abnormalities:  a)  an increased signal in  T2-weighted images ;  b)  an increased global myocardial early enhancement ratio between myocardial and  skeletal muscle  in enhanced  T1 images  and  c)  one or more focal enhancements distributed in a non-vascular pattern in late enhanced T1-weighted images. Additionally, and unlike in other forms of myocarditis, eosinophilic myocarditis may also show enhanced gadolinium uptake in the sub-endocardium. [ 8 ] [ 10 ]  However, the only definitive test for Loeffler endocarditis is cardiac muscle biopsy showing the presence of eosinophilic infiltrates. Since the disorder may be patchy, multiple tissue samples taken during the procedure improve the chances of uncovering the pathology but in any case, negative results do not exclude the diagnosis. [ 7 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5342", "text": "Small studies and  case reports  have directed efforts towards:  a)  supporting cardiac function by relieving heart failure and suppressing life-threatening  abnormal heart rhythms ;  b)  suppressing eosinophil-based cardiac inflammation; and  c)  treating the underlying disorder. In all cases of Loeffler endocarditis that have no specific treatment regimens for the underlying disorder, available studies recommend treating the inflammatory component of this disorder with non-specific  immunosuppressive drugs , principally high-dosage followed by slowly-tapering to low-dosage maintenance  corticosteroid  regimens. Afflicted individuals who fail this regimen or present with  cardiogenic shock  may benefit from treatment with other non-specific immunosuppressive drugs such as  azathioprine  or  cyclophosphamide , as adjuncts to, or replacements for, corticosteroids. However, individuals with an underlying therapeutically accessible disease should be treated for this disease; in seriously symptomatic cases, such individuals may be treated concurrently with a corticosteroid regimen. Examples of diseases underlying Loefflers myocarditis that are recommended for treatments directed at the underlying disease include: [ 10 ] [ 13 ] [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5343", "text": "Mental stress-induced myocardial ischemia  (MSIMI) is a medical condition in which acute  psychological stress  can trigger a transient  myocardial ischemia , which is a state of reduced blood flow to the  heart muscle , often without the presence of significant  coronary artery disease  (CAD). [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 1 ]  It is distinct from conventional stress ischemia caused by physical exertion or pharmacological agents. [ 3 ]  MSIMI is often silent and detected through specific cardiac function tests during mental stress challenges. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5344", "text": "Mental stress triggers various physiological changes in the body, activating mechanisms such as the  autonomic nervous system  (ANS) and the  hypothalamic\u2013pituitary\u2013adrenal axis  (HPA), resulting in  hemodynamic ,  neuroendocrine , and  immune  responses. Typically, these responses are adaptive and help individuals cope with environmental changes, referred to as the \"defense response,\" which prepares them for  fight or flight . Consequently, the risk of cardiovascular (CV) events resulting from mental stress is influenced by external factors and an individual's stress threshold, which is shaped by  genetic predispositions  and life experiences. This variability explains why people respond differently to stressors. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5345", "text": "Mental stress-induced myocardial ischemia involves abnormal microvascular vasoreactivity and  inflammation , with increased  brain activity  in regions that modulate autonomic nervous system reactivity to  emotional stress ,  fear . [ 2 ] [ 7 ]  Emotional responses and certain psychological traits may influence the occurrence of MSIMI. [ 6 ]  MSIMI can occur at lower cardiac workloads, independent of hemodynamic changes, and is not directly related to the severity of  angiographic  CHD. [ 3 ]  It can occur in patients with normal  cardiac stress testing  and can often be  silent . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5346", "text": "MSIMI is associated with a twofold increased risk of  major adverse cardiovascular events  (MACE) compared to those without MSIMI. It is particularly prevalent among young women with  myocardial infarction  (MI) and those with  psychological comorbidities . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5347", "text": "Studies have found that young women who have had a myocardial infarction are twice as likely to develop mental stress-induced myocardial ischemia (MSIMI) compared to men of similar age. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5348", "text": "Various techniques like  electrocardiogram  (ECG),  echocardiography , and  positron emission tomography  (PET) are used to assess MSIMI. The incidence of MSIMI has varied across studies due to different assessment methods and mental stressors. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5349", "text": "Current research focuses on understanding stress pathways in CAD and integrating  mental health ,  behavioral medicine  with routine cardiology care to improve patient outcomes. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5350", "text": "Approximately 30% of CAD patients experience MSIMI under mental stress, which typically is silent and not related to the severity of CAD. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5351", "text": "Mydicar  is a genetically targeted  enzyme replacement therapy  being studied for use in patients with severe  heart failure . It is designed to increase the level of  SERCA 2a, a  sarcoplasmic   endoplasmic reticulum  calcium (Ca 2+ )  ATPase  found in the membrane of the sarcoplasmic reticulum (SR). The SERCA2a gene is delivered to the heart via an  adeno-associated viral  vector. [ 1 ]  Using the \u03b1-myosin heavy chain gene promoter in the  cardiac muscle cells , also called cardiomyocytes, Mydicar is able to direct the gene expression only to the  heart muscle . [ 2 ]  Mydicar is being tested [ when? ]  in a phase 2 study, in which has been compared to a  placebo  in 39 advanced heart failure patients. [ 3 ]  Thus far, patients treated with Mydicar have shown a 52% reduction in the risk of worsening heart failure compared to patients treated with the placebo. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5352", "text": "Normal function of the heart involves proper coordination between the contraction and relaxation of cardiomyocytes. Proper contraction and relaxation depends on the coordinated rise and fall of Ca 2+  in the  cytosol  of the cardiomyocytes. [ 4 ]  The SERCA2a transporter is found in the membrane of the SR and plays an important role in this cycle by removing cytosolic Ca 2+  from the cardiomyocyte and pumping it back into the SR during relaxation of the heart (diastole). SERCA2a restores SR Ca 2+  for the next contraction of cardiomyocytes. [ 5 ]  SERCA2a activity declines in patients experiencing late-stage heart failure. [ 1 ]  This leads to an above normal amount of cytosolic Ca 2+  in the cardiomyocytes during diastole. It also results in less Ca 2+  remaining in the SR for the next contraction of the heart. The altered cycling of Ca 2+  in cardiomyocytes ultimately leads to improper functioning of the heart, indicating a potentially beneficial effect of  gene therapy  using Mydicar. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5353", "text": "Administration of Mydicar occurs via an intracoronary injection of the drug. Mydicar delivers the SERCA2a gene to cardiomyocytes using an adeno-associated viral-vector (AAV). [ 6 ]  In the cardiomyocytes, the viral vector can insert itself into the genome and increase expression of the SERCA2a protein. Delivering the gene via an AAV is beneficial because it readily infects cardiac tissue and can produce stable, long-term expression of the delivered gene. [ 7 ]  AAVs also produce less of an immune response than alternative viral vehicles, such as  adenoviruses . [ 7 ]  AAVs have been studied in multiple patients and have not been known to cause human disease. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5354", "text": "Proper relaxation of the heart in preparation for the next contraction depends largely on the decline of Ca 2+  in the cytosol of cardiomyocytes during diastole. Along with impaired contractility, an increased level of cytosolic Ca 2+  increases the risk of  arrhythmias  and remodeling of the heart. [ 8 ]  Excess Ca 2+  found in the cytosol leads to asynchronous contractions of cardiomyocytes causing  tachyarrhythmias . The unusual increase in contraction and faster beating of the heart leads to  hypertrophy  by increasing the size of the cardiac myocytes in the heart. Excess hypertrophy of the cardiac myocytes leads to further dysfunction of the heart by affecting their ability to relax and contract properly. [ 5 ]  Administration of Mydicar increasing functioning SERCA2a can assist in lessening these negative effects of an increase in cytosolic Ca 2+  during diastole by increasing reuptake into the SR. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5355", "text": "A  myocardial bridge  ( MB ) is a common  congenital heart anomaly  in which one of the  coronary arteries  tunnels through the heart muscle ( myocardium ) itself."}
{"_id": "WikiPedia_Cardio$$$corpus_5356", "text": "In most people, the coronary arteries rest on top of the  heart muscle  and feed  blood  down into smaller  vessels  (e.g. the septal  arteries ) which then carry blood to the heart muscle itself (i.e. populate throughout the myocardium). However, if a band of muscle forms around one of the coronary arteries during the  fetal  stage of development, then a myocardial bridge is formed \u2013 a \"bridge\" of heart muscle over the artery."}
{"_id": "WikiPedia_Cardio$$$corpus_5357", "text": "Every time the heart squeezes to pump blood, the band of muscle exerts pressure and it is very rarely constricts the artery, reducing blood flow to the heart. Even a very thin ex. <1\u00a0 mm  and/or short ex. 20\u00a0mm MB can cause significant symptoms, although this has not been completely proven. [ citation needed ]  MBs can range in length from a few millimetres to 10\u00a0 cm  or more. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5358", "text": "The overall prevalence of myocardial bridge is at 19%, although the prevalence found at autopsies is much higher (42%). Myocardial bridge is usually a harmless condition, and in many cases bridges don't seem to cause any symptoms. However, some people with myocardial bridges may experience  angina , or  chest pain . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5359", "text": "While many people have very tiny myocardial bridges that cause no symptoms, others have longer and/or deeper bridges causing significant symptoms, including children. For example, some patients cannot  run  or  exercise  at all, others can exercise despite symptoms such as  shortness of breath  or  feelings of tightness in the chest , and still others find improvement of symptoms during exercise. Many competitive athletes have had severe myocardial bridges and unroofing surgery. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5360", "text": "The symptoms of myocardial bridges differ slightly from patient to patient depending on the length, depth, and location of the bridge. Common symptoms include: [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5361", "text": "Myocardial bridges can cause numerous complications \u2013 which are often as misunderstood in the medical community as the condition itself. These include:"}
{"_id": "WikiPedia_Cardio$$$corpus_5362", "text": "Note that studies have shown that plaque does not form inside myocardial bridges, yet there is virtually always plaque just before the myocardial bridge in adults."}
{"_id": "WikiPedia_Cardio$$$corpus_5363", "text": "Some common triggers of myocardial bridge symptoms are:"}
{"_id": "WikiPedia_Cardio$$$corpus_5364", "text": "Notably, high heart rate or tachycardia greatly increases  ischemia  (low oxygen to the heart) caused by myocardial bridges. Studies [ 8 ]  have shown that this is because the compressed  artery  reopens only very slowly each heartbeat and thus stays in a state of semi-compression for most or all of the  diastolic period . Thus as the heart rate increases, the time the artery has to reopen (diastolic period) decreases dramatically \u2013 to the point that with very high heart rates, the artery never fully reopens and blood flow is constantly reduced."}
{"_id": "WikiPedia_Cardio$$$corpus_5365", "text": "There are three key tests currently used to diagnose myocardial bridges by  Stanford University : CT scan, cardiac catheterization, and stress ultrasound."}
{"_id": "WikiPedia_Cardio$$$corpus_5366", "text": "As much of the science of testing for MBs is relatively new, patients frequently go undiagnosed.  Stanford 's center for myocardial bridges has offered second opinion services from a distance for some ten years, including to numerous international patients. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5367", "text": "Notably,  EKG  is not a reliable or conclusive diagnostic tool for diagnosing MBs. Some symptomatic MB patients show normal EKG results and others abnormal. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5368", "text": "Many doctors have suggested that there is a need for more awareness of MBs among doctors and better testing, including testing of young people as the disease is congenital. According to a 2007 study: [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5369", "text": "Clinical suspicion of a myocardial bridge would be warranted in all cases of typical or atypical  chest pain  in subjects who have a low probability of  atherosclerosis  because they are free from the traditional  cardiovascular  risk factors, particularly in the young."}
{"_id": "WikiPedia_Cardio$$$corpus_5370", "text": "A 2017 article in  Stanford Medical Center 's official blog  Scope  explains the hardships people with MB face, including the dismissal of their symptoms and obstacles in their lives as a result of the lack of MB education amongst cardiologists: [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5371", "text": "Many of these patients have these heartbreaking stories to tell. They can\u2019t hold a job, they can\u2019t travel, they can\u2019t take care of their families. Most  cardiologists  are completely at a loss. They know myocardial bridges exist, but they have been taught they are benign and never cause problems... When these patients go to the  ER , and they go there a lot, all the cardiology tests come back normal. They\u2019re told, 'Here\u2019s a little  Valium . I think you\u2019re  anxious .' They get belittled, not taken seriously, and they get really  depressed ."}
{"_id": "WikiPedia_Cardio$$$corpus_5372", "text": "Myotomy , commonly known as  unroofing surgery , is the first-line surgical treatment for myocardial bridges. [ 6 ] [ 16 ]  It is the only treatment that actually removes the myocardial bridge itself, releasing the artery from compression. Unroofing surgery today is done via open heart ( sternum ),  thoracotomy  (through the ribs), and also using  robot-assisted surgery  (through tiny keyholes in the  chest ). Full  open heart surgery  is usually reserved for very large myocardial bridges and/or specific situations that make  thoracotomy  difficult. By far,  Stanford University  has done more unroofing surgeries than any other  hospital  in the world, with over 200 unroofings completed since starting a decade ago. In 2019,  University of Chicago  surgeon Dr. Husam Balkhy emerged as a provider of robotic-assisted unroofing surgery, with some patients being possible candidates for this route. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5373", "text": "If done properly, unroofing removes the entire band of muscle affecting the  artery , restoring more  blood flow . Stanford University Medical Center's 2016 study by Pargaonkar et al. [ 18 ]  showed that unroofing surgery \u201csignificantly improves anginal symptoms\u201d and improves \u201call five dimensions of the SAQ\u201d i.e. Seattle Angina Questionnaire. Some residual symptoms caused by complications from a lifetime of living with a myocardial bridge may continue after unroofing surgery such as  endothelial dysfunction ,  vasospasm , plaque, narrowed artery. However, these often improve slowly over a year or more once the myocardial bridge is gone. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5374", "text": "A few cases have occurred in various hospitals in which patients have not been completely unroofed, leaving segments of the MB, resulting in lingering symptoms. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5375", "text": "A critical point is that the endothelial dysfunction and vasospasms caused by myocardial bridges cannot start to heal until unroofing surgery is done, because the MB continues to squeeze on the artery, damaging the artery lining. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5376", "text": "Bypass surgery  is not the first line treatment for myocardial bridges for two main reasons: [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5377", "text": "Notably, many myocardial bridge patients have had bypass surgery only to later need unroofing surgery after the bypass proved unsuccessful. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5378", "text": "However, papers by Ekeke et al., 2015  [ 19 ]  have shown bypass surgery is helpful as an addition to supplement unroofing surgery, but only when there is significant plaque just before (proximal to) the myocardial bridge or anatomic anomalies increase the risk of recurrence of such plaque. A 2013 Russian study by Bockeria et al. [ 20 ]  concludes that this competitive flow problem is much more likely to occur if the LIMA artery is used for the graft rather than the SVG, so the SVG is recommended."}
{"_id": "WikiPedia_Cardio$$$corpus_5379", "text": "Stents  are never indicated as a treatment for myocardial bridges because trials have shown they are prone to breaking when the artery is squeezed each heartbeat. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5380", "text": "Unroofing surgery has been performed in the  United States ,  Belgium ,  Spain ,  Italy ,  England ,  China ,  Russia ,  United Arab Emirates , and  Singapore , among other countries. [ citation needed ]  Hospitals that have performed unroofing surgery include:"}
{"_id": "WikiPedia_Cardio$$$corpus_5381", "text": "In many other countries, including a number of highly  developed countries  such as the  UK ,  Australia ,  New Zealand ,  Ireland  and  Sweden , unroofing surgery for myocardial bridges remains unavailable, and in some, the condition remains unrecognized as a medical problem. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5382", "text": "The true prevalence of MBs is still largely unknown, as studies have made vastly different assessments. As a 2017  Stanford  paper [ 6 ]  points out:"}
{"_id": "WikiPedia_Cardio$$$corpus_5383", "text": "Estimations of the prevalence of MBs vary... at least in part as a result of several key variables, including the means of identification (eg, computed tomography (CT), intravascular ultrasound ( IVUS ), or autopsy), which vessels are examined, and which definition of a bridge is applied (eg, only a \u201cdeep\u201d bridge vs both \u201csuperficial\u201d and \u201cdeep\u201d bridges). Perhaps the most fundamental variable is whether an MB is even considered. Unlike  hypertrophic cardiomyopathy , which will usually be obvious to the  pathologist , MBs can be easily obscured by  epicardial  and  pericardial  fat. As such, autopsy series have estimated the prevalence between 5% and 86%. The largest autopsy report, which included 1056 subjects, found a prevalence of 26%, 88% of which involved the  LAD . One population-based study with CT estimated a prevalence of 22.5%. As a result of these studies and others, an estimated prevalence of approximately 25% is generally accepted."}
{"_id": "WikiPedia_Cardio$$$corpus_5384", "text": "According to Stanford University Medical Center, MBs are often misunderstood by  doctors , who may have been taught that the condition is always benign. [ 6 ]  As a result, patients are often denied treatment. But a great deal of science has emerged in the past decade to clarify the condition. In particular, Stanford has published over 15 articles on MBs since 2014. One commonly recurring reason for denial of treatment is the myth that myocardial bridges do not significantly affect blood flow. But this myth has been debunked by Stanford and also Daoud and Wafa 2012 who say:"}
{"_id": "WikiPedia_Cardio$$$corpus_5385", "text": "Normally, only 15% of  coronary   blood flow  occurs during  systole  and because myocardial bridging is a systolic event on  angiography , its clinical significance and relevance have been questioned. [However] angiographic and  intravascular   ultrasonographic  studies demonstrated that vessel compression during systole is followed by the delay in the increase in  luminal  diameter during diastole, thus affecting the predominant phase of  coronary   perfusion , especially during episodes of  tachycardia . These data suggest that angina, acute coronary syndromes, and  arrhythmias  in patients with myocardial bridging may be explained by the reduced  ischemic  threshold.\u201d [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5386", "text": "In other words, while the myocardial bridge itself only compresses the artery while the heart squeezes ( systolic period ), which is only 15% of the time in the heartbeat cycle, in fact, the artery stays compressed long after the heart relaxes. This is because arteries are sturdy and pliable, so after being compressed they are very slow to reopen, remaining in some level of semi-compression for most if not all of the  diastolic  period i.e. the other 85% of the heartbeat cycle (hence the critical need for dFFR testing in diagnosing myocardial bridges). [ citation needed ]  Thus the coronary artery is fully open to allow normal blood flow for only a small percentage of each heartbeat cycle. [ citation needed ]  This problem is further exacerbated by tachycardia, which can bring the duration of normal blood flow to zero, as explained below. Dr. Ingela Schnittger, head of the Myocardial Bridge Research Center at Stanford, has appeared on  BBC Radio  to explain this. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5387", "text": "Myocardial disarray , also known as  myocyte disarray , is a term to describe the loss of the normal parallel alignment of  myocytes [ 1 ]  (the  muscle   cells  of the  heart ).  Instead, the myocytes usually form circles around foci of  connective tissue .  Myocardial disarray is associated with  myocardial fibrosis  (the replacement of the myocytes with non-contractile  scar tissue )."}
{"_id": "WikiPedia_Cardio$$$corpus_5388", "text": "Myocardial disarray can be seen in a number of disease states, including:"}
{"_id": "WikiPedia_Cardio$$$corpus_5389", "text": "The common factor amongst all these diseases is that they all cause varying degrees of remodelling (myocardial fibrosis) of the  ventricles ."}
{"_id": "WikiPedia_Cardio$$$corpus_5390", "text": "Myocardial rupture  is a laceration of the  ventricles  or  atria  of the  heart , of the  interatrial  or  interventricular septum , or of the  papillary muscles .  It is most commonly seen as a serious  sequela  of an acute  myocardial infarction  (heart attack)."}
{"_id": "WikiPedia_Cardio$$$corpus_5391", "text": "It can also be caused by trauma. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5392", "text": "Symptoms of myocardial rupture are recurrent or persistent  chest pain ,  syncope , and  distension of jugular vein . Sudden death caused by a myocardial rupture is sometimes preceded by no symptoms. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5393", "text": "The most common cause of myocardial rupture is a recent  myocardial infarction , with the rupture typically occurring three to five days after infarction. [ 3 ]  Other causes of rupture include cardiac trauma,  endocarditis  (infection of the heart), [ 4 ] [ 5 ]   cardiac tumors , infiltrative diseases of the heart, [ 4 ]  and  aortic dissection . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5394", "text": "Risk factors for rupture after an acute myocardial infarction include female gender, [ 6 ] [ 7 ]  advanced age of the individual, [ 6 ] [ 7 ]  first ischemic event, and a low  body mass index . [ 6 ]   Other presenting signs associated with myocardial rupture include a pericardial friction rub, sluggish flow in the coronary artery after it is opened i.e. revascularized with an  angioplasty , the  left anterior descending artery  being often the cause of the acute MI, [ 6 ] [ 7 ] [ 8 ]  and delay of revascularization greater than 2 hours. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5395", "text": "Due to the acute hemodynamic deterioration associated with myocardial rupture, the diagnosis is generally made based on physical examination, changes in the vital signs, and clinical suspicion.  The diagnosis can be confirmed with  echocardiography .  The diagnosis is ultimately made at autopsy. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5396", "text": "Myocardial ruptures can be classified as one of three types. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5397", "text": "Another method for classifying myocardial ruptures is by the anatomical portion of the heart that has ruptured.  By far the most dramatic is rupture of the free wall of the left or right ventricles, as this is associated with immediate hemodynamic collapse and death secondary to acute  pericardial tamponade .  Rupture of the interventricular septum will cause a  ventricular septal defect .  Rupture of a papillary muscle will cause acute  mitral regurgitation . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5398", "text": "The rupture will most often occur near the edge of the necrotic myocardium where it abuts healthy (but hyperemic) myocardium where the inflammatory response is at its greatest.  Further, the rupture will occur in an area of greatest  shear stress .  Within the left ventricle, these areas are adjacent to both anterior and posterior papillary muscles (regardless of whether the papillary muscle is involved in the infarction). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5399", "text": "Left ventricular free wall rupture almost always results in hemopericardium (the exception being in the scenario where the patient has had prior open heart surgery and has obliterative fibrous pericardial adhesions; these would prevent egress of blood) and pericardial tamponade.  An accumulation of as little as 75 ml of blood, acquired acutely in a patient without pre-existing pericardial effusion, is sufficient to produce tamponade (wherein the ventricles are incapable of filling and are thus incapable of producing adequate stroke volume). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5400", "text": "The treatment for myocardial rupture is supportive in the immediate setting and surgical correction of the rupture, if feasible. [ citation needed ]   A certain small percentage of individuals do not seek medical attention in the acute setting and survive to see the physician days or weeks later.  In this setting, it may be reasonable to treat the rupture medically and delay or avoid surgery completely, depending on the individual's  comorbid  medical issues. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5401", "text": "The prognosis of myocardial rupture is dependent on a number of factors, including which portion of the myocardium is involved in the rupture.  In one case series, if myocardial rupture involved the free wall of the  left ventricle , the  mortality rate  was 100.0%. [ 6 ]   The chances of survival rise dramatically if the patient: 1. has a witnessed initial event; 2. seeks early medical attention; 3. has an accurate diagnosis by the emergentologist; and 4. happens to be at a facility that has a cardiac surgery service (by whom a quick repair of the rupture can be attempted).  Even if the individual survives the initial hemodynamic sequelae of the rupture, the 30\u2011day mortality is still significantly higher than if rupture did not occur. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5402", "text": "The incidence of myocardial rupture has decreased in the era of urgent revascularization and aggressive  pharmacological therapy  for the treatment of an acute myocardial infarction.  However, the decrease in the incidence of myocardial rupture is not uniform; there is a slight increase in the incidence of rupture if thrombolytic agents are used to abort a myocardial infarction. [ 10 ]   On the other hand, if  primary percutaneous coronary intervention  is performed to abort the infarction, the incidence of rupture is significantly lowered. [ 7 ]   The incidence of myocardial rupture if PCI is performed in the setting of an acute myocardial infarction is about 1 percent. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5403", "text": "Myocardial scarring  is the accumulation of  fibrous  tissue resulting after some form of trauma to the cardiac tissue. [ 1 ] [ 2 ]  Fibrosis is the formation of excess tissue in replacement of  necrotic  or extensively damaged tissue. Fibrosis in the heart is often hard to detect because  fibromas , scar tissue or small tumors formed in one cell line, are often formed. [ 3 ]  Because they are so small, they can be hard to detect by methods such as  magnetic resonance imaging . [ 1 ]  A cell line is a path of fibrosis that follow only a line of cells."}
{"_id": "WikiPedia_Cardio$$$corpus_5404", "text": "A  myocardial infarction , also known as a heart attack, often result in the formation of fibrosis. [ 2 ]  A myocardial infarction is an  ischemic  event, or a restriction of blood flow to body tissue, such as by  atherothrombosis . [ 4 ]  Without blood flow to the myocardium, it is deprived of oxygen, causing tissue death and irreversible damage. [ 5 ]  The tissue destroyed by the infarction is replaced with non-functioning fibrosis, restoring some of the structural integrity of the organ but resulting in impaired myocardial function. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5405", "text": "Coronary heart disease , also known as coronary artery disease, is one of the most common causes of myocardial damage, affecting over three million people in the United States. [ 7 ]  In coronary heart disease, the  coronary arteries  narrow due to the buildup of  atheroma  or fatty deposits on the vessel walls. The atheroma causes the blood flow of the arteries to be restricted. [ 6 ]  By restricting the blood flow, the tissue is still receiving some oxygen, but not enough to sustain the tissue over time. [ 5 ]  The accumulation of the fibrotic tissue is much slower in coronary heart disease compared to an infarction because the tissue is still receiving some oxygen. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5406", "text": "Another form of myocardial scarring results from surgical repairs. [ 2 ]  Surgical repairs are often necessary for a person born with a  congenital defect of the heart . [ 8 ]  While surgical  laparoscopy  still leaves myocardial scarring, the trauma seems to be less damaging then naturally occurring scarring. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5407", "text": "Immediately after damage to the myocardium occurs, the damaged tissue becomes inflamed. Inflammation is the accumulations of  neutrophils ,  macrophages , and  lymphocytes  at the site of the trauma. [ 9 ] [ 10 ]  In addition, \"inflammatory cells upregulate the release of a myriad of signaling cytokines, growth factors, and hormones including transforming growth factor \u03b2, interleukins 1, 2, 6, and 10, tumor necrosis factor \u03b1, interferon \u03b3, chemokines of the CC and CXC families, angiotensin II, norepinephrine, endothelin, natriuretic peptides, and platelet-derived growth factors\". [ 10 ] \u00a0 Both the necrotic cells and the inflamed myocardium secrete and activate matrix  metalloproteinase . Metalloproteinase aids in the destruction and reabsorption of necrotic tissue. After several days,  collagen  accumulation at the site of injury begins to occur. [ 10 ]  As part of the  extracellular matrix , granulated tissue consisting of  fibrin ,  fibronectin ,  laminin , and  glycosaminoglycan  is suspended in a collagen base. [ 10 ] \u00a0 The extracellular matrix acts as scaffolding for the fibrillar collagen to form. The fibrillar collagen is the main constitute of what will become the scar tissue. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5408", "text": "Myocardial stunning  or   transient post-ischemic myocardial dysfunction  is a state of mechanical cardiac dysfunction that can occur in a portion of  myocardium  without  necrosis  after a brief interruption in  perfusion , despite the timely restoration of normal  coronary blood flow . [ 2 ] [ 3 ]  In this situation, even after  ischemia  has been relieved (by for instance  angioplasty  or  coronary artery bypass surgery ) and myocardial blood flow (MBF) returns to normal, myocardial function is still depressed for a variable period of time, usually days to weeks. [ 2 ] [ 1 ]  This reversible reduction of function of  heart contraction [ 4 ]  after  reperfusion  is not accounted for by tissue damage or reduced blood flow, but rather, its thought to represent a perfusion-contraction \"mismatch\". [ 5 ] [ 2 ]  Myocardial stunning was first described in laboratory canine experiments in the 1970s where LV wall abnormalities were observed following coronary artery occlusion and subsequent reperfusion. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5409", "text": "Clinical situations associated with myocardial stunning include: [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5410", "text": "Myocardial stunning has been implicated in the development of  Takotsubo (Stress) cardiomyopathy . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5411", "text": "The underlying mechanisms of myocardial stunning have remained the subject of debate for several decades. [ 7 ]  Two leading hypotheses implicate reperfusion-induced oxygen free-radical damage and altered calcium flux resulting in intracellular hypercalcemia and desensitization of myofilaments. [ 1 ]  After total ischemia occurs, the myocardium switches immediately from  aerobic glycolysis  to  anaerobic glycolysis  resulting in the reduced ability to produce high energy phosphates such as  ATP  and  Creatinine Phosphate . At this point, the lack of the energy and  lactate  accumulation results in cessation of contraction within 60 seconds of  ischemia  (i.e. Vessel Occlusion).  Subsequent to this is a period of \"myocardial stunning,\" in which reversible ischemic damage is taking place.  At approximately 30 minutes after the onset of total ischemia the damage becomes irreversible, [ 6 ]  thereby ending the phase of myocardial stunning. The generation of oxygen-derived [free radicals] during the initial period of reperfusion after ischemia is believed to contribute to the pathogenesis of myocardial stunning. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5412", "text": "Some evidence suggests that brief, repetitive episodes of myocardial ischemia may result in chronic myocardial stunning and ventricular contractile impairment. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5413", "text": "Imaging techniques such as  echocardiography ,  ventriculography , and  nuclear imaging  can be used to detect a contractile dysfunction following reperfusion after an episode of ischemia. [ 1 ]  The area of dysfunction should also maintain normal perfusion, detected via  Positron Emission Tomography , echocardiography with contrast, and/or  thallium scintigraphy  in order for a diagnosis of myocardial stunning to be considered. [ 1 ]  However, there are many practical challenges to diagnosing myocardial stunning using these methods. Accurate detection of regional myocardial blood flow and contraction function abnormalities must be detected at levels of high sensitivity. [ 2 ]   The diagnosis of myocardial stunning must also be differentiated from other conditions such as  hibernating myocardium  and persistent (silent) subendocardial ischemia, which can also co-exist with superimposed stunning. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5414", "text": "Treatment considerations for myocardial stunning should be determined based on the clinical judgment of the cardiologist or physician, the degree of LV impairment and symptoms, and the wishes of the person. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5415", "text": "Some evidence supports the use of  inotropic drugs  in the case of severe myocardial dysfunction. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5416", "text": "Results from canine experimental trials investigating the oxygen free-radical hypothesis for myocardial stunning have shown a reduction in free radical generation and improvement in myocardial function following anti-oxidant infusion. [ 6 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5417", "text": "Myocarditis  is defined as  inflammation  of the  myocardium . Myocarditis can progress to  inflammatory cardiomyopathy  when there are associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. [ 6 ] [ 7 ]  Symptoms can include  shortness of breath ,  chest pain ,  decreased ability to exercise , and an  irregular heartbeat . [ 1 ]  The duration of problems can vary from hours to months. Complications may include  heart failure  due to  dilated cardiomyopathy  or  cardiac arrest . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5418", "text": "Myocarditis is most often due to a  viral infection . [ 1 ]  Other causes include  bacterial infections , certain medications, toxins and  autoimmune disorders . [ 1 ] [ 2 ]  A diagnosis may be supported by an  electrocardiogram  (ECG), increased  troponin ,  heart MRI , and occasionally a heart  biopsy . [ 1 ] [ 2 ]  An  ultrasound of the heart  is important to rule out other potential causes such as  heart valve problems . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5419", "text": "Treatment depends on both the severity and the cause. [ 1 ] [ 2 ]  Medications such as  ACE inhibitors ,  beta blockers , and  diuretics  are often used. [ 1 ] [ 2 ]  A period of no exercise is typically recommended during recovery. [ 1 ] [ 2 ]   Corticosteroids  or  intravenous immunoglobulin  (IVIG) may be useful in certain cases. [ 1 ] [ 2 ]  In severe cases an  implantable cardiac defibrillator  or  heart transplant  may be recommended. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5420", "text": "In 2013, about 1.5 million cases of acute myocarditis occurred. [ 8 ]  While people of all ages are affected, the young are most often affected. [ 9 ]  It is slightly more common in males than females. [ 1 ]  Most cases are mild. [ 2 ]  In 2015  cardiomyopathy , including myocarditis, resulted in 354,000 deaths up from 294,000 in 1990. [ 10 ] [ 5 ]  The initial descriptions of the condition are from the mid-1800s. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5421", "text": "The signs and symptoms associated with myocarditis are varied, and relate either to the actual inflammation of the  myocardium  or to the weakness and dysfunction of the heart muscle that is secondary to the inflammation. While myocarditis may develop over periods ranging from hours to months, patients typically present with signs and symptoms that resemble heart failure, including the following: [ 1 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5422", "text": "Since myocarditis is often due to a viral illness, many patients experience symptoms consistent with a recent viral infection including a fever, rash, loss of appetite, abdominal pain, vomiting,  diarrhea ,  joint pains , and easily becoming tired. [ 13 ]  Additionally, myocarditis is often associated with  pericarditis , and many people with myocarditis present with signs and symptoms that suggest myocarditis and pericarditis at the same time. [ 14 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5423", "text": "Children primarily present with the aforementioned symptoms associated with a viral infection. [ 12 ]  Later stages of the illness can involve the respiratory system and lead to increased work of breathing. These are often mistaken for  asthma . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5424", "text": "Myocarditis can be distinguished as either fulminant or acute based on the severity of symptoms on presentation, as well as the time course over which symptoms develop and persist. This categorization can help predict the treatment, outcomes, and complications of myocarditis. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5425", "text": "Fulminant myocarditis is defined as sudden and severe myocarditis that is associated with signs and symptoms of heart failure while at rest. [ 15 ]  More specifically, fulminant myocarditis is characterized by a distinct, rapid onset of severe heart failure symptoms, such as shortness of breath and chest pain, that develop over the course of hours to days. Additionally, treatment requires the use of medications or mechanical devices to improve heart function. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5426", "text": "Acute non-fulminant myocarditis has a less distinct onset in contrast to fulminant myocarditis, and evolves over days to months. [ 16 ] [ 17 ]  While the symptoms of acute myocarditis overlap with those of fulminant myocarditis, they do not typically occur at rest, and treatment does not require the use of mechanical circulatory support. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5427", "text": "While many causes of myocarditis are known, there are many cases in which a causative agent cannot be identified. In Europe and North America, viruses are common culprits. [ 18 ]  Worldwide, however, the most common cause is  Chagas disease , an illness endemic to Central and South America that results from infection with the protozoan  Trypanosoma cruzi . [ 12 ]  Overall, myocarditis can be caused by infections, immune conditions, toxins, drug reactions, and physical injuries to the heart. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5428", "text": "The most common causes of myocarditis are infectious organisms. Viral infections are the most common cause in developed countries, with a majority of cases being caused by those with single-stranded RNA genomes, such as Coxsackie viruses (especially Coxsackie B3 and B5). [ 19 ] [ 20 ]  Globally,  Chagas disease  is the leading cause of myocarditis, which results from infection with the  protozoan   Trypanosoma cruzi . [ 12 ]  Bacteria can also result in myocarditis, although it is rare in patients with normal heart function and without a preexisting  immunodeficiency . [ 18 ] [ 21 ]  A list of the most relevant infectious organisms is below."}
{"_id": "WikiPedia_Cardio$$$corpus_5429", "text": "Most forms of myocarditis involve the infiltration of heart tissues by one or two types of pro-inflammatory blood cells,  lymphocytes  and  macrophages  plus two respective descendants of these cells,  NK cells  and  macrophages .  Eosinophilic myocarditis  is a subtype of myocarditis in which cardiac tissue is infiltrated by another type of pro-inflammatory blood cell, the  eosinophil . Eosinophilic myocarditis is further distinguished from non-eosinophilic myocarditis by having a different set of causes and recommended treatments. [ 36 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5430", "text": "The pathophysiology of viral myocarditis is not well understood, but it is believed to involve cardiotropic viruses (viruses with a high affinity for the heart muscle) gaining entry to cardiac muscle cells, usually via binding to a transmembrane receptor. [ 31 ]  Over approximately the next 1\u20137 days the virus replicates and causes inflammation leadings to  necrosis  and  apoptosis  of cardiac muscle cells (myocytes) and activation of the innate immune system. [ 31 ]  Over the next 1\u20134 weeks, viral replication continues with subsequent activation of the  acquired immune system  leading to  T cell  infiltration and the formation of antibodies, including possibly auto-antibodies. [ 31 ]  Over the next few months to years, this process either resolves and concludes with viral clearance or it may progress to cause permanent heart damage such as dilated cardiomyopathy, ventricular dysfunction or other cardiomyopathies. [ 31 ]  Coxsackie B, specifically B3 and B5, has been found to interact with coxsackievirus-adenovirus receptor (CAR) and  decay-accelerating factor  (DAF). However, other proteins have also been identified that allow Coxsackieviruses to bind to cardiac cells. The natural function of CAR and mechanism that the Coxsackievirus uses to infect the cardiac muscle is still unknown. [ 19 ]  The mechanism by which coxsackie B viruses (CBVs) trigger inflammation is believed to be through the recognition of CBV virions by  Toll-like receptors . [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5431", "text": "The binding of many types of  coronaviruses , including the  SARS-CoV-2 virus , through  ACE2 receptors  present in heart muscle may be responsible for direct viral injury leading to myocarditis. [ 25 ]  In a study done during the  2002-2004 SARS outbreak ,\u00a0 SARS viral RNA\u00a0 was detected in the autopsy of heart specimens in 35% of the patients in the  Toronto ,  Canada  area who had died due to SARS. [ 37 ]  It was also observed that an already diseased heart has increased expression of ACE2 receptor contrasted to healthy individuals which may lead to greater viral infiltration in the heart muscle. Hyperactive immune responses in COVID-19 patients may lead to the initiation of the  cytokine storm . This excess release of cytokines may lead to myocardial injury. [ 25 ]  In addition to direct cardiac myocyte (heart muscle cell) damage due to SARS-CoV-2 viral infiltration and inflammation, there are other suspected mechanisms that Covid-19 may indirectly cause myocarditis. During COVID-19, the other indirect mechanisms thought to contribute to myocarditis include: oxygen supply-demand mismatch to the heart muscle leading to myocardial (heart muscle) injury; microvascular thrombi, or blood clots in the small blood vessels of the heart causing injury; the systemic hyperinflammatory state in Covid-19 leading to heart muscle injury; or the virus causing indirect damage to the heart by inducing auto-immune mediated damage to the heart muscle (and frequently other organs). [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5432", "text": "Myocarditis refers to an underlying process that causes inflammation and injury of the heart.  It does not refer to inflammation of the heart as a consequence of some other insult.  Many secondary causes, such as a heart attack, can lead to inflammation of the myocardium and therefore the diagnosis of myocarditis cannot be made by evidence of inflammation of the myocardium alone. [ 38 ] [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5433", "text": "Myocardial inflammation can be suspected on the basis of elevated inflammatory markers including  C-reactive protein  (CRP),  erythrocyte sedimentation rate  (ESR), or an increased  IgM  ( serology ) against viruses known to affect the  myocardium . Markers of myocardial damage ( troponin  or  creatine kinase  cardiac isoenzymes) are elevated. [ 12 ]  The CRP and ESR are sometimes elevated in myocarditis but they are not specific as they may be elevated due to many other causes. [ 31 ]  Similarly, CK may be elevated in myocarditis but is also non-specific, as it may be elevated in myositis (skeletal muscle injury). [ 31 ]  High sensitivity troponin is usually elevated in myocarditis and this marker is very specific to myocardial (heart muscle) injury. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5434", "text": "Myocardial inflammation may also be suspected based on ECG findings, but these findings are not specific to myocarditis. [ 40 ]  The ECG finding most commonly seen in myocarditis is sinus tachycardia with non-specific ST or T wave changes. [ 40 ]  But other findings that may be seen in perimyocarditis (a combination of  pericarditis  and myocarditis) include PR segment depression, PR segment depression with associated ST segment elevation, diffuse ST segment elevation (in a pericarditis pattern). [ 40 ]  ST segment elevation was seen in 62% of people with myocarditis. [ 31 ]  The presence of Q waves, a widened  QRS complex , prolongation of the  QT interval , high degree AV nodal blockade, and ventricular tachyarrhythmias are associated with a poor prognosis when seen on ECG in people with myocarditis. [ 40 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5435", "text": "The  gold standard  is the  biopsy  of the myocardium, in general done in the setting of  angiography . A small tissue sample of the  endocardium  and  myocardium  is taken and investigated. The cause of the myocarditis can be only identified by a biopsy. Endomyocardial biopsy samples are assessed for histopathology (how the tissue looks like under the microscope):  myocardial interstitium  may show abundant  edema  and inflammatory infiltrate, rich in  lymphocytes  and  macrophages . Focal destruction of myocytes explains the myocardial pump failure. [ 12 ]  In addition samples may be assessed with   immunohistochemistry  to determine which types of immune cells are involved in the reaction and how they are distributed. Furthermore,  PCR  and/or  RT-PCR  may be performed to identify particular viruses. Finally, further diagnostic methods like microRNA assays and gene-expression profile may be performed. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5436", "text": "Cardiac  magnetic resonance imaging  (cMRI or CMR) has been shown to be very useful in diagnosing myocarditis by visualizing markers for  inflammation  of the  myocardium . [ 41 ]  Cardiac MRI is most sensitive when performed 2\u20133 weeks after the initial clinical presentation of myocarditis and may be repeated 6\u201312 months after onset to monitor the evolution of disease or response to treatment. [ 31 ]  The Lake Louise Criteria (established in 2009) are a commonly used MRI criteria to establish the diagnosis of myocarditis in suspected cases. [ 42 ]  The Lake Louise Criteria include increased signal intensity after gadolinium contrast enhancement (a sign of hyperemia, or increased blood flow to damaged tissue), increased myocardial T2 relaxation time or an increased T2 signal intensity (which are signs of tissue edema or swelling), and late gadolinium contrast enhancement (which is a sign of tissue necrosis (tissue damage) or fibrosis (scarring)). [ 31 ]  In 2018, additional radiographic MRI criteria were added, including increased T1 signal intensity and increased extracellular volume (both of which being signs of myocardial injury). [ 31 ]  The original 2009 Lake Louise Criteria had a 74% sensitivity and 86% specificity in the diagnosis of myocarditis, but when adding the 2018 update to the criteria (in which T1 signal intensity was found to have high diagnostic sensitivity), the sensitivity and specificity in the diagnosis of myocarditis increased to 88% and 96% respectively. [ 31 ] [ 43 ]  Cardiac MRI, if available, is recommended in all cases of suspected myocarditis. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5437", "text": "While myocarditis has many etiologies and a variable constellation of signs and symptoms, many causes do not have a specific treatment thus the primary focus is on supportive care and symptom management. [ 17 ]  In some cases of biopsy-proven myocarditis, the causative cell type may indicate condition specific treatments that are beneficial. These treatments typically consist of corticosteroids, or immunosuppressants. [ 45 ]   Eosinophilic myocarditis ,  giant cell myocarditis  and  cardiac sarcoidosis  are usually responsive to immunosuppressive treatments; in the form of glucocorticoids with or without  azathioprine  and  cyclosporine . [ 31 ]  Some of these immune mediated forms of myocarditis require an extended course (maintenance course) of immunosuppressive therapy. [ 31 ]  It is recommended to rule out drugs and parasites as potential causes of eosinophilic myocarditis as these common causes of the variant can be effectively treated with discontinuation of the offending drug or specific anti-parasitic treatment respectively. [ 31 ]  Empiric IV glucocorticoids are indicated in acute myocarditis with cardiogenic shock, heart failure, ventricular arrhythmias or high degree AV block that is suspected due to auto-immune disease; but the  European Society of Cardiology  also recommends subsequent viral genome testing of endomyocardial biopsy specimens due to risk of viral activation, which may necessitate discontinuation of immunosuppression therapy. [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5438", "text": "In a majority of cases, the main therapies are used to support patients and are dependent on the severity of symptoms and the time course across which myocarditis develops. [ 17 ]  Supportive therapies can be divided into two broad categories, medications and mechanical support. [ 47 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5439", "text": "The specific medications that are used to support patients are directly related to the cause of the symptom or sign. Just as the symptoms of myocarditis mirror those of congestive heart failure, so too do the therapies. [ 45 ]  Additionally, the order in which  therapies are used depends on the degree of heart dysfunction, with stabilization of patient blood pressure and breathing taking highest priority when present. [ 17 ]  This can involve the use of  inotropes , or medications that make the heart contract with greater force, as well as  antiarrhythmic  drugs such as adenosine or carvedilol. [ 15 ]  In patients that have stable and adequate heart function, further treatments are based on heart failure guidelines. [ 45 ]   ACE inhibitors  or  Angiotensin Receptor Blockers  (ARBs) can have a protective benefit to the heart, so either are typically used in any patient with symptomatic myocarditis. [ 31 ]  Simultaneously, beta blockers are used in patients that can tolerate their heart beating at a slower rate. Shortness of breath at rest and swelling can be relieved with diuretics such as furosemide, and the addition of aldosterone receptor blockers can augment the diuresis while preventing the excess loss of potassium. In patients with symptoms while resting, additional medications can be added such as digoxin. [ 45 ] [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5440", "text": "Mechanical support is used in cases of myocarditis in which medications alone do not lead to adequate heart function and the body requires additional support to achieve organ perfusion. [ 15 ] [ 16 ]  Myocarditis cases that require mechanical circulatory support are categorized as fulminant by definition. [ 15 ]  People that require additional support with their heart function can benefit from the use of  ventricular assist devices  like  intra-aortic balloon pumps . [ 15 ] [ 16 ]  In people with myocarditis severe enough to cause cardiac arrest, extracorporeal membrane oxygenation (ECMO) is used to adequately pump blood and provide oxygen if needed. [ 15 ]  Both ventricular assist devices and ECMO can be used as bridge therapy until heart transplantation in patients that are candidates.  Heart transplantation  is reserved for those that do not respond to the aforementioned conventional medical therapies. [ 49 ]  An  implantable cardioverter-defibrillator  (ICD) is sometimes required in those with cardiomyopathy or heart failure caused by myocarditis due to the risk of fatal ventricular arrhythmias. [ 31 ]  The need for ICD is usually assessed 3\u20136 months after the onset of myocarditis, after the acute phase of myocarditis has passed, with a temporary,  wearable cardioverter-defibrillator  acting as a temporary treatment in the interim. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5441", "text": "The prognosis associated with myocarditis is stratified by the severity and time course along which symptoms develop. In addition to symptom severity, there are also several indicators of heart function that can be used to predict patient outcomes, many of which are part of the standard evaluation of patients presenting with cardiovascular dysfunction. Most people with myocarditis have an uncomplicated, self-limited and mild course while making a full recovery. [ 31 ]  However, those with myocarditis that present with a decreased  ejection fraction , or those who present with  heart failure , advanced  atrioventricular block , with sustained  ventricular arrhythmias  or with  hemodynamic instability  have a worse prognosis with an increased risk of death or need for heart transplantation. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5442", "text": "An electrocardiogram is one of the most common screening tools used in cases of suspected cardiac pathology, such as myocarditis. The findings that correlate with poorer outcomes are non-specific and include widened QRS complexes and QT intervals, partial or complete atrial-ventricular heart block, and malignant ventricular arrhythmias like sustained ventricular tachycardia or ventricular fibrillation. [ 50 ]  Electrocardiogram findings of ST elevations with upward concavity and an early repolarization pattern, however, were associated with a better cardiovascular prognosis in general. [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5443", "text": "In cases of acute myocarditis, cardiac magnetic resonance imaging can reveal several prognostic indicators that, similar to ECGs, are non-specific and reflect poorer cardiac physiology. Late gadolinium enhancement on cardiac MRI demonstrates perturbations in extracellular volume as a result of cell necrosis or edema, and is significantly associated with increases in all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events. The association was strongest with any late gadolinium enhancement, but remained true for findings of anterolateral-specific enhancement. [ 51 ] [ 52 ]  A similar relationship was found between a left ventricular ejection fraction < 50%, increased mortality, and increased major adverse cardiovascular events. [ 53 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5444", "text": "Myocarditis has been reported to be a major cause of  sudden cardiac death  (SCD) in infants, adolescents, and young adults, but the reported rates show wide variation (1 to 14 percent) among young people depending on differences in SCD definition and classification/ definition of myocarditis post-mortem as well as heterogeneity of study populations. [ 54 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5445", "text": "In  fulminant  myocarditis, in which an inflammatory cytokine storm occurs, cardiac functions decline rapidly and the death rate is high. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5446", "text": "The prevalence of myocarditis is estimated to be about 1-10 cases per 100,000 persons per year, with higher estimates at 22 cases per 100,000 persons annually. [ 31 ] [ 55 ]  The highest incidence of myocarditis is seen in men between the ages of 20 and 40. [ 31 ]  Fulminant myocarditis, the most severe subtype, has been shown to occur in up to 2.5% of known myocarditis presentations. When looking at different causes of myocarditis, viral infection is the most prevalent, especially in children; however, the prevalence rate of myocarditis is often underestimated as the condition is easily overlooked and is sometimes asymptomatic. [ 55 ]  Viral myocarditis being an outcome of viral infection depends heavily on genetic host factors and the pathogenicity unique to the virus. [ 56 ]  If one tests positive for an acute viral infection, clinical developments have discovered that 1-5% of said population may show some form of myocarditis. [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5447", "text": "In regard to the population affected, myocarditis is more common in pregnant women, children, and those who are immunocompromised. [ 57 ]  Myocarditis, however, has shown to be more common in the male population than in the female. [ 55 ]  Multiple studies report a 1:1.3-1.7 female-male ratio of prevalence of myocarditis. [ 58 ]  In young adults, up to 20% of all cases of  sudden death  are due to myocarditis. [ 12 ]  Young males specifically have a higher incidence rate than any other population due to their testosterone levels creating a greater inflammatory response that increases the chance of cardiac pathologies. [ 55 ]  While males tend to have a higher risk of developing myocarditis, females tend to display more severe signs and symptoms, such as ventricular tachycardia and ventricular fibrillation, but do so at an older age. [ 55 ]  Among patients with HIV, myocarditis is the most common cardiac pathological finding at  autopsy , with a prevalence of 50% or more. [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5448", "text": "Myocarditis is the third most common cause of death among young adults with a cumulative incidence rate globally of 1.5 cases per 100,000 persons annually. [ 57 ]  Myocarditis accounts for approximately 20% of sudden cardiac death in a variety of populations, including adults under the age of 40, young athletes, United States Air Force recruits, and elite Swedish orienteers. [ 12 ]   With individuals who develop myocarditis, the first year is difficult as a collection of cases have shown there is a 20% mortality rate. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5449", "text": "Myocarditis can be seen during  COVID-19 , the disease caused by the  SARS-CoV-2  virus; [ 60 ]  with the myocarditis being associated with a spectrum of severities from asymptomatic to fulminant. The symptoms for myocarditis following a COVID-19 infection can present as chest pain, shortness of breath, fatigue, and irregular heartbeats which can make the accurate diagnosis of myocarditis challenging. [ 61 ]  In one cohort study, comparing the autopsy reports of 277 hearts of people who died from COVID-19, clinically significant myocarditis was seen in approximately 2% of hearts. [ 25 ] [ 62 ] [ 63 ]  Other estimates of the incidence of myocarditis in those with COVID-19 range from 2.4 cases of definite/probable myocarditis (based on clinical criteria) per 1,000 people with COVID-19 to 4.1 cases per 1,000 persons in those who are hospitalized with COVID-19. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5450", "text": "Although myocarditis is relatively rare in those with COVID-19, when it is present it is likely to follow a severe and fulminant course for those previously hospitalized with COVID-19. Of those with COVID-19 and myocarditis, 39% presented with severe myocarditis associated with hemodynamic instability, needing mechanical circulation support or other major interventions. [ 31 ]  Severe myocarditis in COVID-19 is also more likely in those who have COVID-19 pneumonia. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5451", "text": "Myocarditis is a rare adverse side effect from mRNA COVID-19 vaccines. [ 64 ] [ 65 ] [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5452", "text": "Cases of myocarditis have been documented as early as the 1600s, [ 67 ]  but the term \"myocarditis\", implying an inflammatory process of the myocardium, was introduced by German physician Joseph Friedrich Sobernheim in 1837. [ 68 ]  However, the term has been confused with other cardiovascular conditions, such as  hypertension  and  ischemic heart disease . [ 69 ]  Following admonition regarding the indiscriminate use of myocarditis as a diagnosis from authorities such as British cardiologist Sir  Thomas Lewis  and American cardiologist and co-founder of the  American Heart Association   Paul White , myocarditis was under-diagnosed. [ 69 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5453", "text": "Although myocarditis is clinically and pathologically clearly defined as \"inflammation of the myocardium\", its definition, classification, diagnosis, and treatment are subject to continued controversy, but endomyocardial biopsy has helped define the natural history of myocarditis and clarify clinicopathological correlations. [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5454", "text": "Nonbacterial thrombotic endocarditis  ( NBTE ) is a form of  endocarditis  in which small  sterile   vegetations  are deposited on the  valve  leaflets. Formerly known as  marantic endocarditis , which comes from the  Greek   marantikos , meaning \"wasting away\". [ 1 ]  The term \"marantic endocarditis\" is still sometimes used to emphasize the association with a wasting state [ 2 ]  such as  cancer . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5455", "text": "Marantic vegetations are often associated with previous  rheumatic fever . Other risk factors include: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5456", "text": "The disease affects the valves with following predilection:  mitral valve  >  aortic valve  >  tricuspid valve  >  pulmonary valve [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5457", "text": "Grossly, vegetations form along lines of valve closure and are generally symmetric with a smooth or  verrucoid  (warty) texture.  Histologically , lesions are composed of  fibrin [ 5 ]  (eosinophilic) and  platelets  but, unlike  bacterial  etiologies, contain little evidence of  PMNs ,  microorganisms  or  inflammation . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5458", "text": "Due to the non-invasive nature of NBTE, clinical examination may or may not reveal a new  murmur . An embolic stroke may be the first feature to suggest diagnosis of NBTE. An echocardiogram is essential for visualization of the mass. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5459", "text": "1YPO ,  1YPQ ,  1YPU ,  1YXJ ,  1YXK ,  3VLG"}
{"_id": "WikiPedia_Cardio$$$corpus_5460", "text": "4973"}
{"_id": "WikiPedia_Cardio$$$corpus_5461", "text": "108078"}
{"_id": "WikiPedia_Cardio$$$corpus_5462", "text": "ENSG00000173391"}
{"_id": "WikiPedia_Cardio$$$corpus_5463", "text": "ENSMUSG00000030162"}
{"_id": "WikiPedia_Cardio$$$corpus_5464", "text": "P78380"}
{"_id": "WikiPedia_Cardio$$$corpus_5465", "text": "Q9EQ09"}
{"_id": "WikiPedia_Cardio$$$corpus_5466", "text": "NM_001172632 NM_001172633 NM_002543"}
{"_id": "WikiPedia_Cardio$$$corpus_5467", "text": "NM_001301094 NM_001301096 NM_138648"}
{"_id": "WikiPedia_Cardio$$$corpus_5468", "text": "NP_001166103 NP_001166104 NP_002534"}
{"_id": "WikiPedia_Cardio$$$corpus_5469", "text": "NP_001288023 NP_001288025 NP_619589"}
{"_id": "WikiPedia_Cardio$$$corpus_5470", "text": "Oxidized low-density lipoprotein receptor 1  (Ox-LDL receptor 1) also known as  lectin-type oxidized LDL receptor 1  (LOX-1) is a  protein  that in humans is encoded by the  OLR1   gene . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5471", "text": "LOX-1 is the main receptor for oxidized LDL on  endothelial cells ,  macrophages ,  smooth muscle cells , [ 7 ]  and other cell types. [ 8 ]  But minimally oxidized LDL is more readily recognized by the  TLR4  receptor, and highly oxidized LDL is more readily recognized by the  CD36  receptor. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5472", "text": "LOX-1 is a receptor protein which belongs to the  C-type lectin superfamily . Its gene is regulated through the cyclic AMP signaling pathway. The protein binds, internalizes and degrades  oxidized   low-density lipoprotein . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5473", "text": "Normally, LOX-1 expression on endothelial cells is low, but  tumor necrosis factor alpha , oxidized LDL, blood vessel  shear stress , and other atherosclerotic stimuli substantially increase LOX-1 expression. [ 8 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5474", "text": "LOX-1 may be involved in the regulation of  Fas -induced  apoptosis .  Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding. [ 7 ]  Other  ligands  for LOX-1 include oxidized  high-density lipoprotein ,  advanced glycation end-products ,  platelets , and apoptotic cells. [ 7 ] [ 10 ] \nThe binding of platelets to LOX-1 causes a release of vasoconstrictive  endothelin , which induces  endothelial dysfunction . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5475", "text": "This protein may play a role as a scavenger receptor. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5476", "text": "Binding of oxidized LDL to LOX-1 activates  NF-\u03baB , leading to  monocyte  adhesion to enthothelial cells (a pre-requisite for the macrophage  foam cell  formation of atherosclerosis). [ 8 ]  Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized. [ 11 ]  LDL oxidation occurs in the sub-endothelial space, rather than in the circulation. [ 11 ]  But oxidized cholesterol from foods cooked at high temperature can also be a source of  oxysterols . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5477", "text": "Mutations of the OLR1 gene have been associated with  atherosclerosis , risk of  myocardial infarction , and may modify the risk of  Alzheimer's disease . [ 6 ]  When applied to human macrophage-derived foam cells  in vitro , the  dietary supplement   berberine  inhibits the  expression  of the ORL1 gene in response to oxidized  low-density lipoprotein cholesterol , [ 12 ]  but this has not yet been demonstrated in a living animal or human. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5478", "text": "Ostial disease , namely  coronary   ostial   stenosis , is the occlusion of coronary ostium. Causing factors include  atherosclerosis ,  syphilis ,  Kawasaki disease , and  Takayasu's arteritis , etc. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5479", "text": "A  papillary fibroelastoma  is a  primary tumor of the heart  that typically involves one of the  heart valves . [ 1 ]  Papillary fibroelastomas, while considered uncommon, make up about 10 percent of all primary tumors of the heart. [ 2 ]  They are the third most common type of primary tumor of the heart, [ 3 ]  behind  cardiac myxomas  and cardiac  lipomas ."}
{"_id": "WikiPedia_Cardio$$$corpus_5480", "text": "A papillary fibroelastoma is generally considered pathologically benign, [ 4 ]  however outflow obstruction or embolism can be associated with  syncope , [ 5 ]   chest pain ,  heart attack ,  stroke [ 6 ] [ 7 ]  and  sudden cardiac death ."}
{"_id": "WikiPedia_Cardio$$$corpus_5481", "text": "Symptoms due to papillary fibroelastomas are generally due to either mechanical effects of the tumor or due to embolization of a portion of the tumor to a distal organ. In particular, chest pain or syncope may be due to transient occlusion of the  left main coronary artery  by the tumor, [ 8 ]  while a heart attack or sudden cardiac death may be due to embolization of a portion of the tumor into a coronary artery. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5482", "text": "Papillary fibroelastoma are typically found and accurately diagnosed by  imaging . The  diagnosis  is confirmed by  pathology .  Histologically , papillary fibroelastomas have branching  avascular   papillae , composed of  collagen , that are covered by  endothelium . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5483", "text": "If the tumor is found incidentally in an asymptomatic person, the treatment approach is controversial. Certainly a conservative approach is warranted in certain individuals. [ 10 ]  If the tumor is large, greater than 1 cm in asymptomatic patients, [ 11 ]  and pedunculated, a case may be made for surgical excision prior to symptoms developing due to the higher risk of embolism. However, this is still considered controversial. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5484", "text": "If the papillary fibroelastoma is associated with symptoms, surgical excision is generally recommended for relief of symptoms. [ 10 ]  A minimally invasive approach may be possible if the tumor involves the  aortic valve [ 13 ]  or right atrium. [ 14 ]  In the case of aortic valve involvement, excision of the tumor is often valve-sparing, meaning that replacement of the valve with a  prosthetic valve  is not necessary. Repair of the native valve with a pericardial patch has been described. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5485", "text": "The main  pathophysiology  of  heart failure  is a reduction in the efficiency of the heart muscle, through damage or overloading. As such, it can be caused by a wide number of conditions, including myocardial infarction (in which the heart muscle is  starved of oxygen  and dies), hypertension (which increases the force of contraction needed to pump blood) and  cardiac amyloidosis  (in which misfolded proteins are deposited in the heart muscle, causing it to stiffen). [ 1 ]  Over time these increases in workload will produce changes to the heart itself:"}
