One of the currently existing techniques to treat  atrial fibrillation  (AF) is based on thermo-coagulation of AFN. They are typically numerous at the  pulmonary veins  antrum. Several evidences have shown that the AFNs represent the true  substrate  of the AF. Many  congenital  and acquired conditions may cause this type of  myocardium . The higher the number of AFNs the easier the initiation and the longer the AF maintenance. Despite being fundamental in the AF  physiopathology  the long-lasting AF depends on additional factors. The most important is the "Background  Tachycardia " (BKT) which is a focal reentrant tachycardia caused by "Fractal Micro-Reentry". This special tachycardia exists even during AF, keeping the AFNs in a high frequency activation. This  tachycardia  has a unique mechanism of "protection" that prevents it from being reverted by the large amount of surrounding  stimuli  generated by the AF itself.


Recent studies have shown that the BKT occurs within a more developed AFN or when there is a  confluence  of two or more of these elements. By using  spectral analysis , it is possible to observe that the "Fractal Micro-Reentry" phenomenon tends to occur depending on a critical amount of  fibrillar   myocardium . This is a small point in the atrial wall with numerous micro-reentries (in a three-dimensional model) inside the AFN, caused by "cellular electrical disconnection" with progressive  dichotomy  (biological fractal phenomenon), even without the presence of fibrosis and without the need of major  histological  changes. By this way, it may be present even in normal hearts that explain the "Lone Atrial Fibrillation". This intense micro-electrical activity stimulates the surrounding atrial  myocardium  that accepts the activation according to its refractory period. This produces a slightly irregular focal tachycardia, known as "Background  Tachycardia " responsible for AF maintenance with or without the contribution of many others AFNs or even of other BKT. The greater the number of these elements is, the longer the AF may last, even becoming permanent.


Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes  (also known as  AIM-HIGH ) was a  randomized control trial  designed to assess the efficacy of  niacin  (extended-release) added to  statin  therapy in reducing cardiovascular events in patients with established  atherosclerotic cardiovascular disease  (ASCVD). These patients had well-controlled  low-density lipoprotein  (LDL) cholesterol but persistently low  high-density lipoprotein  (HDL) cholesterol and elevated  triglycerides . 3,414 patients with established ASCVD were enrolled. The mean follow-up period was three years. The trial was stopped early due to a lack of efficacy and a trend towards an increase in the incidence of ischemic stroke. [ 1 ]


Low HDL cholesterol and high triglycerides are recognized risk factors for cardiovascular disease, even in individuals with well-controlled LDL cholesterol. Niacin has been shown to increase HDL cholesterol and lower triglycerides, prompting an investigation into whether adding niacin to statin therapy could further reduce cardiovascular risk in this patient population. [ 1 ]


AIM-HIGH was a multicenter, randomized, double-blind, placebo-controlled trial sponsored by the  National Heart, Lung, and Blood Institute  (NHLBI). Additional funding and support was provided by  Abbott Laboratories  and  Merck . The study enrolled 3,414 patients with established ASCVD and dyslipidemia, characterized by low HDL cholesterol (<40 mg/dL for men and <50 mg/dL for women) and elevated triglycerides (150–400 mg/dL). All participants were already on statin therapy to maintain LDL cholesterol levels between 40 and 80 mg/dL. Participants were randomly assigned to receive either extended-release niacin (1500–2000 mg daily) or a matching placebo. The primary endpoint was the time to first major cardiovascular event, including nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or death from coronary heart disease. Secondary endpoints were death from coronary heart disease (CHD), nonfatal myocardial infarction, ischemic stroke, or hospitalization for acute coronary syndrome (ACS). [ 1 ]


The results of the AIM-HIGH trial, published in 2011, showed that adding niacin to statin therapy did not significantly reduce the risk of cardiovascular events compared to statin therapy alone: [ 1 ]


The findings of the AIM-HIGH trial had significant implications for the treatment of dyslipidemia in patients with established ASCVD: [ 1 ]


AIM-HIGH contributed to a shift in clinical practice guidelines, emphasizing the limited additional benefit of niacin in patients with low HDL cholesterol and high triglycerides already receiving effective statin therapy. Subsequent guidelines have focused on intensifying statin therapy or considering other agents for specific lipid abnormalities rather than adding niacin. [ 2 ]


The  Anrep effect  describes the rapid increase in  myocardial   contractility  in response to the sudden rise in  afterload , the pressure the heart must work against to eject blood. [ 1 ] [ 2 ]  This adaptive mechanism allows the  heart  to sustain  stroke volume  and  cardiac output  despite increased resistance. It operates through  homeometric autoregulation , meaning that contractility adjustments occur independently of  preload  (the initial stretch of the heart muscle) or  heart rate . [ 1 ] [ 2 ] [ 3 ]


The Anrep effect is characterized by a two-step elevation in myocardial contractility, in response to elevated afterload, involving two distinct mechanistic phases: a primary, rapid rise in contractility driven by  sarcomeric  strain sensing, and a secondary, sustained phase of contraction mediated by  post-translational modifications  of  contractile proteins . [ 3 ] [ 4 ]  First described by  Gleb von Anrep  in 1912 [ 5 ]  and further elaborated in the 1960s by  Sarnoff  et al., [ 1 ] [ 2 ]  the Anrep effect represents a distinct cardiac regulation mechanism, differing fundamentally from the  Frank-Starling mechanism , [ 6 ]  the slow force response, [ 7 ] [ 8 ]  and the Gregg effect. [ 9 ]


While traditionally considered a short-term adaptation, recent studies suggest that the Anrep effect may also occur in chronic conditions involving persistent afterload elevation, such as  hypertrophic obstructive cardiomyopathy . [ 4 ]


The heart adjusts its pumping efficiency through changes in muscle length and load. When the cardiac muscle is stretched, it triggers a biphasic rise in force generation. The initial phase, governed by the Frank-Starling law (heterometric autoregulation), results in an immediate increase in contractile strength due to increased  end-diastolic volume . This adjustment helps balance cardiac output with changes in filling pressure. The second phase, termed the slow force response, unfolds over several minutes, reflecting a sustained increase in contractility when preload remains constant following the initial stretch. In contrast, the Anrep effect (homeometric autoregulation) enhances ventricular contractility in response to acute afterload elevation, independent of preload or heart rate variations. The Anrep effect is often confused with other regulatory processes (e.g., the slow force response, the Gregg phenomenon) but has unique, very distinct, characteristics:


The Frank-Starling mechanism describes how increased preload (ventricular filling) stretches cardiac muscle fibers, enhancing stroke work through length-dependent activation of the  myofilaments . This process aligns actin and myosin filaments for efficient cross-bridge formation while also recruiting myosin heads from dormant states into contraction-ready configurations. [ 6 ] [ 10 ]  Additionally, stretching the sarcomeres sensitizes the thin (actin) filaments to calcium, promoting stronger and more sustained contractions. [ 6 ]  By contrast, the Anrep effect occurs at constant preload, triggered solely by afterload. [ 1 ] [ 2 ] [ 3 ]  It is characterized by increased contractility (steeper end-systolic pressure-volume relationship) and higher stroke work, without changes in stroke volume or end-diastolic volume. [ 3 ] [ 4 ]


This stretch-related (preload) response involves a gradual rise in contractility over several minutes (from 2 to 15 minutes, depending on species and experimental conditions) [ 7 ] [ 8 ] [ 11 ]  due to  stretch-activated ion channels  and  G-protein-coupled receptors . [ 7 ] [ 12 ]  It is mediated by  angiotensin II  and  endothelin-1 , which increase intracellular sodium and calcium concentrations through  sodium-calcium exchangers . In contrast, the afterload-dependent response of the Anrep effect is initiated in milliseconds and concludes within 10 seconds, bypassing extracellular calcium regulation through the slow force response. [ 3 ]  Additionally,  streptomycin , an inhibitor of stretch-activated ion channels, blocks the slow force response but does not affect the Anrep effect, reinforcing that the two mechanisms operate through distinct pathways. [ 3 ]


This effect describes increased contractility due to improved  coronary perfusion . [ 9 ]  It originates from changes in microvascular volume that trigger stretch-activated ion channels, resulting in increased intracellular calcium transient. [ 13 ]  The Gregg phenomenon generally begins to affect contractility approximately 5 seconds after onset, reaching peak force development within 40 seconds of sustained perfusion. [ 3 ]  However, the Anrep effect persists even in denervated, isolated hearts with constant coronary flow, eliminating perfusion-based explanations. [ 3 ]  Like the slow force response, the Gregg effect is sensitive to streptomycin, while the Anrep effect remains unaffected. [ 3 ]


The activation of the Anrep effect involves recruiting a significant portion of dormant  myosin motors  within  cardiomyocytes , as most myosin heads in each heart cell remain in a resting state. [ 4 ]  This recruitment transitions myosin from its inactive configuration to a contraction-ready state through a biphasic activation process that increases contractility in response to the afterload, and consequently elevates energy consumption:


The Anrep effect can be understood in terms of its  hemodynamic  impact on the heart during afterload increases: [ 3 ] [ 4 ]


These responses ensure the heart maintains stroke volume and cardiac output, despite increased afterload, at the cost of higher energy consumption. [ 4 ]


The Anrep effect was first described by Gleb von Anrep in 1912 [ 5 ]  during experiments involving splanchnic nerve stimulation in dogs. He observed that stimulating the splanchnic nerve caused peripheral vasoconstriction, which increased blood pressure and afterload. In response, cardiac contractility increased, a phenomenon Anrep attributed to the release of adrenaline from the suprarenal glands, independent of preload changes. Later,  Ernest Starling  suggested that enhanced coronary flow, improving myocardial nourishment (a concept later termed the Gregg effect [ 9 ] ), might explain the increase in contractility observed by von Anrep. [ 15 ]  However, both historical and recent research has demonstrated that the Anrep effect arises from an intrinsic property of the myocardium, independent of adrenaline release or coronary flow. [ 1 ] [ 2 ] [ 3 ]  In the mid-20th century, Sarnoff et al. [ 1 ] [ 2 ]  introduced the term homeometric autoregulation to describe the heart’s ability to augment contractility in response to elevated afterload, independent of preload or hormonal stimulation. This concept distinguished the Anrep effect from the Frank-Starling law, which involves heterometric autoregulation, where increased preload enhances contractility by stretching myocardial fibers. Despite Sarnoff’s clarification, some of his experiments reported a brief, transient increase in preload following afterload elevation. He dismissed this effect as non-essential for triggering the Anrep effect, yet this observation led to persistent confusion. To this day, some studies mistakenly associate the Anrep effect with the slow force response, despite clear differences in their underlying physiology.


