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 ]


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 ]


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 ]


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.


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


Regular medical checkups and imaging tests are required after TAVI. [ 19 ]


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 ]


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 ]


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 ]


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.


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 ]


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.


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 ]


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 ]


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 7–8 years. Later prostheses have improved durability. [ 27 ]


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 ]


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–Presbyterian  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 ]


Internationally famous pop singer  Mick Jagger  had the procedure in March 2019 at NewYork–Presbyterian, [ 34 ]  which was said to have raised public awareness. [ 35 ]


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 ]


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 ]


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 ]


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 ]


Active infection, central vein occlusion, coronary occlusion, and need for other surgeries such as for  arrhythmia  are contraindications for TPVR. [ 4 ] [ 1 ]


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 ]


TPVR is not recommended for tracts that are less than 16 mm [ 4 ]  or more than 29 mm in diameter. [ 1 ]


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 ]


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 ]


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 ]


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 ]


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 ]


Death is rare, and is usually attributable to other  comorbidities  rather than from the implantation procedure itself. [ 4 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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.


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.


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.


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.


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 –50 channels are made in each targeted region of the  heart muscle .


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.


TMR is a treatment option for patients who:


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.


TMR is not suitable for patients whose:


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 ]


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 ]


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 ]


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 .


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 ]


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 ]


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.


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 ]


A  jugular venous distension  is the most sensitive clinical sign for acute decompensation. [ 7 ]


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 ]


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 ]


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 ]


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 ]


Nitrates such as  nitroglycerin  ( glyceryl trinitrate ) and  isosorbide dinitrate  are often used as part of the initial therapy for ADHF. [ 9 ]


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 ]


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 ]


The  National Institutes for Health and Care Excellence  (NICE) guidelines do not recommend routinely offering nitrates in acute heart failure. [ 12 ]


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 ]


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.


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 ]


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 ]


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 ]


Inotropes  are indicated if low blood pressure (  SBP  < 90 mmHg ) is present.


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 ]


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 ]


The  National Institutes for Health and Care Excellence  (NICE) guidelines do not recommend routinely offering opioids in acute heart failure. [ 12 ]


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 .


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 ]
One such method is  aquapheresis ultra-filtration


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 ]


The  National Institutes for Health and Care Excellence  (NICE) guidelines do not recommend routinely offering ultrafiltration in acute heart failure. [ 12 ]


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 ]


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.


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 ]


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.


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.


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 ]


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 .


Bradycardia is a slower than normal heartbeat, at around 40–60 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 ]


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 ]


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 ]


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 ]


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 15–20% 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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


The  medical history  of the patient (endurance sports) and  physical examination  (bradycardia, and maybe a  third  or  fourth heart sound ), can give important hints.


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 Foé , 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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


An  atrioventricular fistula  is a  fistula  between an  atrium  and a  ventricle  of the  heart . [ citation needed ]
Formation of an AVF is a potential complication of  catheter ablation . [ 1 ]


This article about a medical condition affecting the circulatory system is a  stub . You can help Wikipedia by  expanding it .


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 ]


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.


There are number of conditions that involves the heart such as:


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:


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).


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).


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 ]


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 ]


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).


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).


Prescribed medications are given to help improve blood flow, low blood pressure and to relax blood vessel walls. [ citation needed ]


A non-surgical procedure called,  Angioplasty , could be done to help dilate the narrowed arteries. [ citation needed ]


Coronary artery bypass surgery  is also another way to treat coronary heart disease. [ citation needed ]


Although there are treatments available to treat heart disease, it is a lifelong condition restricting some daily lifestyle routine and incurable. [ citation needed ]


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).


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 ]


Cardiovascular disease kills one Australian every 11 minutes, and 3·4 million of the country's population are affected, with the Indigenous Australians having a 30% higher rate. In their lifetime, 1·5 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 ]


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 ]


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 ]


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 .


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 ]


Inflammatory damage leads to the following: [ 1 ] [ 2 ]


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 ]


These depend on the amount of  inflammation . These are covered in their relevant articles.


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.


When the condition becomes  chronic , treatment can include debility control and supportive care.


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 .


It has no known effect on function, [ 1 ] [ 2 ]  and is described as being expected or normal in aging. [ 2 ]


Ebb Cade  (17 March 1890 – 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.


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


Cardiac allograft vasculopathy is an accelerated type of  coronary artery disease  in people who have had a heart transplantation. [ 7 ]


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 ]


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 ]


Immunological ( innate  and  adaptive ) and nonimmunological factors contribute to the complex  pathogenesis  of CAV. [ 2 ]


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 ]


Inflammation and  endothelial  injury can be triggered by the donor  arrest ,  organ procurement , and allograft  ischaemia  and  reperfusion . [ 2 ]


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 ]


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 ]


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 ]


IVUS, however, tends to be used for research due to its drawbacks of being invasive, requiring the use of contrast material and cost. [ 8 ]


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 ]


Other noninvasive diagnostics include  positron emission tomography  and  computed tomographic angiography  (CT angiography). [ 2 ]  In addition,  ECGs  may show atypical features of ischaemia. [ 8 ]


Biomarkers  for increased risk of CAV include  C-reactive protein ,  serum brain natriuretic peptide  and  troponin I  have been suggested. [ 2 ]


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 ]


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 ]


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 ]


When combined with immunosuppressants, the progression of CAV could possibly be slowed by  vitamins C  and  E . [ 8 ]


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 ]


On detection of CAV, medications including  mTOR inhibitors   sirolimus  and  everolimus  have been shown to slow disease progression. [ 2 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


The multiple subtypes of cardiac amyloidosis have varying epidemiological, diagnostic, and prognostic characteristics. [ 4 ]


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 ]


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 3.5–4% 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 ]


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 ]


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 ]


Cardiac manifestations include:


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:


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 ]


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 90–95% sensitive and 80–85% 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 ]


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 ]


Holter ECGs  can be used to identify asymptomatic  arrhythmias . [ 2 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


Mass spectrometry  can be used to determine whether the protein is light-chain or familial amyloidosis by identifying the  protein subunit . [ 9 ]


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 ]


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 ]


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 ]


The use of  pacemakers  (both right ventricular pacing and biventricular pacing) or  implantable cardioverter defibrillators  remains questionable in cardiac amyloidosis. [ 17 ]


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 ]


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 ]


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 ]


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 ]


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.


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 ]


Treatment is centered on improving  cardiac function , maintaining  blood oxygen saturation  levels, and stabilizing  total body water  volume and distribution. [ 1 ] [ 4 ]


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 ]


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 ]


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 ]


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:


The diagnosis of cardiac asthma is accomplished through workup of congestive heart failure, complete with:


As well as evaluation of lung function via:


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 ]


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 ]


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 ]


Cardiac tamponade , also known as  pericardial tamponade  ( / ˌ t æ m . p ə ˈ n eɪ 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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 “severe deterioration of end-organ perfusion.” [ 11 ]  Some of the symptoms, as a consequence, include abdominal pain due to liver engorgement.


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 ]


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 ]


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 ]


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 ]