{"_id": "WikiPedia_Cardio$$$corpus_5486", "text": "The heart of a person with heart failure may have a reduced force of contraction due to overloading of the  ventricle . In a healthy heart, increased filling of the ventricle results in increased contraction force (by the  Frank\u2013Starling law of the heart ) and thus a rise in  cardiac output . In heart failure, this mechanism fails, as the ventricle is loaded with blood to the point where heart muscle contraction becomes less efficient. This is due to reduced ability to cross-link  actin  and  myosin  filaments in over-stretched heart muscle. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5487", "text": "A reduced  stroke volume  may occur as a result of a failure of  systole ,  diastole  or both. Increased  end systolic volume  is usually caused by reduced  contractility . Decreased  end diastolic volume  results from impaired ventricular filling; this occurs when the compliance of the ventricle falls (i.e. when the walls stiffen). As the heart works harder to meet normal metabolic demands, the amount cardiac output can increase in times of increased oxygen demand (e.g., exercise) is reduced. This contributes to the exercise intolerance commonly seen in heart failure. This translates to the loss of one's  cardiac reserve , or the ability of the heart to work harder during strenuous physical activity. Since the heart has to work harder to meet the normal metabolic demands, it is incapable of meeting the metabolic demands of the body during exercise. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5488", "text": "A common finding in those with heart failure is an increased heart rate, stimulated by increased  sympathetic activity [ 3 ]  in order to maintain an adequate cardiac output. Initially, this helps compensate for heart failure by maintaining blood pressure and perfusion, but places further strain on the myocardium, increasing coronary perfusion requirements, which can lead to worsening of ischemic heart disease. Sympathetic activity may also cause potentially fatal  abnormal heart rhythms .  An increase in the physical size  of the heart's muscular layer may occur. This is caused by the terminally differentiated heart muscle fibers increasing in size in an attempt to improve contractility. This may contribute to the increased stiffness and thus decrease the ability to relax during diastole. Enlargement of the ventricles can also occur and contributes to the enlargement and spherical shape of the failing heart. The increase in ventricular volume also causes a reduction in stroke volume due to mechanical and inefficient contraction of the heart. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5489", "text": "The general effect is one of reduced cardiac output and increased strain on the heart. This increases the risk of cardiac arrest (specifically due to abnormal ventricular heart rhythms) and reduces blood supply to the rest of the body. In chronic disease the reduced cardiac output causes a number of changes in the rest of the body, some of which are physiological compensations, some of which are part of the disease process: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5490", "text": "The increased peripheral resistance and greater blood volume place further strain on the heart and accelerates the process of damage to the myocardium. Vasoconstriction and fluid retention produce an increased hydrostatic pressure in the capillaries. This shifts the balance of forces in favor of  interstitial fluid  formation as the increased pressure forces additional fluid out of the blood, into the tissue. This results in  edema  (fluid build-up) in the tissues. In right-sided heart failure, this commonly starts in the ankles where venous pressure is high due to the effects of gravity (although if the patient is bed-ridden, fluid accumulation may begin in the sacral region). It may also occur in the abdominal cavity, where the fluid buildup is called ascites. In left-sided heart failure  edema  can occur in the lungs \u2013 this is called cardiogenic  pulmonary edema . This reduces spare capacity for ventilation, causes stiffening of the lungs and reduces the efficiency of gas exchange by increasing the distance between the air and the blood. The consequences of this are  dyspnea  (shortness of breath),  orthopnea  and  paroxysmal nocturnal dyspnea . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5491", "text": "The symptoms of heart failure are largely determined by which side of the heart fails. The left side pumps blood into the systemic circulation, whilst the right side pumps blood into the  pulmonary circulation . Whilst left-sided heart failure will reduce cardiac output to the systemic circulation, the initial symptoms often manifest due to effects on the pulmonary circulation. In systolic dysfunction, the ejection fraction is decreased, leaving an abnormally elevated volume of blood in the left ventricle. In diastolic dysfunction, the end-diastolic ventricular pressure will be high. This increase in volume or pressure backs up to the left atrium and then to the pulmonary veins. Increased volume or pressure in the pulmonary veins impairs the normal drainage of the alveoli and favors the flow of fluid from the capillaries to the lung parenchyma, causing pulmonary edema. This impairs gas exchange. Thus, left-sided heart failure often presents with respiratory symptoms: shortness of breath, orthopnea, and paroxysmal nocturnal dyspnea. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5492", "text": "In severe cardiomyopathy, the effects of decreased cardiac output and poor perfusion become more apparent, and patients will manifest with cold and clammy extremities, cyanosis, claudication, generalized weakness, dizziness, and  fainting . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5493", "text": "The resultant  low blood oxygen  caused by pulmonary edema causes vasoconstriction in the pulmonary circulation, which results in pulmonary hypertension. Since the right ventricle generates far lower pressures than the left ventricle (approximately 20 mmHg versus around 120 mmHg, respectively, in the healthy individual) but nonetheless generates cardiac output exactly equal to the left ventricle, this means that a small increase in pulmonary vascular resistance causes a large increase in amount of work the right ventricle must perform. However, the main mechanism by which left-sided heart failure causes right-sided heart failure is actually not well understood. Some theories invoke mechanisms that are mediated by neurohormonal activation. [ 10 ]  Mechanical effects may also contribute. As the left ventricle distends, the intraventricular septum bows into the right ventricle, decreasing the capacity of the right ventricle."}
{"_id": "WikiPedia_Cardio$$$corpus_5494", "text": "Heart failure caused by systolic dysfunction is more readily recognized. It can be simplistically described as a failure of the pump function of the heart. It is characterized by a decreased ejection fraction (less than 45%). The strength of ventricular contraction is attenuated and inadequate for creating an adequate stroke volume, resulting in inadequate cardiac output. In general, this is caused by dysfunction or destruction of cardiac myocytes or their molecular components. In congenital diseases such as  Duchenne muscular dystrophy , the molecular structure of individual myocytes is affected. Myocytes and their components can be damaged by inflammation (such as in  myocarditis ) or by infiltration (such as in amyloidosis). Toxins and pharmacological agents (such as  ethanol ,  cocaine ,  doxorubicin , and  amphetamines ) cause intracellular damage and oxidative stress. The most common mechanism of damage is ischemia causing infarction and  scar formation . After myocardial infarction, dead myocytes are replaced by scar tissue, deleteriously affecting the function of the myocardium. On echocardiogram, this is manifest by abnormal wall motion (hypokinesia) or absent wall motion (akinesia). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5495", "text": "Because the ventricle is inadequately emptied, ventricular end-diastolic pressure and volumes increase. This is transmitted to the atrium. On the left side of the heart, the increased pressure is transmitted to the pulmonary vasculature, and the resultant hydrostatic pressure favors extravasation of fluid into the lung parenchyma, causing pulmonary edema. On the right side of the heart, the increased pressure is transmitted to the systemic venous circulation and systemic capillary beds, favoring extravasation of fluid into the tissues of target organs and extremities, resulting in dependent  peripheral edema . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5496", "text": "Heart failure caused by diastolic dysfunction is generally described as the backward failure of the ventricle to adequately relax and typically denotes a stiffer ventricular wall. The \"stiffness\" and contractility of the ventricular walls in diastole was first described by Pierre-Simon Laplace. This causes inadequate filling of the ventricle and therefore results in an inadequate stroke volume (SV). SV is a mathematical term amenable to manipulation of many variables. The failure of ventricular relaxation also results in elevated end-diastolic pressures, and the end result is identical to the case of systolic dysfunction (pulmonary edema in left heart failure, peripheral edema in right heart failure). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5497", "text": "Diastolic dysfunction can be caused by processes similar to those that cause systolic dysfunction, particularly causes that affect cardiac remodeling. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5498", "text": "Diastolic dysfunction may not manifest itself except in physiologic extremes if systolic function is preserved. The patient may be completely asymptomatic at rest. However, they are exquisitely sensitive to increases in heart rate, and sudden bouts of tachycardia (which can be caused simply by physiological responses to exertion, fever, or dehydration, or by pathological tachyarrhythmias such as  atrial fibrillation with rapid ventricular response ) may result in  flash pulmonary edema . Adequate rate control (usually with a pharmacological agent that slows down AV conduction such as a calcium channel blocker or a beta-blocker) is, therefore, of key importance to preventing acute decompensation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5499", "text": "Left ventricular diastolic function can be determined through echocardiography by measurement of various parameters such as the  E/A ratio  (early-to-atrial left ventricular filling ratio), the E (early left ventricular filling) deceleration time, and the  isovolumic relaxation time . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5500", "text": "Postpericardiotomy syndrome  (PPS) is an immune phenomenon that occurs days to months (usually 1\u20136 weeks [ 1 ] ) after surgical incision of the  pericardium  (membranes encapsulating the human heart). [ 2 ]  PPS can also be caused after a trauma, a puncture of the cardiac or  pleural  structures (such as a bullet or stab wound), after  percutaneous coronary intervention  (such as  stent  placement after a  myocardial infarction  or heart attack), or due to pacemaker or pacemaker wire placement. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5501", "text": "The typical signs of post-pericardiotomy syndrome include  fever ,  pleuritis  (with possible  pleural effusion ),   pericarditis  (with possible  pericardial effusion ), occasional but rare pulmonary infiltrates, and fatigue. [ 1 ] [ 2 ]  Cough,  pleuritic  or retrosternal chest pain, joint pain and decreased oxygen saturation can also be seen in some cases. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5502", "text": "Other signs include  arthritis , together with  petechiae  on the skin and palate. [ 3 ] :\u200a827"}
{"_id": "WikiPedia_Cardio$$$corpus_5503", "text": "Complications include  pericarditis , pericardial effusion,  pleuritis , pulmonary infiltration, and very rarely  pericardial tamponade . Of these cardiac tamponade is the most life-threatening complication. The pericardial fluid increases intra-pericardial pressure therefore preventing complete expansion of the atria and the ventricles upon the diastole. This causes equilibration of the pressure in all four heart chambers, and results in the common findings of the tamponade which are  pulsus paradoxus ,  Beck's triad  of hypotension, muffled heart sounds, and raised  jugular venous pressure , as well as EKG or Holter monitor findings such as  electrical alternans . Physically the patients who progress to severe pericardial tamponade obtundate, become mentally altered, and lethargic. If left untreated, severe decrease in cardiac output, vascular collapse, and hypoperfusion of body including the brain results in death. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5504", "text": "The cause is believed to be an autoimmune response against damaged cardiac tissue.  This is supported by excellent response to immunosuppressive (steroid) therapy. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5505", "text": "This condition is a febrile illness caused by immune attack of the  pleura  and the  pericardium . Possible cell mediated immunity led by Helper T-cells and Cytotoxic T-cells is postulated to be important in the pathogenesis of this condition. [ 1 ]  There is also possibility of anti-cardiac antibodies created idiopathically, or due to concurrent cross-reactivity of the antibodies produced against viral antigens, however the latter assumption is not fool-proof or completely reliable due to conflicting studies. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5506", "text": "A chest X-ray might depict pleural effusion, pulmonary infiltration, or pericardial effusion. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5507", "text": "During medical doctor examination, a  pericardial friction rub  can be auscultated indicating pericarditis. Auscultation of the lungs can show  crackles  indicating pulmonary infiltration, and there can be retrosternal/pleuritic chest pain worse on  inspiration  (breathing in). Patient can also depict sweating ( diaphoresis ) and agitation or anxiety. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5508", "text": "Colchicine  has been used effectively to prevent  pericarditis , and inflammation that follows surgery of the pericardium. [ 5 ]  Although no current drug on the market prevents post-pericardiotomy syndrome, colchicine seems to provide an effective and safe way to treat pericarditis by reducing inflammation. [ 6 ]  Colchicine is a natural product extracted from plants, and is a secondary metabolite (an organic compound not directly related to growth and development in an organism). [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5509", "text": "Colchicine interferes with the inflammatory process by altering several important steps in the pathway.  Microtubules are structural components of the cytoskeleton that lengthen and shrink for important cell functions.  Colchicine binds to \u03b2- tubulin and forms tubulin-colchicine complexes. [ 5 ] [ 6 ]  These complexes interfere with microtubule formation microtubules. Low doses of colchicine can inhibit the formation of microtubules, while high doses depolymerize or break down a polymer to a monomer. [ 7 ]  Therefore, any process involving cytoskeleton change, including mitosis and motility of white blood cells, is highly impacted. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5510", "text": "Microtubule disruption decreases neutrophil adhesion, an important step for inflammation. [ 7 ]   Neutrophils are recruited to the target location of inflammation via signals from the endothelium where they adhere and play a role in the inflammatory response.  Colchicine diminishes neutrophil adhesion by decreasing expression of selectins, a family of cell adhesion molecules. [ 7 ]  In addition, colchicine prevents the movement and secretion of intercellular granules, substances, proinflammatory enzymes from neutrophils, thus making a significant impact on inflammatory processes within the body. [ 6 ]  The high concentration of colchicine in neutrophils, sixteen times greater compared the plasma levels, can account for the positive therapeutic effects. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5511", "text": "Many mediators are altered to assist neutrophils during inflammation, including the monokine tumor necrosis factor-alpha (TNF\u03b1). [ 8 ]  Cytokines help stimulate the acute phase reaction in response to inflammation.  Colchicine inhibits macrophage production of TNF\u03b1, leading to the interference between TNF\u03b1 and neutrophil interaction. [ 8 ]  There are many more effects of colchicine that are currently under research, and some aspects of this metabolite are not fully understood. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5512", "text": "There was great hope that colchicine could be a primary preventive measure in treating post-pericardiotomy syndrome due to its anti-inflammatory effects. [ 6 ]   In the COPPS-2 trial, however, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastrointestinal adverse effects reduced the potential benefits of colchicine in this setting. Thus colchicine is not likely going to be the ideal way to prevent this problem. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5513", "text": "More common in children and often common in patients receiving cardiac operations that involve opening the pericardium. [ 1 ]   CABG  surgery is a common culprit."}
{"_id": "WikiPedia_Cardio$$$corpus_5514", "text": "Progressive cardiac conduction defect   (PCCD)  is a hereditary cardiac condition marked by a progressive delay in impulse conduction via the His-Purkinje system, resulting in right or left  bundle branch block  (RBBB or LBBB),  syncope , and occasionally  sudden cardiac death . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5515", "text": "When progressive conduction abnormalities in people under 50 with structurally normal hearts are present but skeletal  myopathies  are absent, progressive cardiac conduction defect is primarily diagnosed, particularly if there is a family history of PCCD. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5516", "text": "At the moment, implanting an implantable  pacemaker  is the only proven treatment for PCCD, regardless of the underlying cause. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5517", "text": "The electrical axis of the heart is the net direction in which the wave of  depolarization  travels. It is measured using an  electrocardiogram (ECG) . Normally, this begins at the  sinoatrial node  (SA node); from here the wave of depolarisation travels down to the apex of the heart.  The hexaxial reference system can be used to visualise the directions in which the depolarisation wave may travel."}
{"_id": "WikiPedia_Cardio$$$corpus_5518", "text": "On a hexaxial diagram  (see figure 1):"}
{"_id": "WikiPedia_Cardio$$$corpus_5519", "text": "RAD is an ECG finding that arises either as an anatomically normal variant or an indicator of underlying pathology."}
{"_id": "WikiPedia_Cardio$$$corpus_5520", "text": "There are often no symptoms for RAD and it is usually found by chance during an ECG. Many of the symptoms exhibited by patients with RAD are associated with its different causes. The table below displays the four most common causes and the signs, symptoms and risk factors associated with it. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5521", "text": "Chest pain"}
{"_id": "WikiPedia_Cardio$$$corpus_5522", "text": "Fatigue"}
{"_id": "WikiPedia_Cardio$$$corpus_5523", "text": "Shortness of breath [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5524", "text": "Obesity"}
{"_id": "WikiPedia_Cardio$$$corpus_5525", "text": "Gender"}
{"_id": "WikiPedia_Cardio$$$corpus_5526", "text": "Hypertension"}
{"_id": "WikiPedia_Cardio$$$corpus_5527", "text": "Diabetes"}
{"_id": "WikiPedia_Cardio$$$corpus_5528", "text": "Physical inactivity"}
{"_id": "WikiPedia_Cardio$$$corpus_5529", "text": "Age"}
{"_id": "WikiPedia_Cardio$$$corpus_5530", "text": "Alcohol"}
{"_id": "WikiPedia_Cardio$$$corpus_5531", "text": "Dizziness"}
{"_id": "WikiPedia_Cardio$$$corpus_5532", "text": "Fainting"}
{"_id": "WikiPedia_Cardio$$$corpus_5533", "text": "Pulmonary hypertension"}
{"_id": "WikiPedia_Cardio$$$corpus_5534", "text": "Mitral stenosis"}
{"_id": "WikiPedia_Cardio$$$corpus_5535", "text": "Pulmonary embolism"}
{"_id": "WikiPedia_Cardio$$$corpus_5536", "text": "Congenital heart disease"}
{"_id": "WikiPedia_Cardio$$$corpus_5537", "text": "Arrythmogenic right ventricle cardiomyopathy"}
{"_id": "WikiPedia_Cardio$$$corpus_5538", "text": "Palpitations [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5539", "text": "Drug toxicity (e.g. tricyclic antidepressants [ 5 ] )"}
{"_id": "WikiPedia_Cardio$$$corpus_5540", "text": "Hyperkalaemia"}
{"_id": "WikiPedia_Cardio$$$corpus_5541", "text": "Blockage of the  left posterior fascicle  would lead to activation of the anterior portion of the left ventricle followed by activation of the rest of the ventricle in a superior to inferior direction and directed towards the right. This would lead to right axis deviation findings on an ECG. [ 6 ] \nBifascicular block is a combination of right bundle branch block and either left anterior fascicular block or left posterior fascicular block. Conduction to the ventricle would therefore be via the remaining fascicle. The ECG will show typical features of RBBB plus either left or right axis deviation. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5542", "text": "The lateral wall of the left ventricle is supplied by branches of the  left anterior descending (LAD)  and  left circumflex (LCx) arteries . [ 8 ]  Infarction of the lateral wall will thus lead to deviation of the axis away from the site of infarction. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5543", "text": "Increased thickness of the right ventricle leads to right axis deviation  [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5544", "text": "Pre-excitation refers to early activation of the ventricles due to impulses bypassing the AV node via an accessory pathway. [ 10 ] \nAccessory pathways are abnormal conduction pathways formed during cardiac development. An example of pre-excitation syndromes is  Wolff Parkinson White syndrome . Here, the presence of a left lateral accessory pathway leads to right-axis deviation. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5545", "text": "Fascicular tachycardia usually arises from the posterior fascicle of the left bundle branch. They produce QRS complexes of relatively short durations with a right bundle branch block pattern. Tachycardias originating in the anterior left fascicle would lead to right axis deviation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5546", "text": "Right ventricular outflow tract tachycardia originates from the outflow tract of the right ventricle or the tricuspid annulus. As it arises from the right ventricle, the impulse spreads inferiorly from beneath the pulmonary valve, and there right axis deviation. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5547", "text": "Ventricular ectopy is when the heartbeat is an  abnormal heartbeat  where the QRS complex is significantly wider. When the origin of the ectopic heartbeat is in the anterior fascicule then there is right axis deviation. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5548", "text": "The pathophysiology depends on the specific cause of right axis deviation. Most causes can be attributed to one of four main mechanisms. [ 14 ] [ 15 ]  These include  right ventricular hypertrophy , reduced muscle mass of left ventricle, altered conduction pathways and change in the position of the heart in the chest. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5549", "text": "Enlargement of right ventricular myocardial mass can result in right axis deviation. There are 2 main reasons for this mechanism. [ 15 ]  Firstly, more muscle mass will result in greater amplitude of depolarisation of that side of the heart. [ 15 ]  Secondly, depolarisation of the heart will be slower through the right ventricle relative to the left, and therefore the effects of the right ventricle on the axis of the heart will be dominant. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5550", "text": "Decrease in myocardial mass of the left ventricle will shift the balance of depolarisation towards the right. For example, scarring and atrophy caused by ischaemia of the left ventricle will cause depolarisation of the left side of the heart to be less forceful. [ 15 ]  Hence, depolarisation of the right ventricle will be greater in amplitude than left, shifting the axis to the right. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5551", "text": "Changes in the conduction pathways of the heart can result in right axis deviation. For example, an accessory pathway from the left atrium to the left ventricle, as in Wolff-Parkinson-White Syndrome, will result in the left ventricle finishing depolarisation earlier than the right. [ 16 ]  Hence, the right ventricle will have more of an effect on the axis of the heart. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5552", "text": "The apex of the heart is normally orientated towards the left. A more vertical orientation of the heart, shifts the axis to the right. Physiologically, this can occur in tall and thin individuals. [ 16 ]  Pathologically, conditions such as a left-sided  pneumothorax  and lung hyperinflation (e.g.  COPD ) [ 17 ]  can cause rightwards displacement of the heart. The congenital condition of  dextrocardia  results in right axis deviation."}
{"_id": "WikiPedia_Cardio$$$corpus_5553", "text": "In general, a positive (upwards) deflection of an ECG trace demonstrates an electrical activity that moves towards the measuring electrode, whereas a negative (downwards) deflection of an ECG trace demonstrates an electrical activity that moves away from the measuring electrode. The electrical heart axis can be estimated from the ECG by using the quadrant method or degree method. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5554", "text": "A simple tool to quickly identify axis deviation (Figure 3) is the popular mnemonic;  R eaching for  R ight Axis Deviation and  L eaving for  L eft Axis Deviation. This refers to the appearance of leads I and II. If the QRS complex is negative in lead I and positive in lead II, the QRS complexes appear to be \"reaching\" to touch each other. This signifies right axis deviation. Conversely, if the QRS complex is positive in lead I and negative in lead II the leads have the appearance of \"leaving\" each other. If the QRS complex in lead II is also negative, this confirms a left axis deviation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5555", "text": "Right ventricular hypertrophy   ( RVH ) is a condition defined by an abnormal enlargement of the cardiac muscle surrounding the  right ventricle . The right ventricle is one of the four chambers of the heart. It is located towards the right lower chamber of the heart and it receives deoxygenated blood from the right upper chamber (right atrium) and pumps blood into the lungs."}
{"_id": "WikiPedia_Cardio$$$corpus_5556", "text": "Since RVH is an enlargement of muscle it arises when the muscle is required to work harder. Therefore, the main causes of RVH are pathologies of systems related to the right ventricle such as the  pulmonary artery , the  tricuspid valve  or the airways."}
{"_id": "WikiPedia_Cardio$$$corpus_5557", "text": "RVH can be benign and have little impact on day-to-day life or it can lead to conditions such as  heart failure , which has a poor prognosis."}
{"_id": "WikiPedia_Cardio$$$corpus_5558", "text": "Although presentations vary, individuals with right ventricular hypertrophy can experience symptoms that are associated with  pulmonary hypertension ,  heart failure  and/or a reduced  cardiac output . These include: [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5559", "text": "People may rarely present with the symptoms of  Ortner's syndrome , which include cough, haemoptysis and hoarseness. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5560", "text": "On physical examination, the most prominent features are due to the development of right-sided heart failure. These can include a raised  jugular venous pressure ,  ascites , left  parasternal heave  and a tender, enlarged  liver  on palpation. [ 3 ] \nOn inspection, patients may be chronically ill,  cyanotic ,  cachectic  and occasionally  jaundiced . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5561", "text": "On  auscultation , an accentuated second pulmonary sound (S2), a third heart sound termed a \u2018right ventricular gallop\u2019, as well as a  systolic murmur  over the  tricuspid  area accentuated by inspiration may be present. On occasion, the systolic murmur can be transmitted and auscultated over the liver. Less typically,  diastolic murmur  may also be heard as a result of pulmonary insufficiency. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5562", "text": "RVH usually occurs due to chronic lung disease or structural defects in the heart. One of the most common causes of RVH is  pulmonary hypertension  (PH), [ 3 ]  defined as increased  blood pressure  in the vessels supplying blood to the lungs. PH leads to increased pulmonary artery pressure. The  right ventricle  tries to compensate for this increased pressure by changing its shape and size. Hypertrophy of individual  myocytes  results in an increase in right ventricular wall thickness. [ 3 ]  The worldwide incidence of PH is 4 per million people. [ 4 ]  RVH occurs in approximately 30% of these cases. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5563", "text": "PH is broadly split into five categories by the  World Health Organization , based on the underlying cause. The incidence of RVH varies between the groups. Common causes of PH include  chronic obstructive pulmonary disease  (COPD),  pulmonary embolism , and other restrictive lung diseases. RVH often occurs as a result of these disorders. RVH is seen in 76% of patients with advanced COPD and 50% of patients with restrictive lung disease. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5564", "text": "RVH also occurs in response to structural defects in the heart. One common cause is  tricuspid insufficiency . This is a disorder where the  tricuspid valve  fails to close properly, allowing backward flow of blood. Other structural defects which lead to RVH include  tetralogy of Fallot ,  ventricular septal defects ,  pulmonary valve stenosis , and  atrial septal defects . [ medical citation needed ]  RVH is also associated with  abdominal obesity , elevated fasting blood glucose, high  systolic blood pressure , and fractional shortening of the left ventricular mid-wall. [ medical citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5565", "text": "Other risk factors for RVH include smoking,  sleep apnea , and strenuous activity. These increase the risk of heart and lung disease and hence RVH. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5566", "text": "Right ventricular hypertrophy can be both a physiological and pathophysiological process. It becomes pathophysiological (damaging) when there is excessive hypertrophy. The pathophysiological process mainly occurs through aberrant signalling of the neuroendocrine hormones;  angiotensin II ,  endothelin-1  and the catecholamines (e.g.  noradrenaline ). [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5567", "text": "Angiotensin-II and endothelin-1 are hormones that bind to the angiotensin (AT) and endothelin (ET) receptors. These are  G-protein  coupled receptors that act via internal signalling pathways. Through several intermediates, these pathways directly or indirectly increase  reactive oxygen species  (ROS) production causing accumulation in  myocardial cells . This can subsequently induce necrotic cell death,  fibrosis , and mitochondrial dysfunction. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5568", "text": "This has been demonstrated in animal studies.  Protein Kinase C  (PKC) is an intermediate molecule in the signalling pathway and mice lacking PKC shown resistance to heart failure compared to mice overexpressing PKC which shown heart dysfunction. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5569", "text": "Targeting the  renin\u2013angiotensin (RAAS) system  (using angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers) are a well-recognized clinical approach for reversing maladaptive cardiac hypertrophy independently of blood pressure. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5570", "text": "Catecholamines  levels increase due to increased sympathetic nervous system activity. Catecholamines can act on the alpha-adrenergic receptors and beta-adrenergic receptors which are G-protein coupled receptors. This binding initiates the same intracellular signalling pathways as angiotensin and endothelin. There is also activation of cAMP and an increase in intracellular Ca2+ which leads to contractile dysfunction and fibrosis. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5571", "text": "Hormones are not the only cause of RVH. Hypertrophy can also be caused by mechanical forces, mTOR pathways,  nitric oxide  and  immune cells . Immune cells can cause hypertrophy by inducing inflammation. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5572", "text": "The two main diagnostic tests used to confirm right ventricular hypertrophy are electrocardiography and echocardiography. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5573", "text": "The use of  electrocardiogram  (ECG) to measure cardiac chamber hypertrophy is well established but since the left ventricular activity is dominant on the ECG a large degree of RVH is often required for any detectable changes. Nonetheless, the ECG is used to assist with the diagnosis of RVH. A  post mortem  study on 51 adult male patients concluded that anatomical RVH may be diagnosed using one or more of the following ECG criteria: [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5574", "text": "However, the American Heart Association recommended the use of additional diagnostic tests to diagnose RVH because no single criteria or set of criteria were considered sufficiently reliable. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5575", "text": "Echocardiography  can be used to directly visualise right ventricular wall thickness. The preferred technique is the trans-oesophageal approach giving a view of 4 chambers. The normal thickness of a right ventricular free wall ranges from 2-5 millimetres, with a value above 5\u00a0mm considered to be hypertrophic. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5576", "text": "Right ventricular hypertrophy in itself is not the main issue, but what right ventricular hypertrophy represents is. Right ventricular hypertrophy is the intermediate stage between increased right ventricular pressure (in the early stages) and right ventricle failure (in the later stages). [ 11 ]  As such, management of right ventricular hypertrophy is about either preventing the development of right ventricular hypertrophy in the first place, or preventing the progression towards right ventricle failure. Right ventricular hypertrophy in itself has no (pharmacological) treatment. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5577", "text": "Since the main causes of right ventricular hypertrophy is tricuspid regurgitation or pulmonary hypertension (discussed above), management involves treatment of these conditions. [ 3 ] \nTricuspid regurgitation is typically treated conservatively by aiming to treat the underlying cause and following up the patient regularly. [ 12 ]  Surgery is considered in more serious situations where the patient is severely symptomatic. Surgical options include either: replacement of the valve or repair of the valve (termed annuloplasty). [ 3 ]   When it comes to replacement, there is a choice between a bioprosthetic valve or a mechanical valve, depending upon the specific patient characteristics. Mechanical valve has greater durability, but requires anti-coagulation to reduce the risk of thrombosis. [ 3 ] \nTreatment of pulmonary hypertension will depend on the specific cause of the pulmonary hypertension. On top of this, the following may also be considered: diuretic, oxygen and anti-coagulant therapy. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5578", "text": "After a prolonged period, the right ventricle fails to adapt sufficiently to pump against increased right ventricle pressure, which is termed right ventricular failure. This right ventricular failure is the main complication of right ventricular hypertrophy. The mechanisms underlying the progression from hypertrophy to failure is not well understood, [ 11 ]  and the best management approach involves reducing/minimising the risk factors of progression. Lifestyle changes can often help to reduce the risk of this progression. Lifestyle changes include: eating less salty food as salt consumption leads to greater fluid retention by the body; smoking cessation; avoiding excessive alcohol consumption as alcohol reduces the force of heart contractions.\nOnce right ventricular hypertrophy progresses to right ventricular failure, the treatment becomes that of heart failure. Briefly, this includes the use of: [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5579", "text": "Roemheld syndrome  ( RS ), or  gastrocardiac syndrome , [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  or  gastric cardiac syndrome [ 6 ]  or  Roemheld\u2013Techlenburg\u2013Ceconi syndrome [ 7 ]  or  gastric-cardia , [ 7 ]  was a medical syndrome first coined by  Ludwig von Roemheld  (1871\u20131938) describing a cluster of cardiovascular symptoms stimulated by gastrointestinal changes. Although it is currently considered an obsolete medical diagnosis, recent studies have described similar clinical presentations and highlighted potential underlying mechanisms. [ 3 ] [ 8 ] [ 9 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5580", "text": "Symptoms can be as follows. [ 10 ] [ 11 ]  They are periodic, and occur only during an \"episode\", usually after eating."}
{"_id": "WikiPedia_Cardio$$$corpus_5581", "text": "Mechanically induced Roemheld syndrome is characterized by  pressure  in the epigastric and left  hypochondriac  region. Often the pressure is in the  fundus  of the stomach, the  esophagus  or distention of the bowel. It is believed this leads to elevation of the  diaphragm , and secondary displacement of the heart. This reduces the ability of the heart to fill and increases the  contractility of the heart  to maintain homeostasis."}
{"_id": "WikiPedia_Cardio$$$corpus_5582", "text": "The cranium dysfunction mechanical changes in the gut can compress the  vagus nerve  at any number of locations along the vagus, slowing the heart. As the heart slows, autonomic reflexes are triggered to increase blood pressure and heart rate."}
{"_id": "WikiPedia_Cardio$$$corpus_5583", "text": "This is complemented by gastro-coronary reflexes [ 12 ]  whereby the coronary arteries constrict with \"functional  cardiovascular  symptoms\" similar to chest-pain on the left side and radiation to the left shoulder, dyspnea, sweating, up to angina pectoris-like attacks with  extrasystoles , drop of blood pressure, and tachycardia (high heart rate) or sinus bradycardia (heart rate below 60 bpm). Typically, there are no changes/abnormalities related in the  EKG  detected. This can actually trigger a heart attack in people with cardiac structural abnormalities i.e.  coronary bridge , missing coronary, and  atherosclerosis ."}
{"_id": "WikiPedia_Cardio$$$corpus_5584", "text": "If the heart rate drops too low for too long,  catecholamines  are released to counteract any lowering of blood pressure. Catecholamines bind to  alpha receptors  and  beta receptors , decreasing  vasodilation  and increasing  contractility of the heart . Sustaining this state causes  heart fatigue  which can lead to a decline in systolic and  diastolic function , resulting in fatigue and chest pain."}
{"_id": "WikiPedia_Cardio$$$corpus_5585", "text": "There is significant scope of misdiagnosis of Roemheld syndrome. Diagnosis of Roemheld syndrome usually begins with a cardiac workup, as the gastric symptoms may go unnoticed, and the cardiac symptoms are frightening and can be quite severe. After an  EKG ,  Holter monitor ,  tilt table test ,  cardiac MRI ,  cardiac CT ,  heart catheterization ,  electrophysiology study ,  echocardiogram , and extensive blood work, and possibly a  sleep study , a cardiologist may rule out a heart condition."}
{"_id": "WikiPedia_Cardio$$$corpus_5586", "text": "Often a  psychiatric evaluation  may follow, as conversion disorder may be suspected in the absence of heart disease or structural heart abnormalities."}
{"_id": "WikiPedia_Cardio$$$corpus_5587", "text": "In the absence of heart abnormalities, the diagnosis is often made on the basis of symptoms. A  gastroenterologist  will perform a  colonoscopy ,  endoscopy , and  abdominal ultrasound  to locate or rule out problems in the abdomen."}
{"_id": "WikiPedia_Cardio$$$corpus_5588", "text": "Determining the cause of Roemheld syndrome is still not an exact science. If you have an ultrasound or sleep study, ensure that you know how to reproduce the symptoms, as it is difficult to detect any abnormalities when symptoms have subsided."}
{"_id": "WikiPedia_Cardio$$$corpus_5589", "text": "Treatment of the primary gastroenterological distress is the first concern, mitigation of gastric symptoms will also alleviate cardiac distress."}
{"_id": "WikiPedia_Cardio$$$corpus_5590", "text": "Roemheld syndrome is characterized strictly by abdominal maladies triggering reflexes in the heart. There are a number of pathways through which cardiac reflexes can occur: hormones, mechanical, neurological and immunological. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5591", "text": "Ludwig Roemheld characterized this particular syndrome shortly before his death; one of his research topics around this time was the effects of calorie intake on the heart. In  Elsevier  publications, there is no current research or publishing under the name Roemheld syndrome, and as a result, many cases go undiagnosed. German publishing on the subject remains untranslated as of 2009."}
{"_id": "WikiPedia_Cardio$$$corpus_5592", "text": "sCAR-Fc  ( Soluble Receptor Analogue ) is an experimental prophylactic treatment against  coxsackievirus  B3 (CVB) infections. Coxsackievirus B3 can cause cardiac damage, eventually resulting in a weakened and enlarged heart that is termed  dilated cardiomyopathy . [ 1 ]  While many other treatments inhibit viral proliferation in  myocytes , sCAR-Fc prevents the virus entering the cell by competitively binding to  coxsackie virus and adenovirus receptors  (CAR) on the membrane of myocytes."}
{"_id": "WikiPedia_Cardio$$$corpus_5593", "text": "Coxsackievirus B3 is a single-stranded RNA  enterovirus  and a member of the  Picornavirdae  family. [ 1 ] [ 2 ]  Once the virus penetrates the host's systemic circulation via contaminated water or food, it can travel and infect the heart and cause myocarditis.  Myocarditis  is an inflammation of the heart, most commonly cause by viral infections. Amongst the viruses capable of causing myocarditis, CVB3 is a common agent identified in inducing cardiac damage. Internalization of the virus into myocytes occurs by binding to coxsackievirus-adenovirus receptors (CAR) located in  tight junctions  on cell membranes. [ 1 ] [ 3 ]  Once inside the cytoplasm, the virus can use the host's ribosomal machinery to proliferate and replicate progenies for further infection. [ 4 ]  Extensive cardiac  necrosis  can occur by day three after infection as incubated viruses lyse myocytes, resulting in severe and rapid cardiac decompensation. With loss of cardiac cells increasing progressively, infected individual will experience abnormalities in left ventricular systolic and diastolic function, as well as electrical conduction defects manifesting as  cardiac dysrhythmias . [ 5 ]  As a result,  ejection fraction  decreases substantially. [ 5 ]  The cytolytic destruction of heart cells can lead to dilated cardiomyopathy if not treated appropriately. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5594", "text": "The role of the immune system in response to the presence of a virus has both beneficial and detrimental effects on the cardiac system. [ 1 ]  The arrival of  natural killer cells  (NK cells) at the site of infection limits viral proliferation in myocytes. Conversely, while certain cytokines released from immune cells have protective effects, others such as  tumor necrosis factor-alpha  (TNF\u03b1) have deleterious effects on heart cells. Moreover, peak concentrations of  T cells  in the myocardium during days 7-14 play important roles in both viral clearance and immune mediated cardiac damage. T-cells not only lyse and destroy infected myocytes, but due to molecular mimicry, they also destroy normal, healthy cardiac cells, further driving the heart towards dilated cardiomyopathy. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5595", "text": "A synthetic and soluble form of CAR (sCAR) has been created to prevent viral infection with CVB3. Attaching Fc domain of  immunoglobulin   IgG1  to sCAR (sCAR-Fc) enhances solubility and extends its  half-life . [ 1 ] [ 7 ]  Furthermore, once sCAR-Fc binds the virus,  macrophages  and other phagocytic immune cells with Fc receptor recognition bind to the sCAR-Fc-viral complex to eliminate the virus. Essentially, sCAR-Fc mimics CAR receptors on cardiac cells, competitively inhibiting viral attachment and entry into myocytes. Decreased lesions in cardiac tissues, reduced cell necrosis, and diminished inflammatory responses are observed in sCAR-Fc treated cells (CITE). This suggests protective effects against myocardial damage by CVB3. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5596", "text": "Conformational changes in a viral particle (A-particle) with sCAR-Fc-virus binding causing the loss of the virus\u2019 internal  capsid  protein, VP4. [ 2 ]  This irreversible reaction prevents the virus from interacting with cellular receptors (CAR) on cardiac cells, decreasing infectivity of CVB3. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5597", "text": "Administration of sCAR-Fc beyond three days after initial exposure to the virus does not have any beneficial effects as cardiac damage is too severe. [ 2 ]  As such, the use of sCAR-Fc is currently limited to prophylactic treatments. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5598", "text": "Shone's syndrome  is a rare  congenital heart defect  described by Shone in 1963. In the complete form, four left-sided defects are present: [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5599", "text": "Of these four defects, supravalvular mitral membrane (SVMM) is the first to occur and triggers the development of the other three defects. Partial complexes, or  forme fruste , have also been described. [ 1 ]  The definition is often expanded to include  lesions  of the left side of the  heart  not originally ascribed to Shone's  syndrome , including mitral and  aortic  valvular lesions and supravalvular  aortic stenosis . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5600", "text": "The term  parachute mitral valve  stems from the  morphological  appearance of the valve; that is to say, the mitral valve leaflets appear as the  canopy  of the  parachute , the  chordae  as the strings and the  papillary muscle  as the harness."}
{"_id": "WikiPedia_Cardio$$$corpus_5601", "text": "Shone\u2019s syndrome is a rare  disorder  that is often detected in very young children. The children tend to show symptoms like  fatigue ,  nocturnal cough , and reduced  cardiac output  by the age of two years. They also develop  wheezing  due to the  exudation  of fluid into the lungs. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5602", "text": "In the normal human heart, there are two mitral valve leaflets, each with its own set of chordae. However, in the case of the parachute mitral valve, the chordae insert on only one papillary muscle instead of two distinct  papillary muscles . Often, the chordae are short and thick, which can cause restricted movement of the  mitral valve  leaflets and obstruct the blood flow into the left  ventricle . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5603", "text": "The supramitral ring is a  connective tissue  ring at the base of the atrial surfaces of the  mitral valve  leaflets. They may protrude into the orifice of the mitral valve, leading to fixed obstruction of blood flow from the left atria to the  left ventricles . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5604", "text": "Subaortic stenosis  has been observed in both muscular and  membranous  forms. In either case, a variable degree of obstruction may be observed at the  ventricular  surface of the aortic valve. [ 1 ]  This presents an obstruction of flow of blood from the ventricle to the  aorta ."}
{"_id": "WikiPedia_Cardio$$$corpus_5605", "text": "Coarctation  of the aorta which is, narrowing of a section of the aorta may also be observed. [ 1 ]  Again this presents an  obstruction  to blood flow out from the  left ventricle. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5606", "text": "Since there is obstruction of flow into and out of the left  ventricle , the  prognosis  depends on the degree of obstruction and its effect on  blood flow ."}
{"_id": "WikiPedia_Cardio$$$corpus_5607", "text": "Cardiac magnetic resonance imaging  is best suited to evaluate patients with Shone's syndrome. [ 4 ]  Routine blood tests should be done prior to  cardiac catheterization . The surgeons will repair the mitral valve and partially remove the supramitral ring. [ 5 ]  This surgical method is preferred to a valve replacement procedure."}
{"_id": "WikiPedia_Cardio$$$corpus_5608", "text": "Classifying cardiac lesions in infants is quite difficult, and accurate diagnosis is essential. The diagnosis of Shone\u2019s syndrome requires an  ultrasound  of the heart ( echocardiogram ) and a cardiac catheterization procedure, that is, insertion of a device through  blood vessels  in the groin to the heart that helps identify heart anatomy. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5609", "text": "When treated early, that is, before the onset of  pulmonary hypertension , a good outcome is possible in patients with Shone\u2019s syndrome. However, other surgical methods can be employed depending upon the patient\u2019s medical background. The single most important determinant of poor outcome during the  surgical  management of patients with Shone's syndrome is the degree of involvement of the  mitral valve  and the presence of secondary pulmonary  hypertension . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5610", "text": "In  electrocardiography , a  strain pattern  is a well-recognized marker for the presence of anatomic  left ventricular hypertrophy  (LVH) in the form of  ST depression  and  T wave  inversion on a resting ECG. [ 1 ]  It is an abnormality of  repolarization  and it has been associated with an adverse prognosis in a variety heart disease patients.  It has been important in refining the role of ECG LVH criteria in cardiac  risk stratification . It is thought that a strain pattern could also reflect underlying  coronary heart disease . [ citation needed ]  Floyd strain includes T-wave inversion \"Floyd.\"."}
{"_id": "WikiPedia_Cardio$$$corpus_5611", "text": "Structural heart disease , also known as  structural cardiac disease , is a collection of  heart diseases  that includes  heart failure ,  coronary artery disease ,  hypertrophic cardiomyopathy , and  congenital heart disease . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5612", "text": "Subacute bacterial endocarditis , abbreviated SBE, is a type of  endocarditis  (more specifically,  infective endocarditis ). [ 5 ]  Subacute bacterial endocarditis can be considered a form of  type III hypersensitivity . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5613", "text": "Among the signs of subacute bacterial endocarditis are: [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5614", "text": "It is usually caused by a form of  Viridans group streptococcus  bacteria that normally live in the mouth [ 3 ]  ( Streptococcus mutans , mitis, sanguis  or  milleri ). [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5615", "text": "Other strains of streptococci can cause  subacute  endocarditis as well. These include  streptococcus intermedius , which can cause\nacute or subacute infection (about 15% of cases pertaining to infective endocarditis). [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5616", "text": "Enterococci  from urinary tract infections and  coagulase negative staphylococci  can also be causative agents. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5617", "text": "The mechanism of subacute bacterial endocarditis could be due to malformed stenotic valves which, in the company of bacteremia, become infected via adhesion and subsequent colonization of the surface area. This causes an inflammatory response, with recruitment of matrix metalloproteinases and destruction of collagen. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5618", "text": "Underlying structural  valve  disease is usually present in patients before developing subacute endocarditis, and is less likely to lead to  septic   emboli  than is  acute  endocarditis, but subacute endocarditis has a relatively slow process of  infection  and, if left untreated, can worsen for up to one year before it is fatal. [ medical citation needed ]  In cases of subacute bacterial endocarditis, the causative organism (streptococcus viridans) needs previous heart valve disease to colonize. [ 9 ]  On the other hand, in cases of acute bacterial endocarditis the organism can colonize on the healthy heart valve, causing the disease. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5619", "text": "Subacute bacterial endocarditis can be diagnosed by collecting three blood culture specimens over a 24-hour period for analysis, [ 4 ]  also it can usually be indicated by the existence of:"}
{"_id": "WikiPedia_Cardio$$$corpus_5620", "text": "The standard treatment is with a minimum of four weeks of high-dose intravenous  penicillin  with an  aminoglycoside  such as  gentamicin .\nThe use of high-dose antibiotics is largely based upon animal models. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5621", "text": "Leo Loewe of  Brooklyn Jewish Hospital  was the first to successfully treat subacute bacterial endocarditis with penicillin. Loewe reported at the time seven cases of subacute bacterial endocarditis in 1944. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5622", "text": "It remains a difficult medical challenge to prevent the  sudden cardiac death of athletes , typically defined as natural, unexpected death from  cardiac arrest  within one hour of the onset of collapse symptoms, excluding additional time on mechanical life support. [ 1 ]  (Wider definitions of sudden death are also in use, but not usually applied to the athletic situation.) Most causes relate to  congenital  or acquired  cardiovascular disease  with no symptoms noted before the fatal event. The  prevalence  of any single, associated condition is low, probably less than 0.3% of the population in the athletes' age group, [ citation needed ]  and the  sensitivity and specificity  of common screening tests leave much to be desired. The single most important predictor is  fainting  or near-fainting during exercise, which should require detailed explanation and investigation. [ 2 ]  The victims include many well-known names, especially in professional association football, and close relatives are often at risk for similar cardiac problems."}
{"_id": "WikiPedia_Cardio$$$corpus_5623", "text": "The sudden cardiac deaths of 387 young American athletes (under age 35) were analyzed in a 2003 medical review: [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5624", "text": "While most causes of sudden cardiac death relate to  congenital  or acquired  cardiovascular disease , an exception is  commotio cordis , in which the heart is structurally normal but a potentially fatal loss of  rhythm  occurs because of the accident of timing of a blow to the chest. Its fatality rate is about 65% even with prompt  CPR  and  defibrillation , and more than 80% without. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5625", "text": "Age 35 serves as an approximate borderline for the likely cause of sudden cardiac death. Before age 35, congenital abnormalities of the heart and blood vessels predominate. These are usually asymptomatic prior to the fatal event, although not invariably so. [ 6 ]  Congenital cardiovascular deaths are reported to occur disproportionately in African-American athletes. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5626", "text": "After age 35, acquired  coronary artery disease  predominates (80%), [ 6 ]  and this is true regardless of the athlete's former level of fitness. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5627", "text": "Various  performance-enhancing drugs  can increase cardiac risk, though evidence has been inconclusive about their involvement in sudden cardiac deaths. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5628", "text": "Cardiomyopathies are generally inherited as  autosomal dominants , although recessive forms have been described, and dilated cardiomyopathy can also be inherited in an  X-linked  pattern. Consequently, in addition to tragedy involving an athlete who succumbs, there are medical implications for close relatives. Among family members of  index cases , more than 300 causative  mutations  have been identified. However, not all mutations have the same potential for severe outcomes, and there is not yet a clear understanding of how these mutations (which affect the same  myosin  protein molecule) can lead to the dramatically different  clinical characteristics  and outcomes associated with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5629", "text": "Since HCM, as an example, is typically an autosomal dominant trait, each child of an HCM parent has a 50% chance of inheriting the mutation. In individuals without a family history, the most common cause of the disease is a \"de novo\" mutation of the gene that produces the \u03b2-myosin heavy chain. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5630", "text": "Sudden cardiac death can usually be attributed to cardiovascular disease or commotio cordis, but about 20% of cases show no obvious cause and remain undiagnosed after autopsy. Interest in these \"autopsy-negative\" deaths has centered around the \" ion channelopathies \". These electrolyte channels are pores regulating the movement of sodium, potassium and calcium  ions  into cardiac cells, collectively responsible for creating and controlling the electrical signals that govern the heart's rhythm. Abnormalities in this system occur in relatively rare genetic diseases such as  Long QT syndrome ,  Brugada syndrome , and  Catecholaminergic polymorphic ventricular tachycardia , all associated with sudden death.  Consequently, autopsy-negative sudden cardiac deaths (no physical abnormalities identified) may comprise a larger part of the channelopathies than previously anticipated. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5631", "text": "Heritable connective tissue diseases are rare, each disorder estimated at one to ten per 100,000, of which  Marfan syndrome  is the most common. It is carried by the FBN1 gene on chromosome 15, which encodes the connective protein fibrillin-1, [ 12 ] [ 13 ]  inherited as a dominant trait. This protein is essential for synthesis and maintenance of elastic fibers. Since these fibers are particularly abundant in the  aorta , ligaments, and the  ciliary zonules  of the eye, these areas are among the worst affected. Everyone has a pair of FBN1 genes and, because transmission is dominant, those who have inherited one affected FBN1 gene from either parent will have Marfan syndrome. Although it is most frequently inherited as an autosomal dominant, there is no family history in 25% of cases. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5632", "text": "Recruiting practices aimed at attracting athletes who are unusually tall or who have an unusually wide arm span (characteristics of Marfan syndrome) can increase the prevalence of the syndrome within sports such as basketball and volleyball. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5633", "text": "After a disease-causing mutation has been identified in an index case (which is not always accomplished conclusively), the main task is genetic identification of carriers within a pedigree, a sequential process known as \"cascade testing\". Family members with the same mutation may show different severities of disease, a phenomenon known as \"variable  penetrance \". As a result, some may remain asymptomatic, with little lifelong evidence of disease. Nevertheless, their children remain at risk of inheriting the disorder and potentially being more severely affected. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5634", "text": "Screening athletes for cardiac disease can be problematic because of low prevalence and inconclusive performance of various tests that have been used. Nevertheless, sudden death among seemingly healthy individuals attracts much public and legislator attention because of its visible and tragic nature. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5635", "text": "As an example, the  Texas Legislature  appropriated US$1\u00a0million for a pilot study of statewide athlete screening in 2007. The study employed a combination of questionnaire, examination and  electrocardiography  for 2,506 student athletes, followed by  echocardiography  for 2,051 of them, including any students with abnormal findings from the first three steps. The questionnaire alone flagged 35% of the students as potentially at risk, but there were many  false positive  results, with actual disease being confirmed in less than 2%. Further, a substantial number of screen-positive students declined repeated recommendations for follow-up evaluation. (Individuals who are conclusively diagnosed with cardiac disease are usually told to avoid competitive sports.) It should be stressed that this was a single pilot program, but it was indicative of the problems associated with large-scale screening, and consistent with experience in other locations with low prevalence of sudden death in athletes. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5636", "text": "Sudden cardiac death occurs in approximately one per 200,000 young athletes per year, usually triggered during competition or practice. [ 6 ]  The victim is usually male and associated with  association football ,  basketball ,  ice hockey , or  American football , reflecting the large number of athletes participating in these sustained and strenuous sports. [ 3 ]  For a normally healthy age group, the risk appears to be particularly magnified in competitive basketball, with sudden cardiac death rates as high as one per 3,000 annually for male basketball players in  NCAA  Division I. [ 19 ]  This is still far below the rate for the general population, estimated as one per 1,300\u20131,600 and dominated by the elderly. [ 20 ]  However, a population as large as the United States will experience the sudden cardiac death of a competitive athlete at the average rate of one every three days, often with significant local media coverage heightening public attention. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5637", "text": "In the United States approximately 8 to 10 deaths per year can be attributed to sudden cardiac death in  NCAA  with overall rate of 1 per 43,000. [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5638", "text": "These athletes, with notable careers, experienced sudden cardiac death by age 40."}
{"_id": "WikiPedia_Cardio$$$corpus_5639", "text": "Takotsubo cardiomyopathy  or  takotsubo syndrome  ( TTS ), also known as  stress cardiomyopathy , is a type of non- ischemic   cardiomyopathy  in which there is a sudden temporary weakening of the  muscular portion of the heart . [ 4 ]  It usually appears after a significant stressor, either physical or emotional; when caused by the latter, the condition is sometimes called  broken heart syndrome . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5640", "text": "Examples of physical stressors that can cause TTS are  sepsis ,  shock ,  subarachnoid hemorrhage , and  pheochromocytoma . Emotional stressors include bereavement, divorce, or the loss of a job. [ 6 ]  Reviews suggest that of patients diagnosed with the condition, about 70\u201380% recently experienced a major stressor, including 41\u201350% with a physical stressor and 26\u201330% with an emotional stressor. [ 7 ] [ 8 ]  TTS can also appear in patients who have not experienced major stressors. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5641", "text": "The pathophysiology is not well understood, but a sudden massive surge of  catecholamines  such as  adrenaline  and  noradrenaline  from extreme stress or a tumor secreting these chemicals is thought to play a central role. [ 10 ]   Excess catecholamines, when released directly by nerves that stimulate cardiac muscle cells, have a toxic effect and can lead to decreased cardiac muscular function or \" stunning \". [ 11 ] [ 12 ]  Further, this adrenaline surge triggers the arteries to  tighten , thereby raising blood pressure and placing more stress on the heart, and may lead to  spasm of the coronary arteries  that supply blood to the heart muscle. [ 10 ]  This impairs the arteries from delivering  adequate blood flow and oxygen  to the heart muscle. [ 10 ]  Together, these events can lead to  congestive heart failure  and decrease the  heart's output  of blood with each squeeze. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5642", "text": "Takotsubo cardiomyopathy occurs worldwide. [ 11 ]  The condition is thought to be responsible for 2% of all  acute coronary syndrome  cases presenting to hospitals. [ 11 ]  Although TTS has generally been considered a  self-limiting disease , spontaneously resolving over the course of days to weeks, contemporary observations show that \"a subset of TTS patients may present with symptoms arising from its complications, e.g. heart failure,  pulmonary edema ,  stroke ,  cardiogenic shock , or  cardiac arrest \". This does not imply that rates of shock/death of TTS are comparable to those of acute coronary syndrome, but that patients with acute complications may co-occur with TTS. [ 6 ]   These cases of shock and death have been associated with the occurrence of TTS secondary to an inciting physical stressor such as  hemorrhage , brain injury sepsis,  pulmonary embolism  or severe  chronic obstructive pulmonary disease  (COPD). [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5643", "text": "It occurs more commonly in postmenopausal women. [ 11 ]  The name \"takotsubo\" comes from the Japanese word  takotsubo  \"octopus trap\", because the left ventricle of the heart takes on a shape resembling an  octopus trap  when affected by this condition. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5644", "text": "A study published in the  Journal of the American Heart Association  in October 2021 found a steady annual increase in takotsubo cardiomyopathy among both women and men from 2006 to 2017, with the sharpest increases among women 50 and older. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5645", "text": "The typical presentation of takotsubo cardiomyopathy is chest pain with or without shortness of breath and associated  electrocardiogram  (ECG) changes mimicking a  myocardial infarction  of the  anterior wall . During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging-out of the apex of the heart with preserved function of the base that earned the syndrome the name  takotsubo  (\"octopus trap\")  in  Japan , where it was first described. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5646", "text": "Stress is the main factor in takotsubo cardiomyopathy, with more than 85% of cases set in motion by either a physically or emotionally stressful event that prefaces the start of symptoms. [ 16 ]  Examples of emotional stressors include grief from the death of a loved one, fear of public speaking, arguing with a spouse, relationship disagreements, betrayal, and financial problems. [ 16 ]  Acute  asthma , surgery,  subarachnoid hemorrhage ,  chemotherapy , and  stroke  are examples of physical stressors. [ 16 ]  In a few cases, the stress may be a happy event, such as a wedding, winning a jackpot, a sporting triumph, or a birthday. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5647", "text": "Although there have been documented cases of TTS without a triggering stressor, it is widely recognized that TTS is preceded by a stressful or emotional event. [ 12 ]   Case series looking at large groups of patients report that some patients develop takotsubo cardiomyopathy after experiencing emotional stress. Some patients have a preceding clinical stressor (such as a brain injury,  asthma  attack or exacerbation of a chronic illness) and research has indicated that this type of stress may even occur more often than emotionally stressful triggers. [ 9 ]  Roughly one-third of patients have no preceding stressful event. [ 19 ]  A 2009 large case series from Europe found that takotsubo cardiomyopathy was slightly more frequent during the winter season. This may be related to two possible/suspected pathophysiological causes: coronary spasms of microvessels, which are more prevalent in cold weather, and viral infections \u2013 such as  Parvovirus B19  \u2013 which occur more frequently during the winter. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5648", "text": "Women, specifically postmenopausal women, are at greatest risk of developing TTS. [ 12 ]  This has led some researchers to theorize about the possible protective effects of estrogen in preventing TTS. [ 20 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5649", "text": "It is currently being investigated if certain genetic traits associated with catecholamine receptors found on cardiac muscle cells play a role in the development of TTS. [ 20 ]   There is limited evidence tying TTS directly to a specific genetic expression or mutation, however there is currently a widely held hypothesis supporting the idea of the interaction between environmental factors and the interplay of genetic predisposition leading to the susceptibility to microvascular alterations that contribute to the TTS disease process. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5650", "text": "Certain  endocrine  diseases including  pheochromocytoma  and  thyrotoxicosis  have been identified as potential risk factors for TTS. [ 21 ] [ 22 ]  The relationship between  thyroid  function and stress cardiomyopathy is marked by a dual phenotype, where both impending primary  hyperthyroidism  and a high set point of  thyroid homeostasis  (encoding type 2  allostatic load ) are common phenomena. [ 23 ]  A multi-centre observation study found normal thyroid function to be the exception rather than the rule in TTS. [ 23 ]  Especially hyperthyroidism is highly prevalent in takotsubo cardiomyopathy, and it seems to predict a poor prognosis in terms of complications and mortality. [ 24 ]  This observation was confirmed by results of the international GEIST registry, which demonstrated that thyrotoxicosis is associated with significantly increased fatality, whereas hypothyroidism indicates a better survival. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5651", "text": "The cause of takotsubo cardiomyopathy is not fully understood, but several mechanisms have been proposed. [ 26 ]  It is well documented that elevated catecholamine levels have been implicated in the vast majority of TTS cases. Theories suggest a link between brain activation of stress-related biochemicals (including  neuropeptides ) and the effects these chemicals have on areas of the heart, especially  neuropeptide Y . [ 27 ]  More specifically, adrenal stimulation by the sympathetic nervous system has been noted in cases ranging from physical events such as ischemic stroke, to emotional events such as depression or loss of a loved-one. [ 28 ]  How these increased levels of catecholamines act in the body to produce the changes seen with TTS is not clearly understood. [ 6 ] [ 11 ] [ 12 ] [ 20 ]   Research supports the widely-held understanding that microvascular dysfunction and coronary vasospasm caused by a rapid influx of catecholamines to cardiac myocytes results in apical stunning and transient cardiomyopathy. [ 6 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5652", "text": "It is likely that there are multiple factors at play that could include some amount of vasospasm and failure of the microvasculature. These factors can overlap and create the complex sequela leading to ischemia and left ventricle contraction abnormality. [ 12 ]  For instance, estrogen, which confers protection to women by improving blood flow to heart muscle, is one biochemical pathway implicated in the TTS disease process. Once this protective mechanism is reduced through the decreased production of estrogen after menopause, there is thought to be an increase in endothelial dysfunction predisposing an individual to vasoconstriction and cardiac ischemia. [ 11 ]  An inciting stressful event elicits the release of catecholamines into the blood stream to create increased heart muscle activity and metabolism. This leads to further cardiac microvascular endothelial dysfunction through oxidative stress, alteration of ion-mediated channels, and electrolyte disturbances which ultimately alter myocardial cell membrane permeability and dysfunction. [ 6 ] [ 12 ]  Coupled with direct heart muscle toxicity, this crescendo of factors are implicated in the ballooning and heart failure characteristically seen in TTS. [ 6 ] [ 11 ] [ 12 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5653", "text": "A 2019 case involved a 60-year-old woman presenting with TTS due to over-consumption of  wasabi , mistaking it for  avocado . [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5654", "text": "Several well regarded institutions of medical research have produced clinical criteria useful in diagnosing TTS. One of the first sets of guidelines was initially published in 2004 and again in 2008 by the  Mayo Clinic . Other research institutions proposing diagnostic criteria include the Japanese Takotsubo Cardiomyopathy Study Group,  Gothenburg University ,  Johns Hopkins University , the Takotsubo Italian Network and the Heart Failure Associates TTS Taskforce of the  European Society of Cardiology . [ 36 ]  All of the research institutions agree on at least two main criteria needed to accurately diagnose TTS: 1) transient left ventricular wall motion abnormality and 2) the absence of a condition obviously explaining this wall motion abnormality (coronary artery lesion, hypoperfusion, myocarditis, toxicity, etc.). Other commonly acknowledged criteria necessary for diagnosis include characteristic EKG changes and mild to modest elevation in cardiac  troponin . [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5655", "text": "Transient apical ballooning syndrome or takotsubo cardiomyopathy is found in 1.7\u20132.2% of patients presenting with  acute coronary syndrome . [ 1 ]  While the original case studies reported on individuals in Japan, takotsubo cardiomyopathy has been noted more recently in the United States and Western Europe. It is likely that the syndrome previously went undiagnosed before it was described in detail in the Japanese literature. Evaluation of individuals with takotsubo cardiomyopathy typically includes a  coronary angiogram  to rule out occlusion of the  left anterior descending  artery, which will not reveal any significant blockages that would cause the  left ventricular  dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within two months. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5656", "text": "The diagnosis of takotsubo cardiomyopathy may be difficult upon presentation. The  ECG  findings often are confused with those found during an acute anterior wall  myocardial infarction . [ 37 ] [ 38 ]  It classically mimics ST-segment elevation myocardial infarction, and is characterised by acute onset of transient ventricular apical wall motion abnormalities (ballooning) accompanied by  chest pain ,  shortness of breath , ST-segment elevation, T-wave inversion or QT-interval prolongation on  ECG . Cardiac enzymes are usually negative and are moderate at worst, and cardiac catheterization usually shows absence of significant  coronary artery disease . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5657", "text": "The diagnosis is made by the  pathognomonic  wall motion abnormalities, in which the base of the left ventricle is contracting normally or is hyperkinetic while the remainder of the left ventricle is akinetic or  dyskinetic . This is accompanied by the lack of significant coronary artery disease that would explain the wall motion abnormalities. Although apical ballooning has been described classically as the angiographic manifestation of takotsubo, it has been shown that left ventricular dysfunction in this syndrome includes not only the classic apical ballooning, but also different angiographic morphologies such as mid-ventricular ballooning and, rarely, local ballooning of other segments. [ 1 ] [ 39 ] [ 40 ] [ 41 ] [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5658", "text": "The ballooning patterns were classified by Shimizu et al. as  takotsubo type  for apical akinesia and basal hyperkinesia,  reverse takotsubo  for basal akinesia and apical hyperkinesia,  mid-ventricular type  for mid-ventricular ballooning accompanied by basal and apical hyperkinesia, and  localised type  for any other segmental left ventricular ballooning with clinical characteristics of takotsubo-like left ventricular dysfunction. [ 40 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5659", "text": "In short, the main criteria for the diagnosis of takotsubo cardiomyopathy are: the patient must have experienced a stressor before the symptoms began to arise; the patient's ECG reading must show abnormalities from a normal heart; the patient must not show signs of coronary blockage or other common causes of heart troubles; the levels of cardiac enzymes in the heart must be elevated or irregular; and the patient must recover complete contraction and be functioning normally in a short amount of time. [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5660", "text": "The treatment of takotsubo cardiomyopathy is generally supportive in nature, for it is considered a transient disorder. [ 45 ]  Treatment is dependent on whether patients experience heart failure or acute hypotension and shock. In many individuals, left ventricular function normalizes within two months. [ 46 ] [ 47 ]   Aspirin  and other heart drugs also appear to help in the treatment of this disease, even in extreme cases. [ 48 ] [ 49 ]  After the patient has been diagnosed, and myocardial infarction (heart attack) ruled out, the aspirin regimen may be discontinued, and treatment becomes that of supporting the patient. [ 50 ]  There is currently no internationally agreed protocol for treatment of this condition. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5661", "text": "While medical treatments are important to address the acute symptoms of takotsubo cardiomyopathy, further treatment includes lifestyle changes. [ 51 ]  It is important that the individual stay physically healthy while learning and maintaining methods to manage stress, and to cope with future difficult situations. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5662", "text": "Although the symptoms of takotsubo cardiomyopathy usually go away on their own and the condition completely resolves itself within a few weeks, some serious short and long-term complications can happen that must be treated. [ 52 ]  These most commonly include  congestive heart failure  and very  low blood pressure , and less commonly include  blood clotting  in the apex of the left ventricle,  irregular heart beat , and  tearing of the heart wall . [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5663", "text": "For patients in acute heart failure,  ACE inhibitors ,  angiotensin receptor blockers , and  beta blockers , are considered mainstays of heart failure treatment. But use of beta blockers specifically for takotsubo cardiomyopathy is controversial, because they may confer no benefit. [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5664", "text": "For people with cardiogenic shock, medical treatment is based on whether a  left ventricular outflow tract  (LVOT) obstruction is present. [ 53 ]  Therefore, early  echocardiography  is necessary to determine proper management. For those with obstructed LVOTs  inotropic  agents should not be used, but instead should be managed like patients with  hypertrophic cardiomyopathy , (e.g.  phenylephrine  and  fluid resuscitation ). [ 45 ]  For cases in which the LVOT is not obstructed, inotropic therapy (e.g.  dobutamine  and  dopamine ) may be used, but with the consideration that takotsubo is caused by excess catecholamines. [ 53 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5665", "text": "Furthermore, mechanical circulatory support [ 54 ]  (MCS) with an  intra-aortic balloon pump  (IABP) is well-established as supportive treatment. [ 53 ] [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5666", "text": "Despite the grave initial presentation in some of the patients, most of the patients survive the initial acute event, with a very low rate of in-hospital mortality or complications. Once a patient has recovered from the acute stage of the syndrome, they can expect a favorable outcome and the long-term prognosis is excellent for most. [ 1 ] [ 15 ] [ 39 ]  Even when ventricular systolic function is heavily compromised at presentation, it typically improves within the first few days and normalises within the first few months. [ 1 ] [ 30 ] [ 31 ] [ 32 ]  Although infrequent, recurrence of the syndrome has been reported and seems to be associated with the nature of the trigger. [ 1 ] [ 19 ]  While men experience TTS at much lower rates than women, they also experience much higher rates of complication, reoccurrence, and mortality; the cause of this sex difference is still unknown, but it is hypothesized that the social aspect of the doctor-patient interaction affects the way that physicians recognize and generate individual treatment plans for men compared to women. [ 56 ]  Stress cardiomyopathy is now a well-recognized cause of acute  congestive heart failure , lethal  abnormal heart rhythms , and  rupture of the heart wall . [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5667", "text": "Takotsubo syndrome represents about 2% of all patients (and 5\u20136% of all female patients) who are initially diagnosed with acute coronary syndrome (ACS). [ 6 ] [ 57 ]  It accounts for 0.02% of all hospitalizations in the US. [ 6 ]  About 90% of TTS patients are women, [ 6 ] [ 57 ]  whose mean age is about 68 years, and 80% of whom are older than 50 years. [ 6 ]  About 2.2% of TTS cases had the reversed (basal) variant. [ 57 ]  Recurrence rate of TTS is about 1.8% per-patient year. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5668", "text": "Rees, et al. wrote in 1967 that the death of a close relative increases the risk of dying within one year by a factor of seven. [ 58 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5669", "text": "Engel wrote about sudden and rapid death during psychological stress in 1971 and itemized 8 causation categories: (1) on the impact of the collapse or death of a close person; (2) during acute grief; (3) on threat of loss of a close person; (4) during mourning or on an anniversary; (5) on loss of status or self-esteem; (6) personal danger or threat of injury; (7) after the danger is over; (8) reunion, triumph, or happy ending. He proposed these events provoke neurovegetative responses, involving both the flight-fight and conservation-withdrawal systems, conducive to lethal cardiac events, particularly in individuals with preexisting cardiovascular disease. [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5670", "text": "Although the first scientific description of takotsubo cardiomyopathy was not until the 1990s, Cebelin and Hirsch wrote about human stress cardiomyopathy in 1980. The two looked at homicidal assaults that had happened in  Cuyahoga County, Ohio , the past 30 years, specifically those with autopsies who had no internal injury, but had died of physical assault. They found that 11 of 15 had  myofibrillar  degeneration similar to animal stress studies. In the end, they concluded their data supported \"the theory of catecholamine mediation of these myocardial changes in man and of the lethal potential of stress through its effect on the heart\". [ 60 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5671", "text": "The syndrome reached international audiences through the media in 2005 when the  New England Journal of Medicine  wrote about the syndrome. [ 61 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5672", "text": "Traumatic cardiac arrest  ( TCA ) is a condition in which the  heart  has  ceased  to beat due to  blunt  or  penetrating trauma , such as a  stab wound  to the  thoracic  area. [ 1 ]  It is a  medical emergency  which will always result in death without prompt advanced medical care.  Even with prompt medical intervention, survival without  neurological  complications is rare. [ 2 ]  In recent years, protocols have been proposed to improve survival rate in patients with traumatic cardiac arrest, though the variable causes of this condition as well as many coexisting injuries can make these protocols difficult to standardize. [ 3 ]  Traumatic cardiac arrest is a complex form of  cardiac arrest  often derailing from  advanced cardiac life support  in the sense that the emergency team must first establish the cause of the traumatic arrest and reverse these effects, for example hypovolemia and haemorrhagic shock due to a penetrating injury. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5673", "text": "Traumatic cardiac arrest can occur in patients following any severe blunt or penetrating  injury to the chest . Following the traumatic event, the heart ceases to pump blood through the body. Unlike medical cardiac arrest, there are several potentially reversible causes that may result in cardiac arrest in the setting of trauma. Clinicians will rapidly assess for these causes, and interventions will be directed to the specific cause. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5674", "text": "In both blunt and penetrating trauma, massive  internal  or  external bleeding  may decrease the volume of blood is available to be pumped by the heart to the body. This is considered  preload  dependent arrest. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5675", "text": "Tension pneumothorax  is caused when air is able to enter the space between the  lung  and the  chest wall , but is not able to escape. The increasing pressure within the chest cavity prevents blood from returning from the body to fill the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_5676", "text": "Hemothorax  occurs when injury to the chest results in bleeding into the thoracic cavity. Similar to tension pneumothorax, increasing pressure prevents the return of blood from circulation to the heart."}