Although originally considered an acute and transient response, recent research suggests that the Anrep effect may persist in chronic conditions involving sustained afterload increases. One example is hypertrophic obstructive cardiomyopathy, where  left ventricular outflow tract obstruction  results in persistent afterload elevation, potentially activating the Anrep effect chronically. [ 4 ]  Understanding this mechanism has important implications for cardiac physiology, heart failure management, and therapeutic interventions targeting afterload reduction.


The  Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial , also known as  ALLHAT , was a   randomized, double-blind , active-controlled study comparing at the same time, four different classes of  antihypertensive drugs  with the rate of  coronary heart disease  (CHD) events in ‘high-risk’ people with  hypertension . [ 1 ]  Participants were initially randomised to  chlorthalidone  ( diuretic ) versus  doxazosin  ( alpha-adrenergic blocker ),  lisinopril  ( ACE-inhibitor ), and  amlodipine  ( calcium channel blocker ). [ 2 ] [ 3 ]


The doxazosin arm was discontinued early on in the trial because of a higher rate of combined  cardiovascular events  and admissions for  heart failure  compared with chlorthalidone. The study concluded that major CHD events did not differ between initial use of chlorthalidone versus lisinopril or amlodipine. As a result, the  Joint National Committee  (7) guidelines of 2003, recommended the cheaper but equally effective diuretics as a first line treatment for hypertension. The study also confirmed the previously held views that ACE inhibitors were less effective in blood pressure control and stroke prevention in men of African and Caribbean descent. [ 3 ] [ 4 ]


By the mid-1990s, there was increasing awareness of the relative reduction of risks for stroke and CHD with lowering blood pressure, and the main drugs in use were initially  diuretics  and  beta-blockers . [ 5 ]  Shortly after, other newer classes of blood pressure lowering drugs were developed and the ALLHAT study aimed to clarify their relative values with the aim to also answer which one to use first. [ 3 ]


The trial was supported mainly by the  National Heart, Lung and Blood Institute , part of the  National Institutes of Health  (NIH), and received some support from  Pfizer . [ 6 ]


Since 1971, the  Coordinating Center for Clinical Trials  ( [1] ) at The  University of Texas School of Public Health  has played a leading role in cardiovascular disease and vision research by serving as a coordinating center for 25 nationwide multicenter  clinical trials . The CCCT's primary function is to provide and coordinate all operations, procedures, and activities of a large-scale randomized controlled clinical trial. The CCCT serves as the Clinical Trials Center (Data and Clinical Coordinating Centers) for the ALLHAT. The CTC was led by C. Morton Hawkins (1993-2000) and  Barry R. Davis  (2000-2016).


In February 1994, initially 42,418 people, age over 55 years, with  stage I or II hypertension  or who were taking  medication for high blood pressure  were recruited across 623 centres in Canada, Puerto Rico, the US, and the US Virgin Islands. All had at least one other  CHD risk factor  including previous heart attack or  stroke ,  electrocardiogram  or  echocardiogram  verified  left ventricular hypertrophy  (LVH), a history of  type II diabetes mellitus , current  cigarette smoking , and low  high-density lipoprotein  cholesterol levels. [ 7 ]  35% were African American. [ 5 ]  The doxazosin arm was discontinued in January 2000 because of a higher rate of combined  cardiovascular events  and admissions for  heart failure  compared with chlorthalidone. Follow-up of the remaining 33,357 participants was completed in 2002. [ 7 ]


ALLHAT showed that major CHD events did not differ between initial use of chlorthalidone versus lisinopril or amlodipine. As diuretics proved equally effective and were cheaper, the Joint National Committee 7 guidelines of 2003, recommended diuretics as a first line treatment for hypertension. The study confirmed the previously held views that ACE inhibitors were less effective in blood pressure control and stroke prevention in men of African and Caribbean descent. The study also revealed that calcium channel blockers did not cause higher rates of gastrointestinal bleeding or cancers and they were not less effective than other antihypertensives. [ 3 ]


Aortic valve replacement  is a  cardiac surgery  procedure whereby a failing  aortic valve  is  replaced  with an  artificial heart valve . The aortic valve may need to be replaced because of  aortic regurgitation  (back flow), or if the valve is narrowed by  stenosis .


Current methods for aortic valve replacement include  open-heart surgery ,  minimally invasive cardiac surgery (MICS) ,  surgical aortic valve replacement  (SAVR) and  percutaneous or transcatheter aortic valve replacement  (TAVR; also PAVR, PAVI, TAVI).


A cardiologist can evaluate whether a  heart valve repair  or  valve replacement  would be of benefit. [ 1 ]


During the late 1940s and early 1950s, the first surgical approaches towards treating aortic valve stenosis had limited success. The first attempts were valvotomies, (i.e. cutting the valve while the heart is pumping). A ball valve prosthesis placed on the  descending thoracic aorta  (heterotopically) was developed by Hufnagel, Harvey and others to address aortic stenosis, but had disastrous complications. Later, with the innovation of cardiopulmonary bypass, the ball valve prosthesis was placed orthotopically (i.e. in same place as the original aortic valve). This first generation of prosthetic valves was durable, but needed intense anti-coagulation, and cardiac hemodynamics were compromised. During the mid-1950s, a single-leaflet prosthesis was developed by Bahnson  et al . In early 1960, Ross and  Barratt-Boyes  used allografts. Tissue prosthetic valves were introduced in 1965 by Binet in Paris, but they degenerated quickly because the tissue was insufficiently preserved. Carpentier solved this problem by introducing glutaraldehyde-preserved stent-mounted porcine valves. [ 2 ] [ 3 ]


The aortic valve is one of the two  semilunar valves  of the heart with three cusps. It separates the heart from the  aorta . Each cusp is attached to the aortic wall creating a sinus called an  aortic sinus . The origins of the two  coronary arteries  are sited in two aortic sinuses. Cusps also known as leaflets are separated by  commissures . The posterior leaflet is in continuation with the anterior leaflet of the mitral valve (the tissue is called the aorto-mitral curtain). [ 4 ]  The aortic valve is opened during systole, the driving force for it to open is the difference in pressure between the contracting left ventricle of the heart and the aorta. During cardiac diastole (when the heart chamber gets bigger) the aortic valve closes. [ 5 ]


Aortic stenosis most commonly is the result of calcification of the cusps. Other reasons for stenosis are the  bicuspid valve  (some patients have only two cusps at the aortic valve instead of the usual three) and rheumatic aortic stenosis (now rare in the West). Obstruction at the level of the aortic valve causes increased pressure within the heart's left ventricle. This can lead to hypertrophy and ultimately dysfunction of the heart. While x-ray and ECG might indicate aortic stenosis, echocardiography is the diagnostic procedure of choice. US findings also help in grading the severity of the disease. In cases of symptomatic severe aortic stenosis, AVR is warranted. In cases of asymptomatic but severe aortic stenosis, more factors should be taken into consideration. [ 6 ]


Aortic regurgitation, on the other hand, has many causes: degeneration of the cusps, endocarditis, bicuspid aortic valve, aortic root dilatation, trauma, connective tissue disorders such as Marfan syndrome or Ehlers-Danlos lead to imperfect closure of the valve during diastole, hence the blood is returning from the aorta towards the left ventricle of the heart. Acute aortic regurgitation (caused by endocarditis, aortic dissection or trauma) ends up in pulmonary edema, because of the acute increase in left ventricle (LVEDP) that does not have time to adjust to the regurgitation. Chronic regurgitation, by contrast, gives the heart time to change shape, resulting in  eccentric hypertrophy , which has disastrous effects on the myocardium. Ultrasound is here also the best diagnostic mobility, either it is transthoracic or transesophageal.  [ 7 ]


As long-term data on the survival and quality of life of people following valve replacement have become available, evidence-based guidelines for aortic valve replacement have been developed. These help healthcare professionals decide when aortic valve replacement is the best option for a patient. Two widely accepted sets of guidelines used by surgeons and cardiologists are the American Heart Association and American College of Cardiology Guidelines for the Management of Patients with Valvular Heart Disease, [ 8 ]  and the European Society of Cardiology and the European Association for Cardio‑Thoracic Surgery Guidelines for the management of valvular heart disease. [ 9 ]


Aortic stenosis  is treated with aortic valve replacement in order to avoid  angina ,  syncope , or  congestive heart failure . Individuals with severe aortic stenosis are candidates for aortic valve replacement once they develop symptoms or when their heart function is impacted. Some people with asymptomatic aortic stenosis may also be candidates for aortic valve replacement, especially if symptoms appear during  exercise testing . [ 9 ]  Patients with moderate aortic valve stenosis who need another type of cardiac surgery (i.e.  coronary artery bypass surgery ) should also have their valve addressed by the surgical team if  echocardiography  unveils significant heart problems. [ 10 ]


Low gradient aortic stenosis with concomitant left ventricular dysfunction poses a significant question to the anesthesiologist and the patient. Stress echocardiography (i.e. with dobutamine infusion) can help determine if the ventricle is dysfunctional because of aortic stenosis, or because the myocardium lost its ability to contract. [ 11 ]


Many people with  aortic insufficiency  often do not develop symptoms until they have had the condition for many years. [ 12 ]  Aortic valve replacement is indicated for symptoms such as  shortness of breath , and in cases where the heart has begun to enlarge (dilate) from pumping the increased volume of blood that leaks back through the valve. [ 9 ]


There are two basic types of replacement heart valve: tissue (bioprosthetic) valves and mechanical valves. [ 13 ]


Tissue heart valves are usually made from animal tissue (heterografts) mounted on a metal or polymer support. [ 14 ]  Bovine (cow) tissue is most commonly used, but some are made from porcine (pig) tissue. [ 15 ]  The tissue is treated to prevent rejection and calcification (where calcium builds up on the replacement valve and stops it working properly). [ 16 ]


Occasionally, alternatives to animal tissue valves are used: aortic  homografts  and pulmonary  autografts . An aortic homograft is an aortic valve from a human donor, retrieved either after their death or from their heart if they are undergoing a heart transplant. [ 17 ]  A pulmonary autograft, also known as the  Ross procedure  is where the aortic valve is removed and replaced with the patient's own  pulmonary valve  (the valve between the right ventricle and the pulmonary artery). A pulmonary homograft (a pulmonary valve taken from a cadaver) is then used to replace the patient's own pulmonary valve. This procedure was first performed in 1967 and is used primarily in children, as it allows the patient's own pulmonary valve (now in the aortic position) to grow with the child. [ 17 ]


Tissue valves can last 10–20 years. [ 18 ]  However, they tend to deteriorate more quickly in younger patients. [ 19 ]  New ways of preserving the tissue for longer are being investigated. One such preservation treatment is now being used in a commercially available tissue heart valve. In sheep and rabbit studies, the tissue (called RESILIA tissue) had less  calcification  than control tissue. Mid-term data on the safety and haemodynamic performance of the Inspiris RESILIA aortic bioprosthesis are encouraging. [ 20 ] [ 21 ]


