On December 6, 1967, at  Maimonides Hospital  in Brooklyn, New York,  Adrian Kantrowitz  performed the world's first  pediatric  heart transplant. [ 16 ] [ 20 ]  The infant's new heart stopped beating after 7 hours and could not be restarted. At a following press conference, Kantrowitz emphasized that he did not consider the operation a success. [ 21 ]


Norman Shumway performed the first adult heart transplant in the United States on January 6, 1968, at the  Stanford University Hospital . [ 16 ]  A team led by  Donald Ross  performed the first heart transplant in the United Kingdom on May 3, 1968. [ 22 ]  These were  allotransplants ,  the technical term for a transplant from a non-genetically identical individual of the same species.  Brain death  is the current ethical standard for when a heart donation can be allowed.


Worldwide, more than 100 transplants were performed by various doctors during 1968. [ 23 ]  Only a third of these patients lived longer than three months. [ 24 ]


The next big breakthrough came in 1983 when  cyclosporine  entered widespread usage. This drug enabled much smaller amounts of  corticosteroids  to be used to prevent many cases of rejection (the "corticosteroid-sparing" effect of cyclosporine). [ 25 ]


On June 9, 1984, "JP" Lovette IV of  Denver ,  Colorado , became the world's first successful pediatric heart transplant.  Columbia-Presbyterian Medical Center  surgeons transplanted the heart of 4-year-old John Nathan Ford of Harlem into 4-year-old JP a day after the Harlem child died of injuries received in a fall from a fire escape at his home. JP was born with multiple heart defects. The transplant was done by a surgical team led by Dr. Eric A. Rose, director of cardiac transplantation at  New York–Presbyterian Hospital . Drs. Keith Reemtsma and Fred Bowman also were members of the team for the six-hour operation. [ 26 ]


In 1988, the first "domino" heart transplant was performed, in which a patient in need of a lung transplant with a healthy heart would receive a  heart-lung transplant , and their original heart would be transplanted into someone else. [ 27 ]


Worldwide, about 3,500 heart transplants are performed annually. The majority of these are performed in the United States (2,000–2,300 annually). [ 2 ]   Cedars-Sinai Medical Center  in Los Angeles, California, currently is the largest heart transplant center in the world, having performed 132 adult transplants in 2015 alone. [ 28 ]  About 800,000 people have  NYHA Class IV heart failure symptoms  indicating advanced heart failure. [ 29 ]  The great disparity between the number of patients needing transplants and the number of procedures being performed spurred research into the transplantation of non-human hearts into humans after 1993.  Xenografts  from other species and  artificial hearts  are two less successful alternatives to  allografts . [ 3 ]


The ability of medical teams to perform transplants continues to expand. For example,  Sri Lanka 's first heart transplant was successfully performed at the  Kandy General Hospital  on July 7, 2017. [ 30 ]  In recent years, donor heart preservation has improved and Organ Care System is being used in some centers in order to reduce the harmful effect of cold storage. [ 31 ]


During heart transplant, the  vagus nerve  is severed, thus removing  parasympathetic  influence over the  myocardium . However, some limited return of  sympathetic nerves  has been demonstrated in humans. [ 32 ]


Recently, Australian researchers found a way to give more time for a heart to survive prior to the transplant, almost double the time. [ 33 ]
Heart transplantation using donation after circulatory death (DCD) was recently adopted and can help in reducing waitlist time while increasing transplant rate. [ 34 ]  Critically ill patients that are unsuitable for heart transplantation can be rescued and optimized with mechanical circulatory support, and bridged successfully to heart transplantation afterwards with good outcomes. [ 35 ]


On January 7, 2022,  David Bennett , aged 57, of Maryland became the first person to receive a gene-edited pig heart in a transplant at the  University of Maryland Medical Center . Before the transplant, David was unable to receive a human heart due to the patient's past conditions with heart failure and an irregular heartbeat, causing surgeons to use the pig heart that was genetically modified. [ 36 ] [ 37 ]  Bennett died two months later at University of Maryland Medical Center on March 8, 2022. [ 38 ] [ 39 ]
On April 19, 2023 Stanford Medicine surgeons performed the first beating-heart transplants from cardiac death donors. [ 40 ]


On December 11, 2024, in  Padua , Italy, the world's first heart transplant from a non-beating donor to a fully beating heart was performed. [ 41 ] [ 42 ]


Some patients are less suitable for a heart transplant, especially if they have other  circulatory  conditions related to their heart condition. The following conditions in a patient increase the chances of  complications . [ 43 ]


Absolute contraindications:


Relative contraindications:


Patients who are in need of a heart transplant but do not qualify may be candidates for an  artificial heart [ 2 ]  or a  left ventricular assist device  (LVAD).