{"_id": "WikiPedia_Cardio$$$corpus_5677", "text": "In the setting of trauma,  cardiac tamponade  results from an acute  pericardial effusion , the accumulation of blood within the sac that surrounds the heart. As this sac is filled with fluid, the pressure on the heart is increased, and the chambers of the heart are unable to fill with blood."}
{"_id": "WikiPedia_Cardio$$$corpus_5678", "text": "Inability to maintain  oxygenation  in trauma patients may be a result of  airway  compromise due to mechanical injury or obstruction or due to loss of the  respiratory drive  from  cervical spine  or  peripheral nerve injury . [ 4 ]  These conditions result in the  hypoxia  that may lead to cardiac arrest."}
{"_id": "WikiPedia_Cardio$$$corpus_5679", "text": "Patients will present following a traumatic event most often with  pulseless electrical activity  (PEA). Patients will exhibit low blood pressure with pulses that cannot be palpated. Patients will progress into  asystole  if the underlying condition is not reversed. Other non-specific signs and symptoms associated with impending traumatic cardiac arrest may include sweating,  altered mental status ,  rapid  or  slow breathing , and signs of trauma (bruising,  laceration , fractures, etc.). [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5680", "text": "Diagnosis of traumatic cardiac arrest is initially made with  electrocardiogram  with EMS or in the emergency department. Clinicians will also order diagnostic testing that may include  chest x-ray , bedside ultrasound and  echocardiogram , and blood gas levels. A  type and cross  will be ordered to match the patient to receive blood transfusion if necessary."}
{"_id": "WikiPedia_Cardio$$$corpus_5681", "text": "Other work-up involved in diagnosis of a trauma patient may include  e-FAST ,  RUSH exam ,  CBC , pelvic X-ray, and  CT  of the head, neck, chest, abdomen, and pelvis."}
{"_id": "WikiPedia_Cardio$$$corpus_5682", "text": "Treatment of traumatic cardiac arrest is guided by  advanced trauma life support guidelines . Standard advanced cardiac life support guidelines are inappropriate for use in traumatic cardiac arrest, as they are directed primarily at treating pathology originating within the heart itself. [ 5 ]  As clinicians begin to intervene, they will simultaneously seek reversible causes of the arrest. Management begins by establishing multiple points of IV access and evaluating the patient's airway and breathing. Other interventions may include  thoracostomy  and  thoracotomy , as well as treatment of the underlying cause of arrest."}
{"_id": "WikiPedia_Cardio$$$corpus_5683", "text": "Basic life support  is commonly initiated by bystanders and first responders, but the role of basic life support in traumatic cardiac arrest is unclear. Basic life support is targeted to maintain oxygenation and circulation throughout the body, which can be lifesaving in cases of medical cardiac arrest, but does not address the frequent large volume blood loss encounters in many cases of traumatic cardiac arrest. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5684", "text": "Chest compressions  are considered the most important initial intervention in cases of medical cardiac arrest, however studies evaluating their efficacy have excluded patients with traumatic cardiac arrest. Chest compressions work to replace the cardiac function of pumping blood throughout the body, however cases where the heart is either unable to fill with blood or the total blood volume is depleted, this intervention may be ineffective. Additionally, as many of the interventions targeted at specific causes of arrest are centered around procedures performed around the patient's chest, head, and neck, compressions may interfere with definitive management. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5685", "text": "Current guidelines tailored to treatment of specific causes of traumatic cardiac arrest have improved outcomes for patients, however these guidelines may be difficult to apply in a standardized manner due to differences in pre-hospital care and the wide variety of causes of traumatic cardiac arrest compared to medical cardiac arrest. [ 3 ]  Evolving algorithms are directed at quickly identifying incidences of cardiac arrest with a traumatic source and rapidly intervening to address reversible causes. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5686", "text": "Historically, traumatic cardiac arrest was thought to lead invariably to death. More recently, evolutions of advanced trauma life support guidelines and improved understanding of the underlying causes of traumatic cardiac arrest have improved outcomes for patients. [ 5 ]  Recent studies suggest that the survival rate for traumatic cardiac arrest is similar to that of all-cause cardiac arrest. [ 6 ]  There is wide variability in the estimated survival rate based on factors that include initiation of pre-hospital care and nature of injury. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5687", "text": "Many patients who survive traumatic cardiac arrest may develop long-term neurological damage resulting from lack of circulation to the nervous system during the arrest. This damage may range from moderate disability to a persistent vegetative state. A 2012 review suggests that while survival rates of traumatic cardiac arrest are higher in children, so is the incidence of neurological complication. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5688", "text": "Twiddler's syndrome  is a malfunction of a  pacemaker  due to manipulation of the device and the consequent dislodging of the leads from their intended location.  As the leads move, they stop pacing the heart and can cause strange symptoms such as  phrenic nerve  stimulation resulting in abdominal pulsing or  brachial plexus  stimulation resulting in rhythmic arm twitching. [ 1 ]  Twiddler's syndrome in patients with an implanted  defibrilator  may lead to inadequate, painful defibrillation-shocks. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5689", "text": "Twiddler's syndrome presents with a range of symptoms, contingent on the extent of entanglement, the electrode's subsequent retraction, and the final location of the dislodged lead. [ 3 ]  Leads that become more dislodged up can activate the ipsilateral  phrenic nerves , which can result in  hiccups , involuntary breathing spasms, or diaphragmatic contractions. [ 1 ] [ 4 ]  The  brachial plexus  is stimulated by additional coiling and withdrawal of the lead, which causes regular arm twitches. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5690", "text": "Patient \"twiddling,\" or manipulation, of the pulse generator within its skin pocket results in the device's painless dislodgment; lead dislodgement follows, eventually leading to  pacemaker  malfunction. [ 1 ]  There have also been reports of variations of this phenomenon resulting in the failure of implanted cardioverter- defibrillators  and  cardiac resynchronization therapy , which can be fatal. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5691", "text": "The condition's risk factors include being a woman, being  obese , belonging to an older age group, having  cognitive impairments , and having an implanted device that is smaller than its pocket. [ 7 ] [ 4 ] [ 8 ]  A related increase in subcutaneous tissue laxity, especially in older patients, makes it easier for the device to become dislodged. [ 6 ] [ 7 ]  Furthermore, the newer devices' smaller sizes make it easy for them to rotate inside the skin pocket. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5692", "text": "Given its speed and ability to provide a clear image of the lead coiling and device rotation, the  chest X-ray  is the most straightforward and important diagnostic tool for Twiddler's syndrome. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5693", "text": "Repositioning the pulse generator, implanting a new lead, and uncoiling the lead\u00a0are among the treatments for diagnosed cases. [ 4 ] [ 8 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5694", "text": "Ventricular aneurysms  are one of the many complications that may occur after a  heart attack . The word aneurysm refers to a bulge or 'pocketing' of the wall or lining of a vessel commonly occurring in the blood vessels at the base of the septum, or within the aorta. In the heart, they usually arise from a patch of weakened tissue in a  ventricular wall , which swells into a bubble filled with blood. [ 1 ]  This, in turn, may block the passageways leading out of the heart, leading to severely constricted blood flow to the body. Ventricular aneurysms can be fatal. They are usually non-rupturing because they are lined by scar tissue."}
{"_id": "WikiPedia_Cardio$$$corpus_5695", "text": "A left ventricular aneurysm can be associated with  ST elevation . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5696", "text": "Ventricular aneurysms usually grow at a very slow pace, but can still pose problems. Usually, this type of aneurysm grows in the  left ventricle . This bubble has the potential to block blood flow to the rest of the body, and thus limit the patient's stamina. In other cases, a similarly developed  pseudoaneurysm  (\"false aneurysm\") may burst, sometimes resulting in the death of the patient. Also, blood clots may form on the inside of ventricular aneurysms, and form  embolisms . If such a clot escapes from the aneurysm, it will be moved in the circulation throughout the body. If it gets stuck inside a blood vessel, it may cause  ischemia  in a  limb , a painful condition that can lead to reduced movement and tissue death in the limb. [ 1 ]  Alternatively, if a clot blocks a vessel going to the brain, it can cause a stroke. In certain cases, ventricular aneurysms cause ventricular failure or arrhythmia. At this stage, treatment is necessary. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5697", "text": "Ventricular aneurysms are usually complications resulting from a  heart attack . When the heart muscle ( cardiac muscle ) partially dies during a heart attack, a layer of muscle may survive, and, being severely weakened, start to become an aneurysm. Blood may flow into the surrounding dead muscle and inflate the weakened flap of muscle into a bubble. It may also be congenital. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5698", "text": "When a person visits the hospital or doctor with other symptoms, especially with a history of heart problems, they will normally be required to undergo an electrocardiogram, which monitors electrical activity within the heart and shows abnormalities when a cardiac aneurysm is present. It can also appear as a bulge on a chest x-ray, and a more accurate diagnosis will then be made using an echocardiogram, which uses ultrasound to 'photograph' the heart and how it functions while it beats. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5699", "text": "It should also not be confused with a  pseudoaneurysm , [ 4 ] [ 5 ]   coronary artery aneurysm  or a  myocardial rupture  (which involves a hole in the wall, not just a bulge.)"}
{"_id": "WikiPedia_Cardio$$$corpus_5700", "text": "Cardiac  diverticulum or ventricular diverticulum is defined as a  congenital  malformation of the fibrous or muscular part of the heart which is only visible during chest x-rays or during an  echocardiogram  reading. [ 6 ]  This should not be confused with ventricular diverticulum, as the latter is a sub type derived from the latter in congenital cases. it is usually asymptomatic and is only detected using imaging. Fibrous diverticulum is characterised by a calcification if present at the tip ( apex) or a thrombi that may detaches to form an emboli. Muscular diverticulum is characterised by appendix forming at the ether of the ventricles. [ 7 ]  it is a rare anomaly and can be diagnosed prenatal. Diagnosis is usually done by a chest X-ray and silhouette is viewed around the heart. Echocardiogram reading present a similar picture to ventricular  aneurysms  on the ST segment. Management is dependent on the situation presented and the severity of the case. Usually, surgical resection is advised but in prenatal cases, due to combination with other cardiac abnormalities, especially in latter  trimesters , but  pericardiocentesis  is useful technique to reduce pleural effusion or/ and secondary disorders. [ vague ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5701", "text": "Some people live with this type of aneurysm for many years without any specific treatment. Treatment is limited to surgery ( ventricular reduction ) for this defect of the heart. However, surgery is not required in most cases but, limiting the patient's physical activity levels to lower the risk of making the aneurysm bigger is advised. Also, ACE Inhibitors seem to prevent Left Ventricular remodeling and aneurysm formation. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5702", "text": "Blood thinning agents may be given to help reduce the likelihood of blood thickening and clots forming, along with the use of drugs to correct the irregular rhythm of the heart (seen on the electrocardiogram) [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5703", "text": "Vibroacoustic disease  is a medical condition manifested in those who have had long-term exposure (\u2265 10 yr) to large pressure amplitude (\u2265 90 dB SPL) and  low frequency noise  (\u2264 500 Hz). [ 1 ]  The disease is said to lead to  heart arrhythmia  or even death. [ 2 ] [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5704", "text": "During  protests  over the closure of the  Roosevelt Roads Naval Base  in  Puerto Rico , it was asserted that the noise created by the Navy's testing had negatively affected the health of civilians living on Vieques. In a study conducted for Puerto Rican Governor Calderon, 48 of the 50 Vieques residents tested were diagnosed as suffering from a thickening of heart tissue caused by exposure to sonic booms. [ 2 ]  Simultaneously, the  Ponce School of Medicine  conducted an independent study and found other data to confirm the presence of vibroacoustic disease: 79% of Viequenses fishermen have thickened heart tissue, which is the main symptom of vibroacoustic disease. [ 2 ]  The federal  Agency for Toxic Substances & Disease Registry  reviewed Ponce School of Medicine study and concluded in 2001 that the Vieques heart study failed to provide any \"clinically significant\" evidence of heart disease. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5705", "text": "Viral cardiomyopathy  occurs when viral infections cause  myocarditis  with a resulting thickening of the myocardium and dilation of the ventricles. These viruses include Coxsackie B and adenovirus, echoviruses,  influenza H1N1 ,  Epstein\u2013Barr virus ,  rubella (German measles virus) ,  varicella (chickenpox virus) ,  mumps ,  measles ,  parvoviruses ,  yellow fever ,  dengue fever ,  polio ,  rabies , and the viruses that cause  hepatitis A  and  C , [ 2 ] [ 3 ] [ 4 ]  as well as  COVID-19 , [ 5 ] [ 6 ]  which has been seen to cause this in persons otherwise thought to have a \"low risk\" of the virus's effects. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5706", "text": "Patients with  COVID-19  frequently experience  heart  issues. [ 8 ]  According to studies, people who have had previous cardiovascular conditions like  cardiomyopathy ,  hypertension ,  coronary heart disease , or  arrhythmia  are more likely to become critically ill from  SARS-CoV-2  infection.  Myocarditis  may result from a direct viral infection of the myocardium. [ 8 ]  Cardiovascular biomarkers like  troponin ,  lactate dehydrogenase , high sensitivity amino-terminal  B-type natriuretic peptide ,  creatinine kinase , and creatinine kinase myocardial band, which indicate myocardial damage, increase in concentration in response to COVID-19. [ 8 ]  Hundreds of studies have reported myocarditis/myopericarditis caused by COVID-19 infection in living patients, with a  male  predominance (58%), and a  median age  of 50 years.  [ 8 ]"}
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{"_id": "WikiPedia_Cardio$$$corpus_5709", "text": "Adderall  and  Mydayis [ 11 ]  are  trade names [ note 2 ]  for a  combination drug  containing four  salts  of  amphetamine . The mixture is composed of equal parts  racemic  amphetamine and  dextroamphetamine , which produces a (3:1) ratio between dextroamphetamine and  levoamphetamine , the two  enantiomers  of amphetamine. [ 13 ]  Both enantiomers are  stimulants , but differ enough to give Adderall an  effects profile  distinct from those of racemic amphetamine or dextroamphetamine, [ 1 ] [ 2 ]  which are marketed as Evekeo and Dexedrine/Zenzedi, respectively. [ 1 ] [ 14 ] [ 15 ]  Adderall is used in the treatment of  attention deficit hyperactivity disorder  (ADHD) and  narcolepsy . It is also used illicitly as an  athletic performance enhancer ,  cognitive enhancer ,  appetite suppressant , and recreationally as a  euphoriant . It is a  central nervous system  (CNS)  stimulant  of the  phenethylamine class . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5710", "text": "At therapeutic doses, Adderall causes emotional and cognitive effects such as  euphoria , change in  sex drive , increased  wakefulness , and improved  cognitive control . At these doses, it induces physical effects such as a faster reaction time, fatigue resistance, and increased muscle strength. In contrast, much larger doses of Adderall can impair cognitive control, cause  rapid muscle breakdown , provoke  panic attacks , or induce  psychosis  (e.g.,  paranoia ,  delusions ,  hallucinations ). The side effects vary widely among individuals but most commonly include  insomnia ,  dry mouth ,  loss of appetite  and  weight loss . The risk of developing an  addiction  or  dependence  is insignificant when Adderall is used as prescribed and at fairly low daily doses, such as those used for treating ADHD. However, the routine use of Adderall in larger and daily doses poses a significant risk of addiction or dependence due to the pronounced  reinforcing effects  that are present at high doses. Recreational doses of Adderall are generally much larger than prescribed  therapeutic doses  and also carry a far greater risk of serious adverse effects. [ sources 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5711", "text": "The two amphetamine enantiomers that compose Adderall, such as Adderall tablets/capsules (levoamphetamine and dextroamphetamine), alleviate the symptoms of ADHD and narcolepsy by increasing the activity of the  neurotransmitters   norepinephrine  and  dopamine  in the  brain , which results in part from their interactions with  human trace amine-associated receptor\u00a01  (hTAAR1) and  vesicular monoamine transporter 2  (VMAT2) in  neurons . Dextroamphetamine is a more potent  Central nervous system  ( CNS ) stimulant than levoamphetamine, but levoamphetamine has slightly stronger cardiovascular and peripheral effects and a longer  elimination half-life  than dextroamphetamine. The levoamphetamine component of Adderall has been reported to [ weasel\u00a0words ]  improve the treatment response in some individuals relative to dextroamphetamine alone [ citation needed ] . The  active ingredient  in Adderall, amphetamine, shares many chemical and pharmacological properties with the human  trace amines , particularly  phenethylamine  and  N -methylphenethylamine , the latter of which is a  positional isomer  of amphetamine. [ sources 2 ]  In 2022, Adderall was the fourteenth most commonly prescribed medication in the United States, with more than 34 \u00a0 million prescriptions. [ 35 ] [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5712", "text": "Adderall is commonly used to treat  attention deficit hyperactivity disorder  (ADHD) and  narcolepsy  (a sleep disorder). [ 37 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5713", "text": "Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal  dopamine system  development or nerve damage, [ 38 ] [ 39 ]  but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth. [ 40 ] [ 41 ] [ 42 ]  Reviews of  magnetic resonance imaging  (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right  caudate nucleus  of the  basal ganglia . [ 40 ] [ 41 ] [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5714", "text": "Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD. [ 43 ] [ 44 ] [ 45 ]   Randomized controlled trials  of continuous stimulant therapy for the treatment of ADHD spanning 2\u00a0years have demonstrated treatment effectiveness and safety. [ 43 ] [ 44 ]  Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing  quality of life  and academic achievement, and producing improvements in a large number of functional outcomes [ note 3 ]  across 9\u00a0categories of outcomes related to academics,  antisocial behavior , driving, non-medicinal drug use, obesity, occupation,  self-esteem , service use (i.e., academic, occupational, health, financial, and legal services), and social function. [ 43 ] [ 45 ]  Additionally, a 2024  meta-analytic   systematic review  reported moderate improvements in quality of life when amphetamine treatment is used for ADHD. [ 47 ]  One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5\u00a0 IQ  points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity. [ 44 ]  Another review indicated that, based upon the longest  follow-up studies  conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a  substance use disorder  as an adult. [ 43 ]  A 2025 meta-analytic systematic review of 113 randomized controlled trials demonstrated that stimulant medications significantly improved core ADHD symptoms in adults over a three-month period, with good acceptability compared to other pharmacological and non-pharmacological treatments. [ 48 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5715", "text": "Models of ADHD suggest that it is associated with functional impairments in some of the brain's  neurotransmitter systems ; [ 49 ]  these functional impairments involve impaired  dopamine  neurotransmission in the  mesocorticolimbic projection  and  norepinephrine  neurotransmission in the noradrenergic projections from the  locus coeruleus  to the  prefrontal cortex . [ 49 ]  Stimulants like  methylphenidate  and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. [ 18 ] [ 49 ] [ 50 ]  Approximately 80% of those who use these stimulants see improvements in ADHD symptoms. [ 51 ]  Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans. [ 52 ] [ 53 ]  The  Cochrane  reviews [ note 4 ]  on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse  side effects . [ 55 ] [ 56 ]  A Cochrane review on the treatment of ADHD in children with  tic disorders  such as  Tourette syndrome  indicated that stimulants in general do not make  tics  worse, but high doses of dextroamphetamine could exacerbate tics in some individuals. [ 57 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5716", "text": "Narcolepsy is a chronic sleep-wake disorder that is associated with excessive daytime sleepiness,  cataplexy , and  sleep paralysis . [ 58 ]  Patients with narcolepsy are diagnosed as either type 1 or type 2, with only the former presenting cataplexy symptoms. [ 59 ]  Type 1 narcolepsy results from the loss of approximately 70,000  orexin -releasing neurons in the  lateral hypothalamus , leading to significantly reduced  cerebrospinal  orexin levels; [ 60 ] [ 61 ]  this reduction is a  diagnostic biomarker  for type 1 narcolepsy. [ 59 ]  Lateral hypothalamic orexin neurons innervate every component of the  ascending reticular activating system  (ARAS), which includes  noradrenergic ,  dopaminergic ,  histaminergic , and  serotonergic  nuclei that promote  wakefulness . [ 61 ] [ 62 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5717", "text": "Amphetamine\u2019s therapeutic mode of action in narcolepsy primarily involves increasing  monoamine  neurotransmitter activity in the ARAS. [ 60 ] [ 63 ] [ 64 ]  This includes noradrenergic neurons in the  locus coeruleus , dopaminergic neurons in the  ventral tegmental area , histaminergic neurons in the  tuberomammillary nucleus , and serotonergic neurons in the  dorsal raphe nucleus . [ 62 ] [ 64 ]  Dextroamphetamine, the more dopaminergic enantiomer of amphetamine, is particularly effective at promoting wakefulness because dopamine release has the greatest influence on cortical activation and cognitive arousal, relative to other monoamines. [ 60 ]  In contrast, levoamphetamine may have a greater effect on cataplexy, a symptom more sensitive to the effects of norepinephrine and serotonin. [ 60 ]  Noradrenergic and serotonergic nuclei in the ARAS are involved in the regulation of the  REM  sleep cycle and function as \"REM-off\" cells, with amphetamine's effect on norepinephrine and serotonin contributing to the suppression of REM sleep and a possible reduction of cataplexy at high doses. [ 60 ] [ 59 ] [ 62 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5718", "text": "The  American Academy of Sleep Medicine  (AASM) 2021  clinical practice guideline  conditionally recommends dextroamphetamine for the treatment of both type 1 and type 2 narcolepsy. [ 65 ]  Treatment with pharmaceutical amphetamines is generally less preferred relative to other stimulants (e.g.,  modafinil ) and is considered a  third-line treatment  option. [ 66 ] [ 67 ] [ 68 ]  Medical reviews indicate that amphetamine is safe and effective for the treatment of narcolepsy. [ 60 ] [ 66 ] [ 65 ]  Amphetamine appears to be most effective at improving symptoms associated with  hypersomnolence , with three reviews finding clinically significant reductions in  daytime sleepiness  in patients with narcolepsy. [ 60 ] [ 66 ] [ 65 ]  Additionally, these reviews suggest that amphetamine may dose-dependently improve cataplexy symptoms. [ 60 ] [ 66 ] [ 65 ]  However, the quality of evidence for these findings is low and is consequently reflected in the AASM's conditional recommendation for dextroamphetamine as a treatment option for narcolepsy. [ 65 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5719", "text": "Adderall is available as  immediate-release  (IR) tablets and  extended-release  (XR) capsules. [ 17 ] [ 69 ]  Mydayis is only available as an extended-release formulation. [ 70 ]  Adderall XR is approved to treat ADHD for up to 12 hours in individuals 6 years and older and uses a  double-bead formulation . The capsule can be swallowed like a tablet, or it can be opened and the beads sprinkled over applesauce for comparable absorption. [ 69 ]  Upon ingestion, half of the beads provide immediate administration of medication, while the other half are enveloped in a coating that must dissolve, delaying absorption of its contents. It is designed to provide a therapeutic effect and plasma concentrations identical to taking two doses of Adderall IR four hours apart. [ 69 ]  Mydayis uses a longer-lasting triple-bead formulation and is approved to treat ADHD for up to 16 hours in individuals 13 years and older. [ 70 ]  In the United States, the immediate and extended-release formulations of Adderall are both available as  generic drugs . [ 71 ] [ 72 ]  Generic formulations of Mydayis became available in the US in October 2023. [ 73 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5720", "text": "In 2015, a  systematic review  and a  meta-analysis  of high quality  clinical trials  found that, when used at low (therapeutic) doses, amphetamine produces modest yet unambiguous improvements in cognition, including  working memory , long-term  episodic memory ,  inhibitory control , and some aspects of  attention , in normal healthy adults; [ 74 ] [ 75 ]  these cognition-enhancing effects of amphetamine are known to be partially mediated through the  indirect activation  of both  dopamine D 1  receptor  and  \u03b1 2 -adrenergic receptor  in the  prefrontal cortex . [ 18 ] [ 74 ]  A systematic review from 2014 found that low doses of amphetamine also improve  memory consolidation , in turn leading to improved  recall of information . [ 76 ]  Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals. [ 18 ] [ 77 ]  Amphetamine and other ADHD stimulants also improve  task saliency  (motivation to perform a task) and increase  arousal  (wakefulness), in turn promoting goal-directed behavior. [ 18 ] [ 78 ] [ 79 ]  Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid. [ 18 ] [ 79 ] [ 80 ]  Based upon studies of self-reported illicit stimulant use,  5\u201335%  of college students use  diverted  ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs. [ 81 ] [ 82 ] [ 83 ]  However, high amphetamine doses that are above the therapeutic range can interfere with working memory and other aspects of cognitive control. [ 18 ] [ 79 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5721", "text": "Amphetamine is used by some athletes for its psychological and  athletic performance-enhancing effects , such as increased endurance and alertness; [ 19 ] [ 31 ]  however, non-medical amphetamine use is prohibited at sporting events that are regulated by collegiate, national, and international anti-doping agencies. [ 84 ] [ 85 ]  In healthy people at oral therapeutic doses, amphetamine has been shown to increase  muscle strength , acceleration, athletic performance in  anaerobic conditions , and  endurance  (i.e., it delays the onset of  fatigue ), while improving  reaction time . [ 19 ] [ 86 ] [ 87 ]  Amphetamine improves endurance and reaction time primarily through  reuptake inhibition  and  release  of dopamine in the central nervous system. [ 86 ] [ 87 ] [ 88 ]  Amphetamine and other dopaminergic drugs also increase power output at fixed  levels of perceived exertion  by overriding a \"safety switch\", allowing the  core temperature limit  to increase in order to access a reserve capacity that is normally off-limits. [ 87 ] [ 89 ] [ 90 ]  At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; [ 19 ] [ 86 ]  however, at much higher doses, amphetamine can induce effects that severely impair performance, such as  rapid muscle breakdown  and  elevated body temperature . [ 20 ] [ 86 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5722", "text": "Adderall has been banned in the  National Football League  (NFL),  Major League Baseball  (MLB),  National Basketball Association  (NBA), and the National Collegiate Athletics Association (NCAA). [ 91 ]  In leagues such as the NFL, there is a very rigorous process required to obtain an exemption to this rule even when the athlete has been medically prescribed the drug by their physician. [ 91 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5723", "text": "Adderall has a high potential for misuse as a  recreational drug . [ 92 ] [ 93 ] [ 94 ]  Adderall tablets can either be swallowed, crushed and snorted, or dissolved in water and injected. [ 95 ]  Injection into the bloodstream can be dangerous because  insoluble fillers within the tablets  can block small blood vessels. [ 95 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5724", "text": "Many postsecondary students have reported using Adderall for study purposes in different parts of the developed world. [ 94 ]  Among these students, some of the  risk factors  for misusing ADHD stimulants recreationally include: possessing  deviant personality  characteristics (i.e., exhibiting delinquent or deviant behavior), inadequate accommodation of disability, basing one's  self-worth  on external validation, low  self-efficacy , earning poor grades, and having an untreated  mental health disorder . [ 94 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5725", "text": "The  adverse side effects  of Adderall are many and varied, but the amount of substance consumed is the primary factor in determining the likelihood and severity of side effects. [ 20 ] [ 31 ]  Adderall is currently approved for long-term therapeutic use by the USFDA. [ 20 ]   Recreational use  of Adderall generally involves far larger doses and is therefore significantly more dangerous, involving a much greater risk of serious adverse drug effects than dosages used for therapeutic purposes. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5726", "text": "Cardiovascular  side effects can include  hypertension  or  hypotension  from a  vasovagal response ,  Raynaud's phenomenon  (reduced blood flow to the hands and feet), and  tachycardia  (increased heart rate). [ 20 ] [ 31 ] [ 106 ]  Sexual side effects in males may include  erectile dysfunction , frequent erections, or  prolonged erections . [ 20 ]  Gastrointestinal side effects may include  abdominal pain ,  constipation ,  diarrhea , and  nausea . [ 7 ] [ 20 ] [ 107 ]  Other potential physical side effects include  appetite loss ,  blurred vision ,  dry mouth ,  excessive grinding of the teeth , nosebleed, profuse sweating,  rhinitis medicamentosa  (drug-induced nasal congestion), reduced  seizure threshold ,  tics  (a type of movement disorder), and  weight loss . [ sources 3 ]  Dangerous physical side effects are rare at typical pharmaceutical doses. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5727", "text": "Amphetamine stimulates the  medullary respiratory centers , producing faster and deeper breaths. [ 31 ]  In a normal person at therapeutic doses, this effect is usually not noticeable, but when respiration is already compromised, it may be evident. [ 31 ]  Amphetamine also induces  contraction  in the urinary  bladder sphincter , the muscle which controls urination, which can result in difficulty urinating. [ 31 ]  This effect can be useful in treating  bed wetting  and  loss of bladder control . [ 31 ]  The effects of amphetamine on the gastrointestinal tract are unpredictable. [ 31 ]  If intestinal activity is high, amphetamine may reduce  gastrointestinal motility  (the rate at which content moves through the digestive system); [ 31 ]  however, amphetamine may increase motility when the  smooth muscle  of the tract is relaxed. [ 31 ]  Amphetamine also has a slight  analgesic  effect and can enhance the pain relieving effects of  opioids . [ 7 ] [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5728", "text": "FDA-commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events ( sudden death ,  heart attack , and  stroke ) and the medical use of amphetamine or other ADHD stimulants. [ sources 4 ]  However, amphetamine pharmaceuticals are  contraindicated  in individuals with  cardiovascular disease . [ sources 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5729", "text": "At normal therapeutic doses, the most common psychological side effects of amphetamine include increased  alertness , apprehension,  concentration , initiative,  self-confidence  and sociability, mood swings ( elated mood  followed by mildly  depressed mood ),  insomnia  or  wakefulness , and decreased sense of fatigue. [ 20 ] [ 31 ]  Less common side effects include  anxiety , change in  libido ,  grandiosity ,  irritability , repetitive or  obsessive  behaviors, and restlessness; [ sources 6 ]  these effects depend on the user's personality and current mental state. [ 31 ]   Amphetamine psychosis  (e.g.,  delusions  and  paranoia ) can occur in heavy users. [ 20 ] [ 21 ] [ 115 ]  Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy. [ 20 ] [ 115 ] [ 22 ]  According to the FDA, \"there is no systematic evidence\" that stimulants produce aggressive behavior or hostility. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5730", "text": "Amphetamine has also been shown to produce a  conditioned place preference  in humans taking therapeutic doses, [ 55 ] [ 116 ]  meaning that individuals acquire a preference for spending time in places where they have previously used amphetamine. [ 116 ] [ 117 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5731", "text": "Addiction  is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses; [ 23 ] [ 24 ] [ 66 ]  in fact, lifetime stimulant therapy for ADHD that begins during childhood reduces the risk of developing  substance use disorders  as an adult. [ 43 ]   Pathological overactivation of the  mesolimbic pathway , a  dopamine pathway  that connects the  ventral tegmental area  to the  nucleus accumbens , plays a central role in amphetamine addiction. [ 127 ] [ 128 ]  Individuals who frequently  self-administer  high doses of amphetamine have a high risk of developing an amphetamine addiction, since chronic use at high doses gradually increases the level of  accumbal   \u0394FosB , a \"molecular switch\" and \"master control protein\" for addiction. [ 118 ] [ 129 ] [ 130 ]  Once nucleus accumbens \u0394FosB is sufficiently overexpressed, it begins to increase the severity of addictive behavior (i.e., compulsive drug-seeking) with further increases in its expression. [ 129 ] [ 131 ]  While there are currently no effective drugs for treating amphetamine addiction, regularly engaging in sustained aerobic exercise appears to reduce the risk of developing such an addiction. [ 132 ] [ 133 ]  Exercise therapy improves  clinical  treatment outcomes and may be used as an  adjunct therapy  with behavioral therapies for addiction. [ 132 ] [ 134 ] [ sources 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5732", "text": "Chronic use of amphetamine at excessive doses causes alterations in  gene expression  in the  mesocorticolimbic projection , which arise through  transcriptional  and  epigenetic  mechanisms. [ 130 ] [ 135 ] [ 136 ]  The most important  transcription factors [ note 8 ]  that produce these alterations are  Delta FBJ murine osteosarcoma viral oncogene homolog B  ( \u0394FosB ),  cAMP  response element binding protein  ( CREB ), and  nuclear factor-kappa B  ( NF-\u03baB ). [ 130 ]  \u0394FosB is the most significant biomolecular mechanism in addiction because \u0394FosB  overexpression  (i.e., an abnormally high level of gene expression which produces a pronounced gene-related  phenotype ) in the  D1-type   medium spiny neurons  in the  nucleus accumbens  is  necessary and sufficient [ note 9 ]  for many of the neural adaptations and regulates multiple behavioral effects (e.g.,  reward sensitization  and escalating drug  self-administration ) involved in addiction. [ 118 ] [ 129 ] [ 130 ]  Once \u0394FosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in \u0394FosB expression. [ 118 ] [ 129 ]  It has been implicated in addictions to  alcohol ,  cannabinoids ,  cocaine ,  methylphenidate ,  nicotine ,  opioids ,  phencyclidine ,  propofol , and  substituted amphetamines , among others. [ sources 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5733", "text": "\u0394JunD , a transcription factor, and  G9a , a  histone methyltransferase  enzyme, both oppose the function of \u0394FosB and inhibit increases in its expression. [ 118 ] [ 130 ] [ 140 ]  Sufficiently overexpressing \u0394JunD in the nucleus accumbens with  viral vectors  can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by \u0394FosB). [ 130 ]  Similarly, accumbal G9a hyperexpression results in markedly increased  histone  3  lysine   residue  9  dimethylation  ( H3K9me2 ) and blocks the induction of \u0394FosB-mediated  neural  and  behavioral plasticity  by chronic drug use, [ sources 9 ]  which occurs via  H3K9me2 -mediated  repression  of  transcription factors  for \u0394FosB and H3K9me2-mediated repression of various \u0394FosB transcriptional targets (e.g.,  CDK5 ). [ 130 ] [ 140 ] [ 141 ]  \u0394FosB also plays an important role in regulating behavioral responses to  natural rewards , such as palatable food, sex, and exercise. [ 131 ] [ 130 ] [ 144 ]  Since both natural rewards and addictive drugs  induce the expression  of \u0394FosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction. [ 131 ] [ 130 ]  Consequently, \u0394FosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced  sexual addictions , which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use. [ 131 ] [ 145 ] [ 146 ]  These sexual addictions are associated with a  dopamine dysregulation syndrome  which occurs in some patients taking  dopaminergic drugs . [ 131 ] [ 144 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5734", "text": "The effects of amphetamine on gene regulation are both dose- and route-dependent. [ 136 ]  Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses. [ 136 ]  The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor. [ 136 ]  This suggests that medical use of amphetamine does not significantly affect gene regulation. [ 136 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5735", "text": "As of December 2019, [update]  there is no effective  pharmacotherapy  for amphetamine addiction. [ 147 ] [ 148 ] [ 149 ]  Reviews from 2015 and 2016 indicated that  TAAR1 -selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions; [ 150 ] [ 151 ]  however, as of February 2016, [update]  the only compounds which are known to function as TAAR1-selective agonists are  experimental drugs . [ 150 ] [ 151 ]  Amphetamine addiction is largely mediated through increased activation of  dopamine receptors  and  co-localized   NMDA receptors [ note 10 ]  in the nucleus accumbens; [ 128 ]   magnesium ions  inhibit NMDA receptors by blocking the receptor  calcium channel . [ 128 ] [ 152 ]  One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain. [ 128 ]   Supplemental magnesium [ note 11 ]  treatment has been shown to reduce amphetamine  self-administration  (i.e., doses given to oneself) in humans, but it is not an effective  monotherapy  for amphetamine addiction. [ 128 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5736", "text": "A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in  randomized controlled trials  (RCTs) for amphetamine and methamphetamine addiction; [ 148 ]  it found only low-strength evidence that methylphenidate might reduce amphetamine or methamphetamine self-administration. [ 148 ]  There was low- to moderate-strength evidence of no benefit for most of the other medications used in RCTs, which included antidepressants (bupropion,  mirtazapine ,  sertraline ), antipsychotics ( aripiprazole ), anticonvulsants ( topiramate ,  baclofen ,  gabapentin ),  naltrexone ,  varenicline ,  citicoline ,  ondansetron ,  prometa ,  riluzole ,  atomoxetine , dextroamphetamine, and  modafinil . [ 148 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5737", "text": "A 2018 systematic review and  network meta-analysis  of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that  combination therapy  with both  contingency management  and  community reinforcement approach  had the highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate). [ 153 ]  Other treatment modalities examined in the analysis included  monotherapy  with contingency management or community reinforcement approach,  cognitive behavioral therapy ,  12-step programs , non-contingent reward-based therapies,  psychodynamic therapy , and other combination therapies involving these. [ 153 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5738", "text": "Additionally, research on the  neurobiological effects of physical exercise  suggests that daily aerobic exercise, especially endurance exercise (e.g.,  marathon running ), prevents the development of drug addiction and is an effective  adjunct therapy  (i.e., a supplemental treatment) for amphetamine addiction. [ sources 7 ]  Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions. [ 132 ] [ 134 ] [ 154 ]  In particular,  aerobic exercise  decreases psychostimulant self-administration, reduces the  reinstatement  (i.e., relapse) of drug-seeking, and induces increased  dopamine receptor D 2  (DRD2) density in the  striatum . [ 131 ] [ 154 ]  This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density. [ 131 ]  One review noted that exercise may also prevent the development of a drug addiction by altering \u0394FosB or  c-Fos   immunoreactivity  in the striatum or other parts of the  reward system . [ 133 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5739", "text": "Drug tolerance  develops rapidly in amphetamine abuse (i.e., recreational amphetamine use), so periods of extended abuse require increasingly larger doses of the drug in order to achieve the same effect. [ 155 ] [ 156 ] \nAccording to a Cochrane review on  withdrawal  in individuals who compulsively use amphetamine and methamphetamine, \"when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24\u00a0hours of their last dose.\" [ 157 ]  This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in roughly 88% of cases, and persist for  3\u20134 \u00a0weeks with a marked \"crash\" phase occurring during the first week. [ 157 ]  Amphetamine withdrawal symptoms can include anxiety,  drug craving ,  depressed mood ,  fatigue ,  increased appetite , increased movement or  decreased movement , lack of motivation, sleeplessness or sleepiness, and  lucid dreams . [ 157 ]  The review indicated that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence. [ 157 ]  Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5740", "text": "An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care. [ 158 ] [ 100 ] [ 159 ]  The severity of overdose symptoms increases with dosage and decreases with  drug tolerance  to amphetamine. [ 160 ] [ 100 ]  Tolerant individuals have been known to take as much as 5\u00a0grams of amphetamine in a day, which is roughly 100\u00a0times the maximum daily therapeutic dose. [ 100 ]  Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves convulsions and  coma . [ 99 ] [ 160 ]  In 2013, overdose on amphetamine, methamphetamine, and other compounds implicated in an \" amphetamine use disorder \" resulted in an estimated 3,788\u00a0deaths worldwide ( 3,425\u20134,145 \u00a0deaths,  95%\u00a0confidence ). [ note 12 ] [ 161 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5741", "text": "Amphetamine, the active ingredient of Adderall, works primarily by increasing the activity of the  neurotransmitters   dopamine  and  norepinephrine  in the brain. [ 27 ] [ 50 ]  It also triggers the release of several other hormones (e.g.,  epinephrine ) and neurotransmitters (e.g.,  serotonin  and  histamine ) as well as the synthesis of certain  neuropeptides  (e.g.,  cocaine and amphetamine regulated transcript  (CART) peptides). [ 29 ] [ 187 ]  Both active ingredients of Adderall,  dextroamphetamine  and  levoamphetamine , bind to the same  biological targets , [ 31 ] [ 32 ]  but their  binding affinities  (that is,  potency ) differ somewhat. [ 31 ] [ 32 ]  Dextroamphetamine and levoamphetamine are both potent  full agonists  (activating compounds) of  trace amine-associated receptor\u00a01  (TAAR1) and interact with  vesicular monoamine transporter 2  (VMAT2), with dextroamphetamine being the more potent agonist of TAAR1. [ 32 ]  Consequently, dextroamphetamine produces more  CNS  stimulation than levoamphetamine; [ 32 ] [ 188 ]  however, levoamphetamine has slightly greater cardiovascular and peripheral effects. [ 31 ]  It has been reported that certain children have a better clinical response to levoamphetamine. [ 33 ] [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5742", "text": "In the absence of amphetamine,  VMAT2  will normally move  monoamines  (e.g.,  dopamine ,  histamine ,  serotonin ,  norepinephrine , etc.) from the  intracellular fluid  of a monoamine  neuron  into its  synaptic vesicles , which store neurotransmitters for later release (via  exocytosis ) into the synaptic cleft. [ 29 ]  When amphetamine enters a neuron and interacts with VMAT2, the transporter reverses its direction of transport, thereby releasing stored monoamines inside synaptic vesicles back into the neuron's intracellular fluid. [ 29 ]  Meanwhile, when amphetamine activates  TAAR1 , the receptor causes the neuron's  cell membrane -bound  monoamine transporters  (i.e., the  dopamine transporter ,  norepinephrine transporter , or  serotonin transporter ) to either stop transporting monoamines altogether (via transporter  internalization ) or  transport monoamines out of the neuron ; [ 28 ]  in other words, the reversed membrane transporter will push dopamine, norepinephrine, and serotonin out of the neuron's intracellular fluid and into the  synaptic cleft . [ 28 ]  In summary, by interacting with both VMAT2 and TAAR1, amphetamine releases neurotransmitters from synaptic vesicles (the effect from VMAT2) into the intracellular fluid where they subsequently exit the neuron through the membrane-bound, reversed monoamine transporters (the effect from TAAR1). [ 28 ] [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5743", "text": "The oral  bioavailability  of amphetamine varies with gastrointestinal pH; [ 20 ]  it is well  absorbed  from the gut, and bioavailability is typically 90%. [ 10 ]  Amphetamine is a weak base with a  p K a  of 9.9; [ 189 ]  consequently, when the pH is basic, more of the drug is in its  lipid  soluble  free base  form, and more is absorbed through the lipid-rich  cell membranes  of the gut  epithelium . [ 189 ] [ 20 ]  Conversely, an acidic pH means the drug is predominantly in a water-soluble  cationic  (salt) form, and less is absorbed. [ 189 ]  Approximately  20%  of amphetamine circulating in the bloodstream is bound to  plasma proteins . [ 190 ]  Following absorption, amphetamine readily  distributes  into most tissues in the body, with high concentrations occurring in  cerebrospinal fluid  and  brain  tissue. [ 191 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5744", "text": "The  half-lives  of amphetamine enantiomers differ and vary with urine pH. [ 189 ]  At normal urine pH, the half-lives of dextroamphetamine and levoamphetamine are  9\u201311 \u00a0hours and  11\u201314 \u00a0hours, respectively. [ 189 ]  Highly acidic urine will reduce the enantiomer half-lives to 7\u00a0hours; [ 191 ]  highly alkaline urine will increase the half-lives up to 34\u00a0hours. [ 191 ]  The immediate-release and extended release variants of salts of both isomers reach  peak plasma concentrations  at 3\u00a0hours and 7\u00a0hours post-dose respectively. [ 189 ]  Amphetamine is  eliminated  via the  kidneys , with  30\u201340%  of the drug being excreted unchanged at normal urinary pH. [ 189 ]  When the urinary pH is basic, amphetamine is in its free base form, so less is excreted. [ 189 ]  When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to a high of 75%, depending mostly upon whether urine is too basic or acidic, respectively. [ 189 ]  Following oral administration, amphetamine appears in urine within 3\u00a0hours. [ 191 ]  Roughly 90% of ingested amphetamine is eliminated 3\u00a0days after the last oral dose. [ 191 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5745", "text": "CYP2D6 ,  dopamine \u03b2-hydroxylase  (DBH),  flavin-containing monooxygenase 3  (FMO3),  butyrate-CoA ligase  (XM-ligase), and  glycine  N -acyltransferase  (GLYAT) are the enzymes known to  metabolize  amphetamine or its metabolites in humans. [ sources 11 ]  Amphetamine has a variety of excreted metabolic products, including  4-hydroxyamphetamine ,  4-hydroxynorephedrine ,  4-hydroxyphenylacetone ,  benzoic acid ,  hippuric acid ,  norephedrine , and  phenylacetone . [ 189 ] [ 192 ]  Among these metabolites, the active  sympathomimetics  are  4-hydroxyamphetamine , [ 193 ]   4-hydroxynorephedrine , [ 194 ]  and norephedrine. [ 195 ]  The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation,  N -oxidation,  N -dealkylation, and deamination. [ 189 ] [ 196 ]  The known metabolic pathways, detectable metabolites, and metabolizing enzymes in humans include the following:"}
{"_id": "WikiPedia_Cardio$$$corpus_5746", "text": "The  human metagenome  (i.e., the genetic composition of an individual and all microorganisms that reside on or within the individual's body) varies considerably between individuals. [ 205 ] [ 206 ]  Since the total number of microbial and viral cells in the human body (over 100\u00a0trillion) greatly outnumbers human cells (tens of trillions), [ note 15 ] [ 205 ] [ 207 ]  there is considerable potential for interactions between drugs and an individual's microbiome, including: drugs altering the composition of the  human microbiome ,  drug metabolism  by microbial enzymes modifying the drug's  pharmacokinetic  profile, and microbial drug metabolism affecting a drug's clinical efficacy and  toxicity  profile. [ 205 ] [ 206 ] [ 208 ]  The field that studies these interactions is known as  pharmacomicrobiomics . [ 205 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5747", "text": "Amphetamine has a very similar structure and function to the  endogenous  trace amines, which are naturally occurring  neuromodulator  molecules produced in the human body and brain. [ 28 ] [ 209 ] [ 210 ]  Among this group, the most closely related compounds are  phenethylamine , the parent compound of amphetamine, and  N -methylphenethylamine , a structural  isomer  of amphetamine (i.e., it has an identical molecular formula). [ 28 ] [ 209 ] [ 211 ]  In humans, phenethylamine is produced directly from  L-phenylalanine  by the  aromatic amino acid decarboxylase  (AADC) enzyme, which converts  L-DOPA  into dopamine as well. [ 209 ] [ 211 ]  In turn,  N -methylphenethylamine  is metabolized from phenethylamine by  phenylethanolamine  N -methyltransferase , the same enzyme that metabolizes norepinephrine into epinephrine. [ 209 ] [ 211 ]  Like amphetamine, both phenethylamine and  N -methylphenethylamine  regulate monoamine neurotransmission via  TAAR1 ; [ 28 ] [ 210 ] [ 211 ]  unlike amphetamine, both of these substances are broken down by  monoamine oxidase B , and therefore have a shorter half-life than amphetamine. [ 209 ] [ 211 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5748", "text": "The pharmaceutical company Rexar reformulated their popular weight loss drug  Obetrol  following its mandatory withdrawal from the market in 1973 under the  Kefauver Harris Amendment  to the  Federal Food, Drug, and Cosmetic Act  due to the results of the  Drug Efficacy Study Implementation (DESI)  program (which indicated a lack of efficacy). The new formulation simply replaced the two methamphetamine components with dextroamphetamine and amphetamine components of the same weight (the other two original dextroamphetamine and amphetamine components were preserved), preserved the Obetrol branding, and despite it lacking FDA approval, it still made it onto the market and was marketed and sold by Rexar for many years."}
{"_id": "WikiPedia_Cardio$$$corpus_5749", "text": "In 1994, Richwood Pharmaceuticals acquired Rexar and began promoting Obetrol as a treatment for ADHD (and later narcolepsy as well), now marketed under the new brand name of Adderall, a contraction of the phrase \"A.D.D. for All\" intended to convey that \"it was meant to be kind of an inclusive thing\" for marketing purposes. [ 212 ]  The FDA cited the company for numerous significant CGMP violations related to Obetrol discovered during routine inspections following the acquisition (including issuing a formal warning letter for the violations), then later issued a second formal warning letter to Richwood Pharmaceuticals specifically due to violations of \"the new drug and misbranding provisions of the FD&C Act\". Following extended discussions with Richwood Pharmaceuticals regarding the resolution of a large number of issues related to the company's numerous violations of FDA regulations, the FDA formally approved the first Obetrol labeling/sNDA revisions in 1996, including a name change to Adderall and a restoration of its status as an approved drug product. [ 213 ] [ 214 ]  In 1997 Richwood Pharmaceuticals was acquired by Shire Pharmaceuticals in a $186 million transaction. [ 212 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5750", "text": "Richwood Pharmaceuticals, which later merged with  Shire plc , introduced the current Adderall brand in 1996 as an instant-release tablet. [ 215 ]  In 2006, Shire agreed to sell rights to the Adderall name for the instant-release form of the medication to  Duramed Pharmaceuticals . [ 216 ]  DuraMed Pharmaceuticals was acquired by  Teva Pharmaceuticals  in 2008 during their  acquisition  of  Barr Pharmaceuticals , including Barr's Duramed division. [ 217 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5751", "text": "The first generic version of Adderall IR was introduced to the market in 2002. [ 12 ]  Later on, Barr and Shire reached a settlement agreement permitting Barr to offer a generic form of the extended-release drug beginning in April 2009. [ 12 ] [ 218 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5752", "text": "Chemically, Adderall is a mixture of four amphetamine salts; specifically, it is composed of equal parts (by  mass ) of amphetamine  aspartate monohydrate , amphetamine  sulfate , dextroamphetamine sulfate, and dextroamphetamine  saccharate . [ 69 ]  This drug mixture has slightly stronger  CNS  effects than racemic amphetamine due to the higher proportion of dextroamphetamine. [ 28 ] [ 31 ]  Adderall is produced as both an immediate-release (IR) and extended-release (XR) formulation. [ 12 ] [ 17 ] [ 69 ]  As of December\u00a02013 [update] , ten different companies produced generic Adderall IR, while  Teva Pharmaceutical Industries ,  Actavis , and  Barr Pharmaceuticals  manufactured generic Adderall XR. [ 12 ]  As of 2013 [update] ,  Shire plc , the company that held the original patent for Adderall and Adderall XR, still manufactured brand name Adderall XR, but not Adderall IR. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5753", "text": "Adderall is one of several formulations of pharmaceutical amphetamine, including singular or mixed enantiomers and as an enantiomer prodrug. The table below compares these medications (based on U.S.-approved forms):"}
{"_id": "WikiPedia_Cardio$$$corpus_5754", "text": "In February 2023, news organizations began reporting on shortages of Adderall in the United States that have lasted for over five months. [ 235 ] [ 236 ]  The  Food and Drug Administration  first reported the shortage in October 2022. [ 237 ]  In May 2023, seven months into the shortage, the  Food and Drug Administration  commissioner  Robert Califf  stated that \"a number of generic drugs are in shortage at any given time because there's not enough profit\". He points out that Adderall is a special case because it is a  controlled substance  and the amount available for prescription is controlled by the  Drug Enforcement Administration . He also faults a \"tremendous increase in prescribing\" due to virtual prescribing and general overprescribing and overdiagnosing, adding that \"if only the people that needed these drugs got them, there probably wouldn't be a [stimulant medication] shortage\". [ 238 ] [ 239 ]  The shortage has continued into 2024. [ 240 ] [ 241 ] [ 242 ]  It has led to the creation and expansion of businesses that outsource the search for Adderall. One company charges $50 per U.S. customer to hire workers in the Philippines or another country to make phone calls to all the pharmacies located near the customer and check whether they have any Adderall.  Celebrity endorsements  have contributed to the increased demand for Adderall. [ 243 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5755", "text": "(adenosine may be safe to the fetus in pregnant women)"}
{"_id": "WikiPedia_Cardio$$$corpus_5756", "text": "Adenosine  ( symbol   A ) is an  organic compound  that occurs widely in nature in the form of diverse derivatives. The molecule consists of an  adenine  attached to a  ribose  via a \u03b2-N 9 - glycosidic bond . Adenosine is one of the four  nucleoside  building blocks of  RNA  (and its derivative  deoxyadenosine  is a building block of  DNA ), which are essential for all life on Earth. Its derivatives include the energy carriers  adenosine mono-, di-, and triphosphate , also known as AMP/ADP/ATP.  Cyclic adenosine monophosphate  (cAMP) is pervasive in  signal transduction . Adenosine is used as an intravenous medication for some  cardiac arrhythmias ."}
{"_id": "WikiPedia_Cardio$$$corpus_5757", "text": "Adenosyl  (abbreviated  Ado  or  5'-dAdo ) is the chemical group formed by removal of the 5\u2032-hydroxy (OH) group. It is found in  adenosylcobalamin  (an active form of  vitamin B12 [ 1 ] ) and as a radical in the  radical SAM  enzymes. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5758", "text": "In individuals with  supraventricular tachycardia  (SVT), adenosine is used to help identify and convert the rhythm. [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5759", "text": "Certain SVTs can be successfully terminated with adenosine. [ 6 ]  This includes any  re-entrant arrhythmias  that require the AV node for the re-entry, e.g.,  AV reentrant tachycardia  (AVRT) and  AV nodal reentrant tachycardia  (AVNRT). In addition,  atrial tachycardia  can sometimes be terminated with adenosine. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5760", "text": "Fast rhythms of the heart that are confined to the  atria  (e.g.,  atrial fibrillation  and  atrial flutter ) or  ventricles  (e.g.,  monomorphic ventricular tachycardia ), and do not involve the AV node as part of the re-entrant circuit, are not typically converted by adenosine. However, the ventricular response rate is temporarily slowed with adenosine in such cases. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5761", "text": "Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V  antiarrhythmic agent . When adenosine is used to  cardiovert  an abnormal rhythm, it is normal for the heart to enter ventricular  asystole  for a few seconds. This can be disconcerting to a normally conscious patient, and is associated with angina-like sensations in the chest. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5762", "text": "Adenosine is used as an adjunct to  thallium  (TI 201) or  technetium (Tc99m)   myocardial perfusion scintigraphy  (nuclear stress test) in patients unable to undergo adequate stress testing with exercise. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5763", "text": "When given for the evaluation or treatment of a  supraventricular tachycardia  (SVT), the initial dose is 6\u00a0mg to 12\u00a0mg, depending on standing orders or provider preference, [ 10 ]  given as a rapid  parenteral infusion . Due to adenosine's extremely short half-life, the IV line is started as proximal (near) to the heart as possible, such as the  antecubital fossa . The IV push is often followed with a flush of 10\u201320 mL of normal saline. If this has no effect (i.e., no evidence of transient AV block), a dose of 12\u00a0mg can be given 1\u20132 minutes after the first dose. When given to dilate the arteries, such as in a \"stress test\", the dosage is typically 0.14\u00a0mg/kg/min, administered for 4 or 6 minutes, depending on the protocol."}
{"_id": "WikiPedia_Cardio$$$corpus_5764", "text": "The recommended dose may be increased in patients on theophylline since methylxanthines prevent binding of adenosine at receptor sites. The dose is often decreased in patients on  dipyridamole  (Persantine) and  diazepam  (Valium) because adenosine potentiates the effects of these drugs. The recommended dose is also reduced by half in patients presenting  congestive heart failure ,  myocardial infarction ,  shock ,  hypoxia , and/or chronic liver disease or  chronic kidney disease , and in  elderly  patients."}
{"_id": "WikiPedia_Cardio$$$corpus_5765", "text": "Dipyridamole  potentiates the action of adenosine, requiring the use of lower doses."}
{"_id": "WikiPedia_Cardio$$$corpus_5766", "text": "Methylxanthines  (e.g.  caffeine  found in coffee,  theophylline  found in tea, or  theobromine  found in chocolate) have a  purine  structure and bind to some of the same receptors as adenosine. [ 12 ]  Methylxanthines act as competitive antagonists of adenosine and can blunt its pharmacological effects. [ 13 ]  Individuals taking large quantities of methylxanthines may require increased doses of adenosine."}
{"_id": "WikiPedia_Cardio$$$corpus_5767", "text": "Caffeine  acts by blocking binding of adenosine to the  adenosine A 1  receptor , which enhances release of the neurotransmitter  acetylcholine . [ 14 ]  Caffeine also increases cyclic AMP levels through nonselective inhibition of phosphodiesterase. [ 15 ]  \"Caffeine has a three-dimensional structure similar to that of adenosine,\" which allows it to bind and block its receptors. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5768", "text": "Common  contraindications  for adenosine include"}
{"_id": "WikiPedia_Cardio$$$corpus_5769", "text": "Adenosine is an endogenous purine nucleoside that modulates many physiological processes. Cellular signaling by adenosine occurs through four known adenosine receptor subtypes ( A 1 ,  A 2A ,  A 2B , and  A 3 ). [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5770", "text": "Extracellular adenosine concentrations from normal cells are approximately 300 nM; however, in response to cellular damage (e.g., in inflammatory or  ischemic  tissue), these concentrations are quickly elevated (600\u20131,200 nM). Thus, in regard to stress or injury, the function of adenosine is primarily that of cytoprotection preventing tissue damage during instances of  hypoxia ,  ischemia , and seizure activity. Activation of A 2A  receptors produces a constellation of responses that in general can be classified as anti-inflammatory. [ 19 ]  Enzymatic production of adenosine can be anti- inflammatory  or  immunosuppressive . [ 20 ] [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5771", "text": "All adenosine receptor subtypes (A 1 , A 2A , A 2B , and A 3 ) are  G-protein-coupled receptors . The four receptor subtypes are further classified based on their ability to either stimulate or inhibit  adenylate cyclase  activity. The A 1  receptors couple to G i/o  and decrease cAMP levels, while the A 2  adenosine receptors couple to G s , which stimulates adenylate cyclase activity. In addition, A 1  receptors couple to G o , which has been reported to mediate adenosine inhibition of Ca 2+  conductance, whereas A 2B  and A 3  receptors also couple to G q  and stimulate  phospholipase  activity.\nResearchers at Cornell University have recently shown adenosine receptors to be key in opening the blood-brain barrier (BBB).\nMice dosed with adenosine have shown increased transport across the BBB of amyloid plaque antibodies and prodrugs associated with Parkinson's disease, Alzheimer's, multiple sclerosis, and cancers of the central nervous system. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5772", "text": "Adenosine is an  endogenous   agonist  of the  ghrelin/growth hormone secretagogue receptor . [ 24 ]  However, while it is able to increase  appetite , unlike other agonists of this receptor, adenosine is unable to induce the secretion of  growth hormone  and increase its plasma levels. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5773", "text": "When it is administered intravenously, adenosine causes transient  heart block  in the  atrioventricular (AV) node . This is mediated via the  A 1  receptor , inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing K +  efflux via  inward rectifier K +  channels , subsequently inhibiting Ca 2+  current. [ 25 ] [ 26 ]  It also causes endothelial-dependent relaxation of smooth muscle as is found inside the artery walls. This causes dilation of the \"normal\" segments of arteries, i.e. where the  endothelium  is not separated from the tunica media by  atherosclerotic plaque . This feature allows physicians to use adenosine to test for blockages in the coronary arteries, by exaggerating the difference between the normal and abnormal segments."}