Stented and stentless tissue valves are available. Stented valves come in sizes from 19 mm to 29 mm. [ 22 ]  Stentless valves are directly sutured at the aortic root. The major advantage of stentless valves is that they limit  patient–prosthesis mismatch  (when the area of the prosthetic valve is too small in relation to the size of the patient, increasing the pressure inside the valve [ 23 ] ) and can be helpful when dealing with small aortic root. However, stentless valves take more time than stented valves to implant. [ 24 ]


Mechanical valves are made from synthetic materials, such as titanium or  pyrolytic carbon . [ 25 ]  Their durability is long life, while tissue valves can last for up to 15–20 years. [ 26 ] [ 27 ] [ 13 ]  Since the risk of blood clots forming is higher with mechanical valves than with tissue valves, patients with mechanical heart valves are required to take anticoagulant (blood-thinning) drugs, such as  warfarin , long-life, making them more prone to bleeding (1% per year). [ 13 ]  The sound of the valve can be heard very rarely, often as clicks, and might be disturbing. [ 28 ]  The choice of prosthetic valve should be individualized, carefully considering each patient's unique circumstances. In that context, the new generation aortic mechanical valve (On-X) offers a potential lifetime solution without need for a repeat operation, while minimizing the risks of long-term anticoagulation due to reduced anticoagulation target INR of 1.5 to 2.0. [ 29 ]


Valve choice is a balance between the lower durability of tissue valves and the increased risk of blood clots and bleeding with mechanical valves. Guidelines suggest that patient age, lifestyle and medical history should all be considered when choosing a valve. Tissue valves deteriorate more rapidly in young patients and during pregnancy, but they are preferable for women who wish to have children because pregnancy increases the risk of blood clots. Typically, a mechanical valve is considered for patients under 60 years old, while a tissue valve is considered for patients over the age of 65 years. [ 13 ]


Surgical aortic valve replacement is conventionally done through a  median sternotomy , meaning the incision is made by cutting through the breastbone ( sternum ). Once the protective membrane around the heart ( pericardium ) has been opened, the patient is cannulated (aortic cannulation by a cannula placed on the  aorta  and a venous canulation by a single atrial venous cannula inserted through the right atrium). The patient is put on a  cardiopulmonary bypass  machine, also known as the heart–lung machine. This machine breathes for the patient and pumps their blood around their body while the surgeon replaces the heart valve. [ citation needed ]


Once on cardiopulmonary bypass, the patient's heart is stopped ( cardioplegia ). This can be done with a Y-type cardioplegic infusion catheter placed on the aorta, de-aired and connected to the cardiopulmonary bypass machine. Alternatively, a retrograde cardioplegic cannula can be inserted at the coronary sinus. Some surgeons also opt to place a vent in the left ventricle through the right superior pulmonary vein, because this helps to prevent left ventricular distention before and after cardiac arrest. When the set-up is ready, the aorta is clamped shut with a cross-clamp to stop blood pumping through the heart and cardioplegia is infused. The surgeon incises the aorta a few milometers above the sinotubular junction (just above the coronary ostia, where the coronary arteries join the aorta) – a process known as aortotomy. After this, cardioplegia is delivered directly through the ostia. [ 30 ] [ 31 ]


The heart is now still and the surgeon removes the patient's diseased aortic valve. The cusps of the aortic valve are excised, and calcium is removed (debrided) from the aortic annulus. The surgeon measures the size of the aortic annulus and fits a mechanical or tissue valve of the appropriate size. Usually the valve is fixed in place with sutures, although some sutureless valves are available. If the patient's aortic root is very small, the sutures are placed outside of the aortic root instead of at the annulus, to gain some extra space. [ citation needed ]


Once the valve is in place and the aorta has been closed, patient is placed in a  Trendelenburg position  and the heart is de-aired and restarted. The patient is taken off the cardiopulmonary bypass machine.  Transesophageal echocardiogram  (an ultrasound of the heart done through the esophagus) can be used to verify that the new valve is functioning properly. Pacing wires are usually put in place, so that the heart can be manually controlled should any complications arise after surgery. Drainage tubes are also inserted, to drain fluids from the chest. These are usually removed within 36 hours, while the pacing wires are generally left in place until right before the patient is discharged from the hospital. [ 30 ] [ 31 ]


After surgical aortic valve replacement, the patient will usually stay in an  intensive care unit  for 12–36 hours. Unless complications arise, the patient is then able to go home after approximately four to seven days. [ 32 ]  Common complications include disturbances to the heart's rhythm ( heart block ), which typically require the permanent insertion of a  cardiac pacemaker . [ 33 ]


Recovery from aortic valve replacement takes about three months if the patient is in good health. Patients are advised not to lift anything heavier than 10 lbs for several weeks, and not to do any heavy lifting for 4–6 months after surgery to avoid damaging their breastbone. Often patients will be referred to participate in  cardiopulmonary rehabilitation , which optimizes recovery and physical function in patients with recent cardiac surgeries. This can be done in an outpatient setting. [ 34 ]


Surgery usually relieves the aortic disease symptoms that led the patient to the operating room. The survival curve of patients who undergo aortic valve replacements is slightly inferior to the curve of their corresponding healthy same-aged same sex population. [ 35 ]  Pre-operative severe left ventricular hypertrophy is a contributing factor to morbidity. [ 35 ]


The risk of dying as a result of aortic valve replacement is estimated at 1–3%. [ 36 ] [ 37 ] [ 38 ]  Combining aortic valve replacement with coronary artery bypass grafting increases the risk of mortality. [ 36 ]  Older patients, as well as those who are frail and/or have other health problems ( comorbidities ), have a higher risk of experiencing complications. [ 37 ]  Possible problems include  cardiac infarction  or failure,  arrhythmia  or  heart block  typically requiring the permanent insertion of a  cardiac pacemaker , mediastinal bleeding,  stroke  and infection. Late complications include  endocarditis , thromboembolic events ( blood clots ), prosthetic valve dysfunction and paravalvular leak (blood flowing between the edge of the prosthetic valve and the cardiac tissue). [ 35 ]


When dealing with a small aortic annulus, the surgeon might have to insert a prosthetic aortic valve of small size, with an orifice too small in relation to the size of the patient (patient–prosthesis mismatch). This increases the pressure of the blood flowing through the valve, and can lead to worse outcomes. [ 23 ]  Various techniques, including stentless valves, have been utilized to avoid this problem. [ 39 ]


Since the late 1990s, some cardiac surgeons have been performing aortic valve replacement using an approach referred to as minimally invasive cardiac surgery (MICS). [ 40 ]  Using this approach, the surgeon replaces the valve through a smaller chest incision (6–10 cm) than that for a median sternotomy. MICS typically requires shorter recovery times, and produces less visible scarring. [ 41 ]  Alternatively, aortic valve replacement can be performed with right minithoracotomy approach via the 2nd or 3rd intercostal space. There is growing evidence that this approach can reduce postoperative morbidity allowing less blood loss, less pain,
faster recovery, and a shorter hospital stay with no difference in mortality. [ 42 ]  This approach can be particularly valuable in higher risk and elderly patients. [ 43 ]


Another alternative for many high-risk or elderly patients is transcatheter aortic valve replacement (TAVR, also known as TAVI, transcatheter aortic valve implantation). Rather than removing the existing valve, the new valve is pushed through it in a collapsed state. It is delivered to the site of the existing valve through a tube called a catheter, which may be inserted through the femoral artery in the thigh (transfemoral approach), or using a small incision in the chest and then through a large artery or the tip of the left ventricle (transapical approach). [ 44 ]  Fluoroscopy and  transthoracic echocardiogram  (TTE) are visual aids used to guide the process. [ 44 ]  Once the collapsed replacement valve is in place it is expanded, pushing the old valve's  leaflets  out of the way. [ 45 ]


Guidelines suggest TAVR for most patients aged 75 years and older, and surgical aortic valve replacement for most younger patients. [ 46 ]  Ultimately, the choice of treatment is  based on many factors. [ 47 ] [ 46 ]


Systematic reviews  have addressed this comparison: [ 48 ] [ 49 ]


The  apex beat  (lat.  ictus cordis ), also called the  apical impulse , [ 1 ]  is the  pulse  felt at the  point of maximum impulse  ( PMI ), which is the point on the  precordium  farthest outwards (laterally) and downwards (inferiorly) from the  sternum  at which the  cardiac  impulse can be felt. The cardiac impulse is the vibration resulting from the  heart  rotating, moving forward, and striking against the chest wall during  systole . The PMI is not the  apex of the heart  but is on the precordium not far from it. Another theory for the occurrence of the PMI is the early systolic contraction of the longitudinal fibers of the left ventricle located on the endocardial surface of this chamber. This period of the cardiac cycle is called isovolumic contraction. Because the contraction starts near the base of the left ventricle and spreads toward the apex most of the longitudinal fibers of the left ventricle have shortened before the apex. The rapidly increasing pressure developed by the shortening of these fibers causes the aortic valve to open and the apex to move outward causing the PMI. Anatomical dissection of the musculature of the apex reveals that muscle fibers are no longer longitudinal oriented but form a spiral mass of muscular tissues which may also have an effect on the ability of the apex to contract longitudinally. After the longitudinal fibers contract, the ejection of blood out of the left ventricle is accomplished by the torsional (as one would wring out a face cloth) action of the circumferential muscle fibers of the left ventricle that are in the mid-portion of the ventricle and contract after the longitudinal fibers. During the longitudinal fiber contraction, the volume of the left ventricle has not changed keeping the apex in intimate contact with the chest wall allowing the ability to feel the apex move outward before the heart empties greater than 55% of its volume and the apex falling away from the chest wall.  [ 2 ]


The normal apex beat can be  palpated  in the  precordium  left 5th intercostal space, half-inch medial to the left midclavicular line and 3–4 inches left of left border of sternum.


In children the apex beat occurs in the fourth rib interspace medial to the nipple. The apex beat may also be found at abnormal locations; in many cases of  dextrocardia , the apex beat may be felt on the right side.


Lateral and/or inferior displacement of the apex beat usually indicates enlargement of the heart, called  cardiomegaly . The apex beat may also be displaced by other conditions:


Sometimes, the apex beat may not be palpable, either due to a thick chest wall, or conditions where the  stroke volume  is reduced; such as during  ventricular tachycardia  or  shock .