Potential complications include: [ 46 ]


Since the transplanted heart originates from another organism, the recipient's immune system will attempt to reject it regardless if the donor heart matches the recipient's blood type (unless if the donor is an isograft). Like other solid organ transplants, the risk of rejection never fully goes away, and the patient will be on immunosuppressive drugs for the rest of their life. Usage of these drugs may cause unwanted side effects, such as an increased likelihood of contracting secondary infections or develop certain types of cancer. Recipients can acquire kidney disease from a heart transplant due to the side effects of immunosuppressant medications. Many recent advances in reducing complications due to tissue rejection stem from mouse heart transplant procedures. [ 49 ]


People who have had heart transplants are monitored in various ways to test for possible organ rejection. [ 50 ]


A 2022 pilot study [ 51 ]  examining the acceptability and feasibility of using video directly observed therapy to increase medication adherence in adolescent heart transplant patients showed promising results of 90.1% medication adherence compared to 40-60% typically. Higher medication variability levels can lead to greater organ rejections and other poor outcomes.


The prognosis for heart transplant patients following the orthotopic procedure has improved over the past 20 years, and as of June 5, 2009 the survival rates were: [ 52 ]


In 2007, researchers from the  Johns Hopkins University School of Medicine  discovered that "men receiving female hearts had a 15% increase in the risk of adjusted cumulative mortality" over five years compared to men receiving male hearts. Survival rates for women did not significantly differ based on male or female donors. [ 53 ]


Heart valve repair  is a  cardiac surgery  procedure, carried out to repair one or more faulty  heart valves . In some  valvular heart diseases  repair where possible is preferable to  valve replacement . A  mechanical heart valve  is a replacement valve that is not itself subject to repair.


Valvuloplasty  is the widening of a  stenotic valve  using a  balloon catheter . Types include: [ citation needed ]


Commissurotomy  of  heart valves  is called a  valvulotomy .


Mitral valve repair  is mainly used to treat  stenosis  (narrowing) or  regurgitation  (leakage) of the  mitral valve . [ citation needed ]  A mitral balloon valvuloplasty enlarges the valve opening to allow greater oxygenated blood flow into the left ventricle, and since severe mitral regurgitation can be a major complication, degrees of stenosis, regurgitation, and valve anatomical features are taken into consideration before the procedure. [ 1 ]


Aortic valve repair  is a  surgical procedure  used to correct some  aortic valve  disorders as an alternative to  aortic valve replacement . [ 2 ]  Aortic valve repair is performed less often and is more technically difficult than  mitral valve repair .
There are two surgical techniques of aortic-valve repair:


Tricuspid valve repair is used to correct  tricuspid regurgitation . [ 3 ]


The first two percutaneous ultrasound-guided fetal balloon valvuloplasties, a type of  in utero  surgery  for severe  aortic valve  obstruction, were reported in 1991. [ 4 ]


A  heart–lung transplant  is a procedure carried out to replace both failing  heart  and  lungs  in a single operation. Due to a shortage of suitable donors and because both heart and lung have to be transplanted together, it is a rare procedure; only about a hundred such transplants are performed each year in the United States. [ United States-centric ]


The patient is  anesthetised . When the donor organs arrive, they are checked for fitness; if any organs show signs of damage, they are discarded and the operation cancelled.


Once suitable donor organs are present, the surgeon makes an incision starting above and finishing below the sternum, cutting all the way to the bone. The skin edges are retracted to expose the sternum. Using a bone saw, the sternum is cut down the middle. Rib spreaders are inserted in the cut, and spread the ribs to give access to the heart and lungs of the patient.


The patient is connected to a  heart–lung machine , which circulates and oxygenates blood. The surgeon removes the failing heart and lungs. Most surgeons endeavour to cut blood vessels as close as possible to the heart to leave room for trimming, especially if the donor heart is of a different size than the original organ.


The donor heart and lungs are positioned and sewn into place. As the donor organs warm up to body temperature, the lungs begin to inflate. The heart may  fibrillate  at first – this occurs because the  cardiac muscle  fibres are not contracting synchronously. Internal paddles can be used to apply a small electric shock to the heart to restore proper rhythm.


Once the donor organs are functioning normally, the heart–lung machine is withdrawn, and the chest is closed.


Most candidates for heart–lung transplants have life-threatening damage to both their heart and lungs. In the US, most prospective candidates have between twelve and twenty-four months to live. At any one time, there are about 250 people registered for heart–lung transplantation at the  United Network for Organ Sharing  (UNOS) in the US, of which around forty will die