{"_id": "WikiPedia_Cardio$$$corpus_5774", "text": "The administration of adenosine also reduces blood flow to coronary arteries past the occlusion. Other coronary arteries dilate when adenosine is administered while the segment past the occlusion is already maximally dilated, which is a process called  coronary steal . This leads to less blood reaching the ischemic tissue, which in turn produces the characteristic chest pain."}
{"_id": "WikiPedia_Cardio$$$corpus_5775", "text": "Adenosine used as a  second messenger  can be the result of  de novo   purine biosynthesis  via  adenosine monophosphate  (AMP), though it is possible other pathways exist. [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5776", "text": "When adenosine enters the circulation, it is broken down by  adenosine deaminase , which is present in  red blood cells  and the vessel wall."}
{"_id": "WikiPedia_Cardio$$$corpus_5777", "text": "Dipyridamole , an inhibitor of  adenosine nucleoside transporter , allows adenosine to accumulate in the blood stream. This causes an increase in coronary  vasodilatation ."}
{"_id": "WikiPedia_Cardio$$$corpus_5778", "text": "Adenosine deaminase deficiency  is a known cause of immunodeficiency."}
{"_id": "WikiPedia_Cardio$$$corpus_5779", "text": "The adenosine analog  NITD008  has been reported to directly inhibit the recombinant RNA-dependent  RNA polymerase  of the  dengue virus  by terminating its RNA chain synthesis. This interaction suppresses peak  viremia  and rise in  cytokines  and prevents lethality in infected animals, raising the possibility of a new treatment for this  flavivirus . [ 28 ]  The 7-deaza-adenosine analog has been shown to inhibit the replication of the  hepatitis C virus . [ 29 ]   BCX4430  is protective against  Ebola  and  Marburg  viruses. [ 30 ]  Such adenosine analogs are potentially clinically useful since they can be taken orally."}
{"_id": "WikiPedia_Cardio$$$corpus_5780", "text": "Adenosine is believed to be an  anti-inflammatory  agent at the A 2A  receptor. [ 31 ] [ 32 ]  Topical treatment of adenosine to foot wounds in  diabetes mellitus  has been shown in lab animals to drastically increase tissue repair and reconstruction. Topical administration of adenosine for use in wound-healing deficiencies and diabetes mellitus in humans is currently under clinical investigation."}
{"_id": "WikiPedia_Cardio$$$corpus_5781", "text": "Methotrexate 's anti-inflammatory effect may be due to its stimulation of adenosine release. [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5782", "text": "In general, adenosine has an inhibitory effect in the  central nervous system  (CNS).\n Caffeine 's stimulatory effects are credited primarily (although not entirely) to its capacity to block adenosine receptors, thereby reducing the inhibitory tonus of adenosine in the CNS. This reduction in adenosine activity leads to increased activity of the  neurotransmitters   dopamine  and  glutamate . [ 34 ]  Experimental evidence suggests that adenosine and adenosine agonists can activate  Trk receptor  phosphorylation through a mechanism that requires the adenosine A 2A  receptor. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5783", "text": "Adenosine has been shown to promote thickening of hair on people with thinning hair. [ 36 ] [ 37 ]   A 2013 study compared topical adenosine with  minoxidil  in male  androgenetic alopecia , finding it was as potent as minoxidil (in overall treatment outcomes) but with higher satisfaction rate with patients due to \u201cfaster prevention of hair loss and appearance of the newly grown hairs\u201d (further trials were called for to clarify the findings). [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5784", "text": "Adenosine is a key factor in regulating the body's  sleep-wake cycle . [ 39 ]  Adenosine levels rise during periods of wakefulness and lowers during sleep. Higher adenosine levels correlate with a stronger feeling of  sleepiness , also known as sleep drive or sleep pressure. [ 40 ]   Cognitive behavioral therapy for insomnia  (CBT-I), which is considered one of the most effective treatments for  insomnia , utilizes short-term  sleep deprivation  to raise and regulate adenosine levels in the body, for the intended promotion of consistent and sustained sleep in the long term. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5785", "text": "A principal component of  cannabis   delta-9-tetrahydrocannabinol  (THC) and the  endocannabinoid   anandamide  (AEA) induces  sleep  in  rats  by increasing adenosine levels in the  basal forebrain . These components also significantly increase  slow-wave sleep  during the  sleep cycle , mediated by  CB1 receptor   activation . These findings identify a potential  therapeutic use  of  cannabinoids  to induce sleep in conditions where sleep may be severely attenuated. [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5786", "text": "It also plays a role in regulation of blood flow to various organs through  vasodilation . [ 43 ] [ 44 ] [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5787", "text": "Alifedrine  ( INN Tooltip International Nonproprietary Name ; developmental code name  D-13625 ) is a drug described as a  sympathomimetic  and  cardiotonic  or  positive inotropic agent  which was never marketed. [ 3 ] [ 4 ] [ 5 ] [ 6 ]  It is a  \u03b2-adrenergic receptor   partial agonist  and was studied in the treatment of  heart failure . [ 4 ] [ 1 ] [ 2 ] [ 7 ]  The drug is taken  by mouth  or  intravenously . [ 1 ] [ 2 ]  It is a \u03b2- hydroxylated   substituted amphetamine   derivative . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5788", "text": "This  drug  article relating to the  cardiovascular system  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_5789", "text": "Amphetamine [ note 2 ]  (contracted from  a lpha - m ethyl ph en et hyl amine ) is a  central nervous system  (CNS)  stimulant  that is used in the treatment of  attention deficit hyperactivity disorder  (ADHD),  narcolepsy , and  obesity ; it is also used to treat  binge eating disorder  in the form of its inactive  prodrug   lisdexamfetamine . Amphetamine was discovered as a chemical in 1887 by  Laz\u0103r Edeleanu , and then as a drug in the late 1920s. It exists as two  enantiomers : [ note 3 ]   levoamphetamine  and  dextroamphetamine .  Amphetamine  properly refers to a specific chemical, the  racemic   free base , which is equal parts of the two enantiomers in their pure  amine  forms. The term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an  athletic performance enhancer  and  cognitive enhancer , and recreationally as an  aphrodisiac  and  euphoriant . It is a  prescription drug  in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with recreational use. [ sources 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5790", "text": "The first amphetamine pharmaceutical was  Benzedrine , a brand which was used to treat a variety of conditions.  Pharmaceutical amphetamine  is prescribed as racemic amphetamine,  Adderall , [ note 4 ]   dextroamphetamine , or the inactive  prodrug   lisdexamfetamine . Amphetamine increases  monoamine  and  excitatory   neurotransmission  in the brain, with its most pronounced effects targeting the  norepinephrine  and  dopamine   neurotransmitter systems . [ sources 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5791", "text": "At therapeutic doses, amphetamine causes emotional and cognitive effects such as  euphoria , change in  desire for sex , increased  wakefulness , and improved  cognitive control . It induces physical effects such as improved reaction time, fatigue resistance,  decreased appetite , elevated heart rate, and increased muscle strength. Larger doses of amphetamine may impair cognitive function and induce  rapid muscle breakdown .  Addiction  is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses. Very high doses can result in  psychosis  (e.g.,  hallucinations ,  delusions  and  paranoia ) which rarely occurs at therapeutic doses even during long-term use. Recreational doses are generally much larger than prescribed therapeutic doses and carry a far greater risk of serious side effects. [ sources 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5792", "text": "Amphetamine belongs to the  phenethylamine class . It is also the parent compound of its own structural class, the  substituted amphetamines , [ note 5 ]  which includes prominent substances such as  bupropion ,  cathinone ,  MDMA , and  methamphetamine . As a member of the phenethylamine class, amphetamine is also chemically related to the naturally occurring  trace amine  neuromodulators, specifically  phenethylamine  and  N -methylphenethylamine , both of which are produced within the human body. Phenethylamine is the parent compound of amphetamine, while  N -methylphenethylamine  is a  positional isomer  of amphetamine that differs only in the placement of the  methyl group . [ sources 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5793", "text": "Amphetamine is used to treat  attention deficit hyperactivity disorder  (ADHD),  narcolepsy ,  obesity , and, in the form of  lisdexamfetamine ,  binge eating disorder . [ 1 ] [ 36 ] [ 37 ]  It is sometimes prescribed  off-label  for its past  medical indications , particularly for  depression  and  chronic pain . [ 1 ] [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5794", "text": "Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal  dopamine system  development or nerve damage, [ 53 ] [ 54 ]  but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth. [ 55 ] [ 56 ] [ 57 ]  Reviews of  magnetic resonance imaging  (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right  caudate nucleus  of the  basal ganglia . [ 55 ] [ 56 ] [ 57 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5795", "text": "Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD. [ 45 ] [ 58 ] [ 59 ]   Randomized controlled trials  of continuous stimulant therapy for the treatment of ADHD spanning 2\u00a0years have demonstrated treatment effectiveness and safety. [ 45 ] [ 58 ]  Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing  quality of life  and academic achievement, and producing improvements in a large number of functional outcomes [ note 6 ]  across 9\u00a0categories of outcomes related to academics,  antisocial behavior , driving, non-medicinal drug use, obesity, occupation,  self-esteem , service use (i.e., academic, occupational, health, financial, and legal services), and social function. [ 45 ] [ 59 ]  Additionally, a 2024  meta-analytic   systematic review  reported moderate improvements in quality of life when amphetamine treatment is used for ADHD. [ 61 ]  One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5\u00a0 IQ  points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity. [ 58 ]  Another review indicated that, based upon the longest  follow-up studies  conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a  substance use disorder  as an adult. [ 45 ]  A 2025 meta-analytic systematic review of 113 randomized controlled trials demonstrated that stimulant medications significantly improved core ADHD symptoms in adults over a three-month period, with good acceptability compared to other pharmacological and non-pharmacological treatments. [ 62 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5796", "text": "Models of ADHD suggest that it is associated with functional impairments in some of the brain's  neurotransmitter systems ; [ 63 ]  these functional impairments involve impaired  dopamine  neurotransmission in the  mesocorticolimbic projection  and  norepinephrine  neurotransmission in the noradrenergic projections from the  locus coeruleus  to the  prefrontal cortex . [ 63 ]  Stimulants like  methylphenidate  and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. [ 27 ] [ 63 ] [ 64 ]  Approximately 80% of those who use these stimulants see improvements in ADHD symptoms. [ 65 ]  Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans. [ 66 ] [ 67 ]  The  Cochrane  reviews [ note 7 ]  on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse  side effects . [ 69 ] [ 70 ]  A Cochrane review on the treatment of ADHD in children with  tic disorders  such as  Tourette syndrome  indicated that stimulants in general do not make  tics  worse, but high doses of dextroamphetamine could exacerbate tics in some individuals. [ 71 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5797", "text": "Binge eating disorder  (BED) is characterized by recurrent and persistent episodes of compulsive binge eating. [ 72 ]  These episodes are often accompanied by marked distress and a feeling of loss of control over eating. [ 72 ]  The  pathophysiology  of BED is not fully understood, but it is believed to involve dysfunctional dopaminergic reward circuitry along the  cortico-striatal-thalamic-cortical loop . [ 73 ] [ 74 ]  As of July 2024, lisdexamfetamine is the only  USFDA - and  TGA -approved  pharmacotherapy  for BED. [ 37 ] [ 75 ]  Evidence suggests that lisdexamfetamine's treatment efficacy in BED is underpinned at least in part by a  psychopathological  overlap between BED and ADHD, with the latter conceptualized as a  cognitive control  disorder that also benefits from treatment with lisdexamfetamine. [ 73 ] [ 74 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5798", "text": "Lisdexamfetamine's therapeutic effects for BED primarily involve direct action in the  central nervous system  after conversion to its pharmacologically active metabolite, dextroamphetamine. [ 75 ]  Centrally, dextroamphetamine increases neurotransmitter activity of dopamine and norepinephrine in prefrontal cortical regions that regulate cognitive control of behavior. [ 73 ] [ 75 ]  Similar to its therapeutic effect in ADHD, dextroamphetamine enhances cognitive control and may reduce impulsivity in patients with BED by enhancing the cognitive processes responsible for overriding  prepotent feeding responses  that precede binge eating episodes. [ 73 ] [ 77 ] [ 78 ]  In addition, dextroamphetamine's actions outside of the central nervous system may also contribute to its treatment effects in BED. Peripherally, dextroamphetamine triggers  lipolysis  through noradrenergic signaling in  adipose fat  cells, leading to the release of  triglycerides  into blood plasma to be utilized as a fuel substrate. [ 74 ] [ 79 ]  Dextroamphetamine also activates  TAAR1  in peripheral organs along the  gastrointestinal tract  that are involved in the regulation of food intake and body weight. [ 76 ]  Together, these actions confer an  anorexigenic  effect that promotes  satiety  in response to feeding and may decrease binge eating as a secondary effect. [ 78 ] [ 76 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5799", "text": "Medical reviews of randomized controlled trials have demonstrated that lisdexamfetamine, at doses between 50\u201370\u00a0mg, is safe and effective for the treatment of moderate-to-severe BED in adults. [ sources 5 ]  These reviews suggest that lisdexamfetamine is persistently effective at treating BED and is associated with significant reductions in the number of binge eating days and binge eating episodes per week. [ sources 5 ]  Furthermore, a meta-analytic systematic review highlighted an open-label, 12-month extension safety and tolerability study that reported lisdexamfetamine remained effective at reducing the number of binge eating days for the duration of the study. [ 78 ]  In addition, both a review and a meta-analytic systematic review found lisdexamfetamine to be superior to placebo in several secondary outcome measures, including persistent binge eating cessation, reduction of obsessive-compulsive related binge eating symptoms, reduction of body-weight, and reduction of triglycerides. [ 74 ] [ 78 ]  Lisdexamfetamine, like all pharmaceutical amphetamines, has direct appetite suppressant effects that may be therapeutically useful in both BED and its comorbidities. [ 37 ] [ 78 ]  Based on reviews of  neuroimaging  studies involving BED-diagnosed participants, therapeautic  neuroplasticity  in  dopaminergic and noradrenergic pathways  from long-term use of lisdexamfetamine may be implicated in lasting improvements in the regulation of eating behaviors that are observed even after the drug is discontinued. [ 37 ] [ 75 ] [ 78 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5800", "text": "Narcolepsy is a chronic sleep-wake disorder that is associated with excessive daytime sleepiness,  cataplexy , and  sleep paralysis . [ 81 ]  Patients with narcolepsy are diagnosed as either type 1 or type 2, with only the former presenting cataplexy symptoms. [ 82 ]  Type 1 narcolepsy results from the loss of approximately 70,000  orexin -releasing neurons in the  lateral hypothalamus , leading to significantly reduced  cerebrospinal  orexin levels; [ 18 ] [ 83 ]  this reduction is a  diagnostic biomarker  for type 1 narcolepsy. [ 82 ]  Lateral hypothalamic orexin neurons innervate every component of the  ascending reticular activating system  (ARAS), which includes  noradrenergic ,  dopaminergic ,  histaminergic , and  serotonergic  nuclei that promote  wakefulness . [ 83 ] [ 84 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5801", "text": "Amphetamine\u2019s therapeutic mode of action in narcolepsy primarily involves increasing  monoamine  neurotransmitter activity in the ARAS. [ 18 ] [ 85 ] [ 86 ]  This includes noradrenergic neurons in the  locus coeruleus , dopaminergic neurons in the  ventral tegmental area , histaminergic neurons in the  tuberomammillary nucleus , and serotonergic neurons in the  dorsal raphe nucleus . [ 84 ] [ 86 ]  Dextroamphetamine, the more dopaminergic enantiomer of amphetamine, is particularly effective at promoting wakefulness because dopamine release has the greatest influence on cortical activation and cognitive arousal, relative to other monoamines. [ 18 ]  In contrast, levoamphetamine may have a greater effect on cataplexy, a symptom more sensitive to the effects of norepinephrine and serotonin. [ 18 ]  Noradrenergic and serotonergic nuclei in the ARAS are involved in the regulation of the  REM  sleep cycle and function as \"REM-off\" cells, with amphetamine's effect on norepinephrine and serotonin contributing to the suppression of REM sleep and a possible reduction of cataplexy at high doses. [ 18 ] [ 82 ] [ 84 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5802", "text": "The  American Academy of Sleep Medicine  (AASM) 2021  clinical practice guideline  conditionally recommends dextroamphetamine for the treatment of both type 1 and type 2 narcolepsy. [ 87 ]  Treatment with pharmaceutical amphetamines is generally less preferred relative to other stimulants (e.g.,  modafinil ) and is considered a  third-line treatment  option. [ 48 ] [ 88 ] [ 89 ]  Medical reviews indicate that amphetamine is safe and effective for the treatment of narcolepsy. [ 18 ] [ 48 ] [ 87 ]  Amphetamine appears to be most effective at improving symptoms associated with  hypersomnolence , with three reviews finding clinically significant reductions in  daytime sleepiness  in patients with narcolepsy. [ 18 ] [ 48 ] [ 87 ]  Additionally, these reviews suggest that amphetamine may dose-dependently improve cataplexy symptoms. [ 18 ] [ 48 ] [ 87 ]  However, the quality of evidence for these findings is low and is consequently reflected in the AASM's conditional recommendation for dextroamphetamine as a treatment option for narcolepsy. [ 87 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5803", "text": "In 2015, a  systematic review  and a  meta-analysis  of high quality  clinical trials  found that, when used at low (therapeutic) doses, amphetamine produces modest yet unambiguous improvements in cognition, including  working memory , long-term  episodic memory ,  inhibitory control , and some aspects of  attention , in normal healthy adults; [ 90 ] [ 91 ]  these cognition-enhancing effects of amphetamine are known to be partially mediated through the  indirect activation  of both  dopamine D 1  receptor  and  \u03b1 2 -adrenergic receptor  in the  prefrontal cortex . [ 27 ] [ 90 ]  A systematic review from 2014 found that low doses of amphetamine also improve  memory consolidation , in turn leading to improved  recall of information . [ 92 ]  Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals. [ 27 ] [ 93 ]  Amphetamine and other ADHD stimulants also improve  task saliency  (motivation to perform a task) and increase  arousal  (wakefulness), in turn promoting goal-directed behavior. [ 27 ] [ 94 ] [ 95 ]  Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid. [ 27 ] [ 95 ] [ 96 ]  Based upon studies of self-reported illicit stimulant use,  5\u201335%  of college students use  diverted  ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs. [ 97 ] [ 98 ] [ 99 ]  However, high amphetamine doses that are above the therapeutic range can interfere with working memory and other aspects of cognitive control. [ 27 ] [ 95 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5804", "text": "Amphetamine is used by some athletes for its psychological and  athletic performance-enhancing effects , such as increased endurance and alertness; [ 28 ] [ 41 ]  however, non-medical amphetamine use is prohibited at sporting events that are regulated by collegiate, national, and international anti-doping agencies. [ 100 ] [ 101 ]  In healthy people at oral therapeutic doses, amphetamine has been shown to increase  muscle strength , acceleration, athletic performance in  anaerobic conditions , and  endurance  (i.e., it delays the onset of  fatigue ), while improving  reaction time . [ 28 ] [ 102 ] [ 103 ]  Amphetamine improves endurance and reaction time primarily through  reuptake inhibition  and  release  of dopamine in the central nervous system. [ 102 ] [ 103 ] [ 104 ]  Amphetamine and other dopaminergic drugs also increase power output at fixed  levels of perceived exertion  by overriding a \"safety switch\", allowing the  core temperature limit  to increase in order to access a reserve capacity that is normally off-limits. [ 103 ] [ 105 ] [ 106 ]  At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; [ 28 ] [ 102 ]  however, at much higher doses, amphetamine can induce effects that severely impair performance, such as  rapid muscle breakdown  and  elevated body temperature . [ 29 ] [ 102 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5805", "text": "Amphetamine, specifically the more dopaminergic  dextrorotatory  enantiomer ( dextroamphetamine ), is also used recreationally as a euphoriant and aphrodisiac, and like other  amphetamines ; is used as a  club drug  for its energetic and euphoric high. Dextroamphetamine (d-amphetamine) is considered to have a high potential for misuse in a  recreational manner  since individuals typically report feeling  euphoric , more alert, and more energetic after taking the drug. [ 107 ] [ 108 ] [ 109 ]  A notable part of the 1960s  mod subculture  in the UK was recreational amphetamine use, which was used to fuel all-night dances at clubs like Manchester's  Twisted Wheel . Newspaper reports described dancers emerging from clubs at 5 a.m. with dilated pupils. [ 110 ]  Mods used the drug for  stimulation  and  alertness , which they viewed as different from the  intoxication  caused by alcohol and other drugs. [ 110 ]  Dr. Andrew Wilson argues that for a significant minority, \"amphetamines symbolised the smart, on-the-ball, cool image\" and that they sought \"stimulation not intoxication [...] greater awareness, not escape\" and \" confidence  and articulacy\" rather than the \" drunken  rowdiness of previous generations.\" [ 110 ]  Dextroamphetamine's  dopaminergic  (rewarding) properties affect the  mesocorticolimbic circuit ; a group of neural structures responsible for  incentive salience  (i.e., \"wanting\"; desire or craving for a reward and motivation),  positive reinforcement  and  positively-valenced  emotions, particularly ones involving  pleasure . [ 111 ]  Large recreational doses of dextroamphetamine may produce  symptoms of dextroamphetamine overdose . [ 109 ]  Recreational users sometimes open dexedrine capsules and crush the contents in order to insufflate (snort) it or subsequently dissolve it in water and inject it. [ 109 ]  Immediate-release formulations have higher potential for abuse via insufflation (snorting) or intravenous injection due to a more favorable pharmacokinetic profile and easy crushability (especially tablets). [ 112 ] [ 113 ]  Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels. [ 109 ]  Chronic overuse of dextroamphetamine can lead to severe  drug dependence , resulting in withdrawal symptoms when drug use stops. [ 109 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5806", "text": "According to the  International Programme on Chemical Safety  (IPCS) and the U.S.  Food and Drug Administration  (FDA), [ note 8 ]  amphetamine is  contraindicated  in people with a history of  drug abuse , [ note 9 ]   cardiovascular disease , severe  agitation , or severe anxiety. [ 36 ] [ 29 ] [ 115 ]  It is also contraindicated in individuals with advanced  arteriosclerosis  (hardening of the arteries),  glaucoma  (increased eye pressure),  hyperthyroidism  (excessive production of thyroid hormone), or moderate to severe  hypertension . [ 36 ] [ 29 ] [ 115 ]  These agencies indicate that people who have experienced  allergic reactions  to other stimulants or who are taking  monoamine oxidase inhibitors  (MAOIs) should not take amphetamine, [ 36 ] [ 29 ] [ 115 ]  although safe concurrent use of amphetamine and monoamine oxidase inhibitors has been documented. [ 116 ] [ 117 ]  These agencies also state that anyone with  anorexia nervosa ,  bipolar disorder , depression, hypertension, liver or kidney problems,  mania ,  psychosis ,  Raynaud's phenomenon ,  seizures ,  thyroid  problems,  tics , or  Tourette syndrome  should monitor their symptoms while taking amphetamine. [ 29 ] [ 115 ]  Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in the fetus or newborns (i.e., it is not a human  teratogen ), but amphetamine abuse does pose risks to the fetus. [ 115 ]  Amphetamine has also been shown to pass into breast milk, so the IPCS and the FDA advise mothers to avoid breastfeeding when using it. [ 29 ] [ 115 ]  Due to the potential for reversible growth impairments, [ note 10 ]  the FDA advises monitoring the height and weight of children and adolescents prescribed an amphetamine pharmaceutical. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5807", "text": "The  adverse side effects  of amphetamine are many and varied, and the amount of amphetamine used is the primary factor in determining the likelihood and severity of adverse effects. [ 29 ] [ 41 ]  Amphetamine products such as  Adderall , Dexedrine, and their generic equivalents are currently approved by the U.S. FDA for long-term therapeutic use. [ 38 ] [ 29 ]   Recreational use  of amphetamine generally involves much larger doses, which have a greater risk of serious adverse drug effects than dosages used for therapeutic purposes. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5808", "text": "Cardiovascular  side effects can include  hypertension  or  hypotension  from a  vasovagal response ,  Raynaud's phenomenon  (reduced blood flow to the hands and feet), and  tachycardia  (increased heart rate). [ 29 ] [ 41 ] [ 118 ]  Sexual side effects in males may include  erectile dysfunction , frequent erections, or  prolonged erections . [ 29 ]  Gastrointestinal side effects may include  abdominal pain ,  constipation ,  diarrhea , and  nausea . [ 1 ] [ 29 ] [ 119 ]  Other potential physical side effects include  appetite loss ,  blurred vision ,  dry mouth ,  excessive grinding of the teeth , nosebleed, profuse sweating,  rhinitis medicamentosa  (drug-induced nasal congestion), reduced  seizure threshold ,  tics  (a type of movement disorder), and  weight loss . [ sources 6 ]  Dangerous physical side effects are rare at typical pharmaceutical doses. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5809", "text": "Amphetamine stimulates the  medullary respiratory centers , producing faster and deeper breaths. [ 41 ]  In a normal person at therapeutic doses, this effect is usually not noticeable, but when respiration is already compromised, it may be evident. [ 41 ]  Amphetamine also induces  contraction  in the urinary  bladder sphincter , the muscle which controls urination, which can result in difficulty urinating. [ 41 ]  This effect can be useful in treating  bed wetting  and  loss of bladder control . [ 41 ]  The effects of amphetamine on the gastrointestinal tract are unpredictable. [ 41 ]  If intestinal activity is high, amphetamine may reduce  gastrointestinal motility  (the rate at which content moves through the digestive system); [ 41 ]  however, amphetamine may increase motility when the  smooth muscle  of the tract is relaxed. [ 41 ]  Amphetamine also has a slight  analgesic  effect and can enhance the pain relieving effects of  opioids . [ 1 ] [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5810", "text": "FDA-commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events ( sudden death ,  heart attack , and  stroke ) and the medical use of amphetamine or other ADHD stimulants. [ sources 7 ]  However, amphetamine pharmaceuticals are  contraindicated  in individuals with  cardiovascular disease . [ sources 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5811", "text": "At normal therapeutic doses, the most common psychological side effects of amphetamine include increased  alertness , apprehension,  concentration , initiative,  self-confidence  and sociability, mood swings ( elated mood  followed by mildly  depressed mood ),  insomnia  or  wakefulness , and decreased sense of fatigue. [ 29 ] [ 41 ]  Less common side effects include  anxiety , change in  libido ,  grandiosity ,  irritability , repetitive or  obsessive  behaviors, and restlessness; [ sources 9 ]  these effects depend on the user's personality and current mental state. [ 41 ]   Amphetamine psychosis  (e.g.,  delusions  and  paranoia ) can occur in heavy users. [ 29 ] [ 42 ] [ 43 ]  Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy. [ 29 ] [ 43 ] [ 44 ]  According to the FDA, \"there is no systematic evidence\" that stimulants produce aggressive behavior or hostility. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5812", "text": "Amphetamine has also been shown to produce a  conditioned place preference  in humans taking therapeutic doses, [ 69 ] [ 126 ]  meaning that individuals acquire a preference for spending time in places where they have previously used amphetamine. [ 126 ] [ 127 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5813", "text": "Addiction  is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses; [ 46 ] [ 47 ] [ 48 ]  in fact, lifetime stimulant therapy for ADHD that begins during childhood reduces the risk of developing  substance use disorders  as an adult. [ 45 ]   Pathological overactivation of the  mesolimbic pathway , a  dopamine pathway  that connects the  ventral tegmental area  to the  nucleus accumbens , plays a central role in amphetamine addiction. [ 136 ] [ 137 ]  Individuals who frequently  self-administer  high doses of amphetamine have a high risk of developing an amphetamine addiction, since chronic use at high doses gradually increases the level of  accumbal   \u0394FosB , a \"molecular switch\" and \"master control protein\" for addiction. [ 128 ] [ 138 ] [ 139 ]  Once nucleus accumbens \u0394FosB is sufficiently overexpressed, it begins to increase the severity of addictive behavior (i.e., compulsive drug-seeking) with further increases in its expression. [ 138 ] [ 140 ]  While there are currently no effective drugs for treating amphetamine addiction, regularly engaging in sustained aerobic exercise appears to reduce the risk of developing such an addiction. [ 141 ] [ 142 ]  Exercise therapy improves  clinical  treatment outcomes and may be used as an  adjunct therapy  with behavioral therapies for addiction. [ 141 ] [ 143 ] [ sources 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5814", "text": "Chronic use of amphetamine at excessive doses causes alterations in  gene expression  in the  mesocorticolimbic projection , which arise through  transcriptional  and  epigenetic  mechanisms. [ 139 ] [ 144 ] [ 145 ]  The most important  transcription factors [ note 11 ]  that produce these alterations are  Delta FBJ murine osteosarcoma viral oncogene homolog B  ( \u0394FosB ),  cAMP  response element binding protein  ( CREB ), and  nuclear factor-kappa B  ( NF-\u03baB ). [ 139 ]  \u0394FosB is the most significant biomolecular mechanism in addiction because \u0394FosB  overexpression  (i.e., an abnormally high level of gene expression which produces a pronounced gene-related  phenotype ) in the  D1-type   medium spiny neurons  in the  nucleus accumbens  is  necessary and sufficient [ note 12 ]  for many of the neural adaptations and regulates multiple behavioral effects (e.g.,  reward sensitization  and escalating drug  self-administration ) involved in addiction. [ 128 ] [ 138 ] [ 139 ]  Once \u0394FosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in \u0394FosB expression. [ 128 ] [ 138 ]  It has been implicated in addictions to  alcohol ,  cannabinoids ,  cocaine ,  methylphenidate ,  nicotine ,  opioids ,  phencyclidine ,  propofol , and  substituted amphetamines , among others. [ sources 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5815", "text": "\u0394JunD , a transcription factor, and  G9a , a  histone methyltransferase  enzyme, both oppose the function of \u0394FosB and inhibit increases in its expression. [ 128 ] [ 139 ] [ 149 ]  Sufficiently overexpressing \u0394JunD in the nucleus accumbens with  viral vectors  can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by \u0394FosB). [ 139 ]  Similarly, accumbal G9a hyperexpression results in markedly increased  histone  3  lysine   residue  9  dimethylation  ( H3K9me2 ) and blocks the induction of \u0394FosB-mediated  neural  and  behavioral plasticity  by chronic drug use, [ sources 12 ]  which occurs via  H3K9me2 -mediated  repression  of  transcription factors  for \u0394FosB and H3K9me2-mediated repression of various \u0394FosB transcriptional targets (e.g.,  CDK5 ). [ 139 ] [ 149 ] [ 150 ]  \u0394FosB also plays an important role in regulating behavioral responses to  natural rewards , such as palatable food, sex, and exercise. [ 140 ] [ 139 ] [ 153 ]  Since both natural rewards and addictive drugs  induce the expression  of \u0394FosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction. [ 140 ] [ 139 ]  Consequently, \u0394FosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced  sexual addictions , which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use. [ 140 ] [ 154 ] [ 155 ]  These sexual addictions are associated with a  dopamine dysregulation syndrome  which occurs in some patients taking  dopaminergic drugs . [ 140 ] [ 153 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5816", "text": "The effects of amphetamine on gene regulation are both dose- and route-dependent. [ 145 ]  Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses. [ 145 ]  The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor. [ 145 ]  This suggests that medical use of amphetamine does not significantly affect gene regulation. [ 145 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5817", "text": "As of December 2019, [update]  there is no effective  pharmacotherapy  for amphetamine addiction. [ 156 ] [ 157 ] [ 158 ]  Reviews from 2015 and 2016 indicated that  TAAR1 -selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions; [ 40 ] [ 159 ]  however, as of February 2016, [update]  the only compounds which are known to function as TAAR1-selective agonists are  experimental drugs . [ 40 ] [ 159 ]  Amphetamine addiction is largely mediated through increased activation of  dopamine receptors  and  co-localized   NMDA receptors [ note 13 ]  in the nucleus accumbens; [ 137 ]   magnesium ions  inhibit NMDA receptors by blocking the receptor  calcium channel . [ 137 ] [ 160 ]  One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain. [ 137 ]   Supplemental magnesium [ note 14 ]  treatment has been shown to reduce amphetamine  self-administration  (i.e., doses given to oneself) in humans, but it is not an effective  monotherapy  for amphetamine addiction. [ 137 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5818", "text": "A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in  randomized controlled trials  (RCTs) for amphetamine and methamphetamine addiction; [ 157 ]  it found only low-strength evidence that methylphenidate might reduce amphetamine or methamphetamine self-administration. [ 157 ]  There was low- to moderate-strength evidence of no benefit for most of the other medications used in RCTs, which included antidepressants (bupropion,  mirtazapine ,  sertraline ), antipsychotics ( aripiprazole ), anticonvulsants ( topiramate ,  baclofen ,  gabapentin ),  naltrexone ,  varenicline ,  citicoline ,  ondansetron ,  prometa ,  riluzole ,  atomoxetine , dextroamphetamine, and  modafinil . [ 157 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5819", "text": "A 2018 systematic review and  network meta-analysis  of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that  combination therapy  with both  contingency management  and  community reinforcement approach  had the highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate). [ 161 ]  Other treatment modalities examined in the analysis included  monotherapy  with contingency management or community reinforcement approach,  cognitive behavioral therapy ,  12-step programs , non-contingent reward-based therapies,  psychodynamic therapy , and other combination therapies involving these. [ 161 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5820", "text": "Additionally, research on the  neurobiological effects of physical exercise  suggests that daily aerobic exercise, especially endurance exercise (e.g.,  marathon running ), prevents the development of drug addiction and is an effective  adjunct therapy  (i.e., a supplemental treatment) for amphetamine addiction. [ sources 10 ]  Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions. [ 141 ] [ 143 ] [ 162 ]  In particular,  aerobic exercise  decreases psychostimulant self-administration, reduces the  reinstatement  (i.e., relapse) of drug-seeking, and induces increased  dopamine receptor D 2  (DRD2) density in the  striatum . [ 140 ] [ 162 ]  This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density. [ 140 ]  One review noted that exercise may also prevent the development of a drug addiction by altering \u0394FosB or  c-Fos   immunoreactivity  in the striatum or other parts of the  reward system . [ 142 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5821", "text": "Drug tolerance  develops rapidly in amphetamine abuse (i.e., recreational amphetamine use), so periods of extended abuse require increasingly larger doses of the drug in order to achieve the same effect. [ 163 ] [ 164 ] \nAccording to a Cochrane review on  withdrawal  in individuals who compulsively use amphetamine and methamphetamine, \"when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24\u00a0hours of their last dose.\" [ 165 ]  This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in roughly 88% of cases, and persist for  3\u20134 \u00a0weeks with a marked \"crash\" phase occurring during the first week. [ 165 ]  Amphetamine withdrawal symptoms can include anxiety,  drug craving ,  depressed mood ,  fatigue ,  increased appetite , increased movement or  decreased movement , lack of motivation, sleeplessness or sleepiness, and  lucid dreams . [ 165 ]  The review indicated that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence. [ 165 ]  Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5822", "text": "An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care. [ 1 ] [ 115 ] [ 166 ]  The severity of overdose symptoms increases with dosage and decreases with  drug tolerance  to amphetamine. [ 41 ] [ 115 ]  Tolerant individuals have been known to take as much as 5\u00a0grams of amphetamine in a day, which is roughly 100\u00a0times the maximum daily therapeutic dose. [ 115 ]  Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves convulsions and  coma . [ 29 ] [ 41 ]  In 2013, overdose on amphetamine, methamphetamine, and other compounds implicated in an \" amphetamine use disorder \" resulted in an estimated 3,788\u00a0deaths worldwide ( 3,425\u20134,145 \u00a0deaths,  95%\u00a0confidence ). [ note 15 ] [ 167 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5823", "text": "In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic  neurotoxicity , or damage to dopamine neurons, which is characterized by dopamine  terminal   degeneration  and reduced transporter and receptor function. [ 169 ] [ 170 ]  There is no evidence that amphetamine is directly neurotoxic in humans. [ 171 ] [ 172 ]  However, large doses of amphetamine may indirectly cause dopaminergic neurotoxicity as a result of  hyperpyrexia , the excessive formation of  reactive oxygen species , and increased  autoxidation  of dopamine. [ sources 14 ]   Animal models  of neurotoxicity from high-dose amphetamine exposure indicate that the occurrence of hyperpyrexia (i.e.,  core body temperature \u00a0\u2265\u00a040\u00a0\u00b0C) is necessary for the development of amphetamine-induced neurotoxicity. [ 170 ]  Prolonged elevations of brain temperature above 40\u00a0\u00b0C likely promote the development of amphetamine-induced neurotoxicity in laboratory animals by facilitating the production of reactive oxygen species, disrupting cellular protein function, and transiently increasing  blood\u2013brain barrier  permeability. [ 170 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5824", "text": "An amphetamine overdose can result in a stimulant psychosis that may involve a variety of symptoms, such as delusions and paranoia. [ 42 ] [ 43 ]  A Cochrane review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about  5\u201315%  of users fail to recover completely. [ 42 ] [ 175 ]  According to the same review, there is at least one trial that shows  antipsychotic  medications effectively resolve the symptoms of acute amphetamine psychosis. [ 42 ]  Psychosis rarely arises from therapeutic use. [ 29 ] [ 43 ] [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5825", "text": "Many types of substances are known to  interact  with amphetamine, resulting in altered  drug action  or  metabolism  of amphetamine, the interacting substance, or both. [ 29 ]   Inhibitors of enzymes  that metabolize amphetamine (e.g.,  CYP2D6  and  FMO3 ) will prolong its  elimination half-life , meaning that its effects will last longer. [ 6 ] [ 29 ]  Amphetamine also interacts with  MAOIs , particularly  monoamine oxidase A  inhibitors, since both MAOIs and amphetamine increase  plasma  catecholamines (i.e., norepinephrine and dopamine); [ 29 ]  therefore, concurrent use of both is dangerous. [ 29 ]  Amphetamine modulates the activity of most psychoactive drugs. In particular, amphetamine may decrease the effects of  sedatives  and  depressants  and increase the effects of  stimulants  and  antidepressants . [ 29 ]  Amphetamine may also decrease the effects of  antihypertensives  and  antipsychotics  due to its effects on blood pressure and dopamine respectively. [ 29 ]   Zinc supplementation  may reduce the  minimum effective dose  of amphetamine when it is used for the treatment of ADHD. [ note 16 ] [ 180 ]   Norepinephrine reuptake inhibitors  (NRIs) like  atomoxetine  prevent  norepinephrine  release induced by amphetamines and have been found to reduce the  stimulant ,  euphoriant , and  sympathomimetic  effects of  dextroamphetamine  in humans. [ 181 ] [ 182 ] [ 183 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5826", "text": "In general, there is no significant interaction when consuming amphetamine with food, but the  pH  of gastrointestinal content and urine affects the  absorption  and  excretion  of amphetamine, respectively. [ 29 ]  Acidic substances reduce the absorption of amphetamine and increase urinary excretion, and alkaline substances do the opposite. [ 29 ]  Due to the effect pH has on absorption, amphetamine also interacts with gastric acid reducers such as  proton pump inhibitors  and  H 2  antihistamines , which increase gastrointestinal pH (i.e., make it less acidic). [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5827", "text": "Amphetamine exerts its behavioral effects by altering the use of  monoamines  as neuronal signals in the brain, primarily in  catecholamine  neurons in the reward and executive function pathways of the brain. [ 39 ] [ 64 ]  The concentrations of the main neurotransmitters involved in reward circuitry and executive functioning, dopamine and norepinephrine, increase dramatically in a dose-dependent manner by amphetamine because of its effects on  monoamine transporters . [ 39 ] [ 64 ] [ 184 ]  The  reinforcing  and  motivational salience -promoting effects of amphetamine are due mostly to enhanced dopaminergic activity in the  mesolimbic pathway . [ 27 ]  The  euphoric  and locomotor-stimulating effects of amphetamine are dependent upon the magnitude and speed by which it increases synaptic dopamine and norepinephrine concentrations in the  striatum . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5828", "text": "Amphetamine has been identified as a potent  full agonist  of  trace amine-associated receptor 1  (TAAR1), a  G s -coupled  and  G q -coupled   G protein-coupled receptor  (GPCR) discovered in 2001, which is important for regulation of brain monoamines. [ 39 ] [ 190 ]  Activation of  TAAR1  increases  cAMP Tooltip cyclic adenosine monophosphate  production via  adenylyl cyclase  activation and inhibits  monoamine transporter  function. [ 39 ] [ 191 ]  Monoamine  autoreceptors  (e.g.,  D 2  short ,  presynaptic \u03b1 2 , and  presynaptic 5-HT 1A ) have the opposite effect of TAAR1, and together these receptors provide a regulatory system for monoamines. [ 39 ] [ 40 ]  Notably, amphetamine and  trace amines  possess high binding affinities for TAAR1, but not for monoamine autoreceptors. [ 39 ] [ 40 ]  Imaging studies indicate that monoamine reuptake inhibition by amphetamine and trace amines is site specific and depends upon the presence of TAAR1  co-localization  in the associated monoamine neurons. [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5829", "text": "In addition to the neuronal monoamine  transporters , amphetamine also inhibits both  vesicular monoamine transporters ,  VMAT1  and  VMAT2 , as well as  SLC1A1 ,  SLC22A3 , and  SLC22A5 . [ sources 15 ]  SLC1A1 is  excitatory amino acid transporter 3  (EAAT3), a glutamate transporter located in neurons, SLC22A3 is an extraneuronal monoamine transporter that is present in  astrocytes , and SLC22A5 is a high-affinity  carnitine  transporter. [ sources 15 ]  Amphetamine is known to strongly induce  cocaine- and amphetamine-regulated transcript  (CART)  gene expression , [ 11 ] [ 197 ]  a  neuropeptide  involved in feeding behavior, stress, and reward, which induces observable increases in neuronal development and survival  in vitro . [ 11 ] [ 198 ] [ 199 ]  The CART receptor has yet to be identified, but there is significant evidence that CART binds to a unique  G i /G o -coupled   GPCR . [ 199 ] [ 200 ]  Amphetamine also inhibits  monoamine oxidases  at very high doses, resulting in less monoamine and trace amine metabolism and consequently higher concentrations of synaptic monoamines. [ 23 ] [ 201 ]  In humans, the only post-synaptic receptor at which amphetamine is known to bind is the  5-HT1A  receptor , where it acts as an agonist with low  micromolar  affinity. [ 202 ] [ 203 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5830", "text": "The full profile of amphetamine's short-term drug effects in humans is mostly derived through increased cellular communication or  neurotransmission  of  dopamine , [ 39 ]   serotonin , [ 39 ]   norepinephrine , [ 39 ]   epinephrine , [ 184 ]   histamine , [ 184 ]   CART peptides , [ 11 ] [ 197 ]   endogenous opioids , [ 204 ] [ 205 ] [ 206 ]   adrenocorticotropic hormone , [ 207 ] [ 208 ]   corticosteroids , [ 207 ] [ 208 ]  and  glutamate , [ 188 ] [ 193 ]  which it affects through interactions with  CART ,  5-HT1A ,  EAAT3 ,  TAAR1 ,  VMAT1 ,  VMAT2 , and possibly other  biological targets . [ sources 16 ]  Amphetamine also activates seven human  carbonic anhydrase  enzymes, several of which are expressed in the human brain. [ 209 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5831", "text": "Dextroamphetamine is a more potent agonist of  TAAR1  than levoamphetamine. [ 210 ]  Consequently, dextroamphetamine produces greater  CNS  stimulation than levoamphetamine, roughly three to four times more, but levoamphetamine has slightly stronger cardiovascular and peripheral effects. [ 41 ] [ 210 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5832", "text": "In certain brain regions, amphetamine increases the concentration of dopamine in the  synaptic cleft . [ 39 ]  Amphetamine can enter the  presynaptic neuron  either through  DAT  or by diffusing across the neuronal membrane directly. [ 39 ]  As a consequence of DAT uptake, amphetamine produces competitive reuptake inhibition at the transporter. [ 39 ]  Upon entering the presynaptic neuron, amphetamine activates  TAAR1  which, through  protein kinase A  (PKA) and  protein kinase C  (PKC) signaling, causes DAT  phosphorylation . [ 39 ]  Phosphorylation by either protein kinase can result in DAT  internalization  ( non-competitive  reuptake inhibition), but  PKC-mediated  phosphorylation alone induces the  reversal of dopamine transport  through DAT (i.e., dopamine  efflux ). [ note 16 ] [ 39 ] [ 211 ]  Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through an unidentified  Ca2+/calmodulin-dependent protein kinase  (CAMK)-dependent pathway, in turn producing dopamine efflux. [ 190 ] [ 188 ] [ 189 ]  Through direct activation of  G protein-coupled inwardly-rectifying potassium channels ,  TAAR1  reduces the  firing rate  of dopamine neurons, preventing a hyper-dopaminergic state. [ 186 ] [ 187 ] [ 212 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5833", "text": "Amphetamine is also a substrate for the presynaptic  vesicular monoamine transporter ,  VMAT2 . [ 184 ] [ 185 ]  Following amphetamine uptake at VMAT2, amphetamine induces the collapse of the vesicular pH gradient, which results in the release of dopamine molecules from  synaptic vesicles  into the cytosol via dopamine efflux through VMAT2. [ 184 ] [ 185 ]  Subsequently, the cytosolic dopamine molecules are released from the presynaptic neuron into the synaptic cleft via reverse transport at  DAT . [ 39 ] [ 184 ] [ 185 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5834", "text": "Similar to dopamine, amphetamine dose-dependently increases the level of synaptic norepinephrine, the direct precursor of  epinephrine . [ 49 ] [ 64 ]  Based upon neuronal  TAAR1   mRNA  expression, amphetamine is thought to affect norepinephrine analogously to dopamine. [ 39 ] [ 184 ] [ 211 ]  In other words, amphetamine induces TAAR1-mediated efflux and  non-competitive  reuptake inhibition at phosphorylated  NET , competitive NET reuptake inhibition, and norepinephrine release from  VMAT2 . [ 39 ] [ 184 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5835", "text": "Amphetamine exerts analogous, yet less pronounced, effects on serotonin as on dopamine and norepinephrine. [ 39 ] [ 64 ]  Amphetamine affects serotonin via  VMAT2  and, like norepinephrine, is thought to phosphorylate  SERT  via  TAAR1 . [ 39 ] [ 184 ]  Like dopamine, amphetamine has low, micromolar affinity at the human  5-HT1A receptor . [ 202 ] [ 203 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5836", "text": "Acute amphetamine administration in humans increases  endogenous opioid  release in several brain structures in the  reward system . [ 204 ] [ 205 ] [ 206 ]  Extracellular levels of  glutamate , the primary  excitatory neurotransmitter  in the brain, have been shown to increase in the striatum following exposure to amphetamine. [ 188 ]  This increase in extracellular glutamate presumably occurs via the amphetamine-induced internalization of  EAAT3 , a glutamate reuptake transporter, in dopamine neurons. [ 188 ] [ 193 ]  Amphetamine also induces the selective release of  histamine  from  mast cells  and efflux from  histaminergic neurons  through  VMAT2 . [ 184 ]  Acute amphetamine administration can also increase  adrenocorticotropic hormone  and  corticosteroid  levels in  blood plasma  by stimulating the  hypothalamic\u2013pituitary\u2013adrenal axis . [ 36 ] [ 207 ] [ 208 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5837", "text": "In December 2017, the first study assessing the interaction between amphetamine and human  carbonic anhydrase  enzymes was published; [ 209 ]  of the eleven carbonic anhydrase enzymes it examined, it found that amphetamine potently activates seven, four of which are highly expressed in the  human brain , with low nanomolar through low micromolar activating effects. [ 209 ]  Based upon preclinical research, cerebral carbonic anhydrase activation has cognition-enhancing effects; [ 214 ]  but, based upon the clinical use of  carbonic anhydrase inhibitors , carbonic anhydrase activation in other tissues may be associated with adverse effects, such as  ocular  activation exacerbating  glaucoma . [ 214 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5838", "text": "The oral  bioavailability  of amphetamine varies with gastrointestinal pH; [ 29 ]  it is well  absorbed  from the gut, and bioavailability is typically 90%. [ 10 ]  Amphetamine is a weak base with a  p K a  of 9.9; [ 3 ]  consequently, when the pH is basic, more of the drug is in its  lipid  soluble  free base  form, and more is absorbed through the lipid-rich  cell membranes  of the gut  epithelium . [ 3 ] [ 29 ]  Conversely, an acidic pH means the drug is predominantly in a water-soluble  cationic  (salt) form, and less is absorbed. [ 3 ]  Approximately  20%  of amphetamine circulating in the bloodstream is bound to  plasma proteins . [ 11 ]  Following absorption, amphetamine readily  distributes  into most tissues in the body, with high concentrations occurring in  cerebrospinal fluid  and  brain  tissue. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5839", "text": "The  half-lives  of amphetamine enantiomers differ and vary with urine pH. [ 3 ]  At normal urine pH, the half-lives of dextroamphetamine and levoamphetamine are  9\u201311 \u00a0hours and  11\u201314 \u00a0hours, respectively. [ 3 ]  Highly acidic urine will reduce the enantiomer half-lives to 7\u00a0hours; [ 17 ]  highly alkaline urine will increase the half-lives up to 34\u00a0hours. [ 17 ]  The immediate-release and extended release variants of salts of both isomers reach  peak plasma concentrations  at 3\u00a0hours and 7\u00a0hours post-dose respectively. [ 3 ]  Amphetamine is  eliminated  via the  kidneys , with  30\u201340%  of the drug being excreted unchanged at normal urinary pH. [ 3 ]  When the urinary pH is basic, amphetamine is in its free base form, so less is excreted. [ 3 ]  When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to a high of 75%, depending mostly upon whether urine is too basic or acidic, respectively. [ 3 ]  Following oral administration, amphetamine appears in urine within 3\u00a0hours. [ 17 ]  Roughly 90% of ingested amphetamine is eliminated 3\u00a0days after the last oral dose. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5840", "text": "Lisdexamfetamine is a  prodrug  of dextroamphetamine. [ 215 ] [ 216 ]  It is not as sensitive to pH as amphetamine when being absorbed in the gastrointestinal tract. [ 216 ]  Following absorption into the blood stream, lisdexamfetamine is completely converted by  red blood cells  to dextroamphetamine and the  amino acid   L -lysine  by  hydrolysis  via undetermined  aminopeptidase   enzymes . [ 216 ] [ 215 ] [ 217 ]  This is the  rate-limiting step  in the  bioactivation  of lisdexamfetamine. [ 215 ]  The elimination half-life of lisdexamfetamine is generally less than 1\u00a0hour. [ 216 ] [ 215 ]  Due to the necessary conversion of lisdexamfetamine into dextroamphetamine, levels of dextroamphetamine with lisdexamfetamine peak about one hour later than with an equivalent dose of immediate-release dextroamphetamine. [ 215 ] [ 217 ]  Presumably due to its rate-limited activation by red blood cells,  intravenous administration  of lisdexamfetamine shows greatly delayed time to peak and reduced peak levels compared to intravenous administration of an equivalent dose of dextroamphetamine. [ 215 ]  The pharmacokinetics of lisdexamfetamine are similar regardless of whether it is administered orally,  intranasally , or intravenously. [ 215 ] [ 217 ]  Hence, in contrast to dextroamphetamine,  parenteral  use does not enhance the subjective effects of lisdexamfetamine. [ 215 ] [ 217 ]  Because of its behavior as a prodrug and its pharmacokinetic differences, lisdexamfetamine has a longer duration of therapeutic effect than immediate-release dextroamphetamine and shows reduced misuse potential. [ 215 ] [ 217 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5841", "text": "CYP2D6 ,  dopamine \u03b2-hydroxylase  (DBH),  flavin-containing monooxygenase 3  (FMO3),  butyrate-CoA ligase  (XM-ligase), and  glycine  N -acyltransferase  (GLYAT) are the enzymes known to  metabolize  amphetamine or its metabolites in humans. [ sources 17 ]  Amphetamine has a variety of excreted metabolic products, including  4-hydroxyamphetamine ,  4-hydroxynorephedrine ,  4-hydroxyphenylacetone ,  benzoic acid ,  hippuric acid ,  norephedrine , and  phenylacetone . [ 3 ] [ 12 ]  Among these metabolites, the active  sympathomimetics  are  4-hydroxyamphetamine , [ 218 ]   4-hydroxynorephedrine , [ 219 ]  and norephedrine. [ 220 ]  The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation,  N -oxidation,  N -dealkylation, and deamination. [ 3 ] [ 221 ]  The known metabolic pathways, detectable metabolites, and metabolizing enzymes in humans include the following:"}
{"_id": "WikiPedia_Cardio$$$corpus_5842", "text": "The  human metagenome  (i.e., the genetic composition of an individual and all microorganisms that reside on or within the individual's body) varies considerably between individuals. [ 227 ] [ 228 ]  Since the total number of microbial and viral cells in the human body (over 100\u00a0trillion) greatly outnumbers human cells (tens of trillions), [ note 18 ] [ 227 ] [ 229 ]  there is considerable potential for interactions between drugs and an individual's microbiome, including: drugs altering the composition of the  human microbiome ,  drug metabolism  by microbial enzymes modifying the drug's  pharmacokinetic  profile, and microbial drug metabolism affecting a drug's clinical efficacy and  toxicity  profile. [ 227 ] [ 228 ] [ 230 ]  The field that studies these interactions is known as  pharmacomicrobiomics . [ 227 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5843", "text": "Similar to most  biomolecules  and other  orally administered   xenobiotics  (i.e., drugs), amphetamine is predicted to undergo promiscuous metabolism by  human gastrointestinal microbiota  (primarily bacteria) prior to absorption into the  blood stream . [ 230 ]  The first amphetamine-metabolizing microbial enzyme,  tyramine oxidase  from a strain of  E. coli  commonly found in the human gut, was identified in 2019. [ 230 ]  This enzyme was found to metabolize amphetamine,  tyramine , and phenethylamine with roughly the same binding affinity for all three compounds. [ 230 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5844", "text": "Amphetamine has a very similar structure and function to the  endogenous  trace amines, which are naturally occurring  neuromodulator  molecules produced in the human body and brain. [ 39 ] [ 49 ] [ 231 ]  Among this group, the most closely related compounds are  phenethylamine , the parent compound of amphetamine, and  N -methylphenethylamine , a structural  isomer  of amphetamine (i.e., it has an identical molecular formula). [ 39 ] [ 49 ] [ 232 ]  In humans, phenethylamine is produced directly from  L-phenylalanine  by the  aromatic amino acid decarboxylase  (AADC) enzyme, which converts  L-DOPA  into dopamine as well. [ 49 ] [ 232 ]  In turn,  N -methylphenethylamine  is metabolized from phenethylamine by  phenylethanolamine  N -methyltransferase , the same enzyme that metabolizes norepinephrine into epinephrine. [ 49 ] [ 232 ]  Like amphetamine, both phenethylamine and  N -methylphenethylamine  regulate monoamine neurotransmission via  TAAR1 ; [ 39 ] [ 231 ] [ 232 ]  unlike amphetamine, both of these substances are broken down by  monoamine oxidase B , and therefore have a shorter half-life than amphetamine. [ 49 ] [ 232 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5845", "text": "Amphetamine is a  methyl   homolog  of the mammalian neurotransmitter  phenethylamine  with the chemical formula  C 9 H 13 N . The carbon atom adjacent to the  primary amine  is a  stereogenic center , and amphetamine is composed of a racemic 1:1 mixture of two  enantiomers . [ 11 ]  This racemic mixture can be separated into its optical isomers: [ note 19 ]   levoamphetamine  and  dextroamphetamine . [ 11 ]  At room temperature, the pure free base of amphetamine is a mobile, colorless, and  volatile   liquid  with a characteristically strong  amine  odor, and acrid, burning taste. [ 22 ]  Frequently prepared solid salts of amphetamine include amphetamine adipate, [ 233 ]  aspartate, [ 29 ]  hydrochloride, [ 234 ]  phosphate, [ 235 ]  saccharate, [ 29 ]  sulfate, [ 29 ]  and tannate. [ 236 ]  Dextroamphetamine sulfate is the most common enantiopure salt. [ 50 ]  Amphetamine is also the parent compound of  its own structural class , which includes a number of psychoactive  derivatives . [ 4 ] [ 11 ]  In organic chemistry, amphetamine is an excellent  chiral ligand  for the  stereoselective synthesis  of  1,1'-bi-2-naphthol . [ 237 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5846", "text": "The substituted derivatives of amphetamine, or \"substituted amphetamines\", are a broad range of chemicals that contain amphetamine as a \"backbone\"; [ 4 ] [ 51 ] [ 238 ]  specifically, this  chemical class  includes  derivative  compounds that are formed by replacing one or more hydrogen atoms in the amphetamine core structure with  substituents . [ 4 ] [ 51 ] [ 239 ]  The class includes amphetamine itself, stimulants like methamphetamine, serotonergic  empathogens  like  MDMA , and  decongestants  like  ephedrine , among other subgroups. [ 4 ] [ 51 ] [ 238 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5847", "text": "Since the first preparation was reported in 1887, [ 240 ]  numerous synthetic routes to amphetamine have been developed. [ 241 ] [ 242 ]  The most common route of both legal and illicit amphetamine synthesis employs a non-metal reduction known as the  Leuckart reaction  (method\u00a01). [ 50 ] [ 243 ]  In the first step, a reaction between phenylacetone and  formamide , either using additional  formic acid  or formamide itself as a reducing agent, yields  N -formylamphetamine . This intermediate is then hydrolyzed using hydrochloric acid, and subsequently basified, extracted with organic solvent, concentrated, and distilled to yield the free base. The free base is then dissolved in an organic solvent, sulfuric acid added, and amphetamine precipitates out as the sulfate salt. [ 243 ] [ 244 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5848", "text": "A number of  chiral resolutions  have been developed to separate the two enantiomers of amphetamine. [ 241 ]  For example, racemic amphetamine can be treated with  d- tartaric acid  to form a  diastereoisomeric  salt which is  fractionally  crystallized to yield dextroamphetamine. [ 245 ]  Chiral resolution remains the most economical method for obtaining optically pure amphetamine on a large scale. [ 246 ]  In addition, several  enantioselective  syntheses of amphetamine have been developed. In one example,  optically pure   ( R )-1-phenyl-ethanamine  is condensed with phenylacetone to yield a chiral  Schiff base . In the key step, this intermediate is reduced by  catalytic hydrogenation  with a transfer of chirality to the carbon atom alpha to the amino group. Cleavage of the  benzylic  amine bond by hydrogenation yields optically pure dextroamphetamine. [ 246 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5849", "text": "A large number of alternative synthetic routes to amphetamine have been developed based on classic organic reactions. [ 241 ] [ 242 ]  One example is the  Friedel\u2013Crafts  alkylation of  benzene  by  allyl chloride  to yield beta chloropropylbenzene which is then reacted with ammonia to produce racemic amphetamine (method\u00a02). [ 247 ]  Another example employs the  Ritter reaction  (method\u00a03). In this route,  allylbenzene  is reacted  acetonitrile  in sulfuric acid to yield an  organosulfate  which in turn is treated with sodium hydroxide to give amphetamine via an  acetamide  intermediate. [ 248 ] [ 249 ]  A third route starts with  ethyl 3-oxobutanoate  which through a double alkylation with  methyl iodide  followed by  benzyl chloride  can be converted into  2-methyl-3-phenyl-propanoic  acid. This synthetic intermediate can be transformed into amphetamine using either a  Hofmann  or  Curtius rearrangement  (method\u00a04). [ 250 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5850", "text": "A significant number of amphetamine syntheses feature a  reduction  of a  nitro ,  imine ,  oxime , or other nitrogen-containing  functional groups . [ 242 ]  In one such example, a  Knoevenagel condensation  of  benzaldehyde  with  nitroethane  yields  phenyl-2-nitropropene . The double bond and nitro group of this intermediate is  reduced  using either catalytic  hydrogenation  or by treatment with  lithium aluminium hydride  (method\u00a05). [ 243 ] [ 251 ]  Another method is the reaction of  phenylacetone  with  ammonia , producing an imine intermediate that is reduced to the primary amine using hydrogen over a palladium catalyst or lithium aluminum hydride (method\u00a06). [ 243 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5851", "text": "Amphetamine is frequently measured in urine or blood as part of a  drug test  for sports, employment, poisoning diagnostics, and forensics. [ sources 18 ]  Techniques such as  immunoassay , which is the most common form of amphetamine test, may cross-react with a number of sympathomimetic drugs. [ 255 ]  Chromatographic methods specific for amphetamine are employed to prevent false positive results. [ 256 ]  Chiral separation techniques may be employed to help distinguish the source of the drug, whether prescription amphetamine, prescription amphetamine prodrugs, (e.g.,  selegiline ),  over-the-counter drug  products that contain  levomethamphetamine , [ note 20 ]  or illicitly obtained substituted amphetamines. [ 256 ] [ 259 ] [ 260 ]  Several prescription drugs produce amphetamine as a  metabolite , including  benzphetamine ,  clobenzorex ,  famprofazone ,  fenproporex ,  lisdexamfetamine ,  mesocarb , methamphetamine,  prenylamine , and  selegiline , among others. [ 2 ] [ 261 ] [ 262 ]  These compounds may produce positive results for amphetamine on drug tests. [ 261 ] [ 262 ]  Amphetamine is generally only detectable by a standard drug test for approximately 24\u00a0hours, although a high dose may be detectable for  2\u20134 \u00a0days. [ 255 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5852", "text": "For the assays, a study noted that an  enzyme multiplied immunoassay technique  (EMIT) assay for amphetamine and methamphetamine may produce more false positives than  liquid chromatography\u2013tandem mass spectrometry . [ 259 ]   Gas chromatography\u2013mass spectrometry  (GC\u2013MS) of amphetamine and methamphetamine with the derivatizing agent  ( S )-(\u2212)-trifluoroacetylprolyl  chloride allows for the detection of methamphetamine in urine. [ 256 ]  GC\u2013MS of amphetamine and methamphetamine with the chiral derivatizing agent  Mosher's\u00a0acid chloride  allows for the detection of both dextroamphetamine and dextromethamphetamine in urine. [ 256 ]  Hence, the latter method may be used on samples that test positive using other methods to help distinguish between the various sources of the drug. [ 256 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5853", "text": "Amphetamine was first synthesized in 1887 in Germany by Romanian chemist  Laz\u0103r Edeleanu  who named it  phenylisopropylamine ; [ 240 ] [ 264 ] [ 265 ]  its stimulant effects remained unknown until 1927, when it was independently resynthesized by  Gordon Alles  and reported to have  sympathomimetic  properties. [ 265 ]  Amphetamine had no medical use until late 1933, when  Smith, Kline and French  began selling it as an  inhaler  under the brand name  Benzedrine  as a decongestant. [ 30 ]  Benzedrine sulfate was introduced 3\u00a0years later and was used to treat a wide variety of  medical conditions , including  narcolepsy ,  obesity ,  low blood pressure ,  low libido , and  chronic pain , among others. [ 52 ] [ 30 ]  During  World War II , amphetamine and  methamphetamine  were used extensively by both the  Allied  and  Axis  forces for their stimulant and performance-enhancing effects. [ 240 ] [ 266 ] [ 267 ]  As the addictive properties of the drug became known, governments began to place strict controls on the sale of amphetamine. [ 240 ]  For example, during the early 1970s in the United States, amphetamine became a  schedule\u00a0II controlled substance  under the  Controlled Substances Act . [ 9 ]  In spite of strict government controls, amphetamine has been used legally or illicitly by people from a variety of backgrounds, including authors, [ 268 ]  musicians, [ 269 ]  mathematicians, [ 270 ]  and athletes. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5854", "text": "Amphetamine is illegally synthesized in  clandestine labs  and sold on the  black market , primarily in European countries. [ 271 ]  Among European Union (EU) member states in 2018, [update]  11.9\u00a0million adults of ages  15\u201364  have used amphetamine or methamphetamine at least once in their lives and 1.7\u00a0million have used either in the last year. [ 272 ]  During 2012, approximately 5.9\u00a0 metric tons  of illicit amphetamine were seized within EU member states; [ 273 ]  the \"street price\" of illicit amphetamine within the EU ranged from  \u20ac 6\u201338 \u00a0per gram during the same period. [ 273 ]  Outside Europe, the illicit market for amphetamine is much smaller than the market for methamphetamine and MDMA. [ 271 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5855", "text": "As a result of the  United Nations  1971  Convention on Psychotropic Substances , amphetamine became a schedule\u00a0II controlled substance, as defined in the treaty, in all 183 state parties. [ 31 ]  Consequently, it is heavily regulated in most countries. [ 274 ] [ 275 ]  Some countries, such as South Korea and Japan, have banned substituted amphetamines even for medical use. [ 276 ] [ 277 ]  In other nations, such as Brazil ( class A3 ), [ 278 ]  Canada ( schedule\u00a0I drug ), [ 279 ]  the Netherlands ( List I drug ), [ 280 ]  the United States ( schedule II drug ), [ 9 ]  Australia ( schedule\u00a08 ), [ 281 ]  Thailand ( category\u00a01 narcotic ), [ 282 ]  and United Kingdom ( class\u00a0B drug ), [ 283 ]  amphetamine is in a restrictive national drug schedule that allows for its use as a medical treatment. [ 271 ] [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5856", "text": "Several currently marketed amphetamine formulations contain both enantiomers, including those marketed under the brand names Adderall, Adderall\u00a0XR, Mydayis, [ note 1 ]  Adzenys\u00a0ER,  Adzenys XR-ODT , Dyanavel\u00a0XR, Evekeo, and Evekeo\u00a0ODT. Of those, Evekeo (including Evekeo\u00a0ODT) is the only product containing only racemic amphetamine (as amphetamine sulfate), and is therefore the only one whose  active moiety  can be accurately referred to simply as \"amphetamine\". [ 1 ] [ 36 ] [ 119 ]  Dextroamphetamine, marketed under the brand names Dexedrine and Zenzedi, is the only  enantiopure  amphetamine product currently available. A  prodrug  form of dextroamphetamine,  lisdexamfetamine , is also available and is marketed under the brand name Vyvanse. As it is a prodrug, lisdexamfetamine is structurally different from dextroamphetamine, and is inactive until it metabolizes into dextroamphetamine. [ 38 ] [ 216 ]  The free base of racemic amphetamine was previously available as Benzedrine, Psychedrine, and Sympatedrine. [ 2 ]  Levoamphetamine was previously available as Cydril. [ 2 ]  Many current amphetamine pharmaceuticals are  salts  due to the comparatively high volatility of the free base. [ 2 ] [ 38 ] [ 50 ]  However, oral suspension and  orally disintegrating tablet  (ODT)  dosage forms  composed of the free base were introduced in 2015 and 2016, respectively. [ 119 ] [ 284 ] [ 285 ]  Some of the current brands and their generic equivalents are listed below."}
{"_id": "WikiPedia_Cardio$$$corpus_5857", "text": "Asthmador  was a  nonprescription  treatment for the relief of bronchial  asthma  made by the R. Schiffmann Company."}
{"_id": "WikiPedia_Cardio$$$corpus_5858", "text": "It consisted of a mixture of  belladonna ,  stramonium  and  potassium perchlorate , [ 1 ]  and was a fine powder intended to be burned and the smoke inhaled. The primary  alkaloid  present in the mixture was  hyoscyamine , and when the powder was ingested rather than burned, could be used to induce hallucinations. In severe overdose it could hospitalize the patient or cause death."}