The character of the apex beat may provide vital  diagnostic  clues:


Sustained apex beat, namely prolonged upward cardiac force during  systole  in a  physical exam , can be seen in some  chronic  conditions such as  hypertension  and  aortic stenosis , especially in elderly and females. [ 3 ]


An algorithm for the classification of some common apex beat characteristics is shown in the image


The  arteriovenous oxygen difference , or  a-vO 2  diff , is the difference in the  oxygen  content of the  blood  between the  arterial blood  and the  venous blood . It is an indication of how much oxygen is removed from the blood in  capillaries  as the blood  circulates  in the body. The a-vO 2  diff and  cardiac output  are the main factors that allow variation in the body's total oxygen consumption, and are important in measuring  VO 2 . The a-vO 2  diff is usually measured in  millilitres  of oxygen per 100 millilitres of blood (mL/100 mL). [ 1 ]


The arteriovenous oxygen difference is usually taken by comparing the difference in the oxygen concentration of  oxygenated blood  in the  femoral ,  brachial , or  radial artery  and the oxygen concentration in the  deoxygenated blood  from the mixed supply found in the  pulmonary artery  (as an indicator of the typical mixed venous supply). [ citation needed ]


Put in simple terms:


The usual unit for a-vO 2  diff is millilitres of oxygen per 100 millilitres of blood (mL/100 mL), [ 1 ]  however, particularly in medical uses, other units may be used, such as  micro   moles  per millilitre (μmol/mL). [ 2 ]


In practice, a-vO 2  diff may be determined using the  Fick Principle  rather than by taking direct blood samples. In order to do so oxygen consumption (VO 2 ) may be measured using a  spirometer  to detect gaseous concentrations in exhaled air compared to inhaled air, while  cardiac output  can be determined using a  Doppler ultrasound . [ 3 ]


Arterial blood will generally contain an oxygen concentration of around 20 mL/100 mL. [ 1 ]  Venous blood with an oxygen concentration of 15 mL/100 mL would therefore lead to typical values of the a-vO 2  diff at rest of around 5 mL/100 mL. During intense exercise, however, the a-vO 2  diff can increase to as much as 16 mL/100 mL due to the working  muscles  extracting far more oxygen from the blood than they do at rest. [ citation needed ]


Alternatively, in order to find the efficiency of the  lungs  in replenishing blood oxygen levels, the a-vO 2  diff may instead be taken by comparing blood from the pulmonary artery and the  pulmonary vein ; in this case a negative value for a-vO 2  diff would be obtained as the oxygen content of the blood would have increased. [ citation needed ]


Physical exercise  leads to an increase in the arteriovenous oxygen difference in all individuals. As exercise intensities increase, the muscles increase the amount of oxygen they extract from the blood, and this therefore results in further increases in a-vO 2  diff. [ 4 ]


The maximum a-vO 2  diff is also usually greater in  trained   athletes  than in untrained individuals. [ citation needed ]  This is a result of  aerobic exercise  leading to  hypertrophy  of the  slow twitch muscle fibres  mainly due to increased capillarisation. The increase in capillary beds in the muscle means that blood supply to that muscle can be greater and  diffusion  of oxygen,  carbon dioxide , and other  metabolites  increases. [ 5 ]  With training the muscles also improve in their ability to extract oxygen from the blood and process the oxygen, [ 5 ]  possibly due to adaptations of the  mitochondria  and an increase in the muscle's  myoglobin  content. [ citation needed ]


Research has shown that following the commencement of exercise there is a delay in the increase of the a-vO 2  diff, and that a-vO 2  diff only has a marginal impact in the total change in VO 2  in the early stages of exercise. The bulk of the early increase in oxygen consumption after a sudden change in exercise levels results from increased cardiac output. [ 3 ]  However it has also been found that the increase in the maximal a-vO 2  diff resulting from adaptations to a physical training program can account for most of the difference in  VO 2  max  in subjects participating in sub-maximal exercise. [ 6 ]


Arteriovenous oxygen difference is also used in other areas of study such as  medicine  and  medical research . For example, the a-vO 2  diff has been used to measure  cerebral blood flow  in  comatose  patients, assisting with their  diagnosis  and  treatment . [ 2 ]  The a-vO 2  diff has also been used to determine the effects of physical training in  coronary patients . [ 6 ]


An  artificial heart  is an  artificial organ  device that replaces the  heart . Artificial hearts are typically used to bridge the time to complete  heart transplantation  surgery, but research is ongoing to develop a device that could permanently replace the heart in the case that a heart transplant (from a deceased human or, experimentally, from a deceased genetically engineered pig) is unavailable or not viable. As of December 2023 [update] , there are two commercially available full artificial heart devices; in both cases, they are for temporary use, of less than a year, for total heart failure patients awaiting a human heart to be transplanted into their bodies.


Although other similar inventions preceded it from the late 1940s, the first artificial heart to be successfully implanted in a human was the Jarvik-7 in 1982, designed by a team including  Willem Johan Kolff ,  William DeVries   and  Robert Jarvik . [ 1 ]


An artificial heart is distinct from a  ventricular assist device  (VAD; for either one or both of the ventricles, the heart's lower chambers), which can be a permanent solution also, or the  intra-aortic balloon pump  – both devices are designed to support a failing heart. It is also distinct from a  cardiopulmonary bypass  machine, which is an external device used to provide the functions of both the heart and  lungs , used only for a few hours at a time, most commonly during  cardiac surgery . It is also distinct from a ventilator, used to support failing lungs, or the  extracorporeal membrane oxygenation  (ECMO), which is used to support those with both inadequate heart and lung function for up to days or weeks, unlike the bypass machine.


A synthetic replacement for a heart remains a long-sought "holy grail" of modern medicine. The obvious benefit of a functional artificial heart would be to lower the need for  heart transplants  because the demand for organs always greatly exceeds supply.


Although the heart is conceptually a pump, it embodies subtleties that defy straightforward emulation with synthetic materials and power supplies. [ citation needed ]  Artificial hearts have historically had issues from both a biomedical standpoint, regarding clotting and foreign object rejection, as well as longevity and practicality, regarding the lifespan of the device as well as the equipment required to run it.


Since the inception of the device, artificial hearts have been continually improved as medical technology has. More recent devices, such as the Carmat heart, have sought to improve upon their predecessors by reducing complications resultant from device implant, such as  foreign-body rejection  and  thrombus . [ 2 ]


The first artificial heart was made by the Soviet scientist  Vladimir Demikhov  in 1938. It was implanted in a dog.


On July 2, 1952, 41-year-old  Henry Opitek , suffering from shortness of breath, made medical history at  Harper University Hospital [ 3 ]  at  Wayne State University  in Michigan. The  Dodrill-GMR  heart machine, considered to be the first operational mechanical heart, was successfully used while performing heart surgery. [ 4 ] [ 5 ]
Ongoing research was done on calves at  Hershey Medical Center , Animal Research Facility, in Hershey, Pennsylvania, during the 1970s.


Forest Dewey Dodrill , working closely with Matthew Dudley, used the machine in 1952 to bypass Henry Opitek's left ventricle for 50 minutes while he opened the patient's left atrium and worked to repair the mitral valve. In Dodrill's post-operative report, he notes, "To our knowledge, this is the first instance of survival of a patient when a mechanical heart mechanism was used to take over the complete body function of maintaining the blood supply of the body while the heart was open and operated on." [ 6 ]


A  heart–lung machine  was first used in 1953 during a successful open heart surgery.  John Heysham Gibbon , the inventor of the machine, performed the operation and developed the heart–lung substitute himself.


Following these advances, scientific interest for the development of a solution for heart disease developed in numerous research groups worldwide.


In 1949, a precursor to the modern artificial heart pump was built by doctors William Sewell and  William Glenn  of the  Yale School of Medicine  using an  Erector Set , assorted odds and ends, and dime-store toys. The external pump successfully bypassed the heart of a dog for more than an hour. [ 7 ]


On December 12, 1957,  Willem Johan Kolff , the world's most prolific inventor of artificial organs, implanted an artificial heart into a dog at Cleveland Clinic. The dog lived for 90 minutes.


In 1958,  Domingo Liotta  initiated the studies of TAH (Total Artificial Heart) replacement at Lyon, France, and in 1959–60 at the  National University of Córdoba , Argentina. He presented his work at the meeting of the American Society for Artificial Internal Organs held in Atlantic City in March 1961. At that meeting, Liotta described the implantation of three types of orthotopic (inside the pericardial sac) TAHs in dogs, each of which used a different source of external energy: an implantable electric motor, an implantable rotating pump with an external electric motor, and a pneumatic pump. [ 8 ] [ 9 ]


Paul Winchell  designed a model of artificial heart with the assistance of  Henry Heimlich  (the inventor of the  Heimlich maneuver ) and submitted a patent for a mechanically driven artificial heart implementing a cam driven roller mechanism to compress flexible bags containing blood, on February 6, 1961. [ 10 ]  This is contrary to the popular claim that Winchell submitted the patent in the summer of 1956, as well as contrary to the claim that Winchell "invented" the artificial heart. [ 11 ]  In fact, two patents existed prior to Winchell's submission. These patents were filed April 10, 1956, [ 12 ]  and April 17, 1959, [ 13 ]  respectively. Winchell also claims that the design within his patent was used in later models of the Jarvik hearts, a claim in which Robert Jarvik, the principle designer of those hearts, denies on the basis that his pneumatically driven hearts share little in common with Winchell's mechanically actuated patent. [ 14 ]


In 1964, the  National Institutes of Health  started the Artificial Heart Program, with the goal of putting an artificial heart into a human by the end of the decade. [ 15 ]   The purpose of the program was to develop an implantable artificial heart, including the power source, to replace a failing heart. [ 16 ]


In February 1966,  Adrian Kantrowitz  rose to international prominence when he performed the world's first permanent implantation of a partial mechanical heart (left ventricular assist device) at  Maimonides Medical Center . [ 17 ]


In 1967, Kolff left Cleveland Clinic to start the Division of Artificial Organs at the  University of Utah  and pursue his work on the artificial heart.


Over the years, more than 200 physicians, engineers, students and faculty developed, tested and improved Kolff's artificial heart. To help manage his many endeavors, Kolff assigned project managers. Each project was named after its manager. Graduate student Robert Jarvik was the project manager for the artificial heart projects, for which the Jarvik line of artificial hearts get their name from. There, physician-engineer  Clifford Kwan-Gett  invented two components of an integrated pneumatic artificial heart system: a ventricle with hemispherical diaphragms that did not crush red blood cells (a problem with previous artificial hearts) and an external heart driver that inherently regulated blood flow without needing complex control systems. [ 18 ]  Jarvik also combined several modifications: an ovoid shape to fit inside the human chest, a more blood-compatible  polyurethane  developed by biomedical engineer Donald Lyman, and a fabrication method by Kwan-Gett that made the inside of the ventricles smooth and seamless to reduce dangerous stroke-causing blood clots. [ 19 ]


On April 4, 1969,  Domingo Liotta  and  Denton A. Cooley  replaced a dying man's heart with a mechanical heart inside the chest at  The Texas Heart Institute  in  Houston  as a bridge for a transplant. The man woke up and began to recover. After 64 hours, the pneumatic-powered artificial heart was removed and replaced by a donor heart. However thirty-two hours after transplantation, the man died of what was later proved to be an acute pulmonary infection, extended to both lungs, caused by fungi, most likely caused by an  immunosuppressive drug  complication. [ 20 ]


The original prototype of Liotta-Cooley artificial heart used in this historic operation is prominently displayed in the  Smithsonian Institution 's  National Museum of American History  "Treasures of American History" exhibit in Washington, D.C. [ 21 ]


The first clinical use of an artificial heart designed for permanent implantation rather than a bridge to transplant occurred in 1982 at the  University of Utah .


In 1981,  William DeVries  submitted a request to the FDA for permission to implant the Jarvik-7 into a human being. On December 1, 1982, William DeVries implanted the Jarvik-7 artificial heart into Barney Clark, a retired dentist from Seattle who had severe  congestive heart failure . Clark's case was highly publicized and received much media attention, garnering attention from television networks, newspapers and periodicals. Clark lived for 112 days tethered to the UtahDrive pneumatic drive console, a device weighing some 400 pounds (180 kg). During that time Clark required several re-operations, suffered seizures, experienced prolonged periods of confusion and a number of instances of bleeding and asked several times to be allowed to die. Clark, however, still believed his being part of the initial experiment was an important contribution to medicine, and maintained an overall positive outlook on his condition. [ 22 ] [ 23 ]  Barney Clark died on March 23, 1983, of multiorgan system failure. Despite the complications, DeVries considered Clark's case a success. [ 24 ]


DeVries subsequently moved his practice to Humana Hospital Audubon in Louisville, Kentucky to continue studies using the Jarvik-7. DeVries' first artificial heart patient in Louisville was  Bill Schroeder . DeVries replaced Schroeder's failing heart with a Jarvik-7 on November 25, 1984. Like Clark, Schroeder suffered from bleeding that required re-operation to resolve. In the first weeks the outlook was good and Schroeder was allowed to have a can of Coors beer and he was given a phone call by President  Reagan , in which he famously asked the president for an update on a late Social Security check. [ 25 ]  However, 19 days after the operation, Schroeder suffered the first of four  strokes . Despite this, his recovery continued and was allowed to live in a specially outfitted apartment near the hospital for a period of time, as well as use a newly developed battery-powered portable drive unit for the heart which allowed him to venture out of the hospital for short periods. Schroeder's health continued to decline as three more strokes plagued his time with the artificial heart. He died on August 6, 1986, from complications from a stroke, respiratory failure and sepsis, after 620 days with the artificial heart. [ 26 ]


Three more patients received the Jarvik-7 as a permanent heart. Murray Haydon, DeVries' third patient, received a Jarvik-7 on February 17, 1985. Haydon suffered pulmonary issues and was required to be on a mechanical ventilator for the duration of his time with the artificial heart. Haydon died of infection and kidney failure on June 19, 1986, after 488 days with his artificial heart. On April 7, 1985, Dr. Bjarne Semb of Karolinska Hospital in Stockholm Sweden implanted a Jarvik-7 in Swedish businessman Leif Stenberg. Stenberg lived 229 largely-uneventful days with the heart but suffered from a stroke and subsequently died on November 21, 1985. Jack Burcham was DeVries' fourth and final patient to receive a Jarvik-7 as a destination therapy. Burcham received his heart on April 14, 1985, but due to complications from the size of the device, bleeding and kidney failure, Burcham died just 10 days later on April 25, 1985. [ 27 ]


In the mid-1980s, artificial hearts were powered by large pneumatic drive consoles. Moreover, two sizable catheters had to cross the body wall to carry the pneumatic pulses to the implanted heart, greatly increasing the risk of infection. To speed development of a new generation of technologies, the  National Heart, Lung, and Blood Institute  opened a competition for implantable electrically powered artificial hearts. Three groups received funding:  Cleveland Clinic  in Cleveland, Ohio; the College of Medicine of  Pennsylvania State University  ( Penn State Milton S. Hershey Medical Center ) in Hershey, Pennsylvania; and AbioMed, Inc. of Danvers, Massachusetts. Despite considerable progress, the Cleveland program was discontinued after the first five years.


On July 19, 1963, E. Stanley Crawford and  Domingo Liotta  implanted the first clinical  Left Ventricular Assist Device  (LVAD) at  The Methodist Hospital  in Houston, Texas, in a patient who had a cardiac arrest after surgery. The patient survived for four days under mechanical support but did not recover from the complications of the cardiac arrest; finally, the pump was discontinued, and the patient died.


On 21 April 1966,  Michael DeBakey  and Liotta implanted the first clinical LVAD in a paracorporeal position (where the external pump rests at the side of the patient) at The Methodist Hospital in Houston, in a patient experiencing cardiogenic shock after heart surgery. The patient developed neurological and pulmonary complications and died after few days of LVAD mechanical support. In October 1966, DeBakey and Liotta implanted the paracorporeal Liotta-DeBakey LVAD in a new patient who recovered well and was discharged from the hospital after 10 days of mechanical support, thus constituting the first successful use of an LVAD for  postcardiotomy  shock.


In 1990, Brian Williams was discharged from the  University of Pittsburgh Medical Center  (UPMC), becoming the first VAD patient to be discharged with Food and Drug Administration (FDA) approval. [ 29 ]  The patient was supported in part by bioengineers from the University of Pittsburgh's McGowan Institute. [ 29 ] [ 30 ]


SynCardia Systems  is a company based in Tucson, Arizona, which currently has two separate models of their artificial heart available. It is available in a 70cc and 50cc size. The 70cc model is used for biventricular heart failure in adult men, while the 50cc is for children and women. [ 31 ]  As of 2014, more than 1,250 patients have received SynCardia artificial hearts. [ 32 ] [ 33 ]


The device has two drive systems available for patients to use; the Companion 2 in-hospital driver, approved by the FDA in 2012, or the Freedom Driver System, approved in 2014. The Companion 2 replaced the Circulatory Support System Console, which was the original drive system for the heart. The Freedom Driver System is a compact portable driver for greater mobility and can allow some patients to return home. [ 34 ] [ 35 ]  To power the heart, the drivers send pulsed air through the drivelines into the heart. The drivers also monitor blood flow for each ventricle. [ 36 ]


In 1991 the rights to the Jarvik-7 were transferred to CardioWest, who resumed testing of the heart. Following good results with the TAH as a bridge to  heart transplant , a trial of the CardioWest TAH was initiated in 1993 and completed in 2002. [ 37 ]  After the completion of this trial, CardioWest became SynCardia. The SynCardia total artificial heart was first approved for use in 2004 by the  US Food and Drug Administration . [ 34 ]


Though the SynCardia shares its design with the Jarvik-7, improvements have been made throughout its lifespan, reducing the occurrence of stroke and bleeding. [ 33 ]  Lifespan while being supported by the device has also drastically improved, with one patient being supported by the device for over 1,700 days. [ 38 ]


In 2016, SynCardia filed for bankruptcy protection and was later acquired by the private equity firm Versa Capital Management. [ 39 ]  In 2021, SynCardia was acquired by Hunniwell Lake Ventures under its portfolio company, Picard Medical. [ 40 ]  In April 2023, SynCardia filed to become a publicly traded company via  SPAC . [ 41 ]


On October 27, 2008, French professor and leading  heart transplant  specialist  Alain F. Carpentier  announced a timeline that a fully implantable artificial heart would be ready for clinical trial by 2011 and for alternative transplant in 2013. It was developed and would be manufactured by his biomedical firm  CARMAT SA , [ 42 ]  and venture capital firm Truffle Capital. The prototype used embedded electronic sensors and was made from chemically treated animal tissues, called "biomaterials", or a "pseudo-skin" of  biosynthetic ,  microporous materials . [ 43 ]


According to a press-release by Carmat dated December 20, 2013, the first implantation of its artificial heart in a 75-year-old patient was performed on December 18, 2013, by the Georges Pompidou European Hospital team in Paris (France). [ 44 ]  The patient died 75 days after the operation. [ 45 ]


In Carmat's design, called the Aeson, two chambers are each divided by a membrane that holds hydraulic fluid on one side. A motorized pump moves hydraulic fluid in and out of the chambers. The pumped fluid causes the membrane to move, causing blood to pump through the heart. The blood-facing side of the membrane is made of tissue obtained from a sac that surrounds a cow's heart, to make the device more biocompatible. The Carmat device also uses valves made from cow heart tissue and has sensors to detect increased pressure within the device. Cardiac information is sent to an internal control system that can adjust the flow rate in response to increased demand, such as when a patient is exercising. [ 46 ]


The Carmat Aeson is aimed to be used in cases of terminal heart failure, instead of being used as a bridge device while the patient awaits a transplant. [ 47 ]  At 900 grams it weighs nearly three times the typical heart and is targeted primarily towards obese men. It also requires the patient to carry around an additional  Li-Ion  battery. The projected lifetime of the artificial heart is around 5 years (230 million beats). [ 48 ]


In 2016, trials for the Carmat "fully artificial heart" were banned by the National Agency for Security and Medicine in Europe after short survival rates were confirmed. The ban was lifted in May 2017. At that time, a European report stated that Celyad's C-Cure cell therapy for ischemic heart failure [ 49 ]  "Could only help a subpopulation of Phase III study participants, and Carmat will hope that its artificial heart will be able to treat a higher proportion of heart failure patients". [ 50 ]


The Carmat artificial heart was approved for sale in the European Union, receiving a  CE marking  on December 22, 2020. [ 51 ]  As of December 2023 [update] , the Carmat is only available in Europe as a bridge-to-transplant, for up to 180 days while awaiting a human heart transplant. In the United States it is only available in clinical trials. [ 52 ]


The  U.S. Army  artificial heart pump was a compact, air-powered unit developed by Kenneth Woodward at  Harry Diamond Laboratories  in the early to mid-1960s. [ 53 ] [ 54 ]  The Army's heart pump was partially made of  plexiglass , and consisted of two valves, a chamber, and a suction flapper. [ 53 ]  The pump operated without any moving parts under the principle of fluid amplification – providing a pulsating air pressure source resembling a heartbeat. [ 54 ]


The Jarvik line of hearts was developed by the now-defunct medical device company Symbion, by medical device researchers Willem Kolff and Robert Jarvik in conjunction with the University of Utah. These hearts were developed through animal trials and culminated in the Jarvik-7 100, the original model that was used in the first clinical trials of the heart. Jarvik-7 hearts were made primarily of a biocompatible plastics and polymers. These hearts used four Medtronic-Hall valves and consisted of two “ventricles” which contained multi-layer low-stress diaphragms. [ 55 ]  The Jarvik-7 was powered pneumatically by two transcutaneous drivelines attached to a large compressed-air drive console, originally called the Utahdrive. The drive console contained two independent drive systems for redundancy, data recording devices and backup compressed air cylinders. [ 56 ]


The Jarvik-7 was later developed in a smaller 70cc variant so that it would fit better in the chest cavities of more patients. Another development that came to the Jarvik-7 was the introduction of a battery-powered portable drive system the size of a briefcase that later patients took advantage of.