{"_id": "WikiPedia_Cardio$$$corpus_5859", "text": "Prior to the introduction of rescue inhalers in the mid-1950s this was an over-the-counter remedy for asthma attacks. Asthmador was sold in packets like cigarettes, in tins like pipe tobacco, or as an incense. The  paroxysms  would abate within a few minutes of inhaling the mixture. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5860", "text": "This  hallucinogen -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_5861", "text": "AZD1305  is an experimental drug candidate that is under investigation for the management and reversal of  cardiac arrhythmias , specifically  atrial fibrillation  and  flutter .  In vitro  studies have shown that this combined-ion channel blocker inhibits rapidly the activating delayed-rectifier potassium current (IKr), L-type calcium current, and inward sodium current (INa). [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5862", "text": "Atrial fibrillation (AF) is a form of cardiac arrhythmia that arises with disorganized and rapid action upotentials conducted through the atria, resulting in irregular atrial contraction. [ 2 ]   Causes of AF include hypertension, cardiomyopathies, alcohol consumption, viral infections, and sleep apnea, which can cause AF by increasing the occurrence of early after depolarizations (EADs). [ 3 ]  EAD is an abnormal depolarization and increase in action potential frequency that occurs in cardiac myocytes before normal repolarization is complete. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5863", "text": "AZD1305 possesses class III anti-arrhythmic activity by blocking the  human ether-a-go-go-related gene  (hERG) potassium channel. [ 4 ]  hERG contributes to the formation of potassium ion channel proteins that are responsible for the conduction of the rapid delayed rectifying potassium current. [ 6 ]  Blocking this current prolongs action potential duration (APD), increases refractory period, and delays repolarization of cardiac myocytes in the ventricles and atria. [ 4 ]  Delayed repolarizations increase susceptibility to EAD."}
{"_id": "WikiPedia_Cardio$$$corpus_5864", "text": "AZD 1305 also acts on voltage gated sodium channels (Nav1.5) by attenuating the peak (INapeak) and late sodium current (INalate), though the latter current is more potently inhibited. [ 5 ]  Attenuation of INalate by AZD1305 is concentration-dependent and decreases the slope of depolarization and delays repolarization. INalate blockade by AZD1305 depressed the threshold of sodium channel excitation and prolongs APD. [ 7 ]  Blockade of IKr may lead to excessive prolongation of APD and repolarization instability, which may promote arrhythmic conditions in the heart, including EAD and Torsade de Pointes (TdP). [ 5 ]  Under IKr blockade a pronounced INalate can contribute to the development of arrhythmias by increasing repolarization variability. AZD1305 blockade of the INalate  modulates IKr-blockade induced APD instability, repolarization vulnerability, and variability in beat-to-beat APD. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5865", "text": "In vivo ,  as well as in vitro studies discovered that inhibition of INa and IKr by AZD1305 is much greater in atrial versus ventricular myocytes. [ 1 ] [ 7 ]  This atrial-selective activity of AZD1305 prolongs effective refractory period (ERF) and induces post-repolarization refractoriness (PRR) in atrial myocytes, which aids in suppressing atrial fibrillation. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5866", "text": "AF and TdP may be induced with L-type calcium channel hyperactivity and increased calcium release from the sarcoplasmic reticulum. The L-type calcium current is also blocked by AZD 1305 which suppresses the intracellular rises in calcium levels and calcium oscillations that produce EADs. [ 1 ] [ 4 ]  The combined block of INa, IKr, and L-type calcium current is key to the anti-arrhythmic potential of AZD1305 compared IKr blockade alone. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5867", "text": "Available anti-arrhythmic agents (AAD) used for the maintenance of AF are often accompanied with the risk of developing ventricular pro-arrhythmias, as they are often limited to targeting a single ion channel (i.e., Dofeiltide) and have homogenous activity throughout the heart. [ 4 ]  AZD1305 offers the advantage of being an atrial-selective AAD and combined ion channel blocker that provides protection against EAD,  repolarization dispersion, and ventricular pro-arrhythmias. [ 1 ] [ 4 ] [ 7 ]  Simultaneously, AZD1305 suppresses AF in a safe and efficacious manner, which could potentially be an ideal first-line treatment option in the future. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5868", "text": "Cardiovascular agents  are drugs used to treat diseases associated with the heart or blood vessels. These medications are available for purchase only with a physician\u2019s  prescription . They include, but are not limited to, drugs that target  hypertension  ( antihypertensives ),  hyperlipidemia  ( antihyperlipidemics ) and  blood clotting  (blood-thinners) to reduce the risk of  cardiovascular diseases ."}
{"_id": "WikiPedia_Cardio$$$corpus_5869", "text": "Antihypertensive agents are classified according to their mechanism of actions. The most common classes prescribed are  diuretics ,  angiotensin-converting enzyme inhibitors  (ACEIs),  angiotensin II receptor blockers  (ARBs),  calcium channel blockers  (CCBs) and  beta-blockers ."}
{"_id": "WikiPedia_Cardio$$$corpus_5870", "text": "Antihyperlipidemic agents most often prescribed are  statins ,  ezetimibe  and  fibrates . They either lower  low-density lipoprotein cholesterol  (LDL-C) or  triglyceride  (TG) levels in blood to manage  hypercholesterolaemia ."}
{"_id": "WikiPedia_Cardio$$$corpus_5871", "text": "Blood-thinning agents, particularly  antiplatelets  and  anticoagulants , maintain smooth blood flow by preventing blood clot formation in blood vessels. Two main categories of antiplatelets are COX-1 inhibitors and  ADP receptor inhibitors , while anticoagulants include  vitamin K antagonists , direct oral anticoagulants (DOACs) and indirect thrombin inhibitors."}
{"_id": "WikiPedia_Cardio$$$corpus_5872", "text": "Since cardiovascular agents have narrow  therapeutic windows , a slight rise in dose may result in severe  toxicity . Hence, monitoring at baseline and during therapy is needed. For  drug overdose , stabilisation and  antidotes  help lower drug concentrations."}
{"_id": "WikiPedia_Cardio$$$corpus_5873", "text": "Cardiovascular agents are drugs that affect the rate and intensity of cardiac contraction, blood vessel diameters, blood volume, blood clotting and blood  cholesterol  levels. [ 1 ]  They are indicated to treat diseases related to the heart or the vascular system (blood vessels), such as  hypertension ,  hyperlipidemia ,  coagulation disorders ,  heart failure  and  coronary artery disease . [ 1 ]  These drugs are  prescription-only medicines , meaning that they should be administered strictly under a doctor\u2019s instruction and can only be obtained by means of a doctor\u2019s prescription."}
{"_id": "WikiPedia_Cardio$$$corpus_5874", "text": "Antihypertensive agents  comprise multiple classes of compounds that are intended to manage hypertension (high blood pressure). \u00a0Antihypertensive therapy aims to maintain a blood pressure goal of <140/90 mmHg in all patients, as well as to prevent the progression or recurrence of  cardiovascular diseases  (CVD) in hypertensive patients with established CVD. [ 2 ]  An optimal blood pressure control is essential to prevent target-organ damage associated with complications of hypertension such as  heart failure ,  ischemic heart diseases ,  stroke , and  renal failure , ultimately reducing the risk of premature mortality. [ 2 ]  Antihypertensives are classified by different mechanisms or sites of action. Some of the most commonly used drugs to treat hypertension include  diuretics ,  angiotensin-converting enzyme inhibitors  (ACEI),  angiotensin II receptor blockers  (ARBs),  calcium channel blockers  (CCBs), and  beta-blockers ."}
{"_id": "WikiPedia_Cardio$$$corpus_5875", "text": "Diuretics  act primarily by reducing the reabsorption of sodium at different sites of the renal tubular system and consequently promoting the elimination of sodium and water with increased urine output. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5876", "text": "For loop diuretics, thiazide diuretics and thiazide-like diuretics, their common side effects include  hypokalemia ,  hyponatremia ,  metabolic alkalosis  and  hyperglycaemia . [ 4 ]  For potassium-sparing diuretics, its common side effects include  hyponatremia ,  hyperkalemia ,  metabolic acidosis  and sexual dysfunction specifically for spironolactone. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5877", "text": "The use of diuretics should be avoided in patients with severe dehydration,  anuria  (absence of urine production). [ 4 ]  Diuretics are contraindicated in cases of severe electrolyte abnormalities and should not be administered until an electrolyte balance is restored. Special attention should be given to the use of thiazide and loop diuretics as they may exacerbate  diabetes  and  gout . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5878", "text": "Angiotensin-converting-enzyme inhibitors  (ACEI) block the conversion of angiotensin I to angiotensin II by inhibiting the action of angiotensin-converting-enzyme, causing the reduction of blood volume and peripheral vascular resistance. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5879", "text": "Some side effects of ACEI include hypotension,  renal insufficiency , and hyperkalemia. [ 7 ]  Dry cough is also a common side effect believed to be associated with decreased  bradykinin  breakdown.  Angioedema  is another possible but rare complication due to elevated levels of bradykinin. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5880", "text": "ACEI should not be used in combinations with angiotensin II receptor blockers (ARBs) or  direct renin inhibitors  and is contraindicated in people with a history of  angioedema  and pregnancy. [ 6 ] [ 8 ]  \u201cTriple whammy\u201d, the concurrent use of an ACEI with  diuretics  and  non-steroidal anti-inflammatory drugs  (NSAIDs), is also contraindicated as this combination has been correlated with an increased risk of  acute kidney injury . [ 8 ] [ 7 ]  ACEI should be used with caution in patients with renal impairment, and renal failure risk in severe bilateral  renal stenosis . [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5881", "text": "Angiotensin II receptor blockers  (ARBs) work by inhibiting the action of angiotensin II on, specifically AT1 receptors to prevent the vasoconstrictor effects of this receptor and block the peripheral sympathetic activity. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5882", "text": "ARBs are generally well-tolerated, in which they are less likely to cause cough or angioedema compared to ACEI. Common side effects include hypotension,  renal insufficiency , and hyperkalemia. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5883", "text": "The contraindications of ARBs are similar to those of ACEI, including the contraindicated combinations with ACEI or direct renin inhibitors, \"triple whammy\" (the concurrent use of an ARB with diuretics and NSAIDs) and in patients with a history of  angioedema  and pregnancy. [ 6 ] [ 7 ] [ 8 ]  In addition, ARB should be used with caution in patients with renal impairment and renal failure risk in severe bilateral  renal stenosis [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5884", "text": "Calcium channel blockers  (CCBs) preferentially block the  L-type voltage-gated calcium channels  to prevent the flow of calcium influx in the blood vessels and the heart, thereby reducing peripheral vascular resistance and cardiac output respectively. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5885", "text": "In general, the side effects of CCBs include  peripheral edema  and  gingival hyperplasia  when CCBs are used chronically. [ 11 ] [ 12 ]  To add on, DHP may cause  reflex tachycardia  and  peripheral edema , while non-DHP may cause  bradycardia  and worsening of cardiac function due to reduced cardiac contractility and cardiac conduction. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5886", "text": "Non-dihydropyridines are contraindicated in patients with  heart failure with reduced ejection fraction  (HFrEF), and second- or third-degree  atrioventricular block . [ 13 ]  Special attention should be given to the coadministration of non-DHP with  beta-blockers  or  ivabradine  due to the increased risk of bradycardia. [ 13 ]  Since both DHP and non-DHP are metabolized through the  CYP3A4  system, grapefruit juice containing  furanocoumarins  (the potent inhibitors of the CYP3A4 enzyme) should be avoided. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5887", "text": "Beta-blockers  act as competitive antagonists that block the effects of  catecholamines  at  beta-adrenergic receptor  sites, resulting in reduced rate and force of contraction of the heart, as well as reduced peripheral vascular resistance. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5888", "text": "Some common side effects include increased airway resistance for non-selective beta-blockers, exacerbation of peripheral vascular diseases, and hypotension [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5889", "text": "Beta-blockers are contraindicated in patients with second- or third-degree  atrioventricular block . In particular, beta-blockers with intrinsic sympathomimetic activity are contraindicated in patients with  myocardial infarction ,  heart failure  or severe  bradycardia . [ 15 ] [ 16 ]  Beta-blockers should be used with caution in patients with  asthma  or  chronic obstructive pulmonary disease  (COPD) due to bronchoconstriction, and in patients with  diabetes mellitus  (DM) due to masking of  hypoglycaemia . [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5890", "text": "Antihyperlipidemic agents  are drugs used for the treatment of  dyslipidemia , a condition of abnormal lipid levels in the body. It is characterised by elevations of  low-density lipoprotein cholesterol  (LDL-C) and  triglycerides  (TGs) in the blood. [ 17 ]   Hypercholesterolaemia  induces the formation of plaques due to the buildup of excess cholesterol within the arterial wall. This increases the risk of, or aggravate,  atherosclerotic cardiovascular disease  (ASCVD). Therefore, antihyperlipidemic drugs are introduced for primary and secondary  coronary heart disease  prevention, as well as for reduction in mortality from acute coronary outcomes. [ 18 ]  These drugs include  statins ,  ezetimibe  and  fibrates ."}
{"_id": "WikiPedia_Cardio$$$corpus_5891", "text": "Statins , also known as beta-hydroxy-beta-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitors, are the  first-line  drugs for  hypercholesterolaemia . [ 19 ]  Examples of this drug class are  atorvastatin ,  rosuvastatin ,  fluvastatin ,  simvastatin ,  pravastatin  and  lovastatin ."}
{"_id": "WikiPedia_Cardio$$$corpus_5892", "text": "Most efficacious in lowering LDL-C levels, statins block the action of  HMG-CoA reductase  through  competitive inhibition . [ 18 ]  HMG-CoA reductase, an enzyme found in  hepatocytes , is responsible for the conversion of  HMG-CoA  to  mevalonic acid  for cholesterol biosynthesis. Inhibition of this enzyme reduces the synthesis and thus, availability of endogenous cholesterol. This reduction in intracellular cholesterol, in turn, causes an increase in the number of  LDL receptors  on hepatic cells. The elevation of LDL receptor expression decreases the plasma LDL-C level by promoting hepatic uptake of LDL from circulation."}
{"_id": "WikiPedia_Cardio$$$corpus_5893", "text": "While statins are generally well-tolerated, severe adverse effects such as  hepatotoxicity  and myotoxicity may occur in rarity. Statin-induced hepatotoxicity can cause  autoimmune hepatitis  and an elevation in serum levels of hepatic enzymes such as  alanine aminotransferase , impairing liver function. [ 20 ]  Myotoxicity is commonly presented with statin-associated muscle symptoms (SAMS), which include  myalgia  and  myositis . [ 21 ]  In rare cases, they may progress into  rhabdomyolysis , a condition manifested by muscle  necrosis  and  myoglobinuria  due to heightened  creatine kinase  levels. [ 22 ] [ 23 ]  Another consequence of taking statins is the risk of developing new-onset diabetes, which is more prominent in individuals with high TG levels and  body mass index  (BMI). [ 19 ]  However, the risk is far outweighed by the benefits from statin therapy for the reduction in cardiovascular outcomes. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5894", "text": "Given the potential of statins to exacerbate liver and muscle abnormalities, contraindications of statins include  decompensated   liver cirrhosis ,  acute liver failure , unexplained and persistent elevations of serum transaminases, and myopathy. Moreover, statins are not recommended in pregnancy as they may cause foetal harm because of their mechanism of action. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5895", "text": "Metabolised by the  Cytochrome P450  (CYP450) enzyme, a major metabolic enzyme, simvastatin and lovastatin may accumulate in blood when administered with CYP450 inhibitors. [ 18 ] [ 24 ]  Some of these inhibitors are  azole antifungals ,  macrolides ,  CCBs ,  ticagrelor  (antiplatelet) and  grapefruit juice . Concomitant use of statins with CYP450 inhibitors, along with  gemfibrozil  (fibrate), increases the risk of  myopathy . [ 20 ] [ 23 ] [ 25 ]  This is especially significant in patients under  polypharmacy ."}
{"_id": "WikiPedia_Cardio$$$corpus_5896", "text": "Ezetimibe  is a selective  cholesterol absorption inhibitor  that inhibits the intestinal absorption of cholesterol by binding to the  Niemann-Pick C1-Like 1  (NPC1L1) protein on the gastrointestinal epithelium. [ 23 ]  This reduces the delivery of cholesterol to the liver, which then induces the  upregulation  of LDL receptor expression, lowering hepatic cholesterol stores and enhancing  clearance  of circulating LDL. More often prescribed as  second-line therapy  for dyslipidemia, ezetimibe is used in individuals with statin  intolerance  or those who failed to achieve the target LDL-C level on statin  monotherapy . [ 26 ] [ 27 ]  In particular, ezetimibe and statin dual therapy have shown a 15% greater LDL-C decrease compared with same-dose statins alone, favouring recovery from  acute coronary syndrome . [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5897", "text": "Whilst ezetimibe intolerance is uncommon, some reports have been made regarding gastrointestinal and musculoskeletal effects. [ 28 ]  Common adverse reactions of ezetimibe are nausea, abdominal pain, headache, fatigue,  arthralgia ,  myalgia  and  hypersensitivity reactions . [ 29 ]  On rare occasions, ezetimibe may cause  cholecystitis ,  pancreatitis , elevation of serum transaminase level and  rhabdomyolysis ."}
{"_id": "WikiPedia_Cardio$$$corpus_5898", "text": "As  hepatic impairment  hinders the rate of ezetimibe metabolism by the liver, ezetimibe is not recommended in individuals with moderate or severe hepatic insufficiency due to prolonged systemic exposure to the drug. [ 19 ]  In addition, similar to combined statin and fibrate intake, individuals should avoid the concurrent use of ezetimibe with  gemfibrozil  as it would increase ezetimibe concentration in the body. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5899", "text": "Fibrates , known as derivatives of fibric acids, are  peroxisome proliferator-activated receptor alpha  (PPAR-\u03b1)  agonists  primarily used for lowering TG levels and management of  atherogenic  dyslipidemia. [ 30 ] [ 31 ] [ 32 ]  Typical drugs of the class include  fenofibrate ,  bezafibrate ,  ciprofibrate  and  gemfibrozil ."}
{"_id": "WikiPedia_Cardio$$$corpus_5900", "text": "Through activation of PPAR-\u03b1 receptors, fibrates decreases circulating TG via  upregulation  of  lipoprotein lipase  (LPL) expression and  downregulation  of  apolipoprotein C-III  (ApoC-III) gene expression. [ 23 ] [ 29 ]  LPL is a hepatic enzyme involved in  lipolysis , whereas ApoC-III is an inhibitor of LPL."}
{"_id": "WikiPedia_Cardio$$$corpus_5901", "text": "Comparable to statins and ezetimibe, fibrates are usually well-tolerated with mild adverse reactions, with the exception of gemfibrozil. Some of the more prevalent side effects are minor  gastrointestinal disturbances  such as abdominal pain and cholithiasis on account of the increased excretion of biliary cholesterol. [ 23 ]  Among atypical adverse effects,  myositis  can occur in patients under gemfibrozil therapy, especially in those with  renal insufficiency  or under co-treatment with statins. In contrast, the risk of myopathy is much lower if fenofibrate is used in replacement of gemfibrozil owing to its different  pharmacokinetic  pathway. Other rare effects are increased serum  transaminase  levels,  agranulocytosis  and  anaemia . [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5902", "text": "As fenofibrate possess the same binding mechanism as  warfarin  in the blood, this combination should be addressed with caution as fenofibrate may potentiate the anticoagulant effect of warfarin. [ 33 ]  Furthermore, fibrates are contraindicated in patients with active liver disease, severe renal impairment or pre-existing  gallbladder disease , as well as in lactating mothers. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5903", "text": "Blood-thinning agents are divided into two groups,  antiplatelet drugs  and  anticoagulants . They are indicated to facilitate smooth blood flow within blood vessels by preventing the formation of  blood clots  and retarding their growth. [ 34 ]  Blood clots are formed to prevent an injured blood vessel from excessive bleeding by a mechanism called  hemostasis . The body has intrinsic mechanisms to dissolve the blood clot as the injury heals. However, it can be dangerous when clots do not dissolve naturally and develop within vessels, also known as  thrombosis . Hence, blood-thinning medications can be prescribed to reduce the risk of  cardiovascular diseases  led by blood clots, such as  myocardial infarction  (heart attack),  ischemic stroke , and  venous thromboembolism . [ 35 ]   Haemorrhage  (internal bleeding) is the most prominent side effect of blood-thinning therapy. [ 36 ]  Concomitant use of drugs that increase the risk of bleeding is not recommended. Meanwhile, patients should receive education about proper management of cuts, bruises and nosebleeds. The agents can be classified according to different mechanisms of action."}
{"_id": "WikiPedia_Cardio$$$corpus_5904", "text": "Antiplatelet drugs  inhibit blood cells called  platelets  from aggregating to form a clot."}
{"_id": "WikiPedia_Cardio$$$corpus_5905", "text": "Potent antiplatelet medications that irreversibly inhibit the activity of  cyclooxygenase  (COX), an  enzyme  involved in the synthesis of  thromboxane A 2  (TXA2) which is responsible for platelet activation and aggregation. The major member of this class is  aspirin . Some common adverse effects associated with this class of medications include  bronchospasm  and gastrointestinal disturbances such as  dyspepsia  and  nausea . Therefore, this class of drugs should be used with caution in patients with a history of  peptic ulcer disease . [ 34 ] [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5906", "text": "Also known as P2Y12  receptor antagonists , they work by reversibly interacting with the P2Y12 receptor to inhibit the  adenosine diphosphate  (ADP) receptors on platelets, thus preventing the linkage of platelets by  fibrinogen . [ 34 ] [ 35 ]  ADP-induced platelet aggregation and activation are hence hindered. Examples include  clopidogrel ,  prasugrel  and  ticagrelor .  Clopidogrel  has a common drug interaction with  CYP2C19  inhibitors, particularly  omeprazole  and  esomeprazole  which are indicated for treatment of  peptic ulcer  and  gastro-oesophageal reflux disease (GERD) . As the activation of  clopidogrel  requires an enzyme called CYP2C19, its inhibitors should be avoided. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5907", "text": "Anticoagulants  are considered more aggressive than  antiplatelet drugs . [ 34 ]   Anticoagulants  work by interfering with various clotting factors to lengthen the time for  coagulation . This can be achieved by either reducing the formation of bioactive clotting factors or accelerating the inactivation of clotting factors."}
{"_id": "WikiPedia_Cardio$$$corpus_5908", "text": "Drugs that inhibit the formation of the vitamin K-dependent clotting factors and hence  thrombin , an endogenous protein involved in the  coagulation cascade . Vitamin K is an essential cofactor for the synthesis of clotting factors. By inhibiting  vitamin K epoxide reductase , an enzyme for activating the vitamin K available in the body, the formation of bioactive clotting factors can be reduced. Although  warfarin  is commonly prescribed, it exhibits a delayed onset of action, which takes approximately 5 to 7 days to reach its full therapeutic effect. [ 39 ]  Apart from  haemorrhage ,  jaundice  (yellowing of the skin and eyes) is also a common side effect caused by this class of drug. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5909", "text": "DOACs are agents that inhibit the formation of  thrombin  which is the central effector of coagulation derived from  factor Xa . They are categorised into  direct thrombin inhibitors  and  direct factor Xa inhibitors . Direct thrombin inhibitors bind to the active sites of free or clot-bound thrombin to inhibit its effects.  Dabigatran etexilate  is a common example which has a rapid onset of action. [ 40 ]  Whereas direct factor Xa inhibitors including  apixaban  and  rivaroxaban  directly bind to clotting factor Xa to block its activity, thus inhibiting thrombin formation. [ 34 ]  DOACs are advantageous over  warfarin  because of a wider  therapeutic window , which indicates safer and more effective use with minimal adverse effects. DOACs also have more stable and predictable anticoagulation effects. Therefore, routine coagulation monitoring is not required. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5910", "text": "Indirect thrombin inhibitors bind to  antithrombin  to enhance the rate of inactivation of clotting factors, indirectly inactivating thrombin through actions on antithrombin. [ 42 ]   Heparin  is a widely used anticoagulant. It is administered intravenously (into a vein) or subcutaneously (below the skin). Heparin can exert an immediate anti-clotting effect which is useful for the treatment of acute symptoms. [ 36 ]  Besides, heparin therapy is indicated for anticoagulation during pregnancy as it does not cross the  placenta  and is not associated with fetal malformations. [ 43 ] [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5911", "text": "Cardiovascular agents generally have narrow  therapeutic indices , implying that small differences in dose or blood concentration may give rise to adverse drug reactions. [ 45 ]  Serious acute toxicity may result from accidental, intentional or  iatrogenic  overdose. [ 46 ]  Therefore, patients need to be aware of any unusual and serious side effects. Seek immediate medical attention if a  drug overdose  is suspected."}
{"_id": "WikiPedia_Cardio$$$corpus_5912", "text": "General management of acute poisoning requires stabilisation of the airway, breathing, and circulation. [ citation needed ]  Supportive treatment to reduce further absorption of the drug is achievable by the administration of  activated charcoal . [ 47 ]  Antidotes can be used to reverse effects of the overdosed medication if the exact poisoning agent is identified. However, only a few  antidotes  are available for cardiovascular medications."}
{"_id": "WikiPedia_Cardio$$$corpus_5913", "text": "Table 1: antidotes for cardiovascular agent overdose"}
{"_id": "WikiPedia_Cardio$$$corpus_5914", "text": "For patients taking antihyperlipidemic agents,  liver function tests  have to be conducted before and during the therapy to monitor the elevation of liver enzymes which may result in  hepatotoxicity , especially for those undergoing  statin therapy . [ 52 ]  For patients taking blood-thinners, signs of severe bleeding should be monitored. The effect of  aspirin  can be life-threatening if taken over 150\u00a0mg/kg of body weight. [ 47 ]   The medication should be discontinued at the first sign of excessive bleeding."}
{"_id": "WikiPedia_Cardio$$$corpus_5915", "text": "Cathinone  ( / \u02c8 k \u00e6 \u03b8 \u026a n o\u028a n / ; also known as  \u03b2-ketoamphetamine ) is a  monoamine   alkaloid  found in the  shrub   Catha edulis  ( khat ) and is chemically similar to  ephedrine ,  cathine ,  methcathinone  and other  amphetamines . It is probably the main contributor to the  stimulant  effect of  Catha edulis , also known as  khat . Cathinone differs from many other amphetamines in that it has a  ketone   functional group . Other phenethylamines that share this structure include the stimulants  methcathinone ,  MDPV ,  mephedrone  and the  antidepressant   bupropion ."}
{"_id": "WikiPedia_Cardio$$$corpus_5916", "text": "Khat  has been cultivated in the  Horn of Africa  and  Arabian Peninsula  region of the world for thousands of years. It is most commonly chewed for the  euphoric  effect it produces. The active ingredient was first proposed in 1930, when  cathine  was identified as a predominant alkaloid in the plant. [ 4 ]  Cathine was thought to be the main active ingredient in khat until the 1960s, when it was found that the amount of cathine in the khat leaves is insufficient to produce the effects observed. In 1975, the United Nations Narcotic Laboratory analyzed khat leaves from  Yemen ,  Kenya  and  Madagascar  and found evidence of a different alkaloid, cathinone. [ 4 ]  Cathinone is molecularly similar to cathine, but is much more abundant in younger plants.  This finding caused scientists to speculate that cathinone was the true active ingredient in khat. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5917", "text": "A study was conducted in 1994 to test the effects of cathinone. Six volunteers who had never chewed khat were given an active khat sample and a cathinone-free  placebo  sample. [ 5 ]  The researchers analyzed the participants' moods, activity levels and blood pressure before and after consuming the khat or placebo. This analysis showed that cathinone produced amphetamine-like symptoms, leading the researchers to confirm that cathinone, not cathine, is the active ingredient in khat leaves. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5918", "text": "Over 20 million people in the  Arabian Peninsula  and  East Africa  chew khat leaves daily.  It is an important piece of the culture and economy in this region, especially in  Ethiopia  (where khat is said to have originated), Kenya,  Djibouti , Somalia and Yemen.  Men usually chew it during parties or other social gatherings while smoking cigarettes and drinking tea.  Farmers and other workers also use khat in the afternoon to reduce fatigue and hunger as the day goes on.  It functions like the  caffeine  in a strong cup of coffee as an anti-fatigue drug.  Students and drivers have been known to use it to stay alert for longer periods of time. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5919", "text": "In order to produce its desired effects, khat leaves should be chewed fresh.  The fresh leaves have a higher concentration of cathinone.  Waiting too long after cultivation to chew the leaf will allow the cathinone to break down into its less potent form, cathine.  Because of the need for quick chewing, it is a habit that has historically been prevalent only where the plant grows.  However, in the recent years with improvements in road and air transport, khat chewing has spread to all corners of the world."}
{"_id": "WikiPedia_Cardio$$$corpus_5920", "text": "The cultivation of khat in Yemen is a highly profitable industry for farmers.  Khat plants will grow differently depending on the climate they are grown in and each one will produce different amounts of cathinone. [ 7 ]   It generally grows best in coastal, hot climates.  In Yemen, the khat plant is named after the region in which it is grown.  The Nehmi khat plant has the highest known concentration of cathinone, 342.5\u00a0mg/100\u00a0g. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5921", "text": "Internationally, cathinone is a  Schedule I  drug under the  Convention on Psychotropic Substances . [ 8 ]  Circa 1993, the  DEA  added cathinone to the  Controlled Substances Act 's Schedule I."}
{"_id": "WikiPedia_Cardio$$$corpus_5922", "text": "The sale of khat is legal in some jurisdictions, but illegal in others (see  Khat (Regulation) ).  Substituted cathinones  were also often used as the key ingredient of recreational drug mixes commonly known as \" bath salts \" in the United States. [ 9 ] [ 10 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5923", "text": "The table below shows the legality of khat and cathinone in various countries:"}
{"_id": "WikiPedia_Cardio$$$corpus_5924", "text": "Cathinone has been found to stimulate the release of  dopamine  and inhibit the reuptake of  epinephrine ,  norepinephrine  and  serotonin  in the  central nervous system  (CNS). These  neurotransmitters  are all considered  monoamines  and share the general structure of an  aromatic ring  and an  amine  group attached by a two-carbon separator. [ 7 ]  Because cathinone is a  hydrophobic  molecule, it can easily cross cell membranes and other barriers, including the  blood\u2013brain barrier . [ 32 ]  This property allows it to interact with the monoamine transporters in the  synaptic cleft  between  neurons . Cathinone induces the release of  dopamine  from brain striatal preparations that are prelabelled either with dopamine or its precursors. [ 33 ]  It is more specificllay a  norepinephrine\u2013dopamine releasing agent  (NDRA) similarly to  amphetamine . [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5925", "text": "The metabolites of cathinone, cathine and norephedrine, also possess CNS stimulation, but create much weaker effects. [ 34 ]  The effects of cathinone on the body can be countered by a preceding administration of a  dopamine receptor antagonist . [ 34 ]  The antagonist prevents synaptic dopamine released by cathinone from  exerting its effect by binding to dopamine receptors."}
{"_id": "WikiPedia_Cardio$$$corpus_5926", "text": "Cathinone can also affect cholinergic concentrations in the gut and airways by blocking prejunctional  adrenergic receptors  (\u03b1 2  adrenergic) and activating  5-HT7  receptors, thereby inhibiting  smooth muscle  contraction. [ 32 ]  It can also induce dry mouth, blurred vision and increased blood pressure and heart rate. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5927", "text": "Cathinone is a weak agonist of the mouse, rat, and human  trace amine-associated receptor 1  (TAAR1). [ 35 ] [ 36 ]  In contrast to cathinone however, most other  cathinones  are not human TAAR1 agonists. [ 37 ] [ 36 ]  TAAR1 activation may auto-inhibit and constrain the  monoaminergic  effects of  monoamine releasing agents  possessing TAAR1 agonism. [ 37 ] [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5928", "text": "Khat leaves are removed from the plant stalk and are kept in a ball in the cheek and chewed. Chewing releases juices from the leaves, which include the alkaloid cathinone. The absorption of cathinone has two phases: one in the  buccal mucosa  and one in the  stomach  and  small intestine . [ 5 ]  The stomach and small intestine are very important in the absorption of ingested alkaloids. [ 5 ]  At approximately 2.3 hours after chewing khat leaves, the maximum concentration of cathinone in blood plasma is reached. The mean residence time is 5.2\u00a0\u00b1\u00a03.4 hours. [ 5 ]  The elimination half-life of cathinone is 1.5\u00a0\u00b1\u00a00.8 hours. [ 5 ]  A two-compartment model for absorption and elimination best describes this data. However, at most, only 7% of the ingested cathinone is recovered in the urine. [ 5 ]  This indicates that the cathinone is being broken down in the body. Cathinone has been shown to selectively metabolize into R,S-(-)-norephedrine and cathine. The reduction of the  ketone  group in cathinone will produce cathine. This reduction is catalyzed by enzymes in the liver. The spontaneous breakdown of cathinone is the reason it must be chewed fresh after cultivation. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5929", "text": "The first documentation of the khat plant being used in medicine was in a book published by an Arabian physician in the 10th century. [ 7 ]  It was used as an  antidepressant  because it led to feelings of happiness and excitement. Chronic khat chewing can also create drug dependence, as shown by animal studies. [ 7 ]  In such studies, monkeys were trained to push a lever to receive the drug reward. As the monkeys' dependence increased, they pressed the lever at an increasing frequency. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5930", "text": "Khat chewing and the effects of cathinone on the body differ from person to person, but there is a general pattern of behavior that emerges after ingesting fresh cathinone: [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5931", "text": "There are other effects not related to the CNS. The chewer can develop  constipation  and  heartburn  after a khat session. Long-term effects of cathinone can include  gum disease  or  oral cancer ,  cardiovascular disease  and  depression . [ 7 ]  The  withdrawal symptoms  of cathinone include  hot flashes ,  lethargy  and a great urge to use the drug for at least the first two days. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5932", "text": "The synthesis of cathinone in khat begins with L- phenylalanine  and the first step is carried out by L-phenylalanine ammonia lyase (PAL), which cleaves off an ammonia group and creates a carbon-carbon double bond, forming  cinnamic acid . [ 39 ]   After this, the molecule can either go through a beta-oxidative pathway or a non-beta-oxidative pathway.  The beta-oxidative pathway produces  benzoyl-CoA  while the non-beta-oxidative pathway produces  benzoic acid . [ 39 ]   Both of these molecules can be converted to 1-phenylpropane-1,2-dione by a  condensation reaction  catalyzed by a ThDP-dependent enzyme (Thiamine diphosphate-dependent enzyme) with  pyruvate  and producing CO 2 . [ 39 ]   1-phenylpropane-1,2-dione goes through a transaminase reaction to replace a ketone with an ammonia group to form (S)-cathinone.  (S)-Cathinone can then undergo a reduction reaction to produce the less potent but structurally similar cathine or norephedrine, which are also found in the plant. [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5933", "text": "Aside from the beta- and non-beta-oxidative pathways, the biosynthesis of cathinone can proceed through a CoA-dependent pathway. The CoA-dependent pathway is actually a mix between the two main pathways as it starts like the beta-oxidative pathway and then when it loses CoA, it finishes the synthesis in the non-beta-oxidative pathway.  In this pathway, the trans-cinnamic acid produced from L-phenylalanine is ligated to a  Coenzyme A  (CoA), just like the beginning of the beta-oxidative pathway. [ 39 ]  It then undergoes  hydration  at the double bond.  This product then loses the CoA to produce  benzaldehyde , an intermediate of the non-beta-oxidative pathway.  Benzaldehyde is converted into benzoic acid and proceeds through the rest of the synthesis. [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5934", "text": "Cathinone can be synthetically produced from propiophenone through a  Friedel-Crafts  acylation of propionic acid and benzene. [ 32 ]   The resulting  propiophenone  can be brominated, and the bromine can be substituted with ammonia to produce a racemic mixture of cathinone. A different synthetic strategy must be employed to produce enantiomerically pure (S)-cathinone.  This synthetic route starts out with the N-acetylation of the  optically active   amino acid , S-alanine. [ 32 ]   Then,  phosphorus pentachloride  (PCl 5 ) is used to chlorinate the  carboxylic acid  forming an acyl chloride. At the same time, a Friedel-Crafts acylation is preformed on benzene with  aluminum chloride  catalyst.  Finally, the  acetyl  protecting group is removed by heating with  hydrochloric acid  to form enantiomerically pure S-(-)-cathinone. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5935", "text": "Cathinone can be extracted from  Catha edulis , or synthesized from  \u03b1 -bromopropiophenone (which is easily made from  propiophenone ). Because cathinone is both a  primary amine  and a  ketone , it is very likely to  dimerize , especially as a free base isolated from plant matter. [ 40 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5936", "text": "The structure of cathinone is very similar to that of other molecules. By reducing the ketone, it becomes cathine if it retains its stereochemistry, or norephedrine if its stereochemistry is inverted. Cathine is a less potent version of cathinone and cathinone's spontaneous reduction is the reason that older khat plants are not as stimulating as younger ones.  Cathinone and amphetamine are closely related in that amphetamine is only lacking the ketone C=O group. [ 41 ]   Cathinone is structurally related to  methcathinone , in much the same way as  amphetamine  is related to  methamphetamine . Cathinone differs from amphetamine by possessing a  ketone   oxygen  atom (C=O) on the  \u03b2  (beta) position of the side chain. Advancements in synthesizing cyclic cathinones based on \u03b1-tetralone have employed chiral HPLC-CD techniques to determine the absolute configuration of enantiomers, an approach that may contribute to the development of pharmaceutical analogs with antidepressant potential. [ 42 ]  The corresponding substance  cathine , is a less powerful stimulant. The biophysiological conversion from cathinone to cathine is to blame for the depotentiation of  khat  leaves over time. Fresh leaves have a greater ratio of cathinone to cathine than dried ones, therefore having more psychoactive effects."}
{"_id": "WikiPedia_Cardio$$$corpus_5937", "text": "There are many cathinone derivatives that include the addition of an R group to the amino end of the molecule.  Some of these derivatives have medical uses as well.   Bupropion  is one of the most commonly prescribed antidepressants and its structure is Cathinone with a tertiary butyl group attached to the nitrogen and chlorine attached to the benzene ring  meta-  to the main carbon chain. [ 41 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5938", "text": "Other cathinone derivatives are strong psychoactive drugs.  One such drug is  methylone , a drug structurally similar to  MDMA ."}
{"_id": "WikiPedia_Cardio$$$corpus_5939", "text": "Cenderitide  (also known as  chimeric natriuretic peptide  or  CD-NP ) is a  natriuretic peptide  developed by the  Mayo Clinic  as a potential treatment for  heart failure . [ 1 ] [ 2 ] [ 3 ]  Cenderitide is created by the fusion of the 15 amino acid C-terminus of the snake venom  dendroaspis natriuretic peptide  (DNP) with the full  C-type natriuretic peptide  (CNP) structure. [ 2 ]  This peptide chimera is a dual activator of the natriuretic peptide receptors NPR-A and NPR-B and therefore exhibits the  natriuretic  and  diuretic  properties of DNP, as well as the antiproliferative and antifibrotic properties of CNP. [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5940", "text": "When faced with pressure overload, the heart attempts to compensate with a number of structural alterations including  hypertrophy  of cardiomyocytes and increase of extracellular matrix (ECM) proteins. [ 4 ] [ 5 ]  Rapid accumulation of ECM proteins causes excessive  fibrosis  resulting in decreased myocardial compliance and increased myocardial stiffness. [ 5 ] [ 6 ]  The exact mechanisms involved in excessive fibrosis are not fully understood but there is evidence that supports involvement from local growth factors  FGF-2 ,  TGF-beta  and platelet-derived growth factor. [ 7 ] [ 8 ] [ 9 ]  TGF-\u03b21 plays an important role in cardiac remodelling through the stimulation of fibroblast proliferation, ECM deposition and myocyte hypertrophy. [ 10 ] [ 11 ] [ 12 ]  The increase in  TGF-beta 1  expression in a pressure-overloaded heart correlates with the degree of fibrosis, suggesting TGF-beta 1 involvement in the progression from a compensated hypertrophy to failure. [ 13 ] [ 14 ]  Through an autocrine mechanism, TGF-beta 1 acts on  fibroblasts  by binding TGF-beta 1 receptors 1 and 2. Upon receptor activation, the receptor-associated transcription factor  Smad  becomes  phosphorylated  and associates with Co-Smad. [ 15 ]  This newly formed Smad-Co-Smad complex enters the nucleus where it acts as a transcription factor modulating gene expression. [ 15 ] \nCardiac remodelling of the ECM is also regulated by the CNP/NPR-B pathway as demonstrated by the improved outcomes in  transgenic  mice with CNP over-expression subjected to myocardial infarction. [ 16 ] [ 17 ]  Binding of CNP to NPR-B catalyzes the synthesis of cGMP, which is responsible for mediating the anti-fibrotic effects of CNP. [ 18 ] \nFibrotic heart tissue is associated with an increase risk of ventricular dysfunction which can ultimately lead to  heart failure . [ 5 ] [ 19 ]  Thus, anti-fibrotic strategies are a promising approach in the prevention and treatment of  heart failure ."}
{"_id": "WikiPedia_Cardio$$$corpus_5941", "text": "As cenderitide interacts with both NRP-A and NRP-B, this drug has antifibrotic potential. [ 1 ]  Binding of cenderitide to NRP-B elicits an antifibrotic response by catalyzing formation of  cGMP  similar to the response seen with endogenous CNP. Additionally,  in vitro  study of human fibroblasts demonstrates that cenderitide reduces  TGF-beta 1  induced  collagen  production. [ 1 ] [ 20 ]  These two proposed mechanisms illustrate therapeutic potential for the reduction of fibrotic remodelling in the  hypertensive  heart. Through combined effects of CNP and DNP, cenderitide treatment results in a reduction in stress on the heart (through natriuresis/diuresis) and inhibition of pro-fibrotic, remodeling pathways. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5942", "text": "A  cerebral vasodilator  is a  drug  which acts as a  vasodilator  in the  brain . [ 1 ] [ 2 ]  They are used to improve  blood flow  in people with  cerebrovascular insufficiency  and to treat  neurological disorders  secondary to this condition. [ 2 ]  A number of different cerebral vasodilators exist. [ 2 ] [ 1 ] [ 3 ]  An example is  ifenprodil , which has been marketed for use as a cerebral vasodilator in  France ,  Hong Kong , and  Japan . [ 4 ] [ 5 ] [ 6 ]  Other examples include  buphenine  (nylidrin),  isoxsuprine ,  oxyfedrine ,  suloctidil , and  tinofedrine . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5943", "text": "Similar drugs include  cerebral activators , or cerebral metabolism activators, like  bifemelane ,  indeloxazine , and  teniloxazine , which are also used to treat  cerebrovascular disease . [ 8 ] [ 9 ] [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5944", "text": "CXL 1020  is an  experimental drug  that is being investigated as a treatment for  acute decompensated heart failure . CXL 1020 functions as a  nitroxyl  donor; nitroxyl is the reduced,  protonated  version of  nitric oxide . [ 1 ]  Nitroxyl is capable of enhancing  left ventricular   contractility  without increasing  heart rate  by modifying normal Ca 2+  cycling through the  sarcoplasmic reticulum [ 2 ]  as well as increasing the sensitivity of cardiac  myofilaments  to Ca 2+ . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5945", "text": "Patients with acute decompensated heart failure have diminished left ventricular  systolic  and/or  diastolic  functioning. [ 4 ]  Impaired  ventricular function  can be a consequence of decreased sarcoplasmic reticulum Ca 2+  cycling and a corresponding decline in  cardiomyocyte  contraction. [ 2 ]   Reduced ventricular functioning limits the ability of the ventricles to fill with blood and pump blood to the rest of the body."}
{"_id": "WikiPedia_Cardio$$$corpus_5946", "text": "There are two mechanisms through which CXL 1020 is able to enhance the movement of Ca 2+  in and out of the sarcoplasmic reticulum. Sarcoplasmic reticulum CaATPase (SERCA) is an energy-dependent  ion pump  found the sarcoplasmic reticulum of cardiac myocytes that is responsible for transporting Ca 2+  within the  cytosol  back in to the  lumen  of the sarcoplasmic reticulum. [ 2 ]   The nitroxyl group that is donated by CXL 1020 initiates glutathiolation of SERCA at the cysteine 674 site, which in turn activates ATP-dependent Ca2+ transport. [ 5 ]  Therefore, stimulation of SERCA leads to accelerated uptake of Ca 2+  from the cytosol of the cardiac myocyte."}
{"_id": "WikiPedia_Cardio$$$corpus_5947", "text": "Secondly, the nitroxyl group from CXL 1020 interacts with  ryanodine receptors  (RyR), specifically  RyR2 , which is the predominant form found in cardiac tissue. [ 6 ]  Ryanodine receptors are located within the membrane of the sarcoplasmic reticulum and function to release Ca 2+  required for myofilament activation (Guyton, 2006).  Nitroxyl interacts with RyR2 to increase the probability of Ryanodine receptor opening, thereby enhancing Ca 2+  release from the sarcoplasmic reticulum. It is thought that nitroxyl modifies RyR2 function through its interaction with  thiol groups  present in the receptor, although the exact mechanism is unknown. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5948", "text": "Nitroxyl has also been shown to increase the sensitivity to cardiac myocytes to Ca 2+ , which in turn enhances the force of contraction. Its hypothesized that nitroxyl interacts with thiol groups present in myofilament proteins to increase the maximal Ca 2+  activated force of the myofilament, although the exact effect of nitroxyl on the myofilament is unknown. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5949", "text": "Daflon  is an oral micronized purified phlebotonic  flavonoid  fraction containing 90%  diosmin  and 10%  hesperidin . It is manufactured by  Laboratoires Servier  and often used to treat or manage disorders of the blood vessels. [ 1 ] [ 2 ]  Flavonoids are a type of  phytochemical  that have been associated with various effects on human health and are a component of many different  pharmaceutical ,  nutraceutical , and  cosmetic  preparations. [ 3 ]  Diosmin is a flavone  glycoside  that is derived from hesperidin. Hesperidin is a flavone that is extracted from citrus fruits. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5950", "text": "Daflon is not an FDA-approved medication, and therefore it cannot be advertised for treatment of diseases in the United States. Daflon is under preliminary research for its potential use in treating  vein  diseases, [ 5 ]  or  hemorrhoids . [ 6 ]  It is sold as a drug in  France , [ 7 ] [ 8 ]  Spain, [ 9 ]   Malaysia [ 10 ] [ 11 ]  and Belgium."}
{"_id": "WikiPedia_Cardio$$$corpus_5951", "text": "There is moderate certainty evidence for the effectiveness of daflon for slightly reducing oedema compared to placebo in the treatment of  chronic venous insufficiency . [ 12 ]   Little to no differences in quality of life after treatment with Daflon were found and there is low certainty evidence that this class of drugs do not influence ulcer healing. [ 12 ]   Diosmiplex, a micronized purified flavonoid fraction of daflon, with similar venous insufficiency indication, is sold as a prescription  medical food  in the US. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5952", "text": "Daflon plays a crucial role in the prevention of  perivascular   edema  formation and treatment of  venous stasis . This activity can be explained by its antagonist activity against  prostaglandin E2  (PgE2) and  thromboxane  (TxA2) biosynthesis leading to inhibition of inflammatory process. Moreover, it also has a contraction activity on the lymphatic vessels which cause the lymphatic flow maximal. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5953", "text": "For venous insufficiency, the dosage is 2 tablets of 500mg daily. For acute hemorrhoidal attack, the dosage is 6 tablets daily for 4 days, followed by 4 tablets daily over the next 3 days. [ 15 ]  For chronic venous disease, the dosage is 2 tablets a day for at least 2 months. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5954", "text": "Possible side effects include routine  gastric disorders  and neurovegetative disorders, however, toxicology studies indicate that diosmin is quite safe. [ 2 ]  Diosmin interacts in an inhibitory manner with some metabolic enzymes so  drug-interactions  are probable. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5955", "text": "Darapladib  is an inhibitor of  lipoprotein-associated phospholipase A2  (Lp-PLA 2 ) that is in  development  as a  drug  for treatment of  atherosclerosis . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5956", "text": "It was discovered by  Human Genome Sciences  in collaboration with  GlaxoSmithKline  (GSK). [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5957", "text": "In November 2013, GSK announced that the drug had failed to meet Phase III endpoints in a trial of 16,000 patients with  acute coronary syndrome  (ACS). [ 3 ]  An additional trial of 13,000 patients (SOLID-TIMI 52) finished in May 2014. The study failed to reduce the risk of  coronary heart disease  death,  myocardial infarction , and urgent coronary  revascularization  compared with placebo in acute coronary syndrome patients treated with standard medical care. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5958", "text": "In 2022, Darapladib has been found to inhibit  intraerythrocytic  development of the malaria parasite  Plasmodium falciparum  by inhibition of the human host enzyme  peroxiredoxin 6 . [ 5 ]  The authors present data that the original target of Darapladib,  Lp-PLA 2 , is absent in the host  red blood cell ."}
{"_id": "WikiPedia_Cardio$$$corpus_5959", "text": "Ephedrine  is a  central nervous system  (CNS)  stimulant  and  sympathomimetic agent  that is often used to prevent  low blood pressure  during  anesthesia . [ 11 ]  It has also been used for  asthma ,  narcolepsy , and  obesity  but is not the preferred treatment. [ 11 ]  It is of unclear benefit in  nasal congestion . [ 11 ]  It can be taken  by mouth  or by  injection into a muscle ,  vein , or  just under the skin . [ 11 ]  Onset with intravenous use is fast, while injection into a muscle can take 20 \u00a0 minutes, and by mouth can take an hour for effect. [ 11 ]  When given by injection, it lasts about an hour, and when taken by mouth, it can last up to four hours. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5960", "text": "Common  side effects  include  trouble sleeping ,  anxiety ,  headache ,  hallucinations ,  high blood pressure ,  fast heart rate ,  loss of appetite , and  urinary retention . [ 11 ]  Serious side effects include  stroke  and  heart attack . [ 11 ]  While probably safe in  pregnancy , its use in this population is poorly studied. [ 12 ] [ 13 ]  Use during  breastfeeding  is not recommended. [ 13 ]  Ephedrine works by  inducing the release of norepinephrine  and hence indirectly activating the  \u03b1-  and  \u03b2-adrenergic receptors . [ 11 ]  Chemically, ephedrine is a  substituted amphetamine  and is the (1 R ,2 S )- enantiomer  of  \u03b2-hydroxy- N -methylamphetamine . [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5961", "text": "Ephedrine was first  isolated  in 1885 and came into commercial use in 1926. [ 15 ] [ 16 ]  It is on the  World Health Organization's List of Essential Medicines . [ 17 ]  It is available as a  generic medication . [ 11 ]  It can normally be found in plants of the  Ephedra  genus. [ 11 ] [ 18 ]   Over-the-counter   dietary supplements  containing ephedrine are illegal in the  United States , [ 11 ]  with the exception of those used in  traditional Chinese medicine , where its presence is noted by  m\u00e1 hu\u00e1ng . [ 11 ] [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5962", "text": "Ephedrine is a non- catecholamine   sympathomimetic  with cardiovascular effects similar to those of  adrenaline /epinephrine: increased blood pressure, heart rate, and contractility. Like  pseudoephedrine  it is a  bronchodilator , with pseudoephedrine having considerably less effect. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5963", "text": "Ephedrine may decrease  motion sickness , but it has mainly been used to decrease the sedating effects of other medications used for motion sickness. [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5964", "text": "Ephedrine is also found to have quick and long-lasting responsiveness in  congenital myasthenic syndrome  in early childhood and also even in adults with a novel  COLQ  mutation. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5965", "text": "Ephedrine is administered by intravenous boluses. Redosing usually requires increased doses to offset the development of  tachyphylaxis , which is attributed to the depletion of catecholamine stores. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5966", "text": "Ephedrine promotes modest short-term  weight loss , [ 24 ]  specifically fat loss, but its long-term effects are unknown. [ 25 ]  In mice, ephedrine is known to stimulate  thermogenesis  in the  brown adipose tissue , but because adult humans have only small amounts of brown fat, thermogenesis is assumed to take place mostly in the  skeletal muscle . Ephedrine also decreases  gastric emptying .  Methylxanthines  such as  caffeine  and  theophylline  have a synergistic effect with ephedrine for weight loss. This led to the creation and marketing of compound products. [ 26 ]  One of them, known as the  ECA stack , contains ephedrine with caffeine and aspirin. It is a popular supplement taken by  bodybuilders  seeking to cut body fat before a competition. [ 27 ] \nA 2021 systematic review found that ephedrine led to a 2 kilograms (4.4\u00a0lb) weight loss greater than placebo, raised  heart rate , and reduced  LDL  and raised  HDL , with no statistically significant difference in  blood pressure . [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5967", "text": "Ephedrine is available as a  prescription-only   pharmaceutical drug  in the form of an  intravenous   solution , under brand names including Akovaz, Corphedra, Emerphed, and Rezipres as well as in  generic forms , in the  United States . [ 29 ] [ 30 ]  It is also available  over-the-counter  in the form of 12.5 and 25 \u00a0 mg  oral   tablets  for use as a  bronchodilator  and as a 0.5% concentration  nasal spray  for use as a  decongestant . [ 30 ]  The drug is additionally available in  combination  with  guaifenesin  in the form of oral tablets and liquids. [ 30 ]  Ephedrine is provided as the  hydrochloride  or  sulfate   salt  in pharmaceutical formulations. [ 29 ] [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5968", "text": "Ephedrine should not be used in conjunction with certain antidepressants, namely  norepinephrine-dopamine reuptake inhibitors  (NDRIs), as this increases the risk of symptoms due to excessive serum levels of norepinephrine."}
{"_id": "WikiPedia_Cardio$$$corpus_5969", "text": "Bupropion  is an example of an antidepressant with an amphetamine-like structure similar to ephedrine, and it is an NDRI. Its action bears more resemblance to amphetamine than to  fluoxetine  in that its primary mode of therapeutic action involves norepinephrine and to a lesser degree dopamine, but it also releases some  serotonin  from presynaptic clefts. It should not be used with ephedrine, as it may increase the likelihood of side effects."}
{"_id": "WikiPedia_Cardio$$$corpus_5970", "text": "Ephedrine should be used with caution in patients with inadequate fluid replacement, impaired adrenal function,  hypoxia ,  hypercapnia ,  acidosis ,  hypertension ,  hyperthyroidism ,  prostatic hypertrophy ,  diabetes mellitus ,  cardiovascular  disease, during delivery if maternal blood pressure is >130/80 mmHg, and during lactation. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5971", "text": "Contraindications  for the use of ephedrine include:  closed-angle glaucoma ,  phaeochromocytoma ,  asymmetric septal hypertrophy  (idiopathic hypertrophic subaortic stenosis), concomitant or recent (previous 14 days)  monoamine oxidase inhibitor  (MAOI) therapy, general  anaesthesia  with halogenated hydrocarbons (particularly halothane), tachyarrhythmias or ventricular fibrillation, or hypersensitivity to ephedrine or other stimulants. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5972", "text": "Ephedrine should not be used at any time during pregnancy unless specifically indicated by a qualified physician and only when other options are unavailable. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5973", "text": "Ephedrine is a potentially dangerous natural compound; as of 2004 [update]  the US  Food and Drug Administration  had received over 18,000 reports of adverse effects in people using it. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5974", "text": "Adverse drug reactions  (ADRs) are more common with systemic administration (e.g. injection or oral administration) compared to topical administration (e.g. nasal instillations). ADRs associated with ephedrine therapy include  [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5975", "text": "Overdose  of ephedrine may result in  sympathomimetic   symptoms  like  tachycardia  and  hypertension . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5976", "text": "Ephedrine with  monoamine oxidase inhibitors  (MAOIs) like  phenelzine  and  tranylcypromine  can result in  hypertensive crisis . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5977", "text": "Ephedrine, a  sympathomimetic amine , acts on part of the  sympathetic nervous system  (SNS). The principal mechanism of action relies on its indirect stimulation of the  adrenergic receptor  system by increasing activation of  \u03b1-  and  \u03b2-adrenergic receptors  via  induction of norepinephrine release . [ 40 ]  The presence of direct interactions with \u03b1-adrenergic receptors is unlikely but still controversial. [ 41 ] [ 20 ] [ 42 ] [ 43 ]   L -ephedrine, and particularly its stereoisomer  norpseudoephedrine  (which is also present in  Catha edulis ) has indirect  sympathomimetic  effects and due to its ability to cross the  blood\u2013brain barrier , it is a  CNS   stimulant  similar to  amphetamines , but less pronounced, as it releases norepinephrine and  dopamine  in the  brain . [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5978", "text": "The  oral   bioavailability  of ephedrine is 88%. [ 6 ]  The  onset of action  of ephedrine orally is 15 to 60 \u00a0 minutes, via  intramuscular injection  is 10 to 20 \u00a0 minutes, and via  intravenous infusion  is within seconds. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5979", "text": "Its  plasma protein binding  is approximately 24 to 29%, with 5 to 10% bound to  albumin . [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5980", "text": "Ephedrine is largely not  metabolized . [ 6 ]   Norephedrine  (phenylpropanolamine) is an  active metabolite  of ephedrine formed via  N - demethylation . [ 6 ] [ 10 ]  About 8 to 20% of an oral dose of ephedrine is demethylated into norephedrine, about 4 to 13% is  oxidatively   deaminated  into  benzoic acid , and a small fraction is converted into 1,2-dihydroxy-1-phenylpropane. [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5981", "text": "Ephedrine is  eliminated  mainly in  urine , with 60% (range 53\u201379%)  excreted  unchanged. [ 6 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5982", "text": "The  elimination half-life  of ephedrine is 6 \u00a0 hours. [ 6 ]  Its  duration of action  orally is 2 to 4 \u00a0 hours and via intravenous or intramuscular injection is 60 \u00a0 minutes. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5983", "text": "The elimination of ephedrine is dependent on urinary  pH . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5984", "text": "Ephedrine, or (\u2212)-(1 R ,2 S )-ephedrine, also known as (1 R ,2 S )-\u03b2-hydroxy- N -methyl-\u03b1-methyl-\u03b2-phenethylamine or as (1 R ,2 S )-\u03b2-hydroxy- N -methylamphetamine, is a  substituted phenethylamine  and  amphetamine   derivative . It is similar in  chemical structure  to  phenylpropanolamine ,  methamphetamine , and  epinephrine  (adrenaline). It differs from methamphetamine only by the presence of a  hydroxyl  group (\u2013OH). Chemically, ephedrine is an  alkaloid  with a  phenethylamine  skeleton found in various plants in the genus  Ephedra  (family  Ephedraceae ). It is most usually marketed as the  hydrochloride  or  sulfate   salt . [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5985", "text": "It has an experimental  log P  of 1.13, while its predicted log P values range from 0.9 to 1.32. [ 14 ] [ 6 ] [ 46 ]  The  lipophilicity  of amphetamines is closely related to their  brain permeability . [ 47 ]  For comparison to ephedrine, the experimental log P of  methamphetamine  is 2.1, [ 48 ]  of  amphetamine  is 1.8, [ 49 ] [ 48 ]  of  pseudoephedrine  is 0.89, [ 50 ]  of  phenylpropanolamine  is 0.7, [ 51 ]  of  phenylephrine  is -0.3, [ 52 ]  and of  norepinephrine  is -1.2. [ 53 ]  Methamphetamine has high brain permeability, [ 48 ]  whereas phenylephrine and norepinephrine are  peripherally selective drugs . [ 54 ] [ 55 ]  The optimal log P for brain permeation and central activity is about 2.1 (range 1.5\u20132.7). [ 56 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5986", "text": "Ephedrine hydrochloride has a melting point of 187\u2212188 \u00a0 \u00b0C. [ 57 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5987", "text": "The  racemic  form of ephedrine is  racephedrine  ((\u00b1)-ephedrine;  dl -ephedrine; (1 RS ,2 SR )-ephedrine). [ 58 ]  A  stereoisomer  of ephedrine is  pseudoephedrine . [ 58 ]   Derivatives  of ephedrine include  methylephedrine  ( N -methylephedrine),  etafedrine  ( N -ethylephedrine),  cinnamedrine  ( N -cinnamylephedrine), and  oxilofrine  (4-hydroxyephedrine). [ 58 ]   Analogues  of ephedrine include  phenylpropanolamine  (norephedrine) and  metaraminol  (3-hydroxynorephedrine). [ 58 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5988", "text": "The presence of an  N - methyl group  decreases binding affinities at \u03b1-adrenergic receptors, compared with norephedrine. Ephedrine, though, binds better than  N -methylephedrine , which has an additional methyl group at the nitrogen atom. Also, the  steric  orientation of the hydroxyl group is important for receptor binding and functional activity. [ 42 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5989", "text": "Ephedrine exhibits  optical isomerism  and has two  chiral  centres, giving rise to four  stereoisomers . By convention, the pair of  enantiomers  with the stereochemistry (1 R ,2 S ) and (1 S ,2 R ) is designated ephedrine, while the pair of enantiomers with the stereochemistry (1 R ,2 R ) and (1 S ,2 S ) is called pseudoephedrine."}
{"_id": "WikiPedia_Cardio$$$corpus_5990", "text": "The isomer which is marketed is (\u2212)-(1 R ,2 S )-ephedrine. [ 59 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5991", "text": "In the outdated  D / L  system  (+)-ephedrine is also referred to as  D -ephedrine and (\u2212)-ephedrine as  L -ephedrine (in which case, in the  Fisher projection , the  phenyl ring  is drawn at the bottom). [ 59 ] [ 60 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5992", "text": "Often, the  D / L  system (with  small caps ) and the d/l system (with  lower-case ) are confused. The result is that the levorotary l-ephedrine is wrongly named  L -ephedrine and the dextrorotary d-pseudoephedrine (the diastereomer) wrongly  D -pseudoephedrine."}
{"_id": "WikiPedia_Cardio$$$corpus_5993", "text": "The  IUPAC names  of the two enantiomers are (1 R ,2 S )- respectively (1 S ,2 R )-2-methylamino-1-phenylpropan-1-ol. A synonym is  erythro -ephedrine."}
{"_id": "WikiPedia_Cardio$$$corpus_5994", "text": "Ephedrine may be quantified in blood, plasma, or urine to monitor possible abuse by athletes, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation. Many commercial  immunoassay  screening tests directed at the amphetamines cross-react appreciably with ephedrine, but chromatographic techniques can easily distinguish ephedrine from other phenethylamine derivatives. Blood or plasma ephedrine concentrations are typically in the 20\u2013200 \u00a0 \u03bcg/L range in persons taking the drug therapeutically, 300\u20133000 \u00a0 \u03bcg/L in abusers or poisoned patients, and 3\u201320 \u00a0 mg/L in cases of acute fatal overdosage. The current  World Anti-Doping Agency  (WADA) limit for ephedrine in an athlete's urine is 10 \u00a0 \u03bcg/mL. [ 61 ] [ 62 ] [ 63 ] [ 64 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5995", "text": "Ephedrine in its natural form, known as  m\u00e1hu\u00e1ng  (\u9ebb\u9ec4) in  traditional Chinese medicine , has been documented in China since the  Han dynasty  (206 BC \u2013 220 AD) as an  antiasthmatic  and stimulant. [ 65 ]  In traditional Chinese medicine,  m\u00e1hu\u00e1ng  has been used as a treatment for asthma and bronchitis for centuries. [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5996", "text": "In 1885, the chemical synthesis of ephedrine was first accomplished by Japanese  organic chemist   Nagai Nagayoshi  based on his research on  traditional Japanese  and  Chinese herbal medicines ."}
{"_id": "WikiPedia_Cardio$$$corpus_5997", "text": "The industrial manufacture of ephedrine in China began in the 1920s, when  Merck  began marketing and selling the drug as ephetonin. Ephedrine exports from China to the West grew from 4 to 216 tonnes between 1926 and 1928. [ 67 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5998", "text": "Ephedrine was first introduced for medical use in the  United States  in 1926. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_5999", "text": "It was introduced in 1948 in  Vicks  Vatronol nose drops (now discontinued) which contained ephedrine sulfate as the active ingredient for rapid nasal decongestion."}
{"_id": "WikiPedia_Cardio$$$corpus_6000", "text": "Ephedrine  is the  generic name  of the drug and its  BAN Tooltip British Approved Name . [ 58 ] [ 45 ] [ 68 ]  Its  DCF Tooltip D\u00e9nomination Commune Fran\u00e7aise  is  eph\u00e9drine  while its  DCIT Tooltip Denominazione Comune Italiana  is  efedrina . [ 45 ] [ 68 ]  In the case of the  hydrochloride   salt , its generic name is  ephedrine hydrochloride  and this is its  USAN Tooltip United States Adopted Name ,  BANM Tooltip British Approved Name , and  JAN Tooltip Japanese Accepted Name . [ 58 ] [ 45 ] [ 68 ]  In the case of the  sulfate  salt, its generic name is  ephedrine sulfate  or  ephedrine sulphate  and the former is its  USAN Tooltip United States Adopted Name  while the latter is its  BANM Tooltip British Approved Name . [ 58 ] [ 45 ] [ 68 ]  A synonym of ephedrine sulfate is  isofedrol . [ 58 ]  These names all refer to the (1 R ,2 R )- enantiomer  of ephedrine. [ 58 ] [ 45 ]  The  racemic  form of ephedrine is known as  racephedrine  and this is its  INN Tooltip International Nonproprietary Name  and  BAN Tooltip British Approved Name , while the hydrochloride salt of the racemic form is  racephedrine hydrochloride  and this is its  USAN Tooltip United States Adopted Name . [ 69 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6001", "text": "As a  phenethylamine , ephedrine has a similar chemical structure to  amphetamines  and is a  methamphetamine   analog  having the methamphetamine structure with a  hydroxyl  group at the  \u03b2 position . Because of ephedrine's structural similarity to methamphetamine, it can be used to create methamphetamine using  chemical reduction  in which ephedrine's hydroxyl group is removed; this has made ephedrine a highly sought-after chemical precursor in the  illicit manufacture  of  methamphetamine ."}
{"_id": "WikiPedia_Cardio$$$corpus_6002", "text": "The most popular method for reducing ephedrine to methamphetamine is similar to the  Birch reduction , in that it uses  anhydrous ammonia  and  lithium  metal in the reaction. The second-most popular method uses red  phosphorus  and  iodine  in the reaction with ephedrine. Moreover, ephedrine can be synthesized into  methcathinone  via simple  oxidation . As such, ephedrine is listed as a table-I precursor under the  United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances . [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6003", "text": "Ephedrine has been used as a  performance-enhancing drug  in  exercise  and  sports . [ 41 ] [ 71 ] [ 72 ] [ 73 ]  It can increase  heart rate ,  blood pressure , and  cardiac contractility  as well as act as a  psychostimulant . [ 41 ]  Ephedrine is often used in combination with  caffeine  for performance-enhancing purposes. [ 72 ] [ 73 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6004", "text": "In  chemical synthesis , ephedrine is used in bulk quantities as a  chiral auxiliary  group. [ 74 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6005", "text": "In  saquinavir  synthesis, the half-acid is resolved as its salt with l-ephedrine."}
{"_id": "WikiPedia_Cardio$$$corpus_6006", "text": "In January 2002,  Health Canada  issued a voluntary recall of all ephedrine products containing more than 8 \u00a0 mg per dose, all combinations of ephedrine with other stimulants such as caffeine, and all ephedrine products marketed for weight-loss or bodybuilding indications, citing a serious risk to health. [ 75 ]  Ephedrine is still sold as an oral nasal decongestant [ 76 ]  in 8 \u00a0 mg pills as a natural health product, with a limit of 0.4 \u00a0 g (400 \u00a0 mg) per package, the limit established by the Controlled Drugs and Substances Act as it is considered as Class A Precursor. [ 77 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6007", "text": "In 1997, the  FDA  proposed a regulation on ephedra (the herb from which ephedrine is obtained), which limited an ephedra dose to 8 \u00a0 mg (of active ephedrine) with no more than 24 \u00a0 mg per day. [ 78 ]  This proposed rule was withdrawn, in part, in 2000 because of \"concerns regarding the agency's basis for proposing a certain dietary ingredient level and a duration of use limit for these products.\" [ 79 ]  In 2004, the FDA created a ban on ephedrine alkaloids marketed for reasons other than asthma, colds, allergies, other disease, or traditional Asian use. [ 80 ]  On April 14, 2005, the  U.S. District Court for the District of Utah  ruled the FDA did not have proper evidence that low dosages of ephedrine alkaloids are actually unsafe, [ 81 ]  but on August 17, 2006, the  U.S. Court of Appeals for the Tenth Circuit  in Denver upheld the FDA's final rule declaring all dietary supplements containing ephedrine alkaloids adulterated, and therefore illegal for marketing in the United States. [ 82 ]  Furthermore, ephedrine is banned by the NCAA, MLB, NFL, and PGA. [ 83 ]  Ephedrine is, however, still legal in many applications outside of dietary supplements. Purchasing is currently limited and monitored, with specifics varying from state to state."}
{"_id": "WikiPedia_Cardio$$$corpus_6008", "text": "The  House  passed the  Combat Methamphetamine Epidemic Act of 2005  as an amendment to the renewal of the  USA PATRIOT Act . Signed into law by President  George W. Bush  on March 6, 2006, the act amended the  US Code  (21 USC 830) concerning the sale of products containing ephedrine and the closely related drug  pseudoephedrine . Both substances are used as  precursors  in the  illicit production  of  methamphetamine , and to discourage that use the federal statute included the following requirements for merchants who sell these products:"}
{"_id": "WikiPedia_Cardio$$$corpus_6009", "text": "The law gives similar regulations to mail-order purchases, except the monthly sales limit is 7.5 \u00a0 g."}
{"_id": "WikiPedia_Cardio$$$corpus_6010", "text": "As a pure herb or tea,  m\u00e1 hu\u00e1ng , containing ephedrine, is still sold legally in the US. The law restricts/prohibits its being sold as a dietary supplement (pill) or as an ingredient/additive to other products, like diet pills."}