Contrary to popular belief and erroneous articles in several periodicals, the Jarvik-7 heart was not permanently banned for use. After a hostile takeover, Symbion's facilities had lost FDA compliance in 1990 and required that the devices be destroyed. After the rights to the device had been transferred to then CardioWest Technologies, an investigational study was approved in 1993. CardioWest Technologies became SynCardia in 2003 who currently produces the modern version of the Jarvik-7, known as the  SynCardia  temporary Total Artificial Heart. [ 55 ]


Since 1991, the Foundation for Cardiac Surgery Development (FRK) in  Zabrze , Poland, has been working on developing an artificial heart. Nowadays, [ when? ]  the Polish system for heart support POLCAS consists of the artificial ventricle POLVAD-MEV and the three controllers POLPDU-401, POLPDU-402 and POLPDU-501. Presented devices are designed to handle only one patient. The control units of the 401 and 402 series may be used only in hospital due to its big size, method of control and type of power supply. The control [ 57 ]  unit of 501 series is the latest product of FRK. Due to its much smaller size and weight, it is significantly more mobile solution. For this reason, it can be also used during supervised treatment conducted outside the hospital. [ citation needed ]


In June 1996, a 46-year-old man received a total artificial heart implantation done by Jeng Wei at Cheng-Hsin General Hospital [ 58 ]  in  Taiwan . This technologically advanced pneumatic Phoenix-7 Total Artificial Heart was manufactured by Taiwanese dentist  Kelvin K. Cheng , Chinese physician T. M. Kao, and colleagues at the Taiwan TAH Research Center in  Tainan ,  Taiwan . With this experimental artificial heart, the patient's BP was maintained at 90–100/40–50 mmHg and cardiac output at 4.2–5.8 L/min. [ 59 ]  The patient then received the world's first successful combined heart and kidney transplantation after bridging with a total artificial heart. [ 60 ]


The first  AbioCor  to be surgically implanted in a patient was on July 3, 2001. [ 61 ]  The AbioCor is made of titanium and plastic with a weight of 0.9 kg (two pounds), and its internal battery can be recharged with a transduction device that sends power through the skin. [ 61 ]  The internal battery lasts for half an hour, and a wearable external battery pack lasts for four hours. [ 62 ]  The FDA announced on September 5, 2006, that the AbioCor could be implanted for humanitarian uses after the device had been tested on 15 patients. [ 63 ]  It is intended for critically ill patients who cannot receive a heart transplant. [ 63 ]  Some limitations of the current AbioCor are that its size makes it suitable for less than 50% of the female population and only about 50% of the male population, and its useful life is only 1–2 years. [ 64 ]


By combining its valved ventricles with the control technology and roller screw developed at Penn State, AbioMed designed a smaller, more stable heart, the AbioCor II. This pump, which should be implantable in most men and 50% of women with a life span of up to five years, [ 64 ]  had animal trials in 2005, and the company hoped to get FDA approval for human use in 2008. [ 65 ]  After a great deal of experimentation,  AbioMed  has abandoned development of total artificial hearts as of 2015. [ 66 ]  Abiomed as of 2019 only markets heart pumps, [ 67 ]  "intended to help pump blood in patients who need short-term support (up to 6 days)", [ 68 ]  which are not total artificial hearts.


On March 12, 2011, an experimental artificial heart was implanted in 55-year-old Craig Lewis at The Texas Heart Institute in Houston by  O. H. Frazier  and  William Cohn . The device was a combination of two modified  HeartMate II  pumps which had undergone  bovine trials . [ 69 ]


So far, only one person has benefited from Frazier and Cohn's artificial heart. Craig Lewis had  amyloidosis  in 2011 and sought treatment. After obtaining permission from his family, Frazier and Cohn replaced his heart with their device. Lewis survived for another 5 weeks after the operation; he eventually died from liver and kidney failure due to his amyloidosis, after which his family asked that his artificial heart be unplugged. [ 70 ]


On July 10, 2017, Nicholas Cohrs and colleagues presented a new concept of a soft total artificial heart in the Journal of Artificial Organs. [ 71 ]  The heart was developed in the Functionals Materials Laboratory at  ETH Zurich . [ 72 ]  (Cohrs was listed as a doctoral student in a group led by Professor Wendelin Stark at ETH Zurich.) [ 73 ]


The soft artificial heart (SAH) is a silicone monoblock fabricated with the help of  3D bioprinting  technology. It weighs 390g, has a volume of 679 cm 3,  and is operated through pressurized air. "Our goal is to develop an artificial heart that is roughly the same size as the patient's own one and which imitates the human heart as closely as possible in form and function", Cohrs said in an interview. [ 74 ]  The SAH fundamentally moves and works like a natural heart, but the prototype only performed for 3000 beats (about 30 to 50 minutes at an average heart rate) [ 75 ]  in a hybrid mock circulation machine [ citation needed ]  before the silicone membrane (2.3 mm thick) between the Left Ventricle and the Air Expansion Chamber ruptured. [ 76 ]


The working life of a more recent Cohrs prototype (using various polymers instead of silicone) [ citation needed ]  was still limited, according to reports in early 2018, with that model providing a useful life of 1 million heartbeats, roughly ten days in a human body. [ 77 ]  At the time, Cohrs and his team were experimenting with CAD software and 3D printing, striving to develop a model that would last up to 15 years. "We cannot really predict when we could have a final working heart which fulfills all requirements and is ready for implantation. This usually takes years", said Cohrs. [ citation needed ]


Founded in 2008, the BiVACOR company has been developing a total artificial heart based on a rotary centrifugal pump. Artificial heart researchers and cardiologists O. H. Frazier and William Cohn are on the board of the BiVACOR company. The BiVACOR heart seeks to improve the artificial heart by using a magnetically levitated impeller which reduces clotting and only has a single moving part. This also reduces size and complexity, as well as only requiring a battery pack to run. The BiVACOR heart is not pulsatile like previous hearts and contains no valves, but is capable of generating “beats” by rapidly changing the speed of the impeller. [ 78 ] [ 79 ]  BiVACOR has been tested as a replacement for a heart in a sheep. [ 80 ] [ 81 ]


On November 10, 2023, the BiVACOR heart received FDA authorization under the investigational device exemption for use in human trials. [ 82 ]  In July 2024, a successful implantation of the BiVACOR artificial heart in a 57-year-old man with end-stage heart failure was conducted as part of its first-in-human clinical study at  Baylor St. Luke's Medical Center , with four more patients expected to be enrolled in the study. [ 83 ] [ 84 ]  A few weeks later, the second person, a 34-year-old man, had a BiVACOR artificial heart implanted at  Duke University Hospital  as a successful bridge to a heart transplant 10 days later. [ 85 ]


A  centrifugal pump [ 86 ] [ 87 ]  or an  axial-flow pump [ 88 ] [ 89 ]  can be used as an artificial heart, resulting in the patient being alive without a  pulse .


A centrifugal artificial heart which alternately pumps the  pulmonary circulation  and the  systemic circulation , causing a pulse, has been described. [ 90 ]


Researchers have constructed a heart out of foam. The heart is made out of flexible silicone and works with an external pump to push air and fluids through the heart. It currently cannot be implanted into humans, but offers a new concept in artificial hearts. [ 91 ]


Patients who have some remaining heart function but who can no longer live normally may be candidates for ventricular assist devices (VAD), which do not replace the human heart but complement it by taking up much of the function. [ 1 ]


The first Left Ventricular Assist Device (LVAD) system was created by  Domingo Liotta  at  Baylor College of Medicine  in  Houston  in 1962. [ 92 ]


Another VAD, the Kantrowitz CardioVad, designed by  Adrian Kantrowitz , boosts the native heart by taking up over 50% of its function. [ 93 ]  Additionally, the VAD can help patients on the wait list for a heart transplant. In a young person, this device could delay the need for a transplant by 10–15 years, or even allow the heart to recover, in which case the VAD can be removed. [ 93 ]  The artificial heart is powered by a battery that needs to be changed several times while still working. [ citation needed ]


The first heart assist device was approved by the FDA in 1994, and two more received approval in 1998. [ 94 ]  While the original assist devices emulated the pulsating heart, newer versions, such as the Heartmate II, [ 95 ]  developed by The Texas Heart Institute of Houston, provides continuous flow. These pumps (which may be  centrifugal  or  axial flow ) are smaller and potentially more durable and last longer than the current generation of total heart replacement pumps. Another major advantage of a VAD is that the patient keeps the natural heart, which may still function for temporary back-up support if the mechanical pump were to stop. This may provide enough support to keep the patient alive until a solution to the problem is implemented. [ citation needed ]


In August 2006, an artificial heart was implanted into a 15-year-old girl at the  Stollery Children's Hospital  in  Edmonton ,  Alberta . It was intended to act as a temporary fixture until a donor heart could be found. Instead, the artificial heart (called a  Berlin Heart ) allowed for natural processes to occur and her heart healed on its own. After 146 days, the Berlin Heart was removed, and the girl's heart functioned properly on its own. [ 96 ]  On 16 December 2011 the Berlin Heart gained U.S.  FDA  approval. The device has since been successfully implanted in several children including a 4-year-old Honduran girl at  Children's Hospital Boston . [ 97 ]


Several continuous-flow ventricular assist devices have been approved for use in the European Union, and, as of August 2007, were undergoing clinical trials for FDA approval.


In 2012, Craig Lewis, a 55-year-old Texan, presented at the  Texas Heart Institute  with a severe case of  cardiac amyloidosis . He was given an experimental continuous-flow artificial heart transplant which saved his life. Lewis died 5 weeks later of liver failure after slipping into a coma due to the  amyloidosis . [ 98 ]


In 2012, a study published in the New England Journal of Medicine compared the Berlin Heart to extracorporeal membrane oxygenation (ECMO) and concluded that "a ventricular assist device available in several sizes for use in children as a bridge to heart transplantation [such as the Berlin Heart] was associated with a significantly higher rate of survival as compared with ECMO." [ 99 ]  The study's primary author, Charles D. Fraser Jr., surgeon in chief at Texas Children's Hospital, explained: "With the Berlin Heart, we have a more effective therapy to offer patients earlier in the management of their heart failure. When we sit with parents, we have real data to offer so they can make an informed decision. This is a giant step forward." [ 100 ]


Suffering from end-stage heart failure, former Vice President  Dick Cheney  underwent a procedure at INOVA Fairfax Hospital, in Fairfax Virginia in July 2010, to have a Heartmate II VAD implanted. [ 1 ]  In 2012, he received a heart transplant at age 71 after 20 months on a waiting list.


An  artificial heart valve  is a  one-way valve   implanted  into a person's  heart  to replace a  heart valve  that is not functioning properly ( valvular heart disease ). Artificial heart valves can be separated into three broad classes: mechanical heart valves, bioprosthetic tissue valves and engineered tissue valves.