{"_id": "WikiPedia_Cardio$$$corpus_6011", "text": "Ephedrine and all  Ephedra  species that contain it are considered Schedule 4 substances under the  Poisons Standard . A Schedule 4 drug is considered a Prescription Only Medicine, or Prescription Animal Remedy \u2013 Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription under the  Poisons Standard ."}
{"_id": "WikiPedia_Cardio$$$corpus_6012", "text": "In South Africa, ephedrine was moved to schedule 6 on 27 May 2008, [ 84 ]  which makes pure ephedrine tablets prescription only. Pills containing ephedrine up to 30\u00a0mg per tablet in combination with other medications are still available OTC, schedule 1 and 2, for sinus, head colds, and influenza."}
{"_id": "WikiPedia_Cardio$$$corpus_6013", "text": "Ephedrine was freely available in pharmacies in Germany until 2001. Afterward, access was restricted since it was mostly bought for unindicated uses. Similarly, ephedra can only be bought with a prescription. Since April 2006, all products, including plant parts, that contain ephedrine are only available with a prescription. [ 85 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6014", "text": "Ephedrine is obtained from the plant  Ephedra sinica  and other members of the genus  Ephedra ,  from which the name of the substance is derived. Raw materials for the manufacture of ephedrine and traditional Chinese medicines are produced in China on a large scale. As of 2007, companies produced for export US$13 million worth of ephedrine from 30,000 tons of ephedra annually, or about ten times the amount used in traditional Chinese medicine. [ 86 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6015", "text": "Most of the l-ephedrine produced today for official medical use is made synthetically as the extraction and isolation process from  E. sinica  is tedious and no longer cost-effective. [ 87 ] [ unreliable source? ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6016", "text": "Ephedrine was long thought to come from modifying the amino acid  L -phenylalanine. [ 90 ]   L -Phenylalanine would be decarboxylated and subsequently attacked with \u03c9-aminoacetophenone. Methylation of this product would then produce ephedrine. This pathway has since been disproven. [ 90 ]  A new pathway proposed suggests that phenylalanine first forms  cinnamoyl-CoA  via the enzymes  phenylalanine ammonia-lyase  and acyl CoA ligase. [ 88 ]  The cinnamoyl-CoA is then reacted with a hydratase to attach the alcohol functional group. The product is then reacted with a retro-aldolase, forming  benzaldehyde . Benzaldehyde reacts with  pyruvic acid  to attach a 2-carbon unit. This product then undergoes transamination and methylation to form ephedrine and its stereoisomer, pseudoephedrine. [ 89 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6017", "text": "Etafedrine  ( INN Tooltip International Nonproprietary Name ,  BAN Tooltip British Approved Name ), sold under the brand name  Nethaprin  among others and also known as  N -ethylephedrine , is a  sympathomimetic agent  used as a  bronchodilator  to treat  asthma . [ 2 ] [ 3 ] [ 4 ]  It was previously commercially available as both the  free base  and as the  hydrochloride   salt  from Sanofi-Aventis (now  Sanofi ) but is now no longer marketed. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6018", "text": "Unlike  ephedrine  and  tyramine , etafedrine does not  induce the release  of  epinephrine  or  norepinephrine  and instead acts as a  selective   \u03b2 2 -adrenergic receptor agonist , thereby mediating its  bronchodilator  effects. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6019", "text": "Fatty acid oxidation inhibitors  are a new potent class of drugs used in treatment of  stable  angina pectoris  and an addition in treatment of chronic  heart failure ."}
{"_id": "WikiPedia_Cardio$$$corpus_6020", "text": "4-Fluoroephedrine  ( 4-FEP ) is a  \"novel psychoactive substance\"  and  substituted \u03b2-hydroxyamphetamine   derivative  related to  ephedrine . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6021", "text": "Similarly to other  amphetamines , 4-fluoroephedrine acts as a  monoamine reuptake inhibitor  and  monoamine releasing agent . [ 3 ] [ 4 ]  It specifically acts as a  selective   norepinephrine releasing agent . [ 3 ] [ 4 ]  In contrast to many other amphetamines, but similarly to most  cathinones , 4-fluoroephedrine lacks  affinity  for the human  trace amine-associated receptor 1  (hTAAR1). [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6022", "text": "4-Fluoroephedrine, also known as 4-fluoro-\u03b2-hydroxy- N -methylamphetamine, is a  substituted phenethylamine ,  amphetamine , and  \u03b2-hydroxyamphetamine   derivative . [ 6 ] [ 1 ]  It is the 4- fluoro   analogue  of  ephedrine . [ 6 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6023", "text": "The  synthesis  of 4-fluoroephedrine has been described. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6024", "text": "It can serve as a  precursor  in the synthesis of  4-fluoromethamphetamine  (4-FMA). [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6025", "text": "The predicted  log P  ( XLogP3 ) of 4-fluoroephedrine is 1.0. [ 6 ]  For comparison, the predicted log P of ephedrine is 0.9. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6026", "text": "4-Fluoroephedrine was first described in the  scientific literature  by 1991. [ 7 ]  The next mention of it in the literature was in 2013, when it was identified as a \"novel psychoactive substance\". [ 9 ]  The  pharmacology  of 4-fluoroephedrine was characterized in 2015. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6027", "text": "4-Fluoroephedrine is known to be a  metabolite  of  4-fluoromethcathinone  (4-FMC; flephedrone). [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6028", "text": "Glucagon , sold under the brand name  Baqsimi  among others, is a  medication  and  hormone . [ 9 ]  As a medication it is used to treat  low blood sugar ,  beta blocker overdose ,  calcium channel blocker overdose , and those with  anaphylaxis  who do not improve with  epinephrine . [ 10 ]  It is given by  injection into a vein ,  muscle , or  under the skin . [ 10 ]  A version  given in the nose  is also available. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6029", "text": "Common side effects include vomiting. [ 10 ]  Other side effects include  low blood potassium  and  low blood pressure . [ 9 ]  It is not recommended in people who have a  pheochromocytoma  or  insulinoma . [ 10 ]  Use in  pregnancy  has not been found to be harmful to the baby. [ 12 ]  Glucagon is in the  glycogenolytic  family of medications. [ 10 ]  It works by causing the  liver  to break down  glycogen  into  glucose . [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6030", "text": "Glucagon was approved for medical use in the United States in 1960. [ 10 ]  It is on the  World Health Organization's List of Essential Medicines . [ 13 ]   It is a manufactured form of the  glucagon  hormone. [ 10 ]  A generic version became available in the United States in December 2020. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6031", "text": "An injectable form of glucagon may be part of first aid in cases of  low blood sugar  when the person is unconscious or for other reasons cannot take glucose orally or by intravenous. [ 15 ]  The glucagon is given by intramuscular, intravenous or subcutaneous injection, and quickly raises  blood glucose  levels. To use the injectable form, it must be reconstituted prior to use, a step that requires a sterile diluent to be injected into a vial containing powdered glucagon, because the hormone is highly unstable when dissolved in solution.  When dissolved in a fluid state, glucagon can form amyloid fibrils, or tightly woven chains of proteins made up of the individual glucagon peptides, and once glucagon begins to fibrilize, it becomes useless when injected, as the glucagon cannot be absorbed and used by the body.  The reconstitution process makes using glucagon cumbersome, although there are a number of products now in development from a number of companies that aim to make the product easier to use."}
{"_id": "WikiPedia_Cardio$$$corpus_6032", "text": "Anecdotal evidence suggests a benefit of higher doses of glucagon in the treatment of overdose with  beta blockers ; the likely mechanism of action is the increase of cAMP in the  myocardium , in effect bypassing the  \u03b2-adrenergic   second messenger system . [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6033", "text": "Some people who have  anaphylaxis  and are on beta blockers are resistant to  epinephrine . In this situation glucagon intravenously may be useful to treat their low blood pressure. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6034", "text": "Glucagon relaxes the  lower esophageal sphincter  and may be used in those with an  impacted food bolus in the esophagus  (\"steakhouse syndrome\"). [ 18 ]  There is little evidence for glucagon's effectiveness in this condition, [ 19 ] [ 20 ] [ 21 ]  and glucagon may induce nausea and vomiting, [ 21 ]   but considering the safety of glucagon this is still considered an acceptable option as long it does not lead to delays in arranging other treatments. [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6035", "text": "Glucagon's effect of increasing cAMP causes relaxation of splanchnic smooth muscle, allowing  cannulation  of the duodenum during the  endoscopic retrograde cholangiopancreatography  (ERCP) procedure."}
{"_id": "WikiPedia_Cardio$$$corpus_6036", "text": "Glucagon acts very quickly; common side-effects include headache and nausea."}
{"_id": "WikiPedia_Cardio$$$corpus_6037", "text": "Drug interactions: Glucagon interacts only with oral anticoagulants, increasing the tendency to bleed. [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6038", "text": "While glucagon can be used clinically to treat various forms of hypoglycemia, it is contraindicated in patients with  pheochromocytoma , as it can induce the tumor to release  catecholamines , leading to a sudden elevation in blood pressure. [ 4 ]  Likewise, glucagon is contraindicated in patients with an  insulinoma , as its hyperglycemic effect can induce the tumor to release insulin, leading to rebound  hypoglycemia . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6039", "text": "Glucagon binds to the  glucagon receptor , a  G protein-coupled receptor , located in the  plasma membrane . The conformation change in the receptor activates  G proteins , a heterotrimeric protein with \u03b1, \u03b2, and \u03b3 subunits. When the G protein interacts with the receptor, it undergoes a conformational change that results in the replacement of the  GDP  molecule that was bound to the \u03b1 subunit with a  GTP  molecule. This substitution results in the releasing of the \u03b1 subunit from the \u03b2 and \u03b3 subunits.  The alpha subunit specifically activates the next enzyme in the cascade,  adenylate cyclase . [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6040", "text": "Adenylate cyclase manufactures  cyclic adenosine monophosphate  (cyclic AMP or cAMP), which activates  protein kinase A  (cAMP-dependent protein kinase). This enzyme, in turn, activates  phosphorylase kinase , which then phosphorylates  glycogen phosphorylase  b, converting it into the active form called phosphorylase a. Phosphorylase a is the enzyme responsible for the release of  glucose-1-phosphate  from glycogen polymers. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6041", "text": "Additionally, the coordinated control of glycolysis and gluconeogenesis in the liver is adjusted by the phosphorylation state of the enzymes that catalyze the formation of a potent activator of glycolysis called fructose-2,6-bisphosphate. [ 26 ]  The enzyme protein kinase A that was stimulated by the cascade initiated by glucagon will also phosphorylate a single serine residue of the bifunctional polypeptide chain containing both the enzymes fructose-2,6-bisphosphatase and phosphofructokinase-2. This covalent phosphorylation initiated by glucagon activates the former and inhibits the latter. This regulates the reaction catalyzing fructose-2,6-bisphosphate (a potent activator of phosphofructokinase-1, the enzyme that is the primary regulatory step of glycolysis) [ 27 ]  by slowing the rate of its formation, thereby inhibiting the flux of the glycolysis pathway and allowing gluconeogenesis to predominate. This process is reversible in the absence of glucagon (and thus, the presence of insulin)."}
{"_id": "WikiPedia_Cardio$$$corpus_6042", "text": "Glucagon stimulation of PKA also inactivates the glycolytic enzyme  pyruvate kinase . [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6043", "text": "In the 1920s, Kimball and Murlin studied  pancreatic  extracts, and found an additional substance with  hyperglycemic  properties. They described glucagon in 1923. [ 29 ]  The amino acid sequence of glucagon was described in the late 1950s. [ 30 ]  A more complete understanding of its role in physiology and disease was not established until the 1970s, when a specific  radioimmunoassay  was developed."}
{"_id": "WikiPedia_Cardio$$$corpus_6044", "text": "A  nasal version  was approved for use in the United States and Canada in 2019. [ 11 ] [ 31 ] [ 32 ] [ 33 ] [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6045", "text": "In December 2020, the  Committee for Medicinal Products for Human Use  (CHMP) of the  European Medicines Agency  (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Ogluo, intended for the treatment of severe hypoglycemia in diabetes mellitus. [ 35 ]  The applicant for this medicinal product is Xeris Pharmaceuticals Ireland Limited. It was approved for medical use in the European Union in February 2021. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6046", "text": "Hetrombopag  (also known as  rafutrombopag ; trade name  Hengqu ) is a pharmaceutical drug for the treatment of  thrombocytopenia  and  anemia . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6047", "text": "It is a non-peptide small\u2010molecule  thrombopoietin receptor  agonist. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6048", "text": "In China, it is approved for second-line treatment for primary  immune thrombocytopenic purpura  (ITP) and severe  aplastic anemia  (SAA) in adults. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6049", "text": "This  drug  article relating to the  blood  and  blood forming organs  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_6050", "text": "Isoprenaline , also known as  isoproterenol  and sold under the brand name  Isuprel  among others, is a  sympathomimetic   medication  which is used in the treatment of acute  bradycardia  (slow heart rate),  heart block , and rarely for  asthma , among other indications. [ 9 ]  It is used by  injection into a vein ,  muscle ,  fat , or the  heart , by  inhalation , and in the past  under the tongue  or  into the rectum . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6051", "text": "Side effects of isoprenaline include  rapid heart beat ,  heart palpitations , and  arrhythmias , among others. [ 9 ]  Isoprenaline is a  selective   agonist  of the  \u03b2-adrenergic receptors , including both the  \u03b2 1 -  and  \u03b2 2 -adrenergic receptors . [ 9 ]  By activating these  receptors , it increases  heart rate  and the  force of heart contractions . [ 10 ]  Chemically, isoprenaline is a  synthetic   catecholamine  and is the  N - isopropyl   analogue  of  norepinephrine  (noradrenaline) and  epinephrine  (adrenaline). [ 11 ] [ 3 ] [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6052", "text": "Isoprenaline was one of the first  synthetic   sympathomimetic   amines  and was the first  selective  \u03b2-adrenergic receptor agonist. [ 7 ] [ 14 ]  The medication was discovered in 1940 [ 5 ]  and was introduced for medical use in 1947. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6053", "text": "Isoprenaline is used to treat  heart block  and episodes of  Adams\u2013Stokes syndrome  that are not caused by  ventricular tachycardia  or  fibrillation , in emergencies for  cardiac arrest  until  electric shock  can be administered, for  bronchospasm  occurring during  anesthesia , and as an  adjunct  in the treatment of  hypovolemic shock ,  septic shock , low  cardiac output  ( hypoperfusion ) states,  congestive heart failure , and  cardiogenic shock . [ 9 ]  It is also used to prevent  Torsades de Pointes  in patients with  long QT  refractory to  magnesium  and to treat patients with intermittent Torsades de Pointes refractory to treatment with magnesium. [ 16 ]  Isoprenaline is used in the acute management of bradycardia, though not in the chronic treatment of bradycardia. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6054", "text": "Historically, it was used to treat  asthma  via metered aerosol or nebulizing devices; it was also available in sublingual, oral, intravenous, and intramuscular formulations. [ 15 ]  The U.S. National Asthma Education and Prevention Program Expert Panel recommends against its use as a nebulizer for acute bronchoconstriction. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6055", "text": "Many formulations of isoprenaline appear to have been discontinued in the  United States  and many other countries. [ 4 ] [ 1 ] [ 2 ] [ 3 ]  In the United States, it remains available only as an  injectable   solution . [ 4 ]  It was previously also available in the United States as a solution, metered  aerosol , powder, or disc for  inhalation  and as a  tablet  for  sublingual  and  rectal administration , but these formulations were discontinued. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6056", "text": "It should not be used in people with  tachyarrhythmias  (except in special circumstances), [ 19 ]   tachycardia  or  heart block  caused by  digitalis  poisoning,  ventricular arrhythmias  which require  inotropic  therapy, or with  angina . [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6057", "text": "Side effects of isoprenaline may include  nervousness ,  headache ,  dizziness ,  nausea ,  blurred vision ,  tachycardia ,  palpitations ,  angina ,  Adams-Stokes attacks ,  pulmonary edema ,  hypertension ,  hypotension ,  ventricular arrhythmias ,  tachyarrhythmias ,  difficulty breathing ,  sweating , mild  tremors ,  weakness ,  flushing , and  pallor . [ 9 ]  Isoprenaline has been reported to cause  insulin resistance  leading to  diabetic ketoacidosis . [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6058", "text": "Overdose  of isoprenaline may produce effects including  tachycardia ,  arrhythmias ,  palpitations ,  angina ,  hypotension ,  hypertension , and  myocardial necrosis . [ 3 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6059", "text": "Isoprenaline is a  \u03b2 1 -  and  \u03b2 2 -adrenergic receptor   full agonist  and has almost no  activity  at the  \u03b1-adrenergic receptors  at lower concentrations. [ 15 ] [ 21 ]  It has similar  affinity  for the \u03b2 1 - and \u03b2 2 -adrenergic receptors. [ 21 ] [ 8 ]  At higher concentrations, isoprenaline can also evoke responses mediated by \u03b1-adrenergic receptors. [ 8 ] [ 22 ] [ 23 ]  Its agonist effects at the  trace amine-associated receptor 1  (TAAR1) additionally provide it with  pharmacodynamic  effects that resemble those of the endogenous  trace amines , like  tyramine . [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6060", "text": "Isoprenaline's effects on the  cardiovascular system  (non-selective) relate to its actions on  cardiac  \u03b2 1 -adrenergic receptors and \u03b2 2 -adrenergic receptors on  smooth muscle  within the  tunica media  of  arterioles . Isoprenaline has  positive inotropic  and  chronotropic  effects on the heart. \u03b2 2 -Adrenergic receptor stimulation in  arteriolar  smooth muscle induces  vasodilation . Its inotropic and chronotropic effects elevate  systolic   blood pressure , while its vasodilatory effects tend to lower  diastolic  blood pressure. The overall effect is to decrease  mean arterial pressure  due to the vasodilation caused by \u03b2 2 -adrenergic receptor activation. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6061", "text": "The  isopropylamine  group in isoprenaline makes it selective for \u03b2-adrenergic receptors. [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6062", "text": "The adverse effects of isoprenaline are also related to the drug's  cardiovascular  effects. Isoprenaline can produce  tachycardia  (an elevated  heart rate ), which predisposes people who take it to  cardiac arrhythmias . [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6063", "text": "Data on the  absorption  of isoprenaline are limited. [ 3 ]   Oral  isoprenaline is  well-absorbed  but is subject to strong  first-pass metabolism [ 27 ]  and is approximately 1,000 \u00a0 times less  potent  than  intravenous administration . [ 6 ]  Hence, its oral  bioavailability  is very low. [ 5 ] [ 6 ]  Another study suggested that its oral bioavailability, based on  pharmacodynamic  activity via different routes, was slightly less than 4%. [ 27 ] [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6064", "text": "Isoprenaline is minimally able to cross the  blood\u2013brain barrier  and hence is a  peripherally selective drug . [ 29 ] [ 30 ]  This is attributed to its high  hydrophilicity . [ 29 ]  Whereas the extraction of isoprenaline in a single passage of the brain circulation following  intravenous injection  in humans was 3.8%, the extraction of propranolol, which is a more  lipophilic  compound and is readily able to cross into the brain, was 63.0%. [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6065", "text": "The  plasma protein binding  of isoprenaline is 68.8 \u00b1 1.2%. [ 3 ]  It is bound mainly to  albumin . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6066", "text": "Isoprenaline is  metabolized  by  catechol  O -methyltransferase  (COMT) and  conjugation  by  sulfation . [ 7 ] [ 31 ] [ 32 ] [ 3 ]  It does not appear to be  glucuronidated . [ 7 ]  There is very large  interindividual variability  in the sulfation of isoprenaline. [ 7 ]  The free  catechol   hydroxyl  groups keep it susceptible to enzymatic metabolism. [ 26 ]  The drug is a poor  substrate  for  monoamine oxidase  (MAO) and is not metabolized by this enzyme. [ 7 ] [ 9 ]  This is in contrast to  epinephrine  and  norepinephrine . [ 7 ]  Isoprenaline is much more strongly metabolized and conjugated with oral administration than with intravenous administration. [ 6 ]  Its  metabolite  3- O -methylisoprenaline, formed by COMT, is  active  as a weak  \u03b2-adrenergic receptor antagonist . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6067", "text": "Isoprenaline is  excreted  primarily in the  urine , as  sulfate   conjugates . [ 7 ] [ 31 ] [ 32 ] [ 3 ]  It is excreted 59 to 107% in urine and 12 to 27% in  feces . [ 3 ]  A majority of isoprenaline is excreted in urine in conjugated form, whereas 6.5 to 16.2% is excreted as unchanged isoprenaline and 2.6 to 11.4% is excreted as 3-O-methylisoprenaline and conjugates. [ 3 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6068", "text": "The  elimination half-life  of isoprenaline by  intravenous administration  is approximately 2.5 to 5 \u00a0 minutes. [ 3 ]  Its half-life with  oral administration  is approximately 40 \u00a0 minutes. [ 3 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6069", "text": "Isoprenaline, also known as  N -isopropyl-3,4,\u03b2-trihydroxyphenethylamine or as  N -isopropylnorepinephrine, is a  substituted phenethylamine  and  synthetic   catecholamine   derivative . [ 11 ] [ 3 ] [ 12 ] [ 9 ]  It is the  N - isopropyl   analogue  of  norepinephrine  (3,4,\u03b2-trihydroxyphenethylamine) and  epinephrine  (3,4,\u03b2-trihydroxy- N -methylphenethylamine). [ 11 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6070", "text": "Isoprenaline is a  small-molecule   compound  with the  molecular formula  C 11 H 17 NO 3  and a  molecular weight  of 211.26 \u00a0 g/mol. [ 11 ] [ 3 ] [ 12 ] [ 9 ]  It is a  hydrophilic  compound [ 29 ]  with a predicted  log P  of -0.6 to 0.25. [ 11 ] [ 3 ] [ 12 ]  For comparison, the experimental log P values of epinephrine and norepinephrine are -1.37 and -1.24, respectively. [ 33 ] [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6071", "text": "Isoprenaline is used pharmaceutically as the  hydrochloride  and  sulfate   salts . [ 1 ]  It is also used to a much lesser extent as the  free base . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6072", "text": "Isoprenaline is a  racemic mixture  of  levorotatory  and  dextrorotatory   enantiomers . [ 11 ] [ 3 ] [ 12 ]  The levorotatory or ( R )-enantiomer of isoprenaline is known as levisoprenaline ( INN Tooltip International Nonproprietary Name ) but was never marketed. [ 35 ] [ 36 ] [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6073", "text": "Synthetic analogues closely related to isoprenaline include  arbutamine ,  dichloroisoprenaline  (dichloroisoproterenol),  hexoprenaline ,  isoetharine  (\u03b1-ethylisoprenaline),  orciprenaline  (metaproterenol; a  positional isomer  of isoprenaline),  prenalterol , and  soterenol  (3-methanesulfonamidylisoprenaline), among others. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6074", "text": "Isoprenaline was discovered in 1940 [ 5 ]  and was developed in the 1940s. [ 7 ]  It was first approved for medical use in 1947 in the United States. [ 15 ]  Isoprenaline was one of the first  synthetic   sympathomimetic   amines , was the first  selective   \u03b2-adrenergic receptor agonist , and was the first major sympathomimetic agent devoid of  pressor  effects. [ 7 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6075", "text": "Between 1963 and 1968 in England, Wales, Scotland, Ireland, Australia, and New Zealand there was an increase in deaths among people using isoprenaline to treat asthma. This was attributed to unintentional  overdose : the inhalers produced in that area were dispensing five times the dosage dispensed by inhalers produced in the United States and Canada, where the deaths were not observed. [ 38 ] [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6076", "text": "The short  duration of action  and poor  oral  activity of isoprenaline led to the development of the much longer-acting and orally active  orciprenaline  (metaproterenol). [ 40 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6077", "text": "Isoprenaline  is the major  generic name  of the drug and its  INN Tooltip International Nonproprietary Name ,  BAN Tooltip British Approved Name , and  DCF Tooltip D\u00e9nomination Commune Fran\u00e7aise . [ 35 ] [ 1 ] [ 36 ] [ 2 ]   Isoprenalina  is its  Italian  generic name and its  DCIT Tooltip Denominazione Comune Italiana . [ 1 ] [ 2 ]   Isoprenaline hydrochloride  and  isoprenaline sulfate  are its  BANM Tooltip British Approved Name  in the case of the  hydrochloride  and  sulfate   salts , respectively. [ 1 ]   Isoproterenol  is another important synonym of the drug. [ 35 ] [ 1 ] [ 2 ]   Isoproterenol hydrochloride  is its  USAN Tooltip United States Adopted Name  and  JAN Tooltip Japanese Accepted Name  in the case of the hydrochloride salt and  isoproterenol sulfate  is its  USAN  and  JAN  in the case of the sulfate salt. [ 35 ] [ 1 ] [ 36 ] [ 2 ]  Other synonyms of the drug include  isopropylnorepinephrine ,  isopropylnoradrenaline , and  isopropydine . [ 35 ] [ 1 ] [ 36 ] [ 2 ]  It is additionally known by the former developmental code name  WIN-5162 . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6078", "text": "Isoprenaline has been marketed under many brand names worldwide. [ 1 ] [ 2 ]  These include Aleudrina, Asthpul, Iludrin, Iprenol, Isomenyl, Isuprel, Isoprenaline, Isoprenalina, Isoproterenol, Neo-Epinine, Neodrenal, Proternol, and Saventrine, among others. [ 1 ] [ 2 ]  It is also marketed as a  combination drug  with  cromoglicic acid  as Frenal Compositum, in combination with  pronase  as Isopal P, and in combination with  atropine  as Stmerin D. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6079", "text": "Lixivaptan  ( VPA-985 ) is an orally-active, non-peptide, selective vasopressin 2 receptor antagonist being developed as an investigational drug by Palladio Biosciences, Inc. (Palladio), a subsidiary of Centessa Pharmaceuticals plc. As of December\u00a02021 [update] , lixivaptan is in Phase III clinical development for the treatment of  Autosomal dominant polycystic kidney disease  (ADPKD), the most common form of  polycystic kidney disease . The U.S.  Food and Drug Administration  (FDA) has granted  orphan drug  designation to lixivaptan for the treatment of ADPKD."}
{"_id": "WikiPedia_Cardio$$$corpus_6080", "text": "Lixivaptan is a potent,  non-peptide , selective  vasopressin receptor antagonist . It is a member of the  vaptan  class of drugs."}
{"_id": "WikiPedia_Cardio$$$corpus_6081", "text": "V 2  receptor antagonists inhibit the binding of  arginine vasopressin  to  vasopressin receptor 2  (V 2 R) in kidney tubular epithelial cells, thereby having a net effect of  aquaresis , or electrolyte free water excretion. [ 1 ]   This property of vaptans explains their use as therapies to treat  euvolemic  and  hypervolemic  hyponatremia. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6082", "text": "V 2  receptor antagonists may have utility as therapies for ADPKD.  Genetic mutations associated with ADPKD cause an increase in intracellular levels of  cyclic adenosine monophosphate  (cAMP), which results in increased cellular proliferation and  cyst  formation and expansion in the kidney. [ 3 ]   Cyst growth displaces and destroys normal kidney tissue, leading to a decreased number and function of  nephrons .  Because intracellular cAMP is a secondary messenger for vasopressin acting at V 2 R ( vasopressin receptor 2 ), V 2  receptor antagonists can restore normal levels of intracellular cAMP, thereby delaying cyst growth. Treatment with specific V 2  receptor antagonists have shown a reduction in kidney size and cyst volume in animal models of PKD. [ 4 ] [ 5 ]  In particular, lixivaptan has demonstrated beneficial effects on cystic disease progression in rat and mouse models of ADPKD.  [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6083", "text": "Proof of efficacy for V 2  receptor antagonists to treat  ADPKD  has been demonstrated by clinical trials with  tolvaptan , a vasopressin antagonist in the same drug class as lixivaptan. [ 8 ]   In clinical studies, tolvaptan showed a significant decrease in the rate of disease progression in patients with ADPKD, which led to regulatory approvals for tolvaptan as a treatment of ADPKD in many countries, including the U.S., the EU, Japan, Canada, Australia, and Korea, among others. [ 9 ]  However, tolvaptan therapy is associated with potentially life-threatening  liver toxicity  in patients with ADPKD. [ 10 ]  Because of the risk of liver toxicity, in the US, tolvaptan is only available for ADPKD under a restricted distribution program (a  Risk Evaluation and Mitigation Strategies  (REMS program).  The FDA-approved prescribing information for tolvaptan for ADPKD includes a  boxed warning  for the risk of serious liver toxicity. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6084", "text": "Lixivaptan was previously administered to more than 1600 subjects across 36  clinical studies  as part of a prior clinical development program for the treatment of  hyponatremia  sponsored by Cardiokine, Inc. [ 1 ]   Across these studies, lixivaptan showed prolonged inhibition of the  vasopressin V2 receptor , as measured by changes in  pharmacodynamic  markers such as  urine osmolality , plasma copeptin, and  estimated glomerular filtration rate  (eGFR). [ 12 ]   Development of lixivaptan for hyponatremia indications is no longer ongoing."}
{"_id": "WikiPedia_Cardio$$$corpus_6085", "text": "Palladio conducted the ELiSA Phase II study with lixivaptan in 31 ADPKD patients.  In this study, the proportion of study subjects who showed a urine osmolality response consistent with full vasopressin V 2  receptor inhibition was qualitatively and quantitatively similar to the published effect seen in clinical studies conducted with tolvaptan. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6086", "text": "A Phase III study by Palladio to investigate whether it is safe and effective for the treatment of ADPKD was commenced in October 2021. [ 14 ]   The Phase III program with lixivaptan consists of two ongoing clinical trials: the ACTION and ALERT studies."}
{"_id": "WikiPedia_Cardio$$$corpus_6087", "text": "The ACTION study [ 14 ]  is a pivotal registration-enabling  Phase III clinical trial  of lixivaptan in patients with ADPKD.  It is projected to enroll 1350 patients in more than 20 countries worldwide.  If the ACTION study is successful, it will provide the main clinical evidence supporting the potential safety and efficacy of lixivaptan for the treatment of ADPKD."}
{"_id": "WikiPedia_Cardio$$$corpus_6088", "text": "The ACTION trial consists of two main parts. [ 14 ]  In Part 1 of the study, after completing the screening, run-in and titration periods, study subjects will enter a two-arm,  double-blind , placebo-controlled, randomized period during which they will receive lixivaptan or placebo for 12 months. This part of the trial will compare the change in estimated glomerular filtration rate (eGFR) measurements between the two groups to investigate the efficacy of lixivaptan in slowing the decline in kidney function.  This is followed by Part 2 of the study, during which all study participants who complete Part 1 will receive lixivaptan in a single-arm, open-label phase for an additional 12 months.  Part 2 will investigate whether lixivaptan's effect on kidney function continues to accrue over time. Altogether, including the titration periods, participants in the ACTION study will be taking study drug for more than two years, including lixivaptan for at least one year. It is expected that Part 1 will be completed for all participants by February 2025; Part 2 is projected to run until April 2026. [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6089", "text": "The second  Phase III study  with lixivaptan is the ALERT study. [ 15 ]  The goal of this study is to investigate whether lixivaptan can be safely used in patients with  ADPKD  who were previously treated with tolvaptan, but who had to permanently discontinue tolvaptan therapy due to  liver toxicity .  In the study, following  titration  to an optimal dose, up to 50 patients with ADPKD will be enrolled and treated with lixivaptan for 52 weeks.  They will be monitored frequently for signs of liver toxicity for as long as they are taking lixivaptan.  At the completion of the 52 weeks maintenance period, patients will be eligible to continue to receive lixivaptan in an  open label  extension study."}
{"_id": "WikiPedia_Cardio$$$corpus_6090", "text": "Tolvaptan  was studied in DILIsym\u00ae, a state of the art, multiscale  computational model  that uses non-clinical and clinical drug data to predict whether a drug could cause idiosyncratic liver toxicity. [ 16 ]  DILIsym\u00ae replicated accurately the liver toxicity observed with tolvaptan in clinical studies. [ 17 ]   Conversely, results from the DILIsym\u00ae study with lixivaptan suggest that lixivaptan may be less likely to cause idiosyncratic liver toxicity within this modeling system. [ 18 ]   Whether this result reliably predicts a lower risk of liver injury for lixivaptan will require more clinical safety data, which will be collected as part of the two ongoing Phase III clinical studies."}
{"_id": "WikiPedia_Cardio$$$corpus_6091", "text": "Meldonium  ( INN ; trade name  Mildronate , among others) is a pharmaceutical developed in 1970 by  Ivars Kalvi\u0146\u0161  at the  USSR  Latvia Institute of Organic Synthesis. It is now manufactured by the Latvian pharmaceutical company  Grindeks  and various generic producers. Primarily distributed in Eastern Europe, meldonium is used as an anti- ischemia  medication. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6092", "text": "Meldonium is prescribed for cardiovascular, neurological, and metabolic conditions due to its anti-ischaemic and cardioprotective effects, achieved by inhibiting  \u03b2-oxidation  and activating  glycolysis . Athletes have used meldonium to enhance recovery and (controversially) performance, though these claims lack robust scientific support. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6093", "text": "Since 1 January 2016, meldonium has been listed as a  banned  substance by the  World Anti-Doping Agency  (WADA). [ 3 ]  It functions as a metabolic modulator, altering enzymatic reactions in the body. While some athletes, including  Maria Sharapova , used meldonium before its ban, its effectiveness as a performance enhancer remains controversial. Numerous athletes have since been suspended or disqualified for its use. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6094", "text": "Meldonium, also known as Mildronate in Eastern Europe is primarily used for treating cardiovascular and neurological conditions. [ 5 ] [ 2 ]  It is prescribed for heart-related issues such as angina pectoris, heart failure, and coronary artery disease. [ 5 ] [ 6 ]  In some countries, particularly in Eastern Europe, meldonium is used to treat problems with brain circulation and has been reported to elevate mood and improve motor symptoms, dizziness, and nausea. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6095", "text": "Meldonium is available in various pharmaceutical forms to suit different medical needs and administration routes. The most common form is oral capsules, typically containing 250 mg or 500 mg of the active ingredient. [ 7 ]  For more rapid onset of action or in cases where oral administration is not feasible, meldonium is also produced as a solution for injection. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6096", "text": "The mechanism of action of meldonium is to act as a  fatty acid oxidation inhibitor , presumably by  inhibiting enzymes  in the  carnitine biosynthesis  pathway such as  \u03b3-butyrobetaine hydroxylase . [ 8 ]  Although initial reports suggested meldonium is a  non-competitive  and non-hydroxylatable analogue of gamma-butyrobetaine; [ 9 ]  further studies have identified that meldonium is a substrate for  gamma-butyrobetaine dioxygenase . [ 10 ] [ 11 ] [ 12 ]  X-ray crystallographic and  in vitro  biochemical studies suggest that meldonium binds to the substrate pocket of \u03b3-butyrobetaine hydroxylase and acts as an alternative  substrate , and therefore a  competitive inhibitor . [ 13 ]  Normally, this enzyme's action on its substrates \u03b3-butyrobetaine and 2-oxoglutarate gives, in the presence of the further substrate oxygen, the products L-carnitine, succinate, and carbon dioxide; in the presence of this alternate substrate, the reaction yields malonic acid semialdehyde,  formaldehyde  (akin to the action of histone  demethylases ),  dimethylamine , and (1-methylimidazolidin-4-yl)acetic acid, \"an unexpected product with an additional carbon-carbon bond resulting from N-demethylation coupled to oxidative rearrangement, likely via an unusual radical mechanism.\" [ 13 ] [ 12 ]  The unusual mechanism is thought likely to involve a  Steven's type rearrangement . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6097", "text": "Meldonium's inhibition of \u03b3-butyrobetaine hydroxylase gives a  half maximal inhibitory concentration  (IC 50 ) value of 62 micromolar, which other study authors have described as \"potent.\" [ 14 ]  Meldonium is an example of an inhibitor that acts as a non-peptidyl substrate mimic. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6098", "text": "To ensure a continuous guarantee of energy supply, the cell's energy-producing  mitochondria  oxidise considerable amounts of fat along with glucose.  Carnitine  transports long-chain fatty acids from the  cytosol  of the cell into the mitochondrion and is therefore essential for fatty acid oxidation (known as  beta oxidation ). Carnitine is mainly absorbed from the diet, but can be formed through biosynthesis. To produce carnitine,  lysine  residues are methylated to  trimethyllysine . Four enzymes are involved in the conversion of trimethyllysine and its intermediate forms into the final product of carnitine. The last of these 4 enzymes is  gamma-butyrobetaine dioxygenase  (GBB), which hydroxylates  butyrobetaine  into carnitine."}
{"_id": "WikiPedia_Cardio$$$corpus_6099", "text": "The main cardioprotective effects of meldonium are mediated by the inhibition of GBB. By subsequently inhibiting  carnitine biosynthesis , fatty acid transport is reduced and the accumulation of cytotoxic intermediate products of  fatty acid beta-oxidation  in ischemic tissues to produce energy is prevented, therefore blocking this oxygen-consuming process. [ 16 ] [ 17 ]  Treatment with meldonium may shift the myocardial energy metabolism from fatty acid oxidation to the more favorable oxidation of glucose, or  glycolysis , under conditions where oxygen is limited."}
{"_id": "WikiPedia_Cardio$$$corpus_6100", "text": "In fatty acid metabolism, long chain fatty acids in the cytosol cannot cross the mitochondrial membrane because they are negatively charged. The process in which they move into the mitochondria is called the carnitine shuttle. Long chain FA are first activated via  esterification  with  coenzyme A  to produce a  fatty acid-coA  complex which can then cross the external mitochondrial border. The co-A is then exchanged with carnitine (via the enzyme  carnitine palmitoyltransferase I ) to produce a fatty acid-carnitine complex. This complex is then transported through the inner mitochondrial membrane via a transporter protein called  carnitine-acylcarnitine translocase . Once inside, carnitine is liberated (catalysed by the enzyme  carnitine palmitoyltransferase II ) and transported back outside so the process can occur again.  Acylcarnitines  like  palmitoylcarnitine  are produced as intermediate products of the carnitine shuttle."}
{"_id": "WikiPedia_Cardio$$$corpus_6101", "text": "In the mitochondria themselves, meldonium also competitively inhibits the carnitine shuttle protein  SLC22A5 . This results in reduced transportation and metabolism of long-chain fatty acids in the mitochondria (this burden is shifted more to  peroxisomes ). The final effect is a decreased risk of mitochondrial injury from fatty acid oxidation and a reduction of the production of acylcarnitines, which has been implicated in the development of  insulin resistance . [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6102", "text": "The chemical name of meldonium is 3-(2,2,2-trimethylhydraziniumyl) propionate. [ 20 ] [ 21 ]  It is a structural analogue of  \u03b3-butyrobetaine , with an  amino group  replacing the C-4  methylene  of \u03b3-butyrobetaine. \u03b3-Butyrobetaine is a precursor in the biosynthesis of carnitine. [ 22 ] [ better\u00a0source\u00a0needed ] [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6103", "text": "Meldonium is a white crystalline powder, with a melting point of 87\u00a0\u00b0C (189\u00a0\u00b0F). [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6104", "text": "Meldonium was added to the  World Anti-Doping Agency  (WADA) list of banned substances effective 1 January 2016 because of evidence of its use by athletes with the intention of enhancing performance. [ 3 ] [ 25 ]  It was on the 2015 WADA's list of drugs to be monitored. [ 26 ] [ 27 ]  A high prevalence of meldonium use by athletes in sport was demonstrated by the laboratory findings at the  Baku 2015 European Games . 13 medallists or competition winners were taking meldonium at the time of the Baku Games. Meldonium use was detected in athletes competing in 15 of the 21 sports during the Games. Most of the athletes taking meldonium withheld the information of their use from anti-doping authorities by not declaring it on their doping control forms as they should have. Only 23 of the 662 (3.5%) athletes tested declared the personal use of meldonium. However, 66 of the total 762 (8.7%) of athlete urine samples analysed during the Games and during pre-competition tested positive for meldonium. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6105", "text": "WADA classes the drug as a metabolic modulator, just as it does  insulin . [ 29 ]  Metabolic modulators are classified as S4 substances according to the WADA banned substances list. These substances have the ability to modify how some hormones accelerate or slow down different enzymatic reactions in the body. In this way, these modulators can block the body's conversion of testosterone into oestrogen, which is necessary for females. [ 30 ]  On 13 April 2016 it was reported that WADA had issued updated guidelines allowing less than 1 microgram per milliliter of meldonium for tests done before 1 March 2016. [ 31 ]  The agency cited that \"preliminary tests showed that it could take weeks or months for the drug to leave the body\"."}
{"_id": "WikiPedia_Cardio$$$corpus_6106", "text": "On 7 March 2016, former world number one tennis player  Maria Sharapova  announced that she had failed a drug test in Australia due to the detection of meldonium. She said that she had been taking the drug for ten years for various health issues, and had not noticed that it had been banned. [ 32 ] [ 33 ]  On 8 June 2016, she was suspended from playing tennis for two years by the  International Tennis Federation  (ITF), which was reduced to 15 months by  Court of Arbitration for Sport  after appeal. [ 34 ] [ 35 ] [ 36 ]  Earlier the same year (March 7), Russian ice dancer  Ekaterina Bobrova  announced that she had also tested positive for meldonium at the  2016 European Figure Skating Championships . Bobrova said she was shocked about the test result, because she had been made aware of meldonium's addition to the banned list, and had been careful to avoid products containing banned substances. [ 37 ]  In May 2016, Russian professional boxer  Alexander Povetkin \u2014a former two-time  World Boxing Association  (WBA) Heavyweight Champion\u2014tested positive for meldonium. This was discovered just a week prior to his mandatory title match against  World Boxing Council  (WBC) Heavyweight Champion,  Deontay Wilder . As a result, the match\u2014scheduled to take place in Russia\u2014was postponed indefinitely by the WBC. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6107", "text": "Other athletes who are provisionally banned for using meldonium include UFC flyweight Liliya Shakirova, Ethiopian-Swedish middle-distance runner  Abeba Aregawi , [ 39 ]  Ethiopian long-distance runner  Endeshaw Negesse , [ 40 ]  Russian cyclist  Eduard Vorganov , [ 41 ]  and Ukrainian biathletes  Olga Abramova [ 42 ]  and  Artem Tyshchenko . [ 43 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6108", "text": "The  Ice Hockey Federation of Russia  replaced the  Russia men's national under-18 ice hockey team  with an under-17 team for the  2016 IIHF World U18 Championships  after players on the original roster tested positive for meldonium. [ 44 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6109", "text": "More than 170 failed tests by athletes were identified in a relatively brief period after the ban on meldonium was imposed on 1 January 2016. [ 45 ]  Many of the early cases were dropped when athletes claimed that they had ceased use in 2015. [ 45 ]  Notable athletes with positive samples include: [ 46 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6110", "text": "In addition it was reported that five Georgian wrestlers [ 80 ]  and a German wrestler had tested positive for the drug although no further names were released. [ 81 ]  On 25 March 2016 the  F\u00e9d\u00e9ration Internationale de Sambo  confirmed that four wrestlers under their governance (two from Russia and two from other countries) had recorded positive tests for the drug. [ 82 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6111", "text": "A December 2015 study in the journal  Drug Testing and Analysis  argued that meldonium \"demonstrates an increase in endurance performance of athletes, improved rehabilitation after exercise, protection against stress, and enhanced activation of central nervous system (CNS) functions\". [ 83 ]  However the study itself presents no evidence for this claim, and focuses instead on describing two approaches for the reliable identification of meldonium."}
{"_id": "WikiPedia_Cardio$$$corpus_6112", "text": "The manufacturer,  Grindeks , said in a statement that it did not believe meldonium's use should be banned for athletes. It said the drug worked mainly by reducing damage to cells that can be caused by certain byproducts of carnitine. Meldonium \"is used to prevent death of ischemic cells and not to increase performance of normal cells\", the statement said. \"Meldonium cannot improve athletic performance, but it can stop tissue damage in the case of  ischemia \", the lack of blood flow to an area of the body. [ 84 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6113", "text": "The drug was invented in the mid-1970s at the  Institute of Organic Synthesis  of the  Latvian SSR Academy of Sciences  by  Ivars Kalvi\u0146\u0161 . [ 85 ] [ 86 ] [ 87 ]  Kalvi\u0146\u0161 criticized the ban, saying that WADA had not presented scientific proof that the drug can be used for doping. According to him, meldonium does not enhance athletic performance in any way, and was rather used by athletes to prevent damage to the heart and muscles caused by lack of oxygen during high-intensity exercise. He contended that not allowing athletes to take care of their health was a violation of their human rights, and that the decision aimed to remove Eastern European athletes from competitions and his drug from the pharmaceutical market. [ 88 ] [ 89 ]  Liene Kozlovska, the former head of the anti-doping department of the Latvian sports medicine center, rejected claims that the ban is in violation of athletes' rights, saying that meldonium is dangerous in high doses, and should only be used under medical supervision to treat genuine health conditions. She also speculated that Russian athletes may not have received adequate warnings that the drug was banned \u2013 due to the suspension of the  Russian Anti-Doping Agency  in late 2015. [ 90 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6114", "text": "Forbes  reported that anesthesiology professor  Michael Joyner , at the  Mayo Clinic  in  Rochester, Minnesota , who studies how humans respond to physical and mental stress during exercise and other activities, told them that \"Evidence is lacking for many compounds believed to enhance athletic performance. Its use has a sort of urban legend element and there is not much out there that it is clearly that effective. I would be shocked if this stuff [meldonium] had an effect greater than  caffeine  or  creatine  (a natural substance that, when taken as a supplement, is thought to enhance muscle mass).\" [ 91 ]  Ford Vox, a U.S.-based physician specializing in rehabilitation medicine and a journalist reported \"there's not much scientific support for its use as an athletic enhancer\". [ 92 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6115", "text": "Don Catlin , a long-time anti-doping expert and the scientific director of the Banned Substances Control Group (BSCG) said \"There's really no evidence that there's any performance enhancement from meldonium \u2013 Zero percent\". [ 93 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6116", "text": "Meldonium, which is not approved by the  FDA  in the  United States , is registered and prescribed in  Latvia ,  Russia ,  Ukraine ,  Georgia ,  Kazakhstan ,  Azerbaijan ,  Belarus ,  Uzbekistan ,  Moldova ,  Lithuania ,  Albania , and  Kyrgyzstan . [ 83 ] [ 94 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6117", "text": "Meldonium is manufactured by  Grindeks , a Latvian pharmaceutical company, with offices in thirteen Eastern European countries [ 95 ]  as a treatment for heart conditions. [ 96 ] [ 97 ]  The company identifies it as one of their main products. [ 98 ]  It had sales of 65 million euros in 2013. [ 87 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6118", "text": "Mephentermine , sold under the brand name  Wyamine  among others, is a  sympathomimetic   medication  which was previously used in the treatment of  low blood pressure  but is mostly no longer marketed. [ 6 ] [ 5 ] [ 4 ] [ 7 ] [ 8 ]  It is used by  injection into a vein  or  muscle ,  by inhalation , and  by mouth . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6119", "text": "Side effects  of mephentermine include  dry mouth ,  sedation ,  reflex bradycardia ,  arrhythmias , and  hypertension . [ 4 ]  Mephentermine  induces the release of norepinephrine and dopamine  and is described as an indirectly acting sympathomimetic and  psychostimulant . [ 4 ]  Its sympathomimetic effects are mediated by indirect activation of  \u03b1-  and  \u03b2-adrenergic receptors . [ 5 ]  Chemically, it is a  substituted phenethylamine  and  amphetamine  and is closely related to  phentermine  and  methamphetamine . [ 4 ] [ 9 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6120", "text": "Mephentermine was first described and introduced for medical use by 1952. [ 10 ]  It was discontinued in the  United States  between 2000 and 2004. [ 2 ] [ 7 ]  The medication appears to remain available only in  India . [ 4 ] [ 7 ] [ 8 ]   Misuse  of mephentermine for  recreational  and  performance-enhancing purposes  has been increasingly encountered in modern times, especially in India. [ 11 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6121", "text": "For maintenance of blood pressure in hypotensive states, the dose for adults is 30 to 45 \u00a0 mg as a single dose, repeated as necessary or followed by intravenous infusion of 0.1% mephentermine in 5% dextrose, with the rate and duration of administration depending on the patient's response. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6122", "text": "For hypotension secondary to spinal anesthesia in obstetric patients, the dose for adults is 15 \u00a0 mg as a single dose, repeated if needed. The maximum dose 30 \u00a0 mg. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6123", "text": "Mephentermine has also been used as a  decongestant . [ 6 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6124", "text": "Mephentermine is available in the form of 15 and 30 \u00a0 mg/mL  solutions  for  intravenous infusion  or  intramuscular injection  and in the form of 10 \u00a0 mg  oral   tablets . [ 4 ]  It has also been available in the form of  inhalers . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6125", "text": "Low blood pressure caused by  phenothiazines ,  hypertension , and  pheochromocytoma . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6126", "text": "Patients receiving  monoamine oxidase inhibitors . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6127", "text": "For shock due to loss of blood or fluid, give fluid replacement therapy primarily, cardiovascular disease, hypertension,  hyperthyroidism , chronic illnesses, lactation, pregnancy, skin dryness. headache. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6128", "text": "The most common  side effects  of mephentermine are drowsiness, incoherence, hallucinations, convulsions, slow heart rate ( reflex bradycardia ). Fear, anxiety, restlessness, tremor, insomnia, confusion, irritability, and psychosis. Nausea, vomiting, reduced appetite, urinary retention, dyspnea, weakness, and neck pain. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6129", "text": "Potentially fatal reactions are due to atrioventricular block, central nervous system stimulation, cerebral hemorrhage, pulmonary edema, and ventricular arrhythmias. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6130", "text": "Mephentermine antagonizes effect of agents that lower blood pressure. Severe hypertension may occur with monoamine oxidase inhibitors and possibly  tricyclic antidepressants . Additive vasoconstricting effects occur with  ergot  alkaloids, and  oxytocin . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6131", "text": "Potentially fatal drug interactions are the risk of abnormal heart rhythm in people undergoing anesthesia with  cyclopropane  and  halothane . [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6132", "text": "Mephentermine is thought to act as a  releasing agent of norepinephrine and dopamine . [ 4 ]  It is described as an indirectly acting  sympathomimetic ,  cardiac stimulant ,  adrenergic ,  vasoconstrictor ,  antihypotensive agent , and  psychostimulant . [ 1 ] [ 2 ] [ 8 ] [ 4 ]  Its sympathomimetic effects are mediated by indirect activation of  \u03b1-  and  \u03b2-adrenergic receptors . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6133", "text": "Mephentermine appears to act by indirect stimulation of \u03b2-adrenergic receptors through causing the release of norepinephrine from its storage sites. It has a  positive inotropic  effect on the  myocardium . AV conduction and refractory period of  AV node  is shortened with an increase in ventricular conduction velocity. It dilates arteries and arterioles in the skeletal muscle and mesenteric vascular beds, leading to an increase in venous return. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6134", "text": "Its  onset of action  is 5 to 15 \u00a0 minutes with  intramuscular injection  and is immediate with  intravenous administration . [ citation needed ]  Its  duration of action  is 4 \u00a0 hours with intramuscular injection and 30 \u00a0 minutes with intravenous administration. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6135", "text": "Mephentermine, along with  phentermine , is known to be produced as a  metabolite  of the  orally administered   local anesthetic   oxetacaine  (oxethazaine). [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6136", "text": "Mephentermine, also known as  N ,\u03b1,\u03b1-trimethylphenethylamine or  N ,\u03b1-dimethylampetamine, is a  phenethylamine  and  amphetamine   derivative . [ 9 ] [ 1 ] [ 4 ]  It is the  N - methylated   analogue  of  phentermine  (\u03b1-methylamphetamine) and is also known as  N -methylphentermine. [ 9 ] [ 1 ]  In addition, mephentermine is the \u03b1-methylated analogue of  methamphetamine  or the \u03b1,\u03b1-dimethylated derivative of  amphetamine . [ 9 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6137", "text": "Mephentermine can by synthesized beginning with a  Henry reaction  between  benzaldehyde  ( 1 ) and  2-nitropropane  ( 2 ) to give 2-methyl-2-nitro-1-phenylpropan-1-ol ( 3 ). [ 14 ]  The nitro group is reduced with zinc in sulfuric acid giving 2-phenyl-1,1-dimethylethanolamine ( 4 ). Imine formation by dehydration with benzaldehyde gives ( 5 ). Alkylation with  iodomethane  leads to ( 6 ). Halogenation with  thionyl chloride  gives ( 7 ). Lastly, a  Rosenmund reduction  completes the synthesis of mephentermine ( 8 )."}
{"_id": "WikiPedia_Cardio$$$corpus_6138", "text": "Mephentermine can also be synthesized by  condensation  of phentermine with benzaldehyde to get a  Schiff base  which can be alkylated with methyl iodide to give mephentermine. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6139", "text": "Mephentermine was first described in the literature and was introduced for medical use under the brand name Wyamine by 1952. [ 10 ]  It was discontinued in the  United States  between 2000 and 2004. [ 2 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6140", "text": "Mephentermine  is the  generic name  of the drug and its  INN Tooltip International Nonproprietary Name ,  BAN Tooltip British Approved Name , and  DCF Tooltip D\u00e9nomination Commune Fran\u00e7aise . [ 1 ] [ 2 ] [ 3 ]  In the case of the  sulfate   salt , its  USAN Tooltip United States Adopted Name  is  mephentermine sulfate  and its  BANM Tooltip British Approved Name  is  mephentermine sulphate . [ 3 ] [ 2 ] [ 7 ]  Synonyms of mephentermine include  mephetedrine  and  mephenterdrine . [ 2 ] [ 7 ] [ 9 ]  Brand names of mephentermine include  Wyamine  ( US Tooltip United States ),  Fentermin  ( PT Tooltip Portugal ), and  Mephentine  ( IN Tooltip India ). [ 1 ] [ 2 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6141", "text": "Mephentermine is no longer available in the  United States  and remains available in few or no other countries. [ 7 ] [ 8 ]  However, it appears to remain available in  India . [ 8 ] [ 7 ]  It has also remained available in  Brazil  for use in  veterinary medicine . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6142", "text": "Misuse  of mephentermine for  recreational  and/or  performance-enhancing purposes  has been reported along with  addiction  and  dependence  and serious health complications. [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ 5 ] [ 20 ] [ 21 ] [ 22 ] [ 11 ] [ 23 ] [ 24 ] [ 25 ] [ 26 ] [ 4 ]  It has been especially encountered in  India , the only country in which mephentermine appears to remain available for medical use. [ 4 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6143", "text": "Mephentermine has been used as a  performance-enhancing drug  in  exercise  and  sports . [ 6 ] [ 11 ] [ 4 ]  It is on the  World Anti-Doping Agency  (WADA)  list of prohibited substances . [ 27 ] [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6144", "text": "Mephentermine was evaluated in the treatment of  congestive heart failure  in one small clinical study but was found to be ineffective. [ 28 ] [ 29 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6145", "text": "Mephentermine has been used in  veterinary medicine  in  Brazil  under the brand names Potenay and Potemax. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6146", "text": "3-Methylmethcathinone (3-MMC) , also known as  metaphedrone , [ 4 ]  is a  designer drug  from the  substituted cathinone  family. 3-MMC is a  monoamine transporter  substrate (a substance acted upon by monoamine transporters) that potently releases and inhibits the reuptake of  dopamine  and  norepinephrine , as well as displaying moderate  serotonin  releasing activity. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6147", "text": "3-Methylmethcathinone is a  structural isomer  of  mephedrone  (4-methylmethcathinone), and as such is illegal via  blanket bans  in many countries that have banned mephedrone. However, 3-MMC has still appeared on the recreational drug market as an alternative to mephedrone, and was first identified being sold in Sweden in 2012. [ 7 ]  Unlike some other synthetic cathinones, 3-MMC has been evaluated in at least one large mammal study. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6148", "text": "3-MMC was first encountered in Sweden in 2012, [ 8 ]  it was created as a designer drug following the control in many countries of the related compound  mephedrone . It was sold as a research chemical, usually in powdered form. There is no known or reported medical use of 3-MMC, it is primarily used recreationally."}
{"_id": "WikiPedia_Cardio$$$corpus_6149", "text": "3-MMC potently inhibits the reuptake of  monoamines  in the human norepinephrine (NET) and  dopamine  ( DAT ) transporters. It also acts as a triple releasing agent of dopamine, serotonin, and norepinephrine, similar to many other  cathinones . As a releasing agent, it is more selective for dopamine and especially  norepinephrine , suggesting that it has stronger  amphetamine-like stimulant  properties compared to mephedrone or  MDMA . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6150", "text": "3-MMC also binds to serotonin  5-HT1A ,  5-HT2A ,  5-HT2C  receptors and  adrenergic  \u03b11A and \u03b12A receptors. [ 9 ]  It binds much more strongly to the adrenergic receptors than the serotonergic 5-HT receptors, although it still retains significant serotonin-releasing activity (292 nM in one study), thus giving users a subjective \"roll\"."}
{"_id": "WikiPedia_Cardio$$$corpus_6151", "text": "3-MMC is inactive as an  agonist  of the rat and human  TAAR1  ( EC 50 Tooltip half-maximal effective concentration  = >10,000 \u00a0 nM). [ 10 ]  Conversely, it is a low-potency weak  partial agonist  of the mouse TAAR1 ( EC 50  = 3,800 \u00a0 nM,  E max Tooltip maximal efficacy  = 25%). [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6152", "text": "The oral  bioavailability  of 3-methylmethcathinone was determined at 7% [ 2 ]  in one pig study, with peak blood concentrations (T max ) attained within 5 to 10 minutes, and a relatively short  half-life  of 50 minutes. Concentration in  blood plasma  dropped below detectability 24 hours after oral ingestion.  Decreased feeding behavior resulted in weight loss for some."}
{"_id": "WikiPedia_Cardio$$$corpus_6153", "text": "The metabolic pathway of 3-MMC is not well described. Known metabolites include 3-methylephedrine and 3-methylnorephedrine. A possible metabolic pathway is \u03b2-keto-reduction followed by  N-demethylation . [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6154", "text": "A total of 27 fatalities with at least some exposure to 3-MMC have been confirmed as of March 2022. 18 of the 27 reported fatalities involved multiple drugs of abuse, usually  opioids  and uppers ( \"speedballs\" ). [ 13 ]  Of the 13 cases that specified gender, 12 deaths were male and 1 death was female. Of the 7 males whose age was reported, the median age was 27. The fatalities see a wide range of blood concentrations, from 249 to 1600\u00a0ng/mL. [ 14 ]   The  route of administration  in any of these fatalities is not clear."}
{"_id": "WikiPedia_Cardio$$$corpus_6155", "text": "Of the presumably nine monointoxication deaths involving only 3-MMC that have occurred, two monointoxication cases were reported in the  Netherlands  and one was reported in  France . The death in France was determined to be an  accidental overdose . In addition, there has been 291 reported cases of non-fatal 3-MMC intoxications. 213 of these cases (75%) were reported in Poland alone, and 50 cases (17%) were reported in Sweden."}
{"_id": "WikiPedia_Cardio$$$corpus_6156", "text": "The  toxicokinetics  of 3-MMC are thought to be similar to those for mephedrone. The dose-response curve of 3-MMC in humans is not well described in the literature, likely due to limited academic interest to date."}
{"_id": "WikiPedia_Cardio$$$corpus_6157", "text": "3-Methylmethcathinone's IUPAC name is 2-(methylamino)-1-(3-methylphenyl)propan-1-one). It is \none of many synthetic cathinones,  designer drugs  related to  amphetamines . It is a  structural isomer  of  mephedrone , and controlled as such. It can also be seen as the \u03b2-keto analog of  3-methylmethamphetamine"}
{"_id": "WikiPedia_Cardio$$$corpus_6158", "text": "3-MMC contains a  chiral center  at the C-2 carbon. Therefore two  enantiomers  exist, the R and S enantiomer. It is assumed that the S form is more  potent  due to its similarity to cathinone, but further research is needed to confirm this. [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6159", "text": "There are several ways to synthesize 3-MMC. One route adapted from Power et al [ 16 ]  is to add  ethylmagnesium bromide  to  3-methylbenzaldehyde  (I) to form the product  1-(3-methylphenyl)-1-propanol  (II). This product is then oxidized by  pyridinium chlorochromate  (PCC) on  silica gel  to the ketone (III) and brominated with  hydrobromic acid  to yield the bromoketone (IV). This bromoketone is reacted with ethanolic methylamine to produce the 3-MMC free base (V), which can be converted to the  hydrochloride salt  (VI) by addition of ethereal hydrogen chloride (VI). [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6160", "text": "As with  mephedrone , users of 3-MMC typically report effects such as an  elevated mood , pleasant body sensations, feelings of  love  and  empathy ,  euphoria , greater appreciation of music, heightened  libido , and increased  confidence  and sociability. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6161", "text": "Adverse effects range from aggression,  dry mouth , and  jaw clenching , to more serious effects such as  hyponatremia ,  seizures ,  hyperthermia  and  rhabdomyolysis . [ 17 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6162", "text": "Due to its short duration and  dopaminergic  effects, 3-MMC is  addictive  and commonly abused. Repeated dosing within a sitting is typical, sometimes using different routes. Common self-reported doses range from 50 to 150\u00a0mg, up to single 500\u00a0mg doses. Intranasal administration, or snorting, is the most common  route of administration , followed by oral administration. It can also be administered rectally and  injected ."}
{"_id": "WikiPedia_Cardio$$$corpus_6163", "text": "Users may dose repeatedly in order to extend the drugs duration, leading to 0.5\u20142\u00a0gram \"sessions\" that can span an evening. Single-dose effects last from 30 to 60 minutes, typically peaking around 10-minutes post-dose. In a questionnaire-based study of self-reported 3-MMC users in  Slovenia , it was found that 88% of users insufflated the drug while 42% took it orally. The study did not find any instances of users injecting 3-MMC. Moreover, 26% of the users reported taking more than 1.5\u00a0grams of 3-MMC in a single sitting and over 50% reported having consumed more than 0.5\u00a0grams in a single sitting. [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6164", "text": "3-Methylmethcathinone is commonly encountered as a white/off-white crystalline or pasty solid. It can be found sold in capsules. It is assumed to be a  racemic mixture  like mephedrone."}
{"_id": "WikiPedia_Cardio$$$corpus_6165", "text": "In the United States, 3-MMC is illegal as a  positional isomer  of the  controlled substance   mephedrone [ 19 ]  It was explicitly designated as a controlled substance on 13 December 2023. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6166", "text": "Since October 2015, 3-MMC is a  controlled substance  in  China . [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6167", "text": "3-MMC is banned in the  Czech Republic . [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6168", "text": "3-MMC was not banned in 2016 by the  United Nations Office on Drugs and Crime  (UNODC) after a critical review. [ 23 ]  However, following its subsequent abuse beginning in 2019, this decision was overturned and it was placed into  schedule II  of the 1971 convention in March 2023. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6169", "text": "Effective 28 October 2021, 3-MMC has been scheduled under the  Dutch Opium Law  and is therefore illegal in the  Netherlands . [ 24 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6170", "text": "3-MMC was given narcotic status in  India  on 8 February 2024."}
{"_id": "WikiPedia_Cardio$$$corpus_6171", "text": "3-MMC is under development for use as a  pharmaceutical drug  in the potential treatment of  dyskinesias . [ 25 ]  As of August 2023, it is in  preclinical research  for this indication. [ 25 ]  The drug is being developed by Clearmind Medicine. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6172", "text": "3-MMC is currently being developed as a medicine by the American biotech company  MindMed . They have filed for a patent to use 3-MMC for problems such as  social anxiety disorder ,  post-traumatic stress disorder  (PTSD), and as an adjunct in  couples therapy . [ 26 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6173", "text": "3-MMC is also undergoing clinical trials for its use in treating menstrual symptoms. [ 27 ]  A successful trial has been completed in the  University of Maastricht . These efforts are led by the small Dutch company Period Pill. [ 28 ]  The company has filed for patent coverage in  Canada ,  Mexico ,  Croatia , the  United States ,  Morocco ,  Japan ,  Brazil ,  Poland ,  Hungary , and  Korea ."}
{"_id": "WikiPedia_Cardio$$$corpus_6174", "text": "Mitotropes  are a novel class of drugs that aim to improve cardiac performance by influencing the  mitochondria . Their intended effect is similar to the calcium-based  inotropes , and intend to have fewer long-term side effects. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6175", "text": "This  pharmacology -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_6176", "text": "Nesiritide , sold under the brand name  Natrecor , is the  recombinant  form of the 32 amino acid human  B-type natriuretic peptide , which is normally produced by the ventricular myocardium. Nesiritide works to facilitate  cardiovascular  fluid  homeostasis  through counterregulation of the  renin\u2013angiotensin\u2013aldosterone system , stimulating  cyclic guanosine monophosphate , leading to  smooth muscle  cell relaxation."}
{"_id": "WikiPedia_Cardio$$$corpus_6177", "text": "Nesiritide was believed initially to be beneficial for  acute decompensated congestive heart failure . It received approval from the United States'  Food and Drug Administration  for this purpose in 2001 after initial non-approval. In July 2011, the results of the largest study so far for nesiritide was published in  The New England Journal of Medicine . The study failed to show a difference between nesiritide and placebo on mortality or re-hospitalizations. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6178", "text": "Nesiritide is only administered  intravenously , usually by  bolus , followed by IV infusion. For most adults and the  elderly , a normal dosage is 2\u00a0 mg /kg followed by a continuous IV infusion of 0.01\u00a0mg/kg/min. This may be increased every three hours for a maximum of 0.03\u00a0mg/kg/min."}
{"_id": "WikiPedia_Cardio$$$corpus_6179", "text": "In 2005, after several academic papers published by  Jonathan Sackner-Bernstein [ 2 ] [ 3 ] [ 4 ]  on the efficacy and side effects of nesiritide, Johnson & Johnson met with the FDA and altered its stated plans for the drug and agreed to revise its labeling. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6180", "text": "Heart doctors at the   Cleveland Clinic  then voted unanimously not to permit the prescription of the drug to its patients. [ 6 ]   Johnson and Johnson  convened a panel of experts whose advice included the recommendation to conduct the large-scale clinical trial that was subsequently published in 2011. [ 7 ]  Following this, the  United States Department of Justice  announced an inquiry into the marketing of the drug [ 8 ]  that led to a fine against the Scios unit of J&J. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6181", "text": "Common side effects include:"}
{"_id": "WikiPedia_Cardio$$$corpus_6182", "text": "More rare side effects include:"}
{"_id": "WikiPedia_Cardio$$$corpus_6183", "text": "Omecamtiv mecarbil  ( INN [ 1 ] ), previously referred to as  CK-1827452 , is a cardiac-specific  myosin  activator. It is an  experimental drug  being studied for a potential role in the treatment of left ventricular  systolic heart failure . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6184", "text": "Systolic heart failure involves a loss of effective  actin -myosin cross bridges in the  myocytes  (heart muscle cells) of the left ventricle, which leads to a decreased ability of the heart to move blood through the body. This causes peripheral edema (blood pooling), which the  sympathetic nervous system  tries to correct [ 3 ]  by overstimulating the cardiac myocytes, leading to left  ventricular hypertrophy , another characteristic of  chronic heart failure ."}