The human heart contains four valves:  tricuspid valve ,  pulmonary valve ,  mitral valve  and  aortic valve . Their main purpose is to keep blood flowing in the proper direction through the heart, and from the heart into the major blood vessels connected to it (the  pulmonary artery  and the  aorta ). Heart valves can malfunction for a variety of reasons, which can impede the flow of blood through the valve ( stenosis ) and/or let blood flow backwards through the valve ( regurgitation ). Both processes put strain on the heart and may lead to serious problems, including  heart failure . While some dysfunctional valves can be treated with drugs or repaired, others need to be replaced with an artificial valve. [ 2 ]


A heart contains four valves (tricuspid, pulmonary, mitral and aortic valves) which open and close as blood passes through the heart. [ 3 ]  Blood enters the heart in the right atrium and passes through the  tricuspid valve  to the right ventricle. From there, blood is pumped through the  pulmonary valve  to enter the lungs. After being oxygenated, blood passes to the left atrium, where is it pumped through the  mitral valve  to the left ventricle. The left ventricle pumps blood to the aorta through the  aortic valve .


There are many potential causes of heart valve damage, such as birth defects, age related changes, and effects from other disorders, such as rheumatic fever and infections causing  endocarditis .  High blood pressure  and heart failure which can enlarge the heart and arteries, and scar tissue can form after a  heart attack  or injury. [ 4 ]


The three main types of artificial heart valves are mechanical, biological (bioprosthetic/tissue), and tissue-engineered valves. In the US, UK and the European Union, the most common type of artificial heart valve is the bioprosthetic valve. Mechanical valves are more commonly used in Asia and Latin America. [ citation needed ]  Companies that manufacture heart valves include Edwards Lifesciences, [ 5 ]  Medtronic, [ 6 ]  Abbott (St. Jude Medical), [ 7 ]  CryoLife, [ 8 ]  and LifeNet Health. [ 9 ]


Mechanical valves come in three main types – caged ball, tilting-disc and bileaflet – with various modifications on these designs. [ 10 ]  Caged ball valves are no longer implanted. [ 11 ]  Bileaflet valves are the most common type of mechanical valve implanted in patients today. [ 12 ]


The first artificial heart valve was the caged ball valve, a type of  ball check valve , in which a ball is housed inside a cage. When the heart contracts and the blood pressure in the chamber of the heart exceeds the pressure on the outside of the chamber, the ball is pushed against the cage and allows blood to flow. When the heart finishes contracting, the pressure inside the chamber drops and the ball moves back against the base of the valve forming a seal.


In 1952,  Charles A. Hufnagel  implanted caged ball heart valves into ten patients (six of whom survived the operation), marking the first success in prosthetic heart valves. [ citation needed ]  A similar valve was invented by Miles 'Lowell' Edwards and  Albert Starr  in 1960, commonly referred to as the Starr-Edwards silastic ball valve. [ 13 ]  This consisted of a silicone ball enclosed in a  methyl metacrylate  cage welded to a ring. The Starr-Edwards valve was first implanted in a human on August 25, 1960, and was discontinued by Edwards Lifesciences in 2007. [ 13 ]


Caged ball valves are strongly associated with blood clot formation, so people who have one required a high degree of  anticoagulation , usually with a target  INR  of 3.0–4.5. [ 14 ]


Introduced in 1969, the first clinically available tilting-disc valve was the  Bjork-Shiley valve . [ 15 ]  Tilting‑disc valves, a type of  swing check valve , are made of a metal ring covered by an  ePTFE  fabric. The metal ring holds, by means of two metal supports, a disc that opens when the heart beats to let blood flow through, then closes again to prevent blood flowing backwards. The disc is usually made of an extremely hard carbon material ( pyrolytic carbon ), enabling the valve to function for years without wearing out. [ citation needed ]


Introduced in 1979, bileaflet valves are made of two semicircular leaflets that revolve around struts attached to the valve housing. With a larger opening than caged ball or tilting-disc valves, they carry a lower risk of blood clots. They are, however, vulnerable to blood backflow. [ citation needed ]


The major advantage of mechanical valves over bioprosthetic valves is their greater durability. [ 16 ]  Made from metal and/or  pyrolytic carbon , [ 10 ]  they can last 20–30 years. [ 16 ]


One of the major drawbacks of mechanical heart valves is that they are associated with an increased risk of  blood clots . Clots formed by red blood cell and platelet damage can block blood vessels leading to  stroke . People with mechanical valves need to take anticoagulants (blood thinners), such as  warfarin , for the rest of their life. [ 16 ]  Mechanical heart valves can also cause  mechanical hemolytic anemia , a condition where the  red blood cells  are damaged as they pass through the valve. [ citation needed ]   Cavitation , the rapid formation of microbubbles in a fluid such as blood due to a localized drop of pressure, can lead to mechanical heart valve failure, [ 17 ]  so cavitation testing is an essential part of the valve design verification process.


Many of the complications associated with mechanical heart valves can be explained through  fluid mechanics . For example, blood clot formation is a side effect of high  shear stresses  created by the design of the valves. From an engineering perspective, an ideal heart valve would produce minimal pressure drops, have small regurgitation volumes, minimize turbulence, reduce prevalence of high stresses, and not create flow separations in the vicinity of the valve. [ citation needed ]


Implanted mechanical valves can cause foreign body rejection. The blood may coagulate and eventually result in a hemostasis. The usage of anticoagulation drugs will be interminable to prevent thrombosis. [ 18 ] [ non-primary source needed ]


Bioprosthetic valves are usually made from animal tissue (heterograft/ xenograft ) attached to a metal or polymer support. [ 11 ]  Bovine (cow) tissue is most commonly used, but some are made from porcine (pig) tissue. [ 19 ] [ non-primary source needed ]  The tissue is treated to prevent rejection and  calcification . [ citation needed ]


Alternatives to animal tissue valves are sometimes used, where valves are used from human donors, as in aortic  homografts  and pulmonary  autografts . An aortic homograft is an aortic valve from a human donor, retrieved either after their death or from a heart that is removed to be replaced during a heart transplant. [ 12 ]  A pulmonary autograft, also known as the  Ross procedure , is where the aortic valve is removed and replaced with the patient's own  pulmonary valve  (the valve between the right ventricle and the pulmonary artery). A pulmonary homograft (a pulmonary valve taken from a cadaver) is then used to replace the patient's own pulmonary valve. This procedure was first performed in 1967 and is used primarily in children, as it allows the patient's own pulmonary valve (now in the aortic position) to grow with the child. [ 12 ]


Bioprosthetic valves are less likely than mechanical valves to cause blood clots, so do not require lifelong anticoagulation. As a result, people with bioprosthetic valves have a lower risk of bleeding than those with mechanical valves. [ 16 ]


Tissue valves are less durable than mechanical valves, typically lasting 10–20 years. [ 20 ]   This means that people with bioprosthetic valves have a higher incidence of requiring another aortic valve replacement in their lifetime. [ 16 ]  Bioprosthetic valves tend to deteriorate more quickly in younger patients. [ 21 ]


In recent years, scientists have developed a new tissue preservation technology, with the aim of improving the durability of bioprosthetic valves. In sheep and rabbit studies, tissue preserved using this new technology had less  calcification  than control tissue. [ 22 ]  A valve containing this tissue is now marketed, but long-term durability data in patients are not yet available. [ 23 ] [ non-primary source needed ]


Current bioprosthetic valves lack longevity, and will calcify over time. [ 24 ]  When a valve calcifies, the valve cusps become stiff and thick and cannot close completely. [ 24 ]  Moreover, bioprosthetic valves can't grow with or adapt to the patient: if a child has bioprosthetic valves they will need to get the valves replaced several times to fit their physical growth. [ 24 ]


For over 30 years researchers have been trying to grow heart valves  in vitro . [ 25 ]  These tissue‑engineered valves involve seeding human cells on to a scaffold. [ 25 ]  The two main types of scaffold are natural scaffolds, such as decellularized tissue, or scaffolds made from degradable polymers. [ 26 ]  The scaffold acts as an  extracellular matrix , guiding tissue growth into the correct 3D structure of the heart valve. [ 26 ] [ 25 ]  Some tissue-engineered heart valves have been tested in clinical trials, [ 26 ]  but none are commercially available.


Tissue engineered heart valves can be person-specific and 3D modeled to fit an individual recipient [ 27 ]  3D printing is used because of its high accuracy and precision of dealing with different biomaterials. [ 27 ]  Cells that are used for tissue engineered heart valves are expected to secrete the extracellular matrix (ECM). [ 24 ]  Extracellular matrix provides support to maintain the shape of the valves and determines the cell activities. [ 28 ]


Scientists can follow the structure of heart valves to produce something that looks similar to them, but since tissue engineered valves lack the natural cellular basis, they either fail to perform their functions like natural heart valves, or function when they are implanted but gradually degrade over time. [ citation needed ]  An ideal tissue engineered heart valve would be non-thrombogenic, biocompatible, durable, resistant to calcification, grow with the surrounding heart, and exhibit a physiological hemodynamic profile. [ 29 ]  To achieve these goals, the scaffold should be carefully chosen—there are three main candidates: decellularized ECM (xenografts or homografts), natural polymers, and synthetic polymers. [ 29 ]


Mechanical and tissue valves are made of different materials. Mechanical valves are generally made of titanium and carbon. [ 30 ]  Tissue valves are made up of human or animal tissue. The valves composed of human tissue, known as allografts or homografts, are from donors' human hearts. [ 30 ]


Mechanical valves can be a better choice for younger people and people at risk of valve deterioration due to its durability. It is also preferable for people who are already taking blood thinners and people who would be unlikely to tolerate another valve replacement operation. [ citation needed ]


Tissue valves are better for older age groups as another valve replacement operation may not be needed in their lifetime. Due to the risk of forming blood clots for mechanical valves and severe bleeding as a major side effect of taking blood-thinning medications, people who have a risk of blood bleeding and are not willing to take warfarin may also consider tissue valves. Other patients who may be more suitable for tissue valves are people who have other planned surgeries and unable to take blood-thinning medications. People who plan to become pregnant may also consider tissue valves as warfarin causes risks in pregnancy. [ citation needed ]


An artificial heart valve should ideally function like a natural heart valve. [ 11 ]  The functioning of natural heart valves is characterized by many advantages:


The performance of an artificial heart valve can be tested  in vitro  before clinical use by means of a  pulse duplicator . [ 32 ]


Artificial heart valves are expected to last from 10 to 30 years. [ 16 ]


The most common problems with artificial heart valves are various forms of degeneration, including gross billowing of leaflets, ischemic mitral valve pathology, and minor chordal lengthening. [ 24 ]  The repairing process of the artificial heart valve regurgitation and stenosis usually requires an open-heart surgery, and a repair or partial replacement of regurgitant valves is usually preferred. [ 24 ]


Researchers are investigating catheter-based surgery that allows repair of an artificial heart valve without large incisions. [ 33 ]


Researchers are investigating Interchangeable Prosthetic Heart Valve that allows redo and fast-track repair of an artificial heart valve.  [ 34 ]


Atrial flutter  ( AFL ) is a common  abnormal heart rhythm  that starts in the  atrial chambers  of the  heart . [ 1 ]   When it first occurs, it is usually associated with a  fast heart rate  and is classified as a type of  supraventricular tachycardia . [ 2 ]  Atrial flutter is characterized by a sudden-onset (usually) regular abnormal heart rhythm on an  electrocardiogram  (ECG) in which the heart rate is fast. Symptoms may include  a feeling of the heart beating too fast, too hard, or skipping beats , chest discomfort,  difficulty breathing , a feeling as if one's stomach has dropped, a feeling of being light-headed, or  loss of consciousness .