{"_id": "WikiPedia_Cardio$$$corpus_6185", "text": "inotropic  therapies work by increasing the force of cardiac contraction, such as through calcium conduction or modulating  adrenoreceptors . But these are limited by adverse events, including  arrhythmias  related to increased myocardial oxygen consumption, desensitization of  adrenergic receptors , and altering intracellular  calcium  levels. [ 4 ]  Inotropes are also thought to be associated with worse prognosis. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6186", "text": "Cardiac myocytes contract through a cross-bridge cycle between the  myofilaments , actin and myosin.  Chemical energy  in the form of ATP is converted into  mechanical energy  which allows myosin to strongly bind to actin and produce a power stroke resulting in  sarcomere  shortening/contraction. [ 6 ]  Omecamtiv mecarbil specifically targets and activates myocardial  ATPase  and improves energy utilization. This enhances effective myosin cross-bridge formation and duration, while the velocity of contraction remains the same. [ 7 ]  Specifically, it increases the rate of  phosphate  release from myosin by stabilizing the pre-powerstroke and the phosphate release states, [ 8 ]  thereby accelerating the rate-determining step of the cross-bridge cycle, which is the transition of the actin-myosin complex from the weakly bound to the strongly bound state. [ 9 ] [ 2 ]  Furthermore, once myosin is bound to actin, it stays bound dramatically longer in the presence of omecamtiv mecarbil. [ 10 ] [ 11 ] [ 8 ]  The combination of increased and prolonged cross-bridge formation prolongs myocardial contraction. Thus, the overall clinical result of omecamtiv mecarbil is an increase in left ventricular systolic ejection time and ejection fraction. [ 7 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6187", "text": "There is a slight decrease in  heart rate  while myocardial oxygen consumption is unaffected. The increased cardiac output is independent of intracellular calcium and cAMP levels. [ 4 ] [ 12 ]  Thus omecamtiv mecarbil improves systolic function by increasing the systolic ejection duration and stroke volume, without consuming more ATP energy,  oxygen  or altering intracellular calcium levels causing an overall improvement in cardiac efficiency. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6188", "text": "Experimental studies on rats and dogs, proved the efficacy and mechanism of action of omecamtiv mecarbil. [ 4 ]  Clinical studies on humans have shown there is a direct linear relationship between dose and systolic ejection time. [ 2 ] [ 13 ] [ 14 ]  The dose-dependent effects persisted throughout the entire trial, suggesting that  desensitization  does not occur. The maximum tolerated dose was observed to be an infusion of 0.5\u00a0mg/kg/h. Adverse effects, such as ischemia, were only seen at doses beyond this level, due to extreme lengthening of systolic ejection time. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6189", "text": "Omecamtiv mecarbil effectively relieves symptoms and enhances the quality of life of systolic heart failure patients. It improved cardiac performance in short-term studies; [ 2 ] [ 3 ]  however, while the drug reduced the risk of hospitalization or other urgent care for heart failure by 8% in high-risk patients in the  Phase III clinical trial  GALACTIC-HF, patients receiving the drug did not live any longer. [ 15 ]  The drug also did not improve  exercise intolerance  in heart failure patients in the Phase III METEORIC trial. [ 16 ]  The METEORIC-HF  randomized clinical trial  found that omecamtiv mecarbil does not significantly improve exercise capacity. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6190", "text": "Research groups found that omecamtiv mecarbil actually inhibits myosin by enhancing the duty ratio, increasing calcium sensitivity and slowing force development. [ 18 ]  It may still activate muscle as a whole however despite suppressing the working stroke of myosin. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6191", "text": "The US  Food and Drug Administration  (FDA) granted, in May 2020, a  fast-track designation  for omecamtiv mecarbil. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6192", "text": "Omega-3-acid ethyl esters  are a mixture of  ethyl eicosapentaenoic acid  and  ethyl docosahexaenoic acid , which are ethyl esters of the  omega\u22123 fatty acids   eicosapentaenoic acid  (EPA) and  docosahexaenoic acid  (DHA) found in  fish oil . [ 4 ]  Together with dietary changes, they are used to treat  high blood triglycerides  which may reduce the risk of  pancreatitis . [ 4 ] [ 5 ]  They are generally less preferred than  statins , and use is not recommended by  NHS Scotland  as the evidence does not support a decreased risk of  heart disease . [ 4 ] [ 6 ] [ 7 ]  Omega-3-acid ethyl esters are taken by mouth. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6193", "text": "Common side effects include burping, nausea, and an upset abdomen. [ 4 ] [ 6 ]  Serious side effects may include liver problems and  anaphylaxis . [ 4 ]  While use in  pregnancy  has not been well studied, some omega\u22123 fatty acids appear beneficial. [ 1 ]  How it works is not entirely clear. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6194", "text": "Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d. [1]"}
{"_id": "WikiPedia_Cardio$$$corpus_6195", "text": "Omega-3-acid ethyl ester medicines were approved for medical use in the European Union in 2000 and in the United States in 2004. [ 4 ] [ 7 ] [ 8 ]  Beyond the branded prescription formulation, it is also available as a  generic medication  and  over the counter . [ 4 ] [ 6 ]  In 2022, it was the 220th most commonly prescribed medication in the United States, with more than 1 \u00a0 million prescriptions. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6196", "text": "Omega-3-acid ethyl esters are used in addition to changes in diet to reduce  triglyceride  levels in adults with severe (\u2265 500\u00a0mg/dL)  hypertriglyceridemia . [ 3 ]  In the European Union and other major markets outside the US, omega-3-acid ethyl esters are indicated for hypertriglyceridemia by itself, or in combination with a  statin  for people with mixed  dyslipidemia . [ 2 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6197", "text": "Intake of large doses (2.0 to 4.0 g/day) of long-chain omega\u22123 fatty acids as prescription drugs or dietary supplements are generally required to achieve significant (> 15%) lowering of triglycerides, and at those doses, the effects can be significant (from 20% to 35% and even up to 45% in individuals with levels greater than 500\u00a0mg/dL).  It appears that both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglycerides, but DHA appears to raise  LDL cholesterol   more than EPA, while DHA raises  HDL cholesterol  while EPA does not. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6198", "text": "Other omega\u22123 fish oil-based prescription drugs on the market have similar uses and mechanisms of action. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6199", "text": "There are many fish oil dietary supplements on the market. [ 17 ]  There appears to be little difference in effect between dietary supplement and prescription forms of omega\u22123 fatty acids as to ability to lower triglycerides, but the ethyl ester products work less well when taken on an empty stomach or with a low-fat meal. [ 11 ]   The ingredients of dietary supplements are not as carefully controlled as prescription products and have not been tested in clinical trials as such drugs have. [ 18 ]  Prescription omega\u22123 products are more concentrated, requiring fewer softgels for the same daily dose. [ 17 ]  Dietary fish oil is often esterified and then molecularly distilled to attain higher purity and/or concentration. Typical 'concentrated' fish oil supplements have doubled contents of EPA/DHA (ca. 50-65%). There are also products on the market with even higher concentrations of EPA/DHA (ca. 65-85%), labelled with 'triple', 'ultra', or similar wording. Some producers also provide backward conversion of FAE to triglyceride form in assumption of its higher bioavailability, these products usually have 'rTG' in their names."}
{"_id": "WikiPedia_Cardio$$$corpus_6200", "text": "In people with CKD who require hemodialysis, there is a risk that  vascular blockage  due to  clotting , may prevent dialysis therapy from being possible.  Omega\u22123 fatty acids  contribute to the production of  eicosanoid  molecules that reduce clotting. However, a Cochrane review in 2018 did not find clear evidence that omega\u22123 supplementation has any impact on the prevention of vascular blockage in people with CKD. [ 19 ]  There was also moderate certainty that supplementation did not prevent hospitalization or death within a 12-month period. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6201", "text": "Special caution should be taken with people who have  fish and shellfish allergies . [ 3 ]  In addition, as with other omega\u22123 fatty acids, taking omega-3-acid ethyl esters puts people who are on  anticoagulants  at risk for prolonged  bleeding time . [ 3 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6202", "text": "Side effects include  stomach ache , burping, and a bad taste; some people on very high doses (8g/day) in clinical trials had  atrial fibrillation . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6203", "text": "Omega-3-acid ethyl esters have not been tested in pregnant women and are rated  pregnancy category C ; it is excreted in breast milk and the effects on infants are not known. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6204", "text": "After ingestion, omega-3-acid ethyl esters are metabolized mostly in the liver like other dietary fatty acids. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6205", "text": "Ethyl esters and triglycerides of omega\u22123 fatty acids show similar rates of absorption while monoglycerides and free fatty acids are absorbed significantly better. [ 20 ]  Absorption rates depend on the mode of consumption and fat content of the following/accompanying meal. This may explain discrepancies in results of different studies. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6206", "text": "Omega-3-acid ethyl esters, like other omega\u22123 fatty acid-based drugs, appears to reduce production of triglycerides in the liver and to enhance clearance of triglycerides from circulating  very low-density lipoprotein  (VLDL) particles. The way it does that is not clear, but potential mechanisms include increased  breakdown of fatty acids ; inhibition of  diglyceride acyltransferase , which is involved in biosynthesis of triglycerides in the liver; and increased activity of  lipoprotein lipase  in blood. [ 2 ] [ 12 ]  The synthesis of triglycerides is reduced in the liver because EPA and DHA are poor substrates for the enzymes responsible for triglyceride synthesis."}
{"_id": "WikiPedia_Cardio$$$corpus_6207", "text": "The active ingredient is concentrated omega-3-acid ethyl esters that are made from  fish body oils  that are purified and  esterified . [ 21 ]  For the Lovaza product, each 1000\u00a0mg softgel capsule contains 840\u00a0mg omega\u22123 fatty acids:  eicosapentaenoic acid  ethyl ester (460\u00a0mg) and  docosahexaenoic acid  ethyl ester (380\u00a0mg). [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6208", "text": "Pronova BioPharma ASA had its roots in Norway's  codfish liver oil  industry. The company was founded in 1991 as a spinout from the JC Martens company, which in turn was founded in 1838 in Bergen, Norway. [ 22 ]  Pronova developed the concentrated omega-3-acid ethyl esters formulation that is the  active pharmaceutical ingredient  of Lovaza. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6209", "text": "Pronova won approvals to market the drug, called Omacor in Europe (and initially in the US), in several European countries in 2001 after conducting a three-and-a-half-year trial in 11,000 subjects; [ 23 ]  The company partnered with other companies like  Pierre Fabre  in France. [ 24 ]  In 2004, Pronova licensed the US and Puerto Rican rights to Reliant Therapeutics, whose business model was in-licensing of cardiovascular drugs. [ 25 ]  In that same year, Reliant and Pronova won FDA approval for the drug, [ 26 ]  and it was launched in the US and Europe in 2005. Global sales in 2005 were $144M, and by 2008, they were $778M. [ 27 ]   In 2007  GlaxoSmithKline  acquired Reliant for $1.65 billion in cash. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6210", "text": "In 2009, generic companies  Teva Pharmaceuticals  and  Par Pharmaceutical  made clear their intentions to file  Abbreviated New Drug Applications  (\"ANDAs\") to bring generics to market, and in April 2009, Pronova sued them from infringing the key US patents covering Lovaza, US 5,656,667 (due to expire in April 2017), US 5,502,077 (exp March 2013). Subsequently, in May 2012, a district court ruled in Pronova's favor, saying that the patents were valid. [ 29 ] [ 30 ] [ 31 ]  The generic companies appealed, and in September 2013, the Federal Circuit reversed, saying that because more than one year before Pronova's predecessor company applied for a patent, it had sent samples of the fish oil used in Lovaza to a researcher for testing. This event thus constituted \"public use\" that invalidated the patent in question. [ 32 ] [ 33 ]   Generic  versions of Lovaza were introduced in America in April 2014. [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6211", "text": "Pronovo has continued to manufacture the ingredients in Lovaza, and in 2012,  BASF  announced it would acquire Pronova for $844 million. [ 35 ]  The deal closed in 2013. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6212", "text": "Omega\u22123-carboxylic acids [ 1 ]  ( Epanova ) is a formerly marketed yet still not a  Food and Drug Administration  (FDA)-approved prescription medication\u2013since taken off market by the manufacturer\u2013used alongside a  low fat  and low cholesterol diet that lowers high  triglyceride  (fat) levels in adults with very high levels. [ 2 ]  This was the third class of  fish oil -based drug, after  omega\u22123-acid ethyl esters  (Lovaza and Omtryg) and  ethyl eicosapentaenoic acid  (Vascepa), to be approved for use as a drug. [ 3 ]  The first approval in the  United States  by the FDA was granted 05 May 2014. [ 4 ]  These fish oil drugs are similar to fish oil  dietary supplements , but the ingredients are better controlled and have been tested in clinical trials. Specifically, Epanova contained at least 850\u00a0mg omega\u22123-acid ethyl esters per 1\u00a0g capsule. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6213", "text": "Following phase III clinical trial in mixed  dyslipidaemia ,  AstraZeneca  announced on 13 January 2019 that their clinical trials were terminated for futility because no medical benefit of the medication could be found. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6214", "text": "Omega\u22123-carboxylic acids are used in addition to changes in diet to reduce  triglyceride  levels in adults with severe (\u2265 500\u00a0mg/dL)  hypertriglyceridemia . [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6215", "text": "Intake of large doses (2.0 to 4.0 g/day) of long-chain omega\u22123 fatty acids as prescription drugs or dietary supplements are generally required to achieve significant (> 15%) lowering of triglycerides, and at those doses the effects can be significant (from 20% to 35% and even up to 45% in individuals with levels greater that 500\u00a0mg/dL). It appears that both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglycerides. However, DHA appears to raise  LDL cholesterol  more than EPA, and further, DHA raises  HDL cholesterol  while EPA does not. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6216", "text": "There are other omega\u22123 fish oil based drugs on the market that have similar uses and mechanisms of action. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6217", "text": "There are many fish oil dietary supplements on the market. [ 13 ]  There appears to be little difference in effect between dietary supplement and prescription forms of omega\u22123 fatty acids. Importantly, EPA and DHA ethyl esters (prescription forms) work better when taken with a mildly fattening meal of about 350 calories. [ 7 ]  The ingredients of dietary supplements are not as carefully controlled as prescription products and have not been fixed and tested in clinical trials, as prescription drugs have. [ 14 ]  Furthermore, the prescription forms are more concentrated, requiring fewer capsules to be taken and increasing the likelihood of compliance. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6218", "text": "Special caution should be taken with people who have with  fish and shellfish allergies . [ 6 ]  In addition, as with other omega\u22123 fatty acids, taking omega\u22123-carboxylic acids puts people who are on  anticoagulants  at risk for prolonged  bleeding time . [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6219", "text": "Side effects include  diarrhea ,  nausea ,  abdominal pain , and burping. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6220", "text": "Omega\u22123-carboxylic acids have not been tested in pregnant women and are rated  pregnancy category C  because it is excreted in breast milk and the effects on infants are not known. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6221", "text": "Omega\u22123-carboxylic acids are directly absorbed in the small intestine. Maximum plasma concentrations are achieved between 5\u20138 hours after dosing for total EPA and between 5\u20139 hours after dosing for total DHA. Both DHA and EPA are metabolized primarily in the liver, just like other fatty acids derived from food. The half-life of EPA from omega\u22123-carboxylic acids is about 37 hours. For DHA, the half-life is about 46 hours. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6222", "text": "Omega\u22123-carboxylic acids, like other omega\u22123 fatty acid based drugs, appears to reduce production of triglycerides in the liver and to enhance clearance of triglycerides from circulating  very low-density lipoprotein  (VLDL) particles. The way it does that is not clear, but potential mechanisms include increased  breakdown of fatty acids ; inhibition of  diglyceride acyltransferase , which is involved in biosynthesis of triglycerides in the liver; and increased activity of  lipoprotein lipase  in blood. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6223", "text": "Omega\u22123-carboxylic acids are derived from  fish oil  and are a purified mixture of the polyunsaturated  free  fatty acids  docosahexaenoic acid  (DHA) and  eicosapentaenoic acid  (EPA). [ 13 ]  The drug contains a concentration of DHA at 15\u201325% and a concentration of EPA at 50\u201360%. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6224", "text": "Omega\u22123-carboxylic acids was approved by the US FDA in May 2014, [ 15 ]  and such formulation(s) was the third prescription form of an  omega\u22123  product approved in the  United States . A notable difference is that the carboxylic acid treatment was the first approved in free fatty acid form. [ 2 ]  Development was completed and regulatory approval was obtained by  AstraZeneca , [ 15 ]  but omega\u22123-carboxylic acids were first created at Chrysalis Pharma in Switzerland. Later, Princeton-based Omthera obtained rights from Chysalis, and Astrazeneca acquired Omthera in 2013 for $323 million in cash along with up to $120 million in milestones. [ 16 ]  At the time Epanova was approved, AstraZeneca's plan was to develop a combination product with  rosuvastatin , the patent on which was set to expire in 2016. [ 16 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6225", "text": "Clinical trials of Epanova for severe hypertriglyceridemia showed good results. [ 2 ] [ 17 ]  However, a clinical trial on mixed dyslipidaemia (hypertriglyceridemia with hypocholesterolemia) was started on 30 October 2014, [ 18 ]  which was terminated after Phase III clinical trials, on 13 January 2019, due to lack of medical benefit in the results. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6226", "text": "Oxyfedrine , sold under the brand names  Ildamen  and  Myofedrin  among others, is a  sympathomimetic agent  and  coronary vasodilator  which is used in the treatment of  coronary heart disease ,  angina pectoris , and acute  myocardial infarction . [ 1 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]  It is taken  by mouth  or  intravenously . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6227", "text": "The drug acts as a  \u03b2-adrenergic receptor   partial agonist . [ 1 ] [ 7 ]  It may also act as a  norepinephrine releasing agent  via its major  active metabolite   norephedrine . [ 2 ]  Oxyfedrine is a  phenethylamine  and  amphetamine   derivative . [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6228", "text": "Oxyfedrine has been marketed in  Europe ,  Hong Kong ,  India ,  Central America , and elsewhere. [ 4 ] [ 8 ] [ 9 ]  It appears to remain marketed only in India. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6229", "text": "Oxyfedrine is a  \u03b2-adrenergic receptor   partial agonist . [ 1 ] [ 7 ]  It appears to be  non-selective  for the  \u03b2 1 -  and  \u03b2 2 -adrenergic receptors . [ 7 ]  It is selective for the \u03b2-adrenergic receptors over the  \u03b1-adrenergic receptors . [ 7 ]  However, it has also been reported to interact with the \u03b1-adrenergic receptors at high concentrations, acting as a partial agonist or  antagonist  of these receptors. [ 7 ]   Norephedrine , a  norepinephrine releasing agent , is a major  active metabolite  of oxyfedrine, and hence oxyfedrine may additionally act as an indirectly acting sympathomimetic. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6230", "text": "It has been found to depress the tonicity of coronary vessels, improve myocardial metabolism (so that heart can sustain hypoxia better) and also exert a positive chronotropic and inotropic effects, [ 1 ]  thereby not precipitating angina pectoris. The latter property (positive chronotropic and inotropic effects) is particularly important, because other vasodilators used in angina may be counter productive causing coronary steal phenomenon. [ additional citation(s) needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6231", "text": "The drug is chemically and pharmacologically unrelated to any other antianginal drugs. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6232", "text": "Oxyfedrine's  oral   bioavailability  is 85%. [ 1 ]  The  plasma protein binding  is almost 100%. [ 1 ]  Its  elimination half-life  is 4.2 \u00a0 hours. [ 1 ]   Norephedrine  is a major  active metabolite  of oxyfedrine. [ 2 ]  The  excretion  of the  active metabolites  of oxyfedrine is 90% in  urine . [ 1 ]  About 75 to 100% of oxyfedrine is excreted as norephedrine. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6233", "text": "Oxyfedrine is a  substituted phenethylamine  and  amphetamine   derivative . [ 7 ]  It is  l -norephedrine  with a bulky and  lipophilic  3-methoxypropiophenone  substituent  at the  nitrogen  atom. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6234", "text": "Mannich condensation of  phenylpropanolamine  ( 1 ) with  formaldehyde  and  m - acetanisole  (3-acetylanisole) ( 2 ) yields oxyfedrine ( 3 ). [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6235", "text": "Synergistic effects of oxyfedrine with  antibiotics  against  bacteria  have been suggested. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6236", "text": "Phenylpropanolamine  ( PPA ), sold under many brand names, is a  sympathomimetic agent  which is used as a  decongestant  and  appetite suppressant . [ 9 ] [ 1 ] [ 10 ] [ 11 ]  It was previously commonly used in  prescription  and  over-the-counter   cough and cold preparations . The medication is taken  by mouth . [ 4 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6237", "text": "Side effects  of phenylpropanolamine include increased  heart rate  and  blood pressure , among others. [ 13 ] [ 14 ] [ 15 ] [ 12 ]  Rarely, phenylpropanolamine has been associated with  hemorrhagic stroke . [ 11 ] [ 16 ] [ 13 ]  Phenylpropanolamine acts as a  norepinephrine releasing agent , thereby indirectly activating  adrenergic receptors . [ 17 ] [ 18 ] [ 19 ]  As such, it is an indirectly acting  sympathomimetic . [ 17 ] [ 18 ] [ 19 ] [ 10 ]  It was previously thought to act as a mixed acting sympathomimetic with additional direct  agonist  actions on adrenergic receptors, but this proved not to be the case. [ 17 ] [ 18 ] [ 19 ]  Chemically, phenylpropanolamine is a  substituted amphetamine  and is closely related to  ephedrine ,  pseudoephedrine ,  amphetamine , and  cathinone . [ 20 ] [ 21 ] [ 22 ] [ 11 ]  It is most commonly a  racemic mixture  of the (1 R ,2 S )- and (1 S ,2 R )- enantiomers  of  \u03b2-hydroxyamphetamine  and is also known as  dl -norephedrine. [ 21 ] [ 9 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6238", "text": "Phenylpropanolamine was first  synthesized  around 1910 and its  effects on blood pressure  were first characterized around 1930. [ 21 ] [ 11 ]  It was introduced for medical use by the 1930s. [ 23 ] [ 11 ]  The medication was  withdrawn  from many markets starting in 2000 following findings that it was associated with increased risk of hemorrhagic stroke. [ 23 ] [ 11 ]  It was previously available both  over-the-counter  and by  prescription . [ 23 ] [ 2 ] [ 24 ] [ 25 ]  Phenylpropanolamine is available for medical and/or  veterinary use  in some countries. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6239", "text": "Phenylpropanolamine is used as a  decongestant  to treat  nasal congestion . [ 13 ] [ 14 ]  It has also been used to  suppress appetite  and promote  weight loss  in the treatment of  obesity  and has shown effectiveness for this indication. [ 26 ] [ 27 ] [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6240", "text": "Phenylpropanolamine was previously available  over-the-counter  and in certain  combination forms  by  prescription  in the  United States . [ 24 ] [ 25 ]  However, these forms have all been discontinued. [ 24 ] [ 25 ] [ 2 ]  Phenylpropanolamine is available in some countries. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6241", "text": "Phenylpropanolamine produces  sympathomimetic  effects and can cause  side effects  such as increased  heart rate  and  blood pressure . [ 13 ] [ 14 ] [ 15 ] [ 12 ]  It has been associated rarely with incidence of  hemorrhagic stroke . [ 23 ] [ 16 ] [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6242", "text": "Certain drugs increase the chances of  d\u00e9j\u00e0 vu  occurring in the user, resulting in a strong sensation that an event or experience currently being experienced has already been experienced in the past. Some pharmaceutical drugs, when taken together, have also been implicated in the cause of  d\u00e9j\u00e0 vu . [ 29 ]  The  Journal of Clinical Neuroscience  reported the case of an otherwise healthy male who started experiencing intense and recurrent sensations of  d\u00e9j\u00e0 vu  upon taking the drugs  amantadine  and phenylpropanolamine together to relieve flu symptoms. [ 30 ]  He found the experience so interesting that he completed the full course of his treatment and reported it to the psychologists to write up as a case study. Because of the  dopaminergic  action of the drugs and previous findings from electrode stimulation of the brain, [ 31 ]  it was speculated that  d\u00e9j\u00e0 vu  occurs as a result of  hyperdopaminergic action  in the  mesial   temporal  areas of the brain."}
{"_id": "WikiPedia_Cardio$$$corpus_6243", "text": "There has been very little research on  drug interactions  with phenylpropanolamine. [ 4 ]  In one study, phenylpropanolamine taken with  caffeine  was found to quadruple caffeine levels. [ 4 ]  In another study, phenylpropanolamine reduced  theophylline   clearance  by 50%. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6244", "text": "Phenylpropanolamine acts primarily as a  selective   norepinephrine releasing agent . [ 19 ]  It also acts as a  dopamine releasing agent  with around 10-fold lower  potency . [ 19 ]  The stereoisomers of the drug have only weak or negligible  affinity  for  \u03b1-  and  \u03b2-adrenergic receptors . [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6245", "text": "Phenylpropanolamine was originally thought to act as a direct  agonist  of  adrenergic receptors  and hence to act as a mixed acting  sympathomimetic , [ 21 ] [ 22 ]  However, phenylpropanolamine was subsequently found to show only weak or negligible  affinity  for these  receptors  and has been instead characterized as exclusively an indirectly acting sympathomimetic. [ 10 ] [ 17 ] [ 18 ] [ 19 ]  It acts by  inducing norepinephrine release  and thereby indirectly activating adrenergic receptors. [ 17 ] [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6246", "text": "Many sympathetic hormones and neurotransmitters are based on the phenethylamine skeleton, and function generally in \"fight or flight\" type responses, such as increasing heart rate, blood pressure, dilating the pupils, increased energy, drying of mucous membranes, increased sweating, and a significant number of additional effects. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6247", "text": "Phenylpropanolamine has relatively low  potency  as a sympathomimetic. [ 21 ]  It is about 100 to 200 \u00a0 times less potent than  epinephrine  (adrenaline) or  norepinephrine  (noradrenaline) in its sympathomimetic effects, although responses are variable depending on  tissue . [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6248", "text": "Phenylpropanolamine is readily- and  well-absorbed  with  oral administration . [ 6 ] [ 7 ] [ 5 ]   Immediate-release  forms of the drug reached  peak  levels about 1.5 \u00a0 hours (range 1.0 to 2.3 \u00a0 hours) following administration. [ 4 ] [ 7 ]  Conversely,  extended-release  forms of phenylpropanolamine reach peak levels after 3.0 to 4.5 \u00a0 hours. [ 4 ]  The  pharmacokinetics  of phenylpropanolamine are linear across an oral dose range of 25 to 100 \u00a0 mg. [ 4 ]   Steady-state  levels of phenylpropanolamine are achieved within 12 \u00a0 hours when the drug is taken once every 4 \u00a0 hours. [ 4 ]  There is 62%  accumulation  of phenylpropanolamine at steady state in terms of peak levels, whereas  area-under-the-curve  levels are not increased with steady state. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6249", "text": "The  volume of distribution  of phenylpropanolamine is 3.0 to 4.5 \u00a0 L/kg. [ 4 ]  Levels of phenylpropanolamine in the  brain  are about 40% of those in the  heart  and 20% of those in the  lungs . [ 6 ]  The  hydroxyl group  of phenylpropanolamine at the \u03b2 carbon increases its  hydrophilicity , reduces its permeation through the  blood\u2013brain barrier , and limits its  central nervous system  (CNS) effects. [ 6 ]  Hence, phenylpropanolamine crosses into the brain only to some extent, has only weak CNS effects, and most of its effects are peripheral. [ 14 ] [ 6 ] [ 5 ] [ 21 ]  In any case, phenylpropanolamine can produce  amphetamine -like  psychostimulant  effects at very high doses. [ 21 ] [ 6 ] [ 5 ]  Phenylpropanolamine is more lipophilic than  structurally related  sympathomimetics with hydroxyl groups on the  phenyl ring  like  epinephrine  (adrenaline) and  phenylephrine  and has greater brain permeability than these agents. [ 5 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6250", "text": "The  plasma protein binding  of phenylpropanolamine is approximately 20%. [ 5 ] [ 4 ]  However, it has been said that no recent studies have substantiated this value. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6251", "text": "Phenylpropanolamine is not substantially  metabolized . [ 7 ] [ 5 ]  It also does not undergo significant  first-pass metabolism . [ 7 ]  Only about 3 to 4% of an oral dose of phenylpropanolamine is metabolized. [ 5 ]   Metabolites  include  hippuric acid  (via  oxidative   deamination  of the  side chain ) and  4-hydroxynorephedrine  (via  para - hydroxylation ). [ 4 ] [ 5 ] [ 6 ]  The  methyl group  at the \u03b1 carbon of phenylpropanolamine blocks metabolism by  monoamine oxidases  (MAOs). [ 6 ] [ 5 ] [ 14 ]  Phenylpropanolamine is also not a  substrate  of  catechol  O -methyltransferase . [ 14 ]  The  hydroxyl group  at the \u03b2 carbon of phenylpropanolamine also helps to increase  metabolic stability . [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6252", "text": "Approximately 90% of a dose of phenylpropanolamine is  excreted  in the  urine  unchanged within 24 \u00a0 hours. [ 4 ] [ 6 ] [ 7 ] [ 5 ]  About 4% of excreted material is in the form of  metabolites . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6253", "text": "The  elimination half-life  of  immediate-release  phenylpropanolamine is about 4 \u00a0 hours, with a range in different studies of 3.7 to 4.9 \u00a0 hours. [ 6 ] [ 7 ] [ 4 ]  The half-life of  extended-release  phenylpropanolamine has ranged from 4.3 to 5.8 \u00a0 hours. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6254", "text": "The  elimination  of phenylpropanolamine is dependent on urinary  pH . [ 4 ] [ 5 ]  At a more  acidic  urinary pH, the elimination of phenylpropanolamine is accelerated and its half-life and duration are shortened, whereas at more  basic  urinary pH, the elimination of phenylpropanolamine is reduced and its half-life and duration are extended. [ 5 ]   [ 4 ]   Urinary acidifying agents  like  ascorbic acid  and  ammonium chloride  can increase the excretion of and thereby reduce exposure to  amphetamines  including phenylpropanolamine, whereas  urinary alkalinizing agents  including  antacids  like  sodium bicarbonate  as well as  acetazolamide  can reduce the excretion of these agents and thereby increase exposure to them. [ 36 ] [ 5 ] [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6255", "text": "Total body  clearance  of phenylpropanolamine has been reported to be 0.546 \u00a0 L/h/kg, while renal clearance was 0.432 \u00a0 L/h/kg. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6256", "text": "As phenylpropanolamine is not extensively metabolized, it would probably not be affected by  hepatic impairment . [ 4 ]  Conversely, there is likely to be accumulation of phenylpropanolamine with  renal impairment  due to its dependence on urinary excretion. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6257", "text": "Norephedrine is a minor  metabolite  of  amphetamine  and  methamphetamine , as shown below. [ 4 ]  It is also a minor metabolite of  ephedrine  and a major metabolite of  cathinone . [ 4 ] [ 6 ] [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6258", "text": "Phenylpropanolamine, also known as (1 RS ,2 SR )-\u03b1-methyl-\u03b2-hydroxyphenethylamine or as (1 RS ,2 SR )-\u03b2-hydroxyamphetamine, is a  substituted phenethylamine  and  amphetamine   derivative . [ 9 ] [ 20 ] [ 49 ]  It is closely related to the  cathinones  (\u03b2-ketoamphetamines). [ 20 ]   \u03b2-Hydroxyamphetamine  exists as four  stereoisomers , which include  d - ( dextrorotatory ) and  l -norephedrine ( levorotatory ), and  d -  and  l -norpseudoephedrine . [ 49 ] [ 10 ]   d -Norpseudoephedrine is also known as  cathine , [ 9 ] [ 49 ]  and is found  naturally  in  Catha edulis  ( khat ). [ 50 ]   Pharmaceutical drug   preparations  of phenylpropanolamine have varied in their stereoisomer composition in different countries, which may explain differences in  misuse  and  side effect  profiles. [ 10 ]  In any case,  racemic   dl -norephedrine, or (1 RS ,2 SR )-phenylpropanolamine, appears to be the most commonly used formulation of phenylpropanolamine pharmaceutically. [ 21 ] [ 9 ] [ 1 ]   Analogues  of phenylpropanolamine include  ephedrine ,  pseudoephedrine ,  amphetamine ,  methamphetamine , and  cathinone . [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6259", "text": "Phenylpropanolamine, structurally, is in the substituted phenethylamine class, consisting of a cyclic benzene or phenyl group, a two carbon ethyl moiety, and a terminal nitrogen, hence the name  phen-ethyl-amine . [ 51 ]  The methyl group on the  alpha carbon  (the first carbon before the nitrogen group) also makes this compound a member of the  substituted amphetamine  class. [ 51 ]   Ephedrine  is the  N -methyl analogue of phenylpropanolamine."}
{"_id": "WikiPedia_Cardio$$$corpus_6260", "text": "Exogenous compounds in this family are degraded too rapidly by  monoamine oxidase  to be active at all but the highest doses. [ 51 ]  However, the addition of the \u03b1-methyl group allows the compound to avoid metabolism and confer an effect. [ 51 ]  In general,  N -methylation of primary amines increases their potency, whereas \u03b2-hydroxylation decreases CNS activity, but conveys more selectivity for  adrenergic  receptors. [ 51 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6261", "text": "Phenylpropanolamine is a  small-molecule   compound  with the  molecular formula  C 9 H 13 NO and a  molecular weight  of 151.21 \u00a0 g/mol. [ 52 ] [ 8 ]  It has an experimental  log P  of 0.67, while its predicted log P values range from 0.57 to 0.89. [ 52 ] [ 8 ]  The compound is relatively  lipophilic , [ 5 ]  but is also more  hydrophilic  than other amphetamines. [ 6 ]  The lipophilicity of amphetamines is closely related to their brain permeability. [ 53 ]  For comparison to phenylpropanolamine, the experimental log P of  methamphetamine  is 2.1, [ 54 ]  of  amphetamine  is 1.8, [ 55 ] [ 54 ]  of  ephedrine  is 1.1, [ 56 ]  of  pseudoephedrine  is 0.7, [ 57 ]  of  phenylephrine  is -0.3, [ 58 ]  and of  norepinephrine  is -1.2. [ 59 ]  Methamphetamine has high brain permeability, [ 54 ]  whereas phenylephrine and norepinephrine are  peripherally selective drugs . [ 60 ] [ 61 ]  The optimal log P for brain permeation and central activity is about 2.1 (range 1.5\u20132.7). [ 62 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6262", "text": "Phenylpropanolamine has been used pharmaceutically exclusively as the  hydrochloride   salt . [ 9 ] [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6263", "text": "Phenylpropanolamine was first  synthesized  in the early 20th century, in or around 1910. [ 21 ] [ 11 ]  It was  patented  as a  mydriatic  in 1913. [ 21 ]  The  pressor  effects of phenylpropanolamine were characterized in the late 1920s and the 1930s. [ 21 ]  Phenylpropanolamine was first introduced for medical use by the 1930s. [ 23 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6264", "text": "In the United States, phenylpropanolamine is no longer sold due to an increased risk of  haemorrhagic stroke . [ 16 ]  In a few countries in  Europe , however, it is still available either by prescription or sometimes over-the-counter. In  Canada , it was withdrawn from the market on 31 May 2001. [ 63 ]  It was voluntarily withdrawn from the Australian market by July 2001. [ 64 ]  In  India , human use of phenylpropanolamine and its formulations was banned on 10 February 2011, [ 65 ]  but the ban was overturned by the judiciary in September 2011. [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6265", "text": "Phenylpropanolamine  is the  generic name  of the drug and its  INN Tooltip International Nonproprietary Name ,  BAN Tooltip British Approved Name , and  DCF Tooltip D\u00e9nomination Commune Fran\u00e7aise , while  phenylpropanolamine hydrochloride  is its  USAN Tooltip United States Adopted Name  and  BANM Tooltip British Approved Name  in the case of the  hydrochloride   salt . [ 9 ] [ 1 ] [ 10 ] [ 2 ]  It is also known by the synonym  norephedrine . [ 9 ] [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6266", "text": "Brand names of phenylpropanolamine include Acutrim, Appedrine, Capton Diet, Control, Dexatrim, Emagrin Plus A.P., Glifentol, Kontexin, Merex, Monydrin, Mydriatine, Prolamine, Propadrine, Propagest, Recatol, Rinexin, Tinaroc, and Westrim, among many others. [ 9 ] [ 1 ] [ 2 ]  It has also been used in  combinations  under brand names including Allerest, Demazin, Dimetapp, and Sinarest, among others. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6267", "text": "Phenylpropanolamine is available for medical and  veterinary use  in some countries. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6268", "text": "There has been interest in phenylpropanolamine as a  performance-enhancing drug  in  exercise  and  sports . [ 67 ]  However, clinical studies suggest that phenylpropanolamine is not effective in this regard. [ 67 ] [ 6 ]  Phenylpropanolamine is not on the  World Anti-Doping Agency  (WADA)  list of prohibited substances  as of 2024. [ 68 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6269", "text": "In Sweden, phenylpropanolamine is still available in prescription decongestants; [ 69 ]  Phenylpropanolamine is also still available in Germany. It is used in some  polypill  medications like Wick DayMed capsules."}
{"_id": "WikiPedia_Cardio$$$corpus_6270", "text": "In the United Kingdom, phenylpropanolamine was available in many \"all in one\" cough and cold medications which usually also feature  paracetamol  or another  analgesic  and  caffeine  and could also be purchased on its own; however, it is no longer approved for human use. A European Category 1 Licence is required to purchase phenylpropanolamine for academic use."}
{"_id": "WikiPedia_Cardio$$$corpus_6271", "text": "In the United States, the  Food and Drug Administration  (FDA) issued a public health advisory [ 70 ]  against the use of the drug in November 2000. In this advisory, the FDA requested but did not require that all drug companies discontinue marketing products containing phenylpropanolamine. The agency estimates that phenylpropanolamine caused between 200 and 500 strokes per year among 18-to-49-year-old users. In 2005, the FDA removed phenylpropanolamine from over-the-counter sale and removed its \"generally recognized as safe and effective\" (GRASE) status. [ 71 ]  Under the 2020  CARES Act , it requires FDA approval before it can be marketed again effectively banning the drug even as a prescription drug. [ 72 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6272", "text": "Because of its potential use in  amphetamine  manufacture, phenylpropanolamine is controlled by the  Combat Methamphetamine Epidemic Act of 2005 . It is still available for veterinary use in dogs, however, as a treatment for  urinary incontinence ."}
{"_id": "WikiPedia_Cardio$$$corpus_6273", "text": "Internationally, an item on the agenda of the 2000  Commission on Narcotic Drugs  session called for including the stereoisomer norephedrine in Table I of  United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances . [ 73 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6274", "text": "Drugs containing phenylpropanolamine were banned in India on 27 January 2011. [ 74 ]  On 13 September 2011, Madras High Court revoked a ban on manufacture and sale of pediatric drugs phenylpropanolamine and  nimesulide . [ 75 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6275", "text": "Phenylpropanolamine is available for use in  veterinary medicine . [ 25 ]  It is used to control  urinary incontinence  in dogs. [ 76 ] [ 77 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6276", "text": "In June 2024, the US  Food and Drug Administration  (FDA) approved Phenylpropanolamine Hydrochloride chewable tablets for the control of urinary incontinence due to a weakening of the muscles that control urination (urethral sphincter hypotonus) in dogs. [ 78 ] [ 79 ] [ 80 ]  This is the first generic phenylpropanolamine hydrochloride chewable tablets for dogs. [ 78 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6277", "text": "Urinary incontinence happens when a dog loses its ability to control when it urinates. [ 78 ]  Urinary incontinence due to urethral sphincter hypotonus can happen as dogs age and as the dog\u2019s muscle in its urethra (the body part that leads from the dog\u2019s bladder to outside its body) weakens and loses control over its ability to hold urine. [ 78 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6278", "text": "Phenylpropanolamine Hydrochloride chewable tablets contain the same active ingredient (phenylpropanolamine hydrochloride) in the same concentration and dosage form as the approved brand name drug product, Proin chewable tablets, which were first approved in August 2011. [ 78 ]  In addition, the FDA determined that Phenylpropanolamine Hydrochloride chewable tablets contain no inactive ingredients that may significantly affect the bioavailability of the active ingredient. [ 78 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6279", "text": "Polycap  is a specific five-in-one  fixed dose combination   polypill  created by  Cadila Pharmaceuticals Limited  of  Ahmedabad ,  India  that combines moderate levels of five different medications in a single, one-a-day pill aimed at reducing/preventing  heart attacks  and  strokes ."}
{"_id": "WikiPedia_Cardio$$$corpus_6280", "text": "Polycap containing three generic blood pressure medications and a statin dramatically reduces the risk of heart-related illness in people with no prior history of heart problems, according to the results of a recent clinical trial presented at the  American Heart Association 's Scientific Sessions 2020."}
{"_id": "WikiPedia_Cardio$$$corpus_6281", "text": "This result comes as part of the International Polycap Study (TIPS)-3, a randomized, placebo-controlled trial to test the effectiveness of this fixed-dose  combination therapy . The study investigators also examined the impact of  aspirin  alone and in combination with the  polypill . When taken on its own, Polycap reduces by 20% the risk of heart attack, stroke, procedures to reopen clogged arteries and other heart disease, the researchers reported. The Polycap combined with daily low-dose aspirin is even more effective, reducing heart health problems by up to 40%. The study results were published online in  The New England Journal of Medicine . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6282", "text": "Polycap combines 100 milligrams of aspirin, with  simvastatin  (a generic version of Zocor, the cholesterol-lowering statin; 20\u00a0mg) and low doses of three blood pressure medications,  beta blocker   atenolol  (50\u00a0mg),  ACE inhibitor   ramipril  (5\u00a0mg) and  diuretic   hydrochlorothiazide  (12.5\u00a0mg). And despite containing multiple drugs, the pill has a fairly small size which can facilitate swallowing. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6283", "text": "The International Polycap Study 3 (TIPS-3) was a 2x2x2 factorial design study presented in two parts during the late-breaking clinical trial session. In TIPS-3, investigators randomized 5713 participants across 9 countries to determine if a fixed-dose combination tablet reduced the risk of major cardiovascular outcomes in a primary prevention population. As part of the factorial design, the additional interventions included aspirin alone compared with placebo as well as polypill plus aspirin compared with double placebo."}
{"_id": "WikiPedia_Cardio$$$corpus_6284", "text": "To be included in the study, patients had to be at intermediate risk for myocardial infarction, stroke, and cardiovascular death. The participants\u2019 average age was 64 years. Men 50 years and older and women 55 years and older with an INTERHEART risk score \u2265 10 (or men and women 65 years and older with an INTERHEART risk score \u2265 5) were included in the international study. Roughly 53% of study participants were women. Mean LDL cholesterol level and  systolic blood pressure  at baseline were 121\u00a0mg/dL and 144.5\u00a0mm Hg, respectively. [ 4 ]  For the trial, participants were randomly assigned to one of four groups. They were asked to take one of the following daily: both the polypill and aspirin, the polypill alone, aspirin alone, or only a placebo. The top-enrolling countries were India, the Philippines, Columbia, and Bangladesh; Canada enrolled 131 patients. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6285", "text": "Medications included in the polypill were atenolol, 100\u00a0mg; ramipril, 10\u00a0mg; hydrochlorothiazide, 25\u00a0mg; and simvastatin, 40\u00a0mg."}
{"_id": "WikiPedia_Cardio$$$corpus_6286", "text": "Only 4.4% of those who took the polypill alone had a heart attack, stroke, artery-reopening procedure or died of heart disease, compared to 5.5% who took the placebo. About 4.1% of those who took aspirin alone developed heart-related illness, compared to 4.7% of those with the placebo."}
{"_id": "WikiPedia_Cardio$$$corpus_6287", "text": "Combining a polypill with aspirin provided the best benefits, the study authors said. The polypill/aspirin combination reduced heart problems and deaths by 31%, the researchers discovered. People who continued to take the pill without interruption for about four years saw a 40% reduced risk of heart problems. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6288", "text": "The trial included a follow-up period of 5 years. During which, participants were monitored for nonfatal  myocardial infarctions , nonfatal  strokes , heart failure, cardiac arrest, and cardiovascular death."}
{"_id": "WikiPedia_Cardio$$$corpus_6289", "text": "The study was 95% funded by charitable organizations like the  Wellcome Trust  UK, parent company Cadila Pharmaceuticals and other government agencies."}
{"_id": "WikiPedia_Cardio$$$corpus_6290", "text": "A study called The Indian Polycap Study (TIPS) was sponsored by Cadila Pharmaceuticals Limited, (where the drug development program was coordinated by JP Parswani, President, and Dr. Arun Maseeh, Vice-President Medical Affairs), and led by Dr. Salim Yusuf of  McMaster University  in  Hamilton, Ontario , and Dr. Prem Pais of  St. John's Medical College  in  Bangalore , India. The results of the randomized, controlled, double-blind study, reported in March 2009 at an  American College of Cardiology  conference and published online by  The Lancet , documented the outcome of 2,000 individuals with an average age of 54 given the medication, all of whom had at least one heart disease risk factor:  diabetes ,  hypercholesterolemia ,  hypertension ,  obesity  or  smoking . [ 3 ]  The study was registered with  ClinicalTrials.gov , number NCT00443794. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6291", "text": "During a 12-week treatment period, 400 of the study participants were given Polycap. The remainder were divided into eight groups of 200 who were given either individual components or groups of them. [ 3 ]  Three of the groups of 200 received only aspirin, simvastatin or thiazide respectively; Three groups received two of the three blood pressure medications; Another received all three blood pressure medications, while the last received all three combined with aspirin. [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6292", "text": "The individuals who were given Polycap saw their  blood pressure  drop from six to seven points for both their systolic and diastolic levels. These reductions in blood pressure could cut the risk of heart disease by 62% and of stroke by 48% based on the results of other studies that showed risk reductions from cutting blood pressure levels. The combined pill was almost as effective as the individual pills with no increase in side effects. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6293", "text": "Generic versions of the five components cost $17 per month in the United States as of 2009. Estimates are that the combined dose would sell for far less while offering the psychological benefit of reducing the \" pill burden \" on patients taking multiple medications. Distribution would require approval by the  U.S. Food and Drug Administration  and other regulatory bodies worldwide. [ 3 ]  Details of the polycap data were widely reported in the popular media, including USA Today, The Guardian (UK), BBC, CBS Healthwatch, ABC News, India Today."}
{"_id": "WikiPedia_Cardio$$$corpus_6294", "text": "The Polycap (Cadila) has been found to be safe and effective for reducing multiple cardiovascular risk factors.  Bioavailability  of each component of PolycapTM and absence of their mutual interaction relative to single component reference formulations have been evaluated by a group of scientists led by Dr. Bhaswat Chakraborty. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6295", "text": "Bioavailability of the components of the Polycap ( aspirin ,  ramipril ,  simvastatin ,  atenolol  and  hydrochlorothiazide ) when formulated as a single capsule was compared to identical capsules with each of its components administered separately in a five arm, randomized, single-dose, two-period, two-treatment, two-sequence, crossover trial with at least 2 week washout period in a total of 195 healthy humans.  Plasma concentrations of each drug and where applicable its active metabolite were measured using validated LC-MS/MS and UPLC. Mean pharmacokinetic parameters and their standard deviations were computed for each analyte.  Comparative bioavailability and absence of drug-drug interaction for each component were computed based on a point estimate of test/reference (T/R) ratio of geometric means falling within 80-125% for Cmax, AUC0-t and AUC0-\u221e. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6296", "text": "The ratio of Cmax, AUC0-t and AUC0-\u221e for Polycap and reference drugs was within 80-125% for atenolol, hydrochlorothiazide, ramipril, ramiprilat and dose normalized salicylic acid. However, for simvastatin the point estimate of Cmax, AUC0-t and AUC0-\u221e for Ln-transformed data were significantly lower (~25%) and for its active metabolite,  simvastatin acid, it was significantly higher (~60%). Thus, the increased bioavailability of active simvastatin acid compensated for the loss of bioavailability of simvastatin alone. There was no indication of kinetic drug-drug interaction in any of components. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6297", "text": "Pseudoephedrine , sold under the brand name  Sudafed  among others, is a  sympathomimetic  medication which is used as a  decongestant  to treat  nasal congestion . [ 1 ] [ 13 ] [ 2 ]  It has also been used  off-label  for certain other indications, like treatment of  low blood pressure . [ 14 ] [ 15 ] [ 16 ]  At higher doses, it may produce various additional effects including  stimulant , [ 17 ] [ 1 ]   appetite suppressant , [ 18 ]  and  performance-enhancing  effects. [ 19 ] [ 20 ]  In relation to this, non-medical use of pseudoephedrine has been encountered. [ 17 ] [ 1 ] [ 18 ] [ 19 ] [ 20 ]  The medication is taken  by mouth . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6298", "text": "Side effects of pseudoephedrine include  insomnia , elevated  heart rate , increased  blood pressure ,  restlessness ,  dizziness ,  anxiety , and  dry mouth , among others. [ 21 ] [ 2 ] [ 1 ] [ 22 ]  Rarely, pseudoephedrine has been associated with serious  cardiovascular complications  like  heart attack  and  hemorrhagic stroke . [ 18 ] [ 23 ] [ 15 ]  Some people may be more sensitive to its  cardiovascular  effects. [ 22 ] [ 1 ]  Pseudoephedrine acts as a  norepinephrine releasing agent , thereby indirectly activating  adrenergic receptors . [ 24 ] [ 2 ] [ 25 ] [ 1 ]  As such, it is an indirectly acting  sympathomimetic . [ 24 ] [ 2 ] [ 25 ] [ 1 ]  Pseudoephedrine significantly crosses into the  brain , but has some  peripheral selectivity  due to its  hydrophilicity . [ 25 ] [ 26 ]  Chemically, pseudoephedrine is a  substituted amphetamine  and is closely related to  ephedrine ,  phenylpropanolamine , and  amphetamine . [ 1 ] [ 13 ] [ 2 ]  It is the (1 S ,2 S )- enantiomer  of  \u03b2-hydroxy- N -methylamphetamine . [ 27 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6299", "text": "Along with ephedrine, pseudoephedrine occurs  naturally  in  ephedra , which has been used for thousands of years in  traditional Chinese medicine . [ 13 ] [ 28 ]  It was first  isolated  from ephedra in 1889. [ 28 ] [ 13 ] [ 29 ]  Subsequent to its  synthesis  in the 1920s, pseudoephedrine was introduced for medical use as a decongestant. [ 13 ]  Pseudoephedrine is widely available  over-the-counter  (OTC) in both single-drug and  combination   preparations . [ 30 ] [ 22 ] [ 13 ] [ 2 ]  Availability of pseudoephedrine has been restricted starting in 2005 as it can be used to synthesize  methamphetamine . [ 13 ] [ 2 ]   Phenylephrine  has replaced pseudoephedrine in many over-the-counter  oral  decongestant products. [ 2 ]  However, oral phenylephrine appears to be ineffective as a decongestant. [ 31 ] [ 32 ]  In 2022, the combination with  brompheniramine  and  dextromethorphan  was the 265th most commonly prescribed medication in the United States, with more than 1 \u00a0 million prescriptions. [ 33 ] [ 33 ] [ 34 ]  In 2022, the combination with  loratadine  was the 289th most commonly prescribed medication in the United States, with more than 500,000 prescriptions. [ 33 ] [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6300", "text": "Pseudoephedrine is a  sympathomimetic  and is well-known for shrinking swollen nasal mucous membranes, so it is often used as a  decongestant . It reduces tissue  hyperemia ,  edema , and  nasal congestion  commonly associated with  colds  or  allergies . Other beneficial effects may include increasing the drainage of  sinus  secretions, and opening of obstructed  Eustachian tubes . The same  vasoconstriction  action can also result in  hypertension , which is a noted side effect of pseudoephedrine."}
{"_id": "WikiPedia_Cardio$$$corpus_6301", "text": "Pseudoephedrine can be used either as oral or as  topical decongestant . Due to its  stimulating  qualities, however, the oral preparation is more likely to cause adverse effects, including  urinary retention . [ 36 ] [ 37 ]  According to one study, pseudoephedrine may show effectiveness as an  antitussive  drug (suppression of  cough ). [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6302", "text": "Pseudoephedrine is  indicated  for the treatment of nasal congestion, sinus congestion, and Eustachian tube congestion. [ 39 ]  Pseudoephedrine is also indicated for  vasomotor rhinitis  and as an adjunct to other agents in the optimum treatment of  allergic rhinitis ,  croup ,  sinusitis ,  otitis media , and  tracheobronchitis . [ 39 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6303", "text": "Amphetamine-type stimulants  and other  catecholaminergic  agents are known to have  wakefulness-promoting effects  and are used in the treatment of  hypersomnia  and  narcolepsy . [ 40 ] [ 41 ] [ 42 ]  Pseudoephedrine at therapeutic doses does not appear to improve or worsen daytime  sleepiness , daytime  fatigue , or  sleep quality  in people with  allergic rhinitis . [ 1 ] [ 43 ]  Likewise,  somnolence  was not lower in children with the  common cold  treated with pseudoephedrine for nasal congestion. [ 44 ]  In any case,  insomnia  is a known  side effect  of pseudoephedrine, although the incidence is low. [ 21 ]  In addition, doses of pseudoephedrine above the normal therapeutic range have been reported to produce  stimulant  effects including insomnia and fatigue resistance. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6304", "text": "There has been interest in pseudoephedrine as an  appetite suppressant  for the treatment of  obesity . [ 18 ]  However, due to lack of clinical data and potential cardiovascular side effects, this use is not recommended. [ 18 ]  Only a single  placebo - controlled  study of pseudoephedrine for  weight loss  exists (120 \u00a0 mg/day  slow-release  for 12 \u00a0 weeks) and found no significant difference in weight lost compared to placebo (-4.6 \u00a0 kg vs. -4.5 \u00a0 kg). [ 18 ] [ 45 ]  This was in contrast to  phenylpropanolamine , which has been found to be more effective at promoting weight loss compared to placebo and has been more widely studied and used in the treatment of obesity. [ 46 ] [ 47 ] [ 45 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6305", "text": "Pseudoephedrine has been used limitedly in the treatment of  orthostatic intolerance  including  orthostatic hypotension [ 14 ]  and  postural orthostatic tachycardia syndrome  (POTS). [ 16 ] [ 48 ] [ 49 ]  However, its effectiveness in the treatment of POTS is controversial. [ 16 ] [ 48 ]  Pseudoephedrine has also been used limitedly in the treatment of refractory  hypotension  in  intensive care units . [ 15 ]  However, data on this use are limited to  case reports  and  case series . [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6306", "text": "Pseudoephedrine is also used as a first-line prophylactic for recurrent  priapism . [ 50 ]   Erection  is largely a  parasympathetic  response, so the sympathetic action of pseudoephedrine may serve to relieve this condition. Data for this use are however  anecdotal  and effectiveness has been described as variable. [ 50 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6307", "text": "Treatment of  urinary incontinence  is an  off-label use  for pseudoephedrine and related medications. [ 51 ] [ 52 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6308", "text": "Pseudoephedrine is available by itself  over-the-counter  in the form of 30 and 60 \u00a0 mg  immediate-release  and 120 and 240 \u00a0 mg  extended-release   oral   tablets  in the  United States . [ 30 ] [ 53 ] [ 54 ] [ 55 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6309", "text": "Pseudoephedrine is also available over-the-counter and  prescription-only   in combination  with numerous other drugs, including  antihistamines  ( acrivastine ,  azatadine ,  brompheniramine ,  cetirizine ,  chlorpheniramine ,  clemastine ,  desloratadine ,  dexbrompheniramine ,  diphenhydramine ,  fexofenadine ,  loratadine ,  triprolidine ),  analgesics  ( acetaminophen ,  codeine ,  hydrocodone ,  ibuprofen ,  naproxen ),  cough suppressants  ( dextromethorphan ), and  expectorants  ( guaifenesin ). [ 30 ] [ 53 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6310", "text": "Pseudoephedrine has been used in the form of the  hydrochloride  and  sulfate   salts  and in a polistirex form. [ 30 ]  The drug has been used in more than 135 over-the-counter and prescription formulations. [ 22 ]  Many prescription formulations containing pseudoephedrine have been discontinued over time. [ 30 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6311", "text": "Pseudoephedrine is  contraindicated  in patients with  diabetes mellitus ,  cardiovascular disease , severe or uncontrolled  hypertension , severe  coronary artery disease ,  prostatic hypertrophy ,  hyperthyroidism ,  closed-angle glaucoma , or by  pregnant  women. [ 56 ]  The safety and effectiveness of nasal decongestant use in children is unclear. [ 57 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6312", "text": "Common side effects with pseudoephedrine therapy may include  central nervous system  (CNS)  stimulation ,  insomnia ,  restlessness ,  excitability ,  dizziness , and  anxiety . [ 18 ] [ 15 ] [ 58 ]  Infrequent side effects include  tachycardia  or  palpitations . [ 18 ]  Rarely, pseudoephedrine therapy may be associated with  mydriasis  (dilated pupils),  hallucinations ,  arrhythmias ,  hypertension ,  seizures , and  ischemic colitis ; as well as severe  skin reactions  known as recurrent pseudo-scarlatina,  systemic contact dermatitis , and non-pigmenting  fixed drug eruption . [ 18 ] [ 59 ] [ 56 ]  Pseudoephedrine, particularly when combined with other drugs including  narcotics , may also play a role in the precipitation of episodes of  psychosis . [ 18 ] [ 60 ]  It has also been reported that pseudoephedrine, among other  sympathomimetic  agents, may be associated with the occurrence of  hemorrhagic stroke  and other  cardiovascular complications . [ 18 ] [ 23 ] [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6313", "text": "Due to its sympathomimetic effects, pseudoephedrine is a  vasoconstrictor  and  pressor agent  (increases  blood pressure ), a  positive chronotrope  (increases  heart rate ), and a  positive inotrope  (increases  force of heart contractions ). [ 18 ] [ 1 ] [ 22 ] [ 19 ] [ 20 ]  The influence of pseudoephedrine on blood pressure at clinical doses is controversial. [ 1 ] [ 22 ]  A closely related sympathomimetic and decongestant,  phenylpropanolamine , was  withdrawn  due to associations with markedly increased blood pressure and incidence of hemorrhagic stroke. [ 22 ]  There has been concern that pseudoephedrine may likewise dangerously increase blood pressure and thereby increase the risk of stroke, whereas others have contended that the risks are exaggerated. [ 1 ] [ 22 ]  Besides hemorrhagic stroke,  myocardial infarction ,  coronary vasospasm , and  sudden death  have also rarely been reported with sympathomimetic  ephedra  compounds like pseudoephedrine and  ephedrine . [ 18 ] [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6314", "text": "A 2005  meta-analysis  found that pseudoephedrine at recommended doses had no meaningful effect on  systolic  or  diastolic blood pressure  in healthy individuals or people with controlled  hypertension . [ 1 ] [ 22 ]  Systolic blood pressure was found to slightly increase by 0.99 \u00a0 mm \u00a0 Hg on average and heart rate was found to slightly increase by 2.83 \u00a0 bpm on average. [ 1 ] [ 22 ]  Conversely, there was no significant influence on diastolic blood pressure, which increased by 0.63 \u00a0 mg \u00a0 Hg. [ 22 ]  In people with controlled hypertension, systolic hypertension increased by a similar degree of 1.20 \u00a0 mm \u00a0 Hg. [ 22 ]   Immediate-release  preparations, higher doses, being male, and shorter duration of use were all associated with greater cardiovascular effects. [ 22 ]  A small subset of individuals with  autonomic instability , perhaps in turn resulting in greater adrenergic receptor sensitivity, may be substantially more sensitive to the cardiovascular effects of sympathomimetics. [ 22 ]  Subsequent to the 2005 meta-analysis, a 2015  systematic review  and a 2018 meta-analysis found that pseudoephedrine at high doses (>170 \u00a0 mg) could increase heart rate and physical performance with larger  effect sizes  than lower doses. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6315", "text": "A 2007  Cochrane review  assessed the side effects of short-term use of pseudoephedrine at recommended doses as a nasal decongestant. [ 21 ]  It found that pseudoephedrine had a small risk of  insomnia  and this was the only side effect that occurred at rates significantly different from placebo. [ 21 ]  Insomnia occurred at a rate of 5% and had an  odds ratio  (OR) of 6.18. [ 21 ]  Other side effects, including  headache  and  hypertension , occurred at rates of less than 4% and were not different from placebo. [ 21 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6316", "text": "Tachyphylaxis  is known to develop with prolonged use of pseudoephedrine, especially when it is re-administered at short intervals. [ 1 ] [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6317", "text": "There is a case report of temporary  depressive symptoms  upon  discontinuation  and  withdrawal  from pseudoephedrine. [ 18 ] [ 61 ]  The withdrawal symptoms included worsened  mood  and  sadness , profoundly decreased  energy , a worsened view of oneself, decreased concentration,  psychomotor retardation , increased  appetite , and increased need for  sleep . [ 18 ] [ 61 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6318", "text": "Pseudoephedrine has psychostimulant effects at high doses and is a  positive reinforcer  with  amphetamine -like effects in animals including rats and monkeys. [ 62 ] [ 63 ] [ 64 ] [ 65 ]  However, it is substantially less  potent  than  methamphetamine  or  cocaine . [ 62 ] [ 63 ] [ 64 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6319", "text": "The maximum total daily dose of pseudoephedrine is 240 \u00a0 mg. [ 1 ]  Symptoms of  overdose  may include  sedation ,  apnea , impaired concentration,  cyanosis ,  coma ,  circulatory collapse ,  insomnia ,  hallucinations ,  tremors ,  convulsions ,  headache ,  dizziness ,  anxiety ,  euphoria ,  tinnitus ,  blurred vision ,  ataxia ,  chest pain ,  tachycardia ,  palpitations ,  increased blood pressure ,  decreased blood pressure ,  thirstiness ,  sweating , difficulty with  urination ,  nausea , and  vomiting . [ 1 ]  In children, symptoms have more often included  dry mouth ,  pupil dilation ,  hot flashes ,  fever , and  gastrointestinal dysfunction . [ 1 ]  Pseudoephedrine may produce  toxic  effects both with use of supratherapeutic doses but also in people who are more sensitive to the effects of sympathomimetics. [ 1 ]   Misuse  of the drug has been reported in one case at massive doses of 3,000 to 4,500 \u00a0 mg (100\u2013150 \u00a0 \u00d7 \u00a0 30-mg tablets) per day, with the doses gradually increased over time by this individual. [ 1 ] [ 66 ]  No fatalities due to pseudoephedrine misuse have been reported as of 2021. [ 17 ]  However, death with pseudoephedrine has been reported generally. [ 1 ] [ 13 ] [ 18 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6320", "text": "Concomitant or recent (previous 14 \u00a0 days)  monoamine oxidase inhibitor  (MAOI) use can lead to  hypertensive reactions , including  hypertensive crisis , and should be avoided. [ 1 ] [ 56 ]  Clinical studies have found minimal or no influence of certain MAOIs like the weak non-selective MAOI  linezolid  and the potent selective MAO-B inhibitor  selegiline  (as a  transdermal patch ) on the  pharmacokinetics  of pseudoephedrine. [ 67 ] [ 68 ] [ 69 ] [ 70 ]  This is in accordance with the fact that pseudoephedrine is not  metabolized  by  monoamine oxidase  (MAO). [ 25 ] [ 11 ] [ 71 ]  However, pseudoephedrine  induces the release of norepinephrine , which MAOIs inhibit the metabolism of, and as such, MAOIs can still potentiate the effects of pseudoephedrine. [ 72 ] [ 1 ] [ 68 ]  No significant pharmacodynamic interactions have been found with selegiline, [ 68 ] [ 70 ]  but linezolid potentiated  blood pressure  increases with pseudoephedrine. [ 67 ] [ 69 ]  However, this was deemed to be without clinical significance in the case of linezolid, though it was noted that some individuals may be more sensitive to the  sympathomimetic  effects of pseudoephedrine and related agents. [ 67 ] [ 69 ]  Pseudoephedrine is  contraindicated  with MAOIs like  phenelzine ,  tranylcypromine ,  isocarboxazid , and  moclobemide  due to the potential for synergistic sympathomimetic effects and hypertensive crisis. [ 1 ] [ 18 ]  It is also considered to be contraindicated with linezolid and selegiline as some individuals may react more sensitively to coadministration. [ 67 ] [ 69 ] [ 68 ] [ 70 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6321", "text": "Concomitant use of pseudoephedrine with other  vasoconstrictors , including  ergot alkaloids  like  ergotamine  and  dihydroergotamine ,  linezolid ,  oxytocin ,  ephedrine ,  phenylephrine , and  bromocriptine , among others, is not recommended due to the possibility of greater increases in blood pressure and risk of  hemorrhagic stroke . [ 1 ]  Sympathomimetic effects and cardiovascular risks of pseudoephedrine may also be increased with  digitalis glycosides ,  tricyclic antidepressants ,  appetite suppressants , and  inhalational anesthetics . [ 1 ]  Likewise, greater sympathomimetic effects of pseudoephedrine may occur when it is combined with other sympathomimetic agents. [ 18 ]  Rare but serious cardiovascular complications have been reported with the combination of pseudoephedrine and  bupropion . [ 13 ] [ 73 ] [ 74 ]  Increase of  ectopic pacemaker  activity can occur when pseudoephedrine is used concomitantly with  digitalis . [ 1 ]  The  antihypertensive  effects of  methyldopa ,  guanethidine ,  mecamylamine ,  reserpine , and  veratrum alkaloids  may be reduced by sympathomimetics like pseudoepehdrine. [ 1 ]   Beta blockers  like  labetalol  may reduce the effects of pseudoephedrine. [ 75 ] [ 76 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6322", "text": "Urinary acidifying agents  like  ascorbic acid  and  ammonium chloride  can increase the  excretion  of and thereby reduce exposure to  amphetamines  including pseudoephedrine, whereas  urinary alkalinizing agents  including  antacids  like  sodium bicarbonate  as well as  acetazolamide  can reduce the excretion of these agents and thereby increase exposure to them. [ 1 ] [ 11 ] [ 77 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6323", "text": "Pseudoephedrine is a  sympathomimetic agent  which acts primarily or exclusively by  inducing the release of norepinephrine . [ 78 ] [ 25 ] [ 2 ] [ 24 ]  Hence, it is an indirectly acting sympathomimetic. [ 78 ] [ 25 ] [ 2 ]  Some sources state that pseudoephedrine has a mixed  mechanism of action  consisting of both indirect and direct effects by binding to and acting as an  agonist  of  adrenergic receptors . [ 1 ] [ 15 ]  However, the  affinity  of pseudoephedrine for adrenergic receptors is described as very low or negligible. [ 78 ]   Animal studies  suggest that the sympathomimetic effects of pseudoephedrine are exclusively due to norepinephrine release. [ 79 ] [ 80 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6324", "text": "Pseudoephedrine  induces monoamine release   in vitro  with an  EC 50 Tooltip half maximal effective concentration  of 224 \u00a0 nM for  norepinephrine  and 1,988 \u00a0 nM for  dopamine , whereas it is inactive for  serotonin . [ 24 ] [ 86 ] [ 82 ]  As such, it is about 9-fold  selective  for induction of norepinephrine release over dopamine release. [ 24 ] [ 86 ] [ 82 ]  The drug has negligible agonistic activity at the  \u03b1 1 -  and  \u03b1 2 -adrenergic receptors  (K act  >10,000 \u00a0 nM). [ 24 ]  At the  \u03b2 1 -  and  \u03b2 2 -adrenergic receptors , it acts as a  partial agonist  with relatively low  affinity  (\u03b2 1  = K act  = 309 \u00a0 \u03bcM,  IA Tooltip intrinsic activity  = 53%; \u03b2 2  = 10 \u00a0 \u03bcM;  IA  = 47%). [ 87 ]  It was an  antagonist  or very weak partial agonist of the  \u03b2 3 -adrenergic receptor  (K act  =  ND ;  IA  = 7%). [ 87 ]  It is about 30,000 to 40,000 \u00a0 times less potent as a \u03b2-adrenergic receptor agonist than  (\u2013)-isoproterenol . [ 87 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6325", "text": "Pseudoephedrine's principal mechanism of action relies on its action on the adrenergic system. [ 88 ] [ 89 ]  The  vasoconstriction  that pseudoephedrine produces is believed to be principally an \u03b1-adrenergic receptor response. [ 90 ]  Pseudoephedrine acts on \u03b1- and \u03b2 2 -adrenergic receptors, to cause vasoconstriction and relaxation of smooth muscle in the bronchi, respectively. [ 88 ] [ 89 ]  \u03b1-Adrenergic receptors are located on the muscles lining the walls of blood vessels. When these receptors are activated, the muscles contract, causing the blood vessels to constrict (vasoconstriction). The constricted blood vessels now allow less fluid to leave the blood vessels and enter the nose, throat, and sinus linings, which results in decreased inflammation of nasal membranes, as well as decreased mucus production. Thus, by constriction of blood vessels, mainly those located in the nasal passages, pseudoephedrine causes a decrease in the symptoms of nasal congestion. [ 2 ]  Activation of \u03b2 2 -adrenergic receptors produces relaxation of the smooth muscle of the bronchi, [ 88 ]  causing bronchial dilation and in turn decreasing congestion (although not fluid) and difficulty breathing."}
{"_id": "WikiPedia_Cardio$$$corpus_6326", "text": "Pseudoephedrine is less  potent  as a sympathomimetic and  psychostimulant  than  ephedrine . [ 1 ] [ 58 ]  Clinical studies have found that pseudoephedrine is about 3.5- to 4-fold less potent than ephedrine as a sympathomimetic agent in terms of  blood pressure  increases and 3.5- to 7.2-fold or more less potent as a  bronchodilator . [ 58 ]  Pseudoephedrine is also said to have much less central effect than ephedrine and to be only a weak psychostimulant. [ 25 ] [ 58 ] [ 2 ] [ 78 ] [ 65 ]   Blood vessels  in the nose are around five times more sensitive than the  heart  to the actions of circulating  epinephrine  (adrenaline), which may help to explain how pseudoephedrine at the low doses used in over-the-counter products can produce nasal decongestion with minimal effects on the heart. [ 2 ]  Compared to  dextroamphetamine , pseudoephedrine is about 30 to 35 \u00a0 times less potent as a norepinephrine releasing agent and 80 to 350 \u00a0 times less potent as a  dopamine releasing agent   in vitro . [ 24 ] [ 83 ] [ 84 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6327", "text": "Pseudoephedrine is a very weak  reversible inhibitor  of  monoamine oxidase  (MAO)  in vitro , including both  MAO-A  and  MAO-B  (K i  = 1,000\u20135,800 \u00a0 \u03bcM). [ 91 ]  It is far less potent in this action than other agents like dextroamphetamine and  moclobemide . [ 91 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6328", "text": "Pseudoephedrine is  orally active  and is readily  absorbed  from the  gastrointestinal tract . [ 1 ] [ 2 ]  Its oral  bioavailability  is approximately 100%. [ 8 ]  The drug reaches  peak  concentrations after 1 to 4 \u00a0 hours (mean 1.9 \u00a0 hours) in the case of the  immediate-release  formulation and after 2 to 6 \u00a0 hours in the case of the  extended-release  formulation. [ 1 ] [ 2 ]  The  onset of action  of pseudoephedrine is 30 \u00a0 minutes. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6329", "text": "Pseudoephedrine, due to its lack of  polar   phenolic   groups , is relatively  lipophilic . [ 11 ]  This is a property it shares with related sympathomimetic and decongestant agents like  ephedrine  and  phenylpropanolamine . [ 11 ]  These agents are widely  distributed  throughout the body and cross the  blood\u2013brain barrier . [ 11 ]  However, it is said that pseudoephedrine and phenylpropanolamine cross the blood-brain barrier only to some extent and that pseudoephedrine has limited  central nervous system  activity, suggesting that it is partially  peripherally selective . [ 25 ] [ 26 ]  The blood-brain barrier permeability of pseudoephedrine, ephedrine, and phenylpropanolamine is reduced compared to other  amphetamines  due to the presence of a  hydroxyl group  at the \u03b2 carbon which decreases their  lipophilicity . [ 26 ]  As such, they have a greater ratio of peripheral cardiovascular to central psychostimulant effect. [ 26 ]  Besides entering the brain, these substances also cross the  placenta  and enter  breast milk . [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6330", "text": "The  plasma protein binding  of pseudoephedrine has been reported to be approximately 21 to 29%. [ 9 ] [ 10 ]  It is bound to  \u03b1 1 -acid glycoprotein  (AGP) and  albumin  (HSA). [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6331", "text": "Pseudoephedrine is not extensively  metabolized  and is subjected to minimal  first-pass metabolism  with oral administration. [ 11 ] [ 1 ] [ 2 ]  Due to its  methyl group  at the \u03b1  carbon  (i.e., it is an  amphetamine ), pseudoephedrine is not a  substrate  for  monoamine oxidase  (MAO) and is not metabolized by this  enzyme . [ 25 ] [ 11 ] [ 71 ] [ 72 ]  It is also not metabolized by  catechol  O -methyltransferase  (COMT). [ 25 ]  Pseudoephedrine is  demethylated  into the  metabolite   norpseudoephedrine  to a small extent. [ 1 ] [ 11 ]  Similarly to pseudoephedrine, this metabolite is  active  and shows  amphetamine -like effects. [ 11 ]  Approximately 1 to 6% of pseudoephedrine is metabolized in the  liver  via  N -demethylation to form norpseudoephedrine. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6332", "text": "Pseudoephedrine is  excreted  primarily via the  kidneys  in  urine . [ 1 ] [ 11 ]  Its urinary excretion is highly influenced by urinary  pH  and is decreased when the urine is  acidic  and is increased when it is  alkaline . [ 1 ] [ 11 ] [ 58 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6333", "text": "The  elimination half-life  of pseudoephedrine on average is 5.4 \u00a0 hours [ 2 ]  and ranges from 3 to 16 \u00a0 hours depending on urinary pH. [ 1 ] [ 11 ]  At a pH of 5.6 to 6.0, the  elimination half-life  of pseudoephedrine was 5.2 to 8.0 \u00a0 hours. [ 11 ]  In one study, a more acidic pH of 5.0 resulted in a half-life of 3.0 to 6.4 \u00a0 hours, whereas a more alkaline pH of 8.0 resulted in a half-life of 9.2 to 16.0 \u00a0 hours. [ 11 ]  Substances that influence urinary acidity and are known to affect the excretion of amphetamine derivatives include  urinary acidifying agents  like  ascorbic acid  and  ammonium chloride  as well as  urinary alkalinizing agents  like  acetazolamide . [ 77 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6334", "text": "A majority of an  oral  dose of pseudoephedrine is excreted unchanged in urine within 24 \u00a0 hours of administration. [ 11 ]  This has been found to range from 43 to 96%. [ 1 ] [ 11 ] [ 2 ]  The amount excreted unchanged is dependent on urinary pH similarly to the drug's half-life, as a longer half-life and duration in the body allows more time for the drug to be metabolized. [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6335", "text": "The  duration of action  of pseudoephedrine, which is dependent on its  elimination , is 4 to 12 \u00a0 hours. [ 1 ] [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6336", "text": "Pseudoephedrine has been reported to accumulate in people with  renal impairment . [ 92 ] [ 93 ] [ 94 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6337", "text": "Pseudoephedrine, also known structurally as (1 S ,2 S )-\u03b1, N -dimethyl-\u03b2-hydroxyphenethylamine or as (1 S ,2 S )- N -methyl-\u03b2-hydroxyamphetamine, is a  substituted phenethylamine ,  amphetamine , and  \u03b2-hydroxyamphetamine   derivative . [ 1 ] [ 13 ] [ 2 ]  It is a  diastereomer  of  ephedrine . [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6338", "text": "Pseudoephedrine is a  small-molecule   compound  with the  molecular formula  C 10 H 15 NO and a  molecular weight  of 165.23 \u00a0 g/mol. [ 27 ] [ 95 ]  It has an experimental  log P  of 0.89, while its predicted log P values range from 0.9 to 1.32. [ 27 ] [ 95 ] [ 96 ]  The compound is relatively  lipophilic , [ 11 ]  but is also more  hydrophilic  than other amphetamines. [ 26 ]  The lipophilicity of amphetamines is closely related to their brain permeability. [ 97 ]  For comparison to pseudoephedrine, the experimental log P of  methamphetamine  is 2.1, [ 98 ]  of  amphetamine  is 1.8, [ 99 ] [ 98 ]  of  ephedrine  is 1.1, [ 100 ]  of  phenylpropanolamine  is 0.7, [ 101 ]  of  phenylephrine  is -0.3, [ 102 ]  and of  norepinephrine  is -1.2. [ 103 ]  Methamphetamine has high brain permeability, [ 98 ]  whereas phenylephrine and norepinephrine are  peripherally selective drugs . [ 2 ] [ 104 ]  The optimal log P for brain permeation and central activity is about 2.1 (range 1.5\u20132.7). [ 105 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6339", "text": "Pseudoephedrine is readily  reduced  into  methamphetamine  or  oxidized  into  methcathinone . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6340", "text": "The  dextrorotary  (+)- or d-  enantiomer  is (1 S ,2 S )-pseudoephedrine, whereas the levorotating (\u2212)- or l- form is (1 R ,2 R )-pseudoephedrine."}
{"_id": "WikiPedia_Cardio$$$corpus_6341", "text": "In the outdated  D/L  system  (+)-pseudoephedrine is also referred to as  L- pseudoephedrine and (\u2212)-pseudoephedrine as  D- pseudoephedrine (in the  Fisher projection  then the phenyl ring is drawn at bottom). [ 106 ] [ 107 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6342", "text": "Often the  D/L  system (with  small caps ) and the  d/l system  (with  lower-case ) are confused. The result is that the dextrorotary d-pseudoephedrine is wrongly named  D- pseudoephedrine and the levorotary l-ephedrine (the diastereomer) wrongly  L- ephedrine."}
{"_id": "WikiPedia_Cardio$$$corpus_6343", "text": "The IUPAC names of the two enantiomers are (1 S ,2 S )- respectively (1 R ,2 R )-2-methylamino-1-phenylpropan-1-ol. Synonyms for both are  psi -ephedrine and  threo -ephedrine."}
{"_id": "WikiPedia_Cardio$$$corpus_6344", "text": "Pseudoephedrine is the  INN Tooltip International Nonproprietary Name  of the (+)-form, when used as pharmaceutical substance. [ 108 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6345", "text": "Pseudoephedrine may be quantified in blood, plasma, or urine to monitor any possible performance-enhancing use by athletes, confirm a diagnosis of poisoning, or to assist in a medicolegal death investigation. Some commercial  immunoassay  screening tests directed at the amphetamines cross-react appreciably with pseudoephedrine, but  chromatographic  techniques can easily distinguish pseudoephedrine from other phenethylamine derivatives. Blood or plasma pseudoephedrine concentrations are typically in the 50 to 300 \u00a0 \u03bcg/L range in persons taking the drug therapeutically, 500 to 3,000 \u00a0 \u03bcg/L in people with substance use disorder involving pseudoephedrine or poisoned patients, and 10 to 70 \u00a0 mg/L in cases of acute fatal  overdose . [ 109 ] [ 110 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6346", "text": "Although pseudoephedrine occurs naturally as an  alkaloid  in certain plant species (for example, as a constituent of extracts from the  Ephedra  species, also known as  ma huang , in which it occurs together with other isomers of  ephedrine ), the majority of pseudoephedrine produced for commercial use is derived from  yeast   fermentation  of  dextrose  in the presence of  benzaldehyde . In this process, specialized strains of yeast (typically a variety of  Candida utilis  or  Saccharomyces cerevisiae ) are added to large vats containing water, dextrose and the enzyme  pyruvate decarboxylase  (such as found in  beets  and other plants). After the yeast has begun fermenting the dextrose, the benzaldehyde is added to the vats, and in this environment, the yeast converts the ingredients to the precursor  l-phenylacetylcarbinol  (L-PAC). L-PAC is then chemically converted to pseudoephedrine via  reductive amination . [ 111 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6347", "text": "The bulk of pseudoephedrine is produced by commercial  pharmaceutical manufacturers  in India and China, where economic and industrial conditions favor its mass production for export. [ 112 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6348", "text": "Pseudoephedrine, along with  ephedrine , occurs  naturally  in  ephedra . [ 13 ] [ 28 ] [ 113 ]  This herb has been used for thousands of years in  traditional Chinese medicine . [ 13 ] [ 28 ] [ 113 ]  Pseudoephedrine was first  isolated  and characterized in 1889 by the German chemists  Ladenburg  and Oelschl\u00e4gel, who used a sample that had been isolated from  Ephedra vulgaris  by the  Merck pharmaceutical corporation  of  Darmstadt , Germany. [ 28 ] [ 29 ] [ 114 ]  It was first  synthesized  in the 1920s in  Japan . [ 13 ]  Subsequently, pseudoephedrine was introduced for medical use as a decongestant. [ 13 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6349", "text": "Pseudoephedrine  is the  generic name  of the drug and its  INN Tooltip International Nonproprietary Name  and  BAN Tooltip British Approved Name , while  pseudo\u00e9ph\u00e9drine  is its  DCF Tooltip D\u00e9nomination Commune Fran\u00e7aise  and  pseudoefedrina  is its  DCIT Tooltip Denominazione Comune Italiana . [ 115 ] [ 116 ] [ 117 ] [ 118 ]   Pseudoephedrine hydrochloride  is its  USAN Tooltip United States Adopted Name  and  BANM Tooltip British Approved Name  in the case of the  hydrochloride   salt ;  pseudoephedrine sulfate  is its  USAN  in the case of the  sulfate  salt;  pseudoephedrine polistirex  its  USAN  in the case of the polistirex form; and  d-isoephedrine sulfate  is its  JAN Tooltip Japanese Accepted Name  in the case of the sulfate salt. [ 115 ] [ 116 ] [ 117 ] [ 118 ]  Pseudoephedrine is also known as  \u03a8-ephedrine  and  isoephedrine . [ 115 ] [ 117 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6350", "text": "The following is a list of consumer medicines that either contain pseudoephedrine or have switched to a less-regulated alternative such as  phenylephrine ."}
{"_id": "WikiPedia_Cardio$$$corpus_6351", "text": "Over-the-counter  pseudoephedrine has been  misused  as a  psychostimulant . [ 17 ]  Six  case reports  and one  case series  of pseudoephedrine misuse have been published as of 2021. [ 17 ]  There is a case report of  self-medication  with pseudoephedrine in massive doses for treatment of  depression . [ 17 ] [ 66 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6352", "text": "Pseudoephedrine has been used as a  performance-enhancing drug  in  exercise  and  sports  due to its sympathomimetic and stimulant effects. [ 19 ] [ 20 ]  Because of these effects, pseudoephedrine can increase  heart rate , elevate  blood pressure , improve  mental energy , and reduce  fatigue , among other performance-enhancing effects. [ 19 ] [ 20 ] [ 22 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6353", "text": "A 2015  systematic review  found that pseudoephedrine lacked performance-enhancing effects at therapeutic doses (60\u2013120 \u00a0 mg) but significantly enhanced athletic performance at supratherapeutic doses (\u2265180 \u00a0 mg). [ 19 ]  A subsequent 2018  meta-analysis , which included seven additional studies, found that pseudoephedrine had a small positive effect on heart rate ( SMD Tooltip standardized mean difference  = 0.43) but insignificant effects on time trials, perceived exertion ratings, blood  glucose  levels, and blood  lactate  levels. [ 20 ]  However, subgroup analyses revealed that  effect sizes  were larger for heart rate increases and quicker time trials in well-trained athletes and younger participants, for shorter exercise sessions with pseudoephedrine administered within 90 \u00a0 minutes beforehand, and with higher doses of pseudoephedrine. [ 20 ]  A  dose\u2013response relationship  was established, with larger doses (>170 \u00a0 mg) showing greater increases in heart rate and faster time trials than with smaller doses (\u2264170 \u00a0 mg) ( SMD  = 0.85 for heart rate and  SMD  = -0.24 for time trials, respectively). [ 20 ]  In any case, the meta-analysis concluded that the performance-enhancing effects of pseudoephedrine were marginal to small and likely to be lower in magnitude than with  caffeine . [ 20 ]  It is relevant in this regard that caffeine is a permitted stimulant in competitive sports. [ 20 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6354", "text": "Pseudoephedrine was on the  International Olympic Committee 's (IOC) banned substances list until 2004 when the  World Anti-Doping Agency  (WADA) list replaced the IOC list. Although WADA initially only  monitored  pseudoephedrine, it went back onto the \"banned\" list on 1 January 2010. [ 122 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6355", "text": "Pseudoephedrine is excreted through urine, and the concentration in urine of this drug shows a large inter-individual spread; that is, the same dose can give a vast difference in urine concentration for different individuals. [ 123 ]  Pseudoephedrine is approved to be taken up to 240\u00a0mg per day. In seven healthy male subjects, this dose yielded a urine concentration range of 62.8 to 294.4 microgram per milliliter (\u03bcg/mL) with mean \u00b1 standard deviation 149 \u00b1 72\u00a0\u03bcg/mL. [ 124 ]  Thus, normal dosage of 240\u00a0mg pseudoephedrine per day can result in urine concentration levels exceeding the limit of 150\u00a0\u03bcg/mL set by WADA for about half of all users. [ 125 ]  Furthermore, hydration status does not affect the urinary concentration of pseudoephedrine. [ 126 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6356", "text": "Its membership in the  amphetamine  class has made pseudoephedrine a sought-after  chemical precursor  in the  illicit manufacture  of  methamphetamine  and  methcathinone . [ 1 ]  As a result of the increasing regulatory restrictions on the sale and distribution of pseudoephedrine, pharmaceutical firms have reformulated medications to use alternative compounds, particularly  phenylephrine , even though its efficacy as an oral decongestant has been demonstrated to be indistinguishable from placebo. [ 136 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6357", "text": "In the United States, federal laws control the sale of pseudoephedrine-containing products. [ 137 ] [ 138 ] [ 139 ]  Retailers in the US have created corporate policies restricting the sale of pseudoephedrine-containing products. [ 140 ] [ 141 ]  Their policies restrict sales by limiting purchase quantities and requiring a minimum age and government issued photographic identification. [ 138 ] [ 139 ]  These requirements are similar to and sometimes more stringent than existing law. Internationally, pseudoephedrine is listed as a  Table I precursor  under the  United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances . [ 142 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6358", "text": "Illicit diversion of pseudoephedrine in Australia has caused significant changes to the way the products are regulated. As of 2006 [update] , all products containing pseudoephedrine have been rescheduled as either \"Pharmacist Only Medicines\" (Schedule 3) or \"Prescription Only Medicines\" (Schedule 4), depending on the amount of pseudoephedrine in the product. A Pharmacist Only Medicine may only be sold to the public if a pharmacist is directly involved in the transaction. These medicines must be kept behind the counter, away from public access."}
{"_id": "WikiPedia_Cardio$$$corpus_6359", "text": "Pharmacists are also encouraged (and in some states required) to log purchases with the online database Project STOP. [ 143 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6360", "text": "As a result, some pharmacies no longer stock Sudafed, the common brand of pseudoephedrine cold/sinus tablets, opting instead to sell Sudafed PE, a  phenylephrine  product that has not been proven effective in clinical trials. [ 136 ] [ 144 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6361", "text": "Until 2024, several formulations of pseudoephedrine were available over-the-counter in Belgium. [ 145 ]  However, new legislation came into effect in November 2024, banning the over-the-counter sale of all medicines containing pseudoephedrine. [ 146 ] [ 147 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6362", "text": "Health Canada  has investigated the risks and benefits of pseudoephedrine and  ephedrine / Ephedra . Near the end of the study, Health Canada issued a warning on their website stating that those who are under the age of 12, or who have heart disease and may have strokes, should avoid taking pseudoephedrine and ephedrine. Also, they warned that everyone should avoid taking ephedrine or pseudoephedrine with other stimulants like  caffeine . They also banned all products that contain both ephedrine (or pseudoephedrine) and caffeine. [ 148 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6363", "text": "Products whose only medicinal ingredient is pseudoephedrine must be kept behind the pharmacy counter. Products containing pseudoephedrine along with other medicinal ingredients may be displayed on store shelves but may be sold only in a pharmacy when a pharmacist is present. [ 149 ] [ 150 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6364", "text": "The Colombian government prohibited the trade of pseudoephedrine in 2010. [ 151 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6365", "text": "Pseudoephedrine is an over-the-counter drug in Estonia. [ 152 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6366", "text": "Pseudoephedrine medicines can only be obtained with a prescription in Finland. [ 153 ] [ failed verification ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6367", "text": "Pseudoephedrine-containing combination products are available over the counter from pharmacies, most commonly with Paracetamol under the brand name \"Dolihrume\". Products combining pseudoephedrine and ibuprofen or certain antihistamines are also available. However, products containing pseudoephedrine as a single ingredient are not sold. [ citation needed ]  In October 2023, the French health department officially warned against the usage of pseudoephedrine for patients with a cold. It also suggested the substance's availability could be restricted in the future, pending its pharmaceutical re-evaluation on  EU  level. [ 154 ] [ 155 ] \nIn December 2024, the government announced pseudoephedrine medicines would henceforth only be obtainable with a prescription."}
{"_id": "WikiPedia_Cardio$$$corpus_6368", "text": "Various pseudoephedrine-containing products in combination with ibuprofen,  aspirin , or antihistamines can be obtained without a prescription upon request at a pharmacy. Common names include Aspirin Complex, Reactine Duo, and RhinoPront. Products containing pseudoephedrine as a single ingredient are not available. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6369", "text": "Medications that contain more than 10% pseudoephedrine are prohibited under the Stimulants Control Law in Japan. [ 156 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6370", "text": "On 23 November 2007, the use and trade of pseudoephedrine in Mexico was made illegal as it was argued that it was extremely popular as a precursor in the synthesis of methamphetamine. [ 157 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6371", "text": "Pseudoephedrine was withdrawn from sale in 1989 due to concerns about adverse cardiac side effects. [ 158 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6372", "text": "Since April 2024, pseudoephedrine has been classified as a restricted (pharmacist-only) drug in the  Misuse of Drugs Act 1975  which allows the purchase of medicines containing pseudoephedrine from a pharmacist without a prescription. [ 159 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6373", "text": "Pseudoephedrine, ephedrine, and any product containing these substances, e.g. cold and flu medicines, were first classified in October 2004 as Class C Part III (partially exempted) controlled drugs, due to being the principal ingredient in methamphetamine. [ 160 ]  New Zealand Customs and police officers continued to make large interceptions of precursor substances believed to be destined for  methamphetamine  production. On 9 October 2009, Prime Minister  John Key  announced pseudoephedrine-based cold and flu tablets would become prescription-only drugs and reclassified as a class B2 drug. [ 161 ]  The law was amended by The Misuse of Drugs Amendment Bill 2010, which passed in August 2011. [ 162 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6374", "text": "On 24 November 2023, the recently-formed  National-led coalition government  announced that the sale of cold medication containing pseudoephedrine would be allowed (as part of the coalition agreement between the National and ACT parties). [ 163 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6375", "text": "Pseudoephedrine is available without a prescription in combination (with  aspirin ) under the brand name \"Aspirin Complex\". There is also a preparation consisting of a single ingredient 120mg extended-release tablet that can be obtained at pharmacies with a prescription or after consultation with a pharmacist. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6376", "text": "In Turkey, medications containing pseudoephedrine are available by prescription only. [ 164 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6377", "text": "In the UK, pseudoephedrine is available over the counter under the supervision of a qualified pharmacist, or on prescription. In 2007, the  MHRA  reacted to concerns over the diversion of ephedrine and pseudoephedrine for the illicit manufacture of methamphetamine by introducing voluntary restrictions limiting over-the-counter sales to one box containing no more than 720\u00a0mg of pseudoephedrine in total per transaction. These restrictions became law in April 2008. [ 165 ]  No form of ID is required."}
{"_id": "WikiPedia_Cardio$$$corpus_6378", "text": "The  United States Congress  has recognized that pseudoephedrine is used in the illegal manufacture of methamphetamine. In 2005, the  Committee on Education and the Workforce  heard testimony concerning education programs and state legislation designed to curb this illegal practice. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6379", "text": "Attempts to control the sale of the drug date back to 1986, when federal officials at the  Drug Enforcement Administration  (DEA) first drafted legislation, later proposed by Senator  Bob Dole , that would have placed several chemicals used in the manufacture of illicit drugs under the  Controlled Substances Act . The bill would have required each transaction involving pseudoephedrine to be reported to the government, and federal approval of all imports and exports. Fearing this would limit legitimate use of the drug, lobbyists from over the counter drug manufacturing associations sought to stop this legislation from moving forward and were successful in exempting from the regulations all chemicals that had been turned into a legal final product, such as Sudafed. [ 166 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6380", "text": "Before the passage of the  Combat Methamphetamine Epidemic Act of 2005 , sales of the drug became increasingly regulated, as DEA regulators and pharmaceutical companies continued to fight for their respective positions. The DEA continued to make greater progress in their attempts to control pseudoephedrine as methamphetamine production skyrocketed, becoming a serious problem in the western United States. When purity dropped, so did the number of people in rehab and people admitted to emergency rooms with methamphetamine in their systems. This reduction in purity was usually short-lived, however, as methamphetamine producers eventually found a way around the new regulations. [ 167 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6381", "text": "Congress passed the Combat Methamphetamine Epidemic Act of 2005 (CMEA) as an amendment to the renewal of the  USA Patriot Act . [ 138 ]  Signed into law by President  George W. Bush  on 6 March 2006, [ 137 ]  the act amended  21\u00a0U.S.C. \u00a0 \u00a7\u00a0830 , concerning the sale of pseudoephedrine-containing products. The law mandated two phases, the first needing to be implemented by 8 April 2006, and the second to be completed by 30 September 2006. The first phase dealt primarily with implementing the new buying restrictions based on the amount, while the second phase encompassed the requirements of storage, employee training, and record keeping. [ 168 ]  Though the law was mainly directed at pseudoephedrine products it also applies to all over-the-counter products containing ephedrine, pseudoephedrine, and phenylpropanolamine, their salts, optical isomers, and salts of optical isomers. [ 168 ] \nPseudoephedrine was defined as a \" scheduled listed chemical product \" under  21\u00a0U.S.C. \u00a0 \u00a7\u00a0802 (45(A)). The act included the following requirements for merchants (\"regulated sellers\") who sell such products:"}
{"_id": "WikiPedia_Cardio$$$corpus_6382", "text": "The requirements were revised in the Methamphetamine Production Prevention Act of 2008 to require that a regulated seller of scheduled listed chemical products may not sell such a product unless the purchaser: [ 139 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6383", "text": "Most states also have laws regulating pseudoephedrine. [ 169 ] [ 170 ] [ 171 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6384", "text": "The states of Alabama, Arizona, Arkansas, California, Colorado, Delaware, Florida, Georgia, Hawaii (as of May\u00a01, 2009 [update] ) Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana (as of August\u00a015, 2009 [update] ), Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, [ 172 ]  Nevada, New Jersey, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, South Dakota, Tennessee, Texas, Utah, Vermont, Virginia, Washington, West Virginia and Wisconsin have laws requiring pharmacies to sell pseudoephedrine \"behind the counter\". Though the drug can be purchased without a prescription, states can limit the number of units sold and can collect personal information from purchasers. [ 173 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6385", "text": "The states of Oregon and Mississippi previously required a prescription for the purchase of products containing pseudoephedrine. However, as of 1 January 2022, these restrictions have been repealed. [ 174 ] [ 175 ]  The state of Oregon reduced the number of methamphetamine lab seizures from  448 in 2004 (the final full year before implementation of the prescription only law) [ 176 ]  to a new low of  13 in 2009. [ 177 ]  The decrease in  meth lab  incidents in Oregon occurred largely before the prescription-only law took effect, according to a NAMSDL report titled  Pseudoephedrine Prescription Laws in Oregon and Mississippi . [ 173 ]  The report posits that the decline in meth lab incidents in both states may be due to other factors: \"Mexican traffickers may have contributed to the decline in meth labs in Mississippi and Oregon (and surrounding states) as they were able to provide ample supply of equal or greater quality meth at competitive prices\". Additionally, similar decreases in meth lab incidents were seen in surrounding states, according to the report, and meth-related deaths in Oregon have dramatically risen since 2007. Some municipalities in Missouri have enacted similar ordinances, including  Washington , [ 178 ]   Union , [ 179 ]   New Haven , [ 180 ]   Cape Girardeau [ 181 ]  and  Ozark . [ 182 ]  Certain pharmacies in  Terre Haute, Indiana  do so as well. [ 183 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6386", "text": "Another approach to controlling the drug on the state level mandated by some state governments to control the purchases of their citizens is the use of electronic tracking systems, which require the electronic submission of specified purchaser information by all retailers who sell pseudoephedrine. Thirty-two states now require the  National Precursor Log Exchange  (NPLEx) to be used for every pseudoephedrine and ephedrine OTC purchase, and ten of the eleven largest pharmacy chains in the US voluntarily contribute all of their similar transactions to NPLEx. These states have seen dramatic results in reducing the number of methamphetamine laboratory seizures. Before the implementation of the system in Tennessee in 2005, methamphetamine laboratory seizures totaled 1,497 in 2004 but were reduced to 955 in 2005, and 589 in 2009. [ 177 ]  Kentucky's program was implemented statewide in 2008, and since statewide implementation, the number of laboratory seizures has significantly decreased. [ 177 ]  Oklahoma initially experienced success with its tracking system after implementation in 2006, as the number of seizures dropped in that year and again in 2007. In 2008, however, seizures began rising again, and have continued to rise in 2009. [ 177 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6387", "text": "NPLEx appears to be successful by requiring the real-time submission of transactions, thereby enabling the relevant laws to be enforced at the point of sale. By creating a multi-state database and the ability to compare all transactions quickly, NPLEx enables pharmacies to deny purchases that would be illegal based on gram limits, age, or even to convicted meth offenders in some states. NPLEx also enforces the federal gram limits across state lines, which was impossible with state-operated systems. Access to the records is by law enforcement agencies only, through an online secure portal. [ 184 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6388", "text": "Pseudoephedrine has been studied in the treatment of  snoring . [ 185 ]  However, data are inadequate to support this use. [ 185 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6389", "text": "A study has found that pseudoephedrine can reduce  milk production  in  breastfeeding  women. [ 186 ] [ 187 ]  This might have been due to suppression of  prolactin   secretion . [ 187 ]  Pseudoephedrine might be useful for  lactation suppression . [ 186 ] [ 187 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6390", "text": "Racephedrine , also known as  racemic ephedrine  and sold under the brand names  Efetonina  and  Ephoxamine  among others, is the  racemic  form of  ephedrine  which has been used as a  bronchodilator  to treat  asthma . [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  More specifically, it is a racemic mixture of (1 R ,2 S )- and (1 S ,2 R )- enantiomers . [ 3 ]  Conversely, ephedrine is the  enantiopure  (1 R ,2 S )-enantiomer. [ 1 ]  Racephedrine has been marketed for medical use in  Italy . [ 1 ]  Like ephedrine, racephedrine is a  releasing agent  of  norepinephrine  and to a much lesser extent of  dopamine . [ 6 ] [ 7 ] [ 8 ] [ 9 ]  Both ephedrine enantiomers are active in this regard, but ephedrine ((1 R ,2 S )-ephedrine) has greater  potency  than (1 S ,2 R )-ephedrine. [ 6 ] [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6391", "text": "Racephedrine has been used in a variety of  combination drugs  with other agents, including  theophylline ,  aminophylline ,  oxtriphylline ,  phenobarbital ,  pentobarbital ,  pyrilamine ,  phenacetin ,  salicylamide ,  ascorbic acid , and  opium , among others. [ 12 ]  Brand names of these combination preparations have included Amiphedrin, Amodrine, Amodrine E C, Asphamal-D, Asthmadrin, Cenamal, Cholarace, Phedrahist, Respirol, Salidin, Synate-M, and Synophedal. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6392", "text": "Selexipag , sold under the brand name  Uptravi , is a medication developed by  Actelion  for the treatment of  pulmonary arterial hypertension  (PAH). [ 3 ] [ 4 ]  Selexipag and its  active metabolite ,  ACT-333679  (or MRE-269, the free  carboxylic acid ), are  agonists  of the  prostacyclin receptor , which leads to  vasodilation  in the pulmonary circulation. [ 5 ]  It is taken  by mouth  or administered intravenously. [ 3 ] [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6393", "text": "The most common side effects include headache, diarrhea, nausea and vomiting, jaw pain, myalgia (muscle pain), pain in the limbs, arthralgia (joint pain) and flushing. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6394", "text": "It is available as a  generic medication . [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6395", "text": "Selexipag is  indicated  for the treatment of pulmonary arterial hypertension. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6396", "text": "In the European Union, use of selexipag together with strong inhibitors of the liver enzyme  CYP2C8 , such as  gemfibrozil , is contraindicated because it increases concentrations of selexipag twofold, and its active metabolite 11-fold, potentially leading to more adverse effects. [ 4 ] [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6397", "text": "The adverse effects of selexipag are similar to those of intravenous  prostacyclins  used for pulmonary arterial hypertension. Common side effects include headache and jaw pain. An increased risk for  hyperthyroidism  has also been noted in people taking selexipag. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6398", "text": "Selexipag and its  active metabolite  ACT-333679 act on the prostacyclin receptor of lung tissue, with the latter being 37-fold more potent. They are selective for the prostacyclin receptor. Binding to this receptor leads to three major effects: increased  vasodilation  of the arteries, decreased  cell proliferation  and inhibition of  platelet  aggregation, [ 9 ]  all beneficial in the treatment of pulmonary arterial hypertension."}
{"_id": "WikiPedia_Cardio$$$corpus_6399", "text": "Selexipag is quickly absorbed from the gut and  hydrolyzed  in the intestines and the liver to ACT-333679 by  carboxylesterases . Absolute  bioavailability  is about 49%, most likely because of a high  first-pass effect . Highest concentrations in the  blood plasma  are reached after one to three hours for selexipag and after three to four hours for the active metabolite. When in the circulation, about 99% of both substances are bound to  plasma proteins , namely to  albumin  and  alpha-1-acid glycoprotein  to equal amounts. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6400", "text": "The liver enzymes  CYP2C8  and, to a lesser extent,  CYP3A4 ,  hydroxylate  and  dealkylate  the active substance, thereby inactivating it. Besides, ACT-333679 is  glucuronidized  by the enzymes  UGT1A3  and  UGT2B7 . The  terminal half-life  of selexipag is 0.8 to 2.5 hours, that of the active metabolite is 6.2 to 13.5 hours. [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6401", "text": "The synthesis of celexipag begins from two inexpensive compounds,  glycine hydrochloride  and  benzil , condensed under basic conditions. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6402", "text": "The U.S.  Food and Drug Administration  (FDA) granted selexipag  orphan drug  designation for pulmonary arterial hypertension [ 12 ]  and for the treatment of chronic thromboembolic pulmonary hypertension. [ 13 ]  It was approved by the FDA in December 2015. [ 3 ] [ 14 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6403", "text": "In the European Union, the drug was approved in May 2016. [ 4 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6404", "text": "The expected price for the drug in the US is $160,000 to $170,000 per patient before  rebates . [ 15 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6405", "text": "Serelaxin  (brand name  Reasanz ; developmental code name  RLX-030 ) is a medication which is marketed in  Russia  for the treatment of  acute heart failure  (AHF), targeting the  relaxin receptor . [ 1 ]  It was also under development in other places in the world, including in the  United States ,  Europe , and  Asia , but ultimately was not marketed in these areas. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6406", "text": "Serelaxin is a recombinant form of human  relaxin -2, a hormone that (among other functions) is produced during pregnancy and mediates the haemodynamic changes that occur during this time, [ 2 ] [ 3 ]  such as increased blood output of the heart and blood flow in the kidney. [ 4 ]  Human-relaxin-2 mediates vasodilation (widening of blood vessels) by increasing the production of  nitric oxide  (NO), a potent  vasodilator . [ 5 ]  Activation of the relaxin receptor  RXFP1  activates several enzymes in a  phosphorylation cascade  that eventually results in the activation of NO synthase in endothelial cells and the subsequent production of NO. [ 6 ]  Relaxin can also bind to a secondary receptor, endothelial B receptor, [ clarification needed ]  which is upregulated as a result of the previous pathway. [ 7 ]  Relaxin binding to endothelial B receptor on endothelial cells also induces vasodilation. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6407", "text": "Relaxin causes vasodilation by an indirect mechanism, where it inhibits the potent vasoconstrictors angiotensin II and endothelin. [ 9 ]  In addition to vasodilation, the effects of relaxin are also seen in the kidneys, by significantly increasing  creatinine  clearance, [ 10 ]  which is a measure of kidney function, as well as increased renal blood flow. [ 8 ]  Relaxin also functions as a cardiac stimulant. [ 6 ]  Studies have demonstrated that relaxin increases calcium sensitivity of cardiac  myofilaments  as well as increasing phosphorylation of the myofilaments by  protein kinase C  (PKC). [ 11 ]  These modifications both function to increase the force generated by the myofilaments without increasing the energy consumption of the cardiac myocytes. [ 11 ]  Thus relaxin and serelaxin can increase  stroke volume , the amount of blood pumped per heart beat, without increasing the energy demand on the already strained heart of acute heart failure patients."}
{"_id": "WikiPedia_Cardio$$$corpus_6408", "text": "Serelaxin has undergone clinical trials in patients with acute heart failure, [ 12 ]  conducted by  Novartis . Serelaxin has completed several clinical trials as a therapy for AHF. Phase I trials examined safety and tolerability, [ 13 ]  while phase II trials evaluated its haemodynamic effects and symptom relief. The Pre-RELAX-AHF phase II trial administered a dose of 30\u00a0\u03bcg/kg/day and showed a decrease in blood pressure, improved  dyspnoea , and increased renal blood flow. [ 8 ]  In phase III the RELAX-AHF trial gave a 48hr intravenous infusion of the same dose. [ 14 ]  It significantly improved patients' dyspnoea, resulted in a 30% reduction in worsening of heart failure symptoms, a decreased hospital stay and a reduction in signs and symptoms of congestion. [ 12 ] [ 15 ]  The FDA granted serelaxin \"breakthrough therapy\" designation, meant to expedite the development and review of drugs for life-threatening conditions. [ 16 ]  On 22 March 2017, Novartis announced that the global Phase III study of serelaxin in patients with acute heart failure did not meet its primary endpoints. [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6409", "text": "Sulmazole  is a  cardiotonic  drug. [ 1 ]  Sulmazole has the chemical formula C 14 H 13 N 3 O 2 S [ 2 ]  and a  molecular weight  of 287.34 g/mol. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6410", "text": "Sulmazole has been shown to improve cardiac index and reduce  pulmonary capillary wedge pressure  without significant changes in a person's  heart rate  or  arterial pressure . [ 3 ]  Sulmazole inhibits the  A1 adenosine receptor  and functionally blocks Gi, an inhibitory regulator. [ 1 ]  Sulmazole is also a  phosphodiesterase inhibitor . [ 3 ]  Sulmazole is classified as an imidazopyridine and a sulfoxide. [ 2 ]  Sulmazole can be taken intravenously or orally. [ 3 ]  Side effects from sulmazole include  blurring vision  and temporary  color blindness . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6411", "text": "Tiazotic acid  (brand names  Thiotriazoline  and  Tiokor ) is an antioxidant.  It is used as a pharmaceutical drug for the treatment of  ischemic heart disease  in Russia, Ukraine, and Uzbekistan. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6412", "text": "It is used as its salt with  morpholine . [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6413", "text": "It has been studied for its potential to improve the cardiac effects of  COVID-19 . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6414", "text": "Tirabrutinib  (brand name  Velexbru ) is a drug used for the treatment of autoimmune disorders and hematological malignancies. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6415", "text": "Tirabrutinib was approved in March 2020 in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. [ 1 ]   In addition, tirabrutinib is in  clinical development  by  Ono Pharmaceutical  and  Gilead Sciences [ 3 ]  in the United States, Europe, and Japan for autoimmune disorders, chronic lymphocytic leukemia, B cell lymphoma, Sjogren's syndrome, pemphigus, and rheumatoid arthritis. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6416", "text": "Tirabrutinib is an  irreversible   inhibitor  of  Bruton's tyrosine kinase . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6417", "text": "Vascular endothelial growth factor  ( VEGF ,  / v \u025b d\u0292 \u02c8 \u025b f / ), originally known as  vascular permeability factor  ( VPF ), [ 1 ]  is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of  growth factors , the  platelet-derived growth factor  family of  cystine-knot  growth factors. They are important signaling  proteins  involved in both  vasculogenesis  (the  de novo  formation of the embryonic  circulatory system ) and  angiogenesis  (the growth of blood vessels from pre-existing vasculature)."}
{"_id": "WikiPedia_Cardio$$$corpus_6418", "text": "It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate such as in hypoxic conditions. [ 2 ]  Serum concentration of VEGF is high in  bronchial asthma  and  diabetes mellitus . [ 3 ] \nVEGF's normal function is to create new blood vessels during  embryonic development , new blood vessels after injury, muscle following exercise, and new vessels ( collateral circulation ) to bypass blocked vessels.\nIt can contribute to disease. Solid cancers cannot grow beyond a limited size without an adequate blood supply; cancers that can express VEGF are able to grow and metastasize. Overexpression of VEGF can cause vascular disease in the  retina  of the eye and other parts of the body. Drugs such as  aflibercept ,  bevacizumab ,  ranibizumab , and  pegaptanib  can inhibit VEGF and control or slow those diseases."}
{"_id": "WikiPedia_Cardio$$$corpus_6419", "text": "In 1970,  Judah Folkman   et al . described a factor secreted by tumors causing angiogenesis and called it  tumor angiogenesis factor . [ 4 ]  In 1983  Senger  et al.  identified a  vascular permeability factor  secreted by tumors in guinea pigs and hamsters. [ 1 ]  In 1989 Ferrara and Henzel described an identical factor in bovine pituitary follicular cells which they purified, cloned and named VEGF. [ 5 ]  A similar VEGF alternative splicing was discovered by Tischer  et al.  in 1991. [ 6 ]  Between 1996 and 1997, Christinger and De Vos obtained the crystal structure of VEGF, first at 2.5 \u00c5 resolution and later at 1.9 \u00c5. [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6420", "text": "Fms-like tyrosine kinase-1  (flt-1) was shown to be a VEGF receptor by Ferrara  et al.  in 1992. [ 10 ]  The  kinase insert domain receptor  (KDR) was shown to be a VEGF receptor by Terman  et al.  in 1992 as well. [ 11 ]  In 1998,  neuropilin 1  and  neuropilin 2  were shown to act as VEGF receptors. [ 12 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6421", "text": "In mammals, the VEGF family comprises five members:  VEGF-A , placenta growth factor ( PGF ),  VEGF-B ,  VEGF-C  and  VEGF-D . The latter members were discovered after VEGF-A; before their discovery, VEGF-A was known as VEGF. A number of VEGF-related proteins encoded by viruses ( VEGF-E ) and in the venom of some snakes ( VEGF-F ) have also been discovered."}
{"_id": "WikiPedia_Cardio$$$corpus_6422", "text": "Activity of VEGF-A, as its name implies, has been studied mostly on cells of the vascular  endothelium , although it does have effects on a number of other cell types (e.g., stimulation  monocyte / macrophage  migration, neurons, cancer cells, kidney epithelial cells). In vitro, VEGF-A has been shown to stimulate endothelial cell  mitogenesis  and  cell migration . VEGF-A is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor."}
{"_id": "WikiPedia_Cardio$$$corpus_6423", "text": "There are multiple isoforms of VEGF-A that result from  alternative splicing  of  mRNA  from a single, 8- exon   VEGFA  gene. These are classified into two groups which are referred to according to their terminal exon (exon 8) splice site: the proximal splice site (denoted VEGF xxx ) or distal splice site (VEGF xxx b). In addition, alternate splicing of exon 6 and 7 alters their  heparin -binding affinity and amino acid number (in humans: VEGF 121 , VEGF 121 b, VEGF 145 , VEGF 165 , VEGF 165 b, VEGF 189 , VEGF 206 ; the rodent orthologs of these proteins contain one fewer amino acids). These domains have important functional consequences for the VEGF splice variants, as the terminal (exon 8) splice site determines whether the proteins are pro-angiogenic (proximal splice site, expressed during angiogenesis) or anti-angiogenic (distal splice site, expressed in normal tissues). In addition, inclusion or exclusion of exons 6 and 7 mediate interactions with  heparan sulfate   proteoglycans  (HSPGs) and  neuropilin  co-receptors on the cell surface, enhancing their ability to bind and activate the  VEGF receptors  (VEGFRs). [ 18 ]  Recently, VEGF-C has been shown to be an important inducer of neurogenesis in the murine subventricular zone, without exerting angiogenic effects. [ 19 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6424", "text": "All members of the VEGF family stimulate cellular responses by binding to  tyrosine kinase  receptors (the  VEGFRs ) on the cell surface, causing them to dimerize and become activated through  transphosphorylation , although to different sites, times, and extents. The VEGF receptors have an extracellular portion consisting of 7 immunoglobulin-like domains, a single transmembrane spanning region, and an intracellular portion containing a split  tyrosine-kinase  domain. VEGF-A binds to VEGFR-1 ( Flt-1 ) and VEGFR-2 ( KDR/Flk-1 ). [ 21 ]  VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF. The function of VEGFR-1 is less well-defined, although it is thought to modulate VEGFR-2 signaling. [ 22 ]  Another function of VEGFR-1 may be to act as a dummy/decoy receptor, sequestering VEGF from VEGFR-2 binding (this appears to be particularly important during vasculogenesis in the embryo). VEGF-C and VEGF-D, but not VEGF-A, are ligands for a third receptor ( VEGFR-3/Flt4 ), which mediates  lymphangiogenesis . The receptor (VEGFR3) is the site of binding of main ligands (VEGFC and VEGFD), which mediates perpetual action and function of ligands on\ntarget cells. Vascular endothelial growth factor-C can stimulate lymphangiogenesis (via VEGFR3) and angiogenesis via VEGFR2. Vascular endothelial growth factor-R3 has been detected in lymphatic endothelial cells in CL of many species, cattle, buffalo and primate. [ 23 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6425", "text": "In addition to binding to  VEGFRs , VEGF binds to receptor complexes consisting of both  neuropilins  and VEGFRs. This receptor complex has increased VEGF signalling activity in  endothelial  cells ( blood vessels ). [ 12 ] [ 24 ]  Neuropilins (NRP) are  pleiotropic  receptors and therefore other molecules may interfere with the signalling of the NRP/VEGFR receptor complexes. For example, Class 3  semaphorins  compete with VEGF 165  for NRP binding and could therefore regulate VEGF-mediated  angiogenesis . [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6426", "text": "VEGF-A production can be induced in a cell that is not receiving enough  oxygen . [ 21 ]  When a cell is deficient in oxygen, it produces HIF,  hypoxia-inducible factor , a transcription factor. HIF stimulates the release of VEGF-A, among other functions (including modulation of erythropoiesis). Circulating VEGF-A then binds to VEGF receptors on endothelial cells, triggering a  tyrosine kinase  pathway leading to angiogenesis. [ clarification needed ]  The expression of  angiopoietin-2  in the absence of VEGF leads to endothelial cell death and vascular regression. [ 26 ]  Conversely, a German study done  in vivo  found that VEGF concentrations actually decreased after a 25% reduction in oxygen intake for 30 minutes. [ 27 ]  HIF1 alpha and HIF1 beta are constantly being produced but HIF1 alpha is highly O 2  labile, so, in aerobic conditions, it is degraded. When the cell becomes hypoxic, HIF1 alpha persists and the HIF1alpha/beta complex stimulates VEGF release. the combined use of microvesicles and 5-FU resulted in enhanced chemosensitivity of squamous cell carcinoma cells more than the use of either 5-FU or microvesicle alone. In addition, down regulation of VEGF gene expression was associated with decreased CD1 gene expression. [ 28 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6427", "text": "VEGF-A and the corresponding receptors are rapidly up-regulated after traumatic injury of the  central nervous system  (CNS). VEGF-A is highly expressed in the acute and sub-acute stages of CNS injury, but the protein expression declines over time. This time-span of VEGF-A expression corresponds with the endogenous  re-vascularization  capacity after injury. [ 25 ]  This would suggest that VEGF-A / VEGF 165  could be used as target to promote angiogenesis after traumatic CNS injuries. However, there are contradicting scientific reports about the effects of VEGF-A treatments in CNS injury models. [ 25 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6428", "text": "Although it has not been associated as a  biomarker  for the diagnosis of acute ischemic  stroke , [ 29 ]  high levels of serum VEGF in the first 48 hours after an cerebral infarct have been associated with a poor prognosis after 6 months [ 30 ]  and 2 years. [ 31 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6429", "text": "VEGF-A has been implicated with poor prognosis in  breast cancer . Numerous studies show a decreased overall survival and disease-free survival in those tumors overexpressing VEGF. The overexpression of VEGF-A may be an early step in the process of  metastasis , a step that is involved in the \"angiogenic\" switch. Although VEGF-A has been correlated with poor survival, its exact mechanism of action in the progression of tumors remains unclear. [ 32 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6430", "text": "VEGF-A is also released in  rheumatoid arthritis  in response to  TNF-\u03b1 , increasing endothelial permeability and swelling and also stimulating angiogenesis (formation of capillaries). [ 33 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6431", "text": "VEGF-A is also important in  diabetic retinopathy  (DR). The microcirculatory problems in the retina of people with  diabetes  can cause retinal ischaemia, which results in the release of VEGF-A, and a switch in the balance of pro-angiogenic VEGF xxx  isoforms over the normally expressed VEGF xxx b isoforms. VEGF xxx  may then cause the creation of new blood vessels in the retina and elsewhere in the eye, heralding changes that may threaten the sight."}
{"_id": "WikiPedia_Cardio$$$corpus_6432", "text": "VEGF-A plays a role in the disease pathology of the wet form  age-related macular degeneration  (AMD), which is the leading cause of blindness for the elderly of the industrialized world. The vascular pathology of AMD shares certain similarities with diabetic retinopathy, although the cause of disease and the typical source of neovascularization differs between the two diseases."}
{"_id": "WikiPedia_Cardio$$$corpus_6433", "text": "VEGF-D serum levels are significantly elevated in patients with  angiosarcoma . [ 34 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6434", "text": "Once released, VEGF-A may elicit several responses. It may cause a  cell  to survive, move, or further differentiate. Hence, VEGF is a potential target for the treatment of  cancer . The first anti-VEGF drug, a  monoclonal antibody  named  bevacizumab , was approved in 2004. Approximately 10\u201315% of patients benefit from bevacizumab therapy; however, biomarkers for bevacizumab efficacy are not yet known."}
{"_id": "WikiPedia_Cardio$$$corpus_6435", "text": "Current studies show that VEGFs are not the only promoters of angiogenesis. In particular,  FGF2  and HGF are potent angiogenic factors."}
{"_id": "WikiPedia_Cardio$$$corpus_6436", "text": "Patients suffering from pulmonary emphysema have been found to have decreased levels of VEGF in the pulmonary arteries."}
{"_id": "WikiPedia_Cardio$$$corpus_6437", "text": "VEGF-D has also been shown to be over expressed in  lymphangioleiomyomatosis  and is currently used as a diagnostic biomarker in the treatment of this rare disease. [ 35 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6438", "text": "In the  kidney , increased expression of VEGF-A in  glomeruli  directly causes the glomerular hypertrophy that is associated with proteinuria. [ 36 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6439", "text": "VEGF alterations can be predictive of early-onset  pre-eclampsia . [ 37 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6440", "text": "Gene therapies  for refractory angina establish expression of VEGF in epicardial cells to promote angiogenesis. [ 38 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6441", "text": "A  vascular-targeting agent  ( VTA ) or  vascular disrupting agent  ( VDA ) is a drug designed to damage the vasculature ( blood vessels ) of  cancer   tumors  causing central  necrosis . [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6442", "text": "VTAs can be small-molecule or  ligand -based."}
{"_id": "WikiPedia_Cardio$$$corpus_6443", "text": "Small-molecule VTAs include:"}
{"_id": "WikiPedia_Cardio$$$corpus_6444", "text": "Phase II\u00a0: ZD6126, CA4P,  plinabulin  (NPI-2358) [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6445", "text": "Phase III\u00a0: DMXAA (ASA404)."}
{"_id": "WikiPedia_Cardio$$$corpus_6446", "text": "This  antineoplastic  or  immunomodulatory   drug  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Cardio$$$corpus_6447", "text": "A  vasoprotective  is a medication which acts to alleviate or prevent conditions or diseases which affect the  blood vessels . The term is used in the  World Health Organization 's  Anatomical Therapeutic Chemical Classification System  to encompass therapeutic agents used in the treatment of  hemorrhoids  or  varicose veins . [ 1 ]  The term may also be used to describe drugs which lower the risk of developing  hypercholesterolemia  or  hypertension . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6448", "text": "Examples of vasoprotectives include  1-methylnicotinamide , [ 3 ]   estrogen , [ 4 ]   tribenoside , [ 5 ]  and  valsartan . [ 6 ] \nMore specifically, arterial vasoprotectors are called angioprotectors."}
{"_id": "WikiPedia_Cardio$$$corpus_6449", "text": "Venalex  is a micronized purified  flavenoid  fraction (MPFF). It is a  vegan ,  gluten-free  nutritional supplement. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6450", "text": "Venalex is used to treat chronic functional or structural  venous insufficiency  of the lower limbs. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6451", "text": "No results of clinical trials have been published. [ citation needed ]  Venalex is not currently approved by the FDA. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6452", "text": "Venalex is made with a 9-1 ratio of  diosmin  and  hesperidin . [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6453", "text": "Hydroxypropol methylcellulose ,  magnesium stearate ."}
{"_id": "WikiPedia_Cardio$$$corpus_6454", "text": "This is a  list of cardiovascular clinical trials , categorized and alphabetized."}
{"_id": "WikiPedia_Cardio$$$corpus_6455", "text": "The  Cardiac Arrhythmia Suppression Trial  ( CAST ) was a double-blind, randomized, controlled study designed to test the hypothesis that suppression of  premature ventricular complexes  (PVC) with class I  antiarrhythmic agents  after a  myocardial infarction  (MI) would reduce  mortality . It was conducted between 1986 and 1989 and included over 1700 patients in 27 centres. [ 1 ]  The study found that the tested drugs increased mortality instead of lowering it as was expected. [ 2 ]  The publication of these results in 1991/92, in combination with large follow-up studies for drugs that had not been tested in CAST, led to a  paradigm shift  in the treatment of MI patients. Class I and III antiarrhythmics are now only used with extreme caution after MI, or they are contraindicated completely. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6456", "text": "The second Cardiac Arrhythmia Suppression Trial (CAST\u00a0II) modified the enrollment criteria to include patients at higher risk for serious arrhythmia. [ 4 ]  This included 1) patients enrolled within 4 to 90 days of a previous MI, 2) a  left ventricular ejection fraction  lower than 40%, 3) prior to enrollment, suppression of PVCs had occurred with the drugs (vs. placebo) using a double-blinded design, and 4) patients having more serious arrhythmias would also be included. [ citation needed ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6457", "text": "The drugs used (encainide, flecainide, and moracizine) successfully reduced the amount of PVCs, but led to more arrhythmia-related deaths. Total mortality was significantly higher with both encainide and flecainide at a mean follow-up period of 10 months. Within about two years after enrollment, encainide and flecainide were discontinued because of increased mortality and sudden cardiac death. CAST\u00a0II compared moracizine to placebo, but was also stopped because of early (within two weeks) cardiac death in the moracizine group, and long-term survival seemed highly unlikely. The excess mortality was attributed to proarrhythmic effects of the agents.\nClass I antiarrhythmics are proarrhythmic during  heart ischemia  in animals.  [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6458", "text": "The  Early versus Late Intervention Trial with Estradiol  ( ELITE ) was a large  randomized controlled trial  that assessed the timing hypothesis that  menopausal hormone therapy  in early but not late  menopause  would improve  cardiovascular  outcomes. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6459", "text": "The  Estrogen in Venous Thromboembolism Trial  ( EVTET ) was a  randomized controlled trial  (RCT) of  menopausal hormone therapy  in 140 postmenopausal women with previous history of  venous thromboembolism  (VTE). [ 1 ] [ 2 ]  It was a  double-blind  RCT of the  estrogen ,  oral   estradiol  2 mg/day, plus the  progestogen ,  norethisterone acetate  (NETA) (n=71) 1\u00a0mg/day (brand name  Kliogest ) versus  placebo  (n=69). [ 1 ]  The results of the trial were published in 2000 and 2001. [ 1 ] [ 2 ]  The incidence of VTE was 10.7% (8 women) in the hormone therapy group and 2.3% (1 woman) in the placebo group, with all events occurring within 261 days after study inclusion. [ 1 ]  The difference did not reach  statistical significance  in the  sequential analysis , but was statistically significant if the sequential design was ignored (p = 0.04). [ 1 ]  Markers of  coagulation  were likewise increased by hormone therapy. [ 2 ]  As a result of the high incidence of VTE in the treatment group, the trial was terminated prematurely. [ 1 ]  The researchers concluded on the basis of their findings that menopausal hormone therapy should not be used in women with a previous history of VTE. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6460", "text": "Although the findings of the EVTET and other studies warrant caution with respect to the use of oral estrogens in women with past VTE, research has found that transdermal estradiol, in contrast to oral estradiol and other oral estrogens, minimally influences coagulation, [ 3 ]  and in  systematic reviews  and  meta-analyses  of  observational studies , has not been associated with increased risk of VTE at doses of up to 100\u00a0\u03bcg/day. [ 4 ] [ 5 ] [ 6 ] [ 7 ]  Similarly, a small study found that transdermal estradiol did not influence coagulation in women with prior VTE, [ 8 ]  and the observational  Menopause, Estrogen and Venous Events  (MEVE) study found that transdermal estradiol was not associated with increased risk of VTE in postmenopausal women with past VTE ( HR Tooltip hazard ratio  = 1.0 (95%  CI Tooltip confidence interval  0.4\u20132.4) for transdermal estradiol vs.  HR  = 6.4 (95%  CI  1.5\u201327.3) for oral estrogens). [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ]  Accordingly, menopausal hormone therapy guidelines state that transdermal estradiol is likely to have less risk of VTE and recommend use of transdermal estradiol in women with past VTE or at high risk for VTE. [ 14 ] [ 15 ] [ 16 ] [ 17 ]  However, RCTs are still needed to confirm the findings. [ 15 ] [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6461", "text": "The  International Studies of Infarct Survival  ( ISIS ) were four  randomized controlled trials  of several  drugs  for treating suspected  acute   myocardial infarction  (\"heart attack\"). More than 134,000 patients from over 20 countries took part in four large simple trials  between 1981 and 1993, coordinated from  Oxford , England. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6462", "text": "The First International Study of Infarct Survival (ISIS-1) was a  placebo-controlled trial  of the  beta-blocker   atenolol . It recruited 16,027 patients and was completed in 1985. [ 3 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6463", "text": "The Second International Study of Infarct Survival (ISIS-2) was a 2\u00d72  factorial  placebo-controlled trial of  aspirin  and the  thrombolytic  drug  streptokinase . It recruited 17,187 patients and was completed in 1988. [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6464", "text": "The Third International Study of Infarct Survival (ISIS-3) was a 3\u00d72  factorial  trial that compared the three  thrombolytic  drugs  streptokinase ,  tissue plasminogen activator  (tPA) and  anistreplase  to each other, and also compared the  anticoagulant   heparin  to no heparin. All patients were also given  aspirin . It recruited 41,299 patients and was completed in 1991. [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6465", "text": "The Fourth International Study of Infarct Survival (ISIS-4) was a 2\u00d72\u00d72  factorial  placebo-controlled trial of the  angiotensin-converting enzyme  inhibitor ( ACE inhibitor )  captopril ,  isosorbide mononitrate  and   magnesium sulphate . It recruited 58,050 patients and was completed in 1993. [ 6 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6466", "text": "The  Menopause, Estrogen and Venous Events  ( MEVE ) study was a  retrospective   observational study  of  menopausal hormone therapy  and  venous thromboembolism  (VTE) in  postmenopausal  women with a previous history of VTE. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  It found that  transdermal   estradiol  was not associated with increased risk of VTE ( HR Tooltip hazard ratio  = 1.0, 95%  CI Tooltip confidence interval  0.4\u20132.4) whereas  oral   estrogens  were associated with a large increase in risk ( HR  = 6.4, 95%  CI  1.5\u201327.3). [ 1 ] [ 3 ] [ 4 ]  The mean dose of transdermal estradiol in the study was 50\u00a0\u03bcg/day, although data on dose were missing for around 50% of women. [ 1 ] [ 2 ]  Similarly, a small study found that transdermal estradiol did not influence coagulation in women with prior VTE. [ 6 ]  These findings are similar to studies in menopausal women without prior history of VTE which have found that transdermal estradiol has minimal influence on  coagulation [ 7 ]  and is not associated with increased risk of VTE at doses of up to 100\u00a0\u03bcg/day. [ 8 ] [ 9 ] [ 10 ] [ 11 ]  Menopausal hormone therapy guidelines have cited the MEVE study and recommended use of transdermal estradiol over oral estrogens in women at high risk for VTE. [ 12 ] [ 13 ] [ 14 ] [ 15 ]  However,  randomized controlled trials  (RCTs) are still needed to definitively confirm findings that transdermal estradiol is safer than oral estrogens in terms of VTE risk. [ 12 ] [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6467", "text": "The  PolyIran  study is a pragmatic open-labeled randomized trial being conducted within Golestan cohort study (GCS) on 31000 subjects in 305 villages of  Golestan Province ,  northeastern  Iran . The pill used in this study namely \"Polypill\", has been successfully evaluated in a pilot study and consists of 4 components. [ 1 ] [ 2 ]  It is estimated to decrease the death rate due to myocardial infarction and stroke by 30-53% . [ 3 ]  Participants were enrolled in the study during February 2011 and April 2013.  The study will directly evaluate the effect of Polypill tablets on cardiovascular death and hospitalizations compared to lifestyle modification during 5 years of follow-up; unlike most of the studies that only investigate the impact of Polypill on indirect surrogate markers of cardiovascular diseases such as blood pressure or lipid profile. The study includes three arms. The first and largest arm (24000 subjects) are being just followed and receive no particular care other than care provided by the governmental health system in Iran (usual care arm). The second arm (3500 subjects) receive recommendations about a healthy lifestyle in face-to-face interviews and pamphlets, undergo blood pressure measurements in 6 months regular intervals, and are referred to secondary or tertiary medical centers for treatment upon necessity(minimal care arm). The third arm (another 3500 subjects)  receive Polypill once daily in addition to the care provided to the minimal care arm (Polypill arm) . [ 1 ] [ 4 ]  In case of a substantial decrease in mortality in Polypill arm at the end of the study, Polypill might be offered to all individuals above 50 years old as a cheap preventive alternative for  cardiovascular diseases  . [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6468", "text": "The  Postmenopausal Estrogen/Progestin Interventions  ( PEPI ) trial was a large  randomized controlled trial  which assessed the influence of  menopausal hormone therapy  on  cardiovascular  and other outcomes. [ 1 ] [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6469", "text": "PREDIMED  ( Prevenci\u00f3n con Dieta Mediterr\u00e1nea  (Prevention with  Mediterranean Diet [ 1 ] )) was a large Spanish  primary prevention  trial which included 7,447 Spanish participants (55\u201380 years, 58% women) who were at high risk for  cardiovascular disease , but otherwise healthy (initially free of cardiovascular disease). They were randomly assigned to receive interventions with intensive education to one of three diets:"}
{"_id": "WikiPedia_Cardio$$$corpus_6470", "text": "The trial was planned for six years, but it was terminated early after a median follow-up of 4.8 years, and demonstrated that both Mediterranean diet groups reached a statistically significant reduction in the rate of the composite cardiovascular primary end-point of  myocardial infarction ,  stroke , or cardiovascular death. [ 2 ]  This corresponded to an absolute reduction in 3 less cardiovascular events per 1000 patient-years, or a 30% relative risk reduction. Other important observed benefits included a strong reduction in  peripheral artery disease , [ 3 ]   breast cancer , [ 4 ]  and  atrial fibrillation  (only associated with the consumption of extra-virgin olive oil). [ 5 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6471", "text": "Some criticisms included that the protocol for the low-fat control group was changed during the trial, there were losses to follow up in the low-fat group which may have biased the results, and that a true low-fat diet was not achieved by the control group. Additionally, participants lived in a Mediterranean country. Thus, it is unclear if the results will be applicable to other non-Mediterranean settings. Despite these criticisms, there is no other dietary pattern with such a strong evidence of cardiovascular benefit, supported by this major trial and by the Lyon Diet-Heart Study but also reinforced by a multitude of other large and well-conducted observational studies. [ 6 ]  The transferability of the Mediterranean diet to other geographical regions far from the Mediterranean Sea represents the next main challenges. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6472", "text": "Arnav Agarwal and  John Ioannidis  note that \"republication may not solve multiple problems that remain, including the inappropriateness of stopping early given the revised results and the effects on over 200 secondary publications\" and \"multiple contradictions between data reported across PREDIMED publications suggest a more generic problem with the trial's quality\". [ 8 ] \nThe core publication was retracted and republished as a non-randomised study. [ 8 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6473", "text": "The trial was multicenter with eleven field centers:"}
{"_id": "WikiPedia_Cardio$$$corpus_6474", "text": "The field work started in 2003 in the vanguard center of PREDIMED-NAVARRA (University of Navarra) [ 9 ]  and the trial was completed in 2011 following the recommendation of the Data and Safety Monitoring Board, Xavier Pi-Sunyer,  Frank B. Hu , Joan Sabat\u00e9 and Carlos A. Gonz\u00e1lez). The main paper with the final cardiovascular results was published in 2013, but retracted and immediately republished in 2018 because of errors in statistical methodology, which were revised in the republished paper. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6475", "text": "The coordinators and principal investigators of the PREDIMED Research Networks were R. Estruch (2003\u20132005) from Hospital Clinic (Barcelona) and  M.A. Martinez-Gonz\u00e1lez  (2006\u20132013) from  University of Navarra  (Spain)."}
{"_id": "WikiPedia_Cardio$$$corpus_6476", "text": "The  Systolic Blood Pressure Intervention Trial  (SPRINT) is a multi-center clinical trial that was performed from 2010 to 2015, and published in November 2015. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6477", "text": "The objective of the trial was to identify whether, in patients with a systolic blood pressure (SBP) of 130\u00a0mm Hg or higher and an increased cardiovascular risk, but without diabetes, treating to a systolic blood pressure target of less than 120\u00a0mm Hg is superior to a target of 140\u00a0mm Hg. [ 1 ]  The primary outcome being measured was  myocardial infarction , other  acute coronary syndromes ,  stroke ,  heart failure , or death from  cardiovascular  causes. [ 1 ]  The study implies that patients receiving \"standard\" therapy were controlled similarly to all adults being treated for hypertension and that patients receiving \"intensive\" therapy had a lower mean SBP compared to all adults being treated for hypertension, but neither conclusion is true when compared to the US National Health and Nutrition Examination Survey. [ 2 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6478", "text": "During the study, 9361 patients were randomly assigned to either a 140\u00a0mm Hg target (referred to in the study as standard treatment) or a 120\u00a0mm Hg target (intensive treatment). [ 1 ]  Patients were prescribed blood pressure reducing medications to reach their assigned goal. Unlike normal hypertension treatment, once the goal was reached, prescriptions were suspended until the patient was no longer at goal. After being followed up for a median of 3.26 years, the study showed a significantly lower rate of the primary outcome in the intensive treatment group (1.65% per year) compared to the standard treatment group (2.19% per year). [ 1 ]  The risk of experiencing a primary outcome (myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes) was 25% lower than in the standard treatment group, and the risk of death from any cause was 27% lower. [ 1 ]  The  number needed to treat  with intensive therapy instead of standard therapy to prevent one death was 90. [ 1 ]  The results were so much more superior for the intensive treatment group that the trial was stopped early. [ 1 ]"}
{"_id": "WikiPedia_Cardio$$$corpus_6479", "text": "Although the trial showed that intensive treatment was associated with lower rates of cardiovascular events and death, intensive treatment was also associated with 4% higher rates of serious adverse effects from anti-hypertensive medications, including syncope, electrolyte abnormalities, acute kidney injury or acute renal failure. [ 1 ]  However, this association was not statistically significant, with a P-value of 0.25, [ 1 ]  and therefore may have occurred by chance. The intensive treatment group were not found to be at a greater risk of injurious falls or  bradycardia , and  orthostatic hypotension  was less common in the intensive treatment group. [ 1 ] \nThe SPRINT study was criticised about the population studied in terms of age, racial and cardiovascular danger [ 3 ]"}