Although this abnormal heart rhythm typically occurs in individuals with cardiovascular disease (e.g.,  high blood pressure ,  coronary artery disease , and  cardiomyopathy ) and  diabetes mellitus , it may occur spontaneously in people with otherwise normal hearts. It is typically not a stable rhythm and often degenerates into  atrial fibrillation  (AF). [ 3 ]   But rarely does it persist for months or years. Similar to the abnormal heart rhythm atrial fibrillation, atrial flutter also leads to poor contraction of the atrial chambers of the heart. This leads to the pooling of the blood in the heart and can lead to the formation of  blood clots  in the heart, which poses a significant risk of  breaking off and traveling through the bloodstream , resulting in  strokes .


A supraventricular tachycardia with a ventricular heart rate of 150 beats per minute is suggestive (though not necessarily diagnostic) of atrial flutter. Administration of  adenosine  in the vein (intravenously) can help medical personnel differentiate between atrial flutter and other forms of supraventricular tachycardia. [ 2 ]  Immediate treatment of atrial flutter centers on slowing the heart rate with medications such as  beta blockers  (e.g.,  metoprolol ) or  calcium channel blockers  (e.g.,  diltiazem ) if the affected person is not having chest pain, has not lost consciousness, and if their blood pressure is normal (known as stable atrial flutter). If the affected person is having chest pain, has lost consciousness, or has  low blood pressure  (unstable atrial flutter), then an urgent  electrical shock to the heart  to restore a normal heart rhythm is necessary. Long-term  use of blood thinners  (e.g.,  warfarin  or  apixaban ) is an important component of treatment to reduce the risk of blood clot formation in the heart and resultant strokes. [ 3 ] [ 4 ]   Medications used to restore a normal heart rhythm (antiarrhythmics)  such as  ibutilide  effectively control atrial flutter about 80% of the time when they are started but atrial flutter recurs at a high rate (70–90% of the time) despite continued use. [ 1 ]  Atrial flutter can be treated more definitively with a technique known as  catheter ablation . This involves the insertion of a catheter through a vein in the groin which is followed up to the heart and is used to identify and interrupt the electrical circuit causing the atrial flutter (by creating a small burn and scar).


Atrial flutter was first identified as an independent medical condition in 1920 by the British physician  Sir Thomas Lewis  (1881–1945) and colleagues. [ 5 ]  AFL is the second most common pathologic supraventricular tachycardia but occurs at a rate less than one-tenth of the most common supraventricular tachycardia (atrial fibrillation). [ 2 ] [ 3 ]  The overall incidence of AFL has been estimated at 88 cases per 100,000  person-years . The incidence of AFL is significantly lower (~5 cases/100,000 person-years) in those younger than age 50 and is far more common (587 cases/100,000 person-years) in those over 80 years of age. [ 3 ]


While atrial flutter can sometimes go unnoticed, its onset is often marked by characteristic sensations of the heart feeling like it is  beating too fast or hard .  Such sensations usually last until the episode resolves, or until the heart rate is controlled. [ 6 ]


Atrial flutter is usually well-tolerated initially (a high heart rate is, for most people just a normal response to exercise); however, people with other underlying heart diseases (such as  coronary artery disease ) or poor exercise tolerance may rapidly develop symptoms, such as  shortness of breath , chest pain, lightheadedness or dizziness,  nausea  and, in some patients, nervousness and feelings of impending doom. [ 6 ]


Prolonged atrial flutter with fast heart rates may lead to decompensation with loss of normal heart function ( heart failure ). This may manifest as exercise intolerance (exertional breathlessness), difficulty breathing at night, or swelling of the legs and/or abdomen. [ 6 ]


Although often regarded as a relatively benign heart rhythm problem, atrial flutter shares the same complications as the related condition  atrial fibrillation .  There is a paucity of published data directly comparing the two, but overall mortality in these conditions appears to be very similar. [ 7 ]


Rapid heart rates may produce significant symptoms in patients with pre-existing heart disease and can lead to  inadequate blood flow to the heart muscle  and even  a heart attack . [ 1 ]


In rare situations, atrial flutter associated with a fast heart rate persists for an extended period of time without being corrected to a normal heart rhythm and leads to a  tachycardia-induced cardiomyopathy . [ 1 ]  Even in individuals with a normal heart, if the heart beats too quickly for a prolonged period of time, this can lead to ventricular decompensation and heart failure. [ citation needed ]


Because there is little, if any, effective contraction of the  atria , there is stasis (pooling) of blood in the atria.  Stasis of blood in susceptible individuals can lead to the formation of a  thrombus  (blood clot) within the heart. A thrombus is most likely to form in the  atrial appendages . A blood clot in the left atrial appendage is particularly important as the left side of the heart supplies blood to the entire body through the arteries. Thus, any thrombus material that dislodges from this side of the heart can  embolize (break off and travel)  to the brain's arteries, with the potentially devastating consequence of a  stroke . Thrombus material can embolize to any other portion of the body, though usually with a less severe outcome. [ 8 ]


Sudden death is not directly associated with atrial flutter.  However, in individuals with a pre-existing accessory conduction pathway, such as the  bundle of Kent  in  Wolff-Parkinson-White syndrome , the accessory pathway  may  conduct activity from the atria to the ventricles at a rate that the AV node would usually block.  Bypassing the AV node, the atrial rate of 300 beats/minute leads to a ventricular rate of 300 beats/minute (1:1 conduction).  Even if the ventricles are able to sustain a cardiac output at such a high rate, 1:1 flutter with time may degenerate into  ventricular fibrillation , causing hemodynamic collapse and  death . [ 9 ]


Atrial flutter is caused by a  re-entrant rhythm . This usually occurs along the cavo-tricuspid isthmus of the right atrium though atrial flutter can originate in the left atrium as well. Typically initiated by a  premature electrical impulse arising in the atria , atrial flutter is propagated due to differences in  refractory periods  of atrial tissue. This creates electrical activity that moves in a localized self-perpetuating loop, which usually lasts about 200 milliseconds for the complete circuit. For each cycle around the loop,  an electric impulse results and propagates through the atria. [ citation needed ]


The impact and symptoms of atrial flutter depend on the heart rate of the affected person. Heart rate is a measure of ventricular rather than atrial activity. Impulses from the atria are conducted to the ventricles through the  atrio-ventricular node (AV node) . In a person with atrial flutter, a 12-lead  electrocardiogram (ECG)  will demonstrate the atrial chambers of the heart contracting at a rate of 280–300 beats per minute whereas the ventricular chambers of the heart typically beat at a rate of 140–150 beats per minute. [ 2 ]  Due primarily to its longer refractory period, the AV node exerts a protective effect on heart rate by blocking atrial impulses in excess of about 180 beats/minute, for the example of a resting heart rate. (This block is dependent on the age of the patient and can be calculated roughly by subtracting patient age from 220).  If the flutter rate is 300 beats per minute, only half of these impulses will be conducted, giving a ventricular rate of 150 beats per minute, or a 2:1  heart block .  The addition of rate-controlling drugs or conduction system disease can increase this block substantially [ 10 ]


Typical atrial flutter is recognized on an electrocardiogram by the presence of characteristic "flutter waves" at a regular rate of 250 to 350 beats per minute. Flutter waves may not be evident on an ECG in atypical forms of atrial flutter. Individual flutter waves may be symmetrical, resembling p-waves, or maybe asymmetrical with a "sawtooth" shape, rising gradually and falling abruptly or vice versa. If atrial flutter is suspected clinically but is not clearly evident on ECG, acquiring a  Lewis lead  ECG may be helpful in revealing flutter waves. [ citation needed ]


There are two types of atrial flutter, the common  type I  and rarer  type II . [ 11 ]   Most individuals with atrial flutter will manifest only one of these.  Rarely someone may manifest both types; however, they can manifest only one type at a time. [ citation needed ]


Type I atrial flutter, also known as common atrial flutter or typical atrial flutter, has an atrial rate of 240 to 340 beats/minute.  However, this rate may be slowed by  antiarrhythmic agents . [ citation needed ]


The reentrant loop circles the right atrium, passing through the  cavo-tricuspid isthmus  – a body of fibrous tissue in the lower atrium between the  inferior vena cava , and the  tricuspid valve . [ 1 ]   Type I flutter is further divided into two subtypes, known as counterclockwise atrial flutter and clockwise atrial flutter depending on the direction of current passing through the loop. [ 1 ]


Type II (atypical) atrial flutter follows a significantly different re-entry pathway to type I flutter, and is typically faster, usually 340–350 beats/minute. [ 12 ]  Atypical atrial flutter rarely occurs in people who have not undergone previous heart surgery or previous catheter ablation procedures. Left atrial flutter is considered atypical and is common after incomplete left atrial ablation procedures. [ 13 ]  Atypical atrial flutter originating from the right atrium and heart's septum have also been described. [ citation needed ]


In general, atrial flutter should be  managed in the same way as atrial fibrillation .  Because both rhythms can lead to the formation of a  blood clot  in the atrium, individuals with atrial flutter usually require some form of  anticoagulation  or  antiplatelet  agent.  Both rhythms can be associated with dangerously fast heart rates and thus require medication to control the heart rate (such as  beta blockers  or  calcium channel blockers ) and/or rhythm control with  class III antiarrhythmics  (such as  ibutilide  or  dofetilide ). However, atrial flutter is more resistant to correction with such medications than atrial fibrillation. [ 1 ]  For example, although the class III antiarrhythmic agent ibutilide is an effective treatment for atrial flutter, rates of recurrence after treatment are quite high (70–90%). [ 1 ]   Additionally, there are some specific considerations particular to treatment of atrial flutter. [ citation needed ]


Atrial flutter is considerably more sensitive to electrical  direct current cardioversion  than atrial fibrillation, with a shock of only 20 to 50 Joules commonly being enough to cause a return to a normal heart rhythm (sinus rhythm). Exact placement of the pads does not appear important. [ 14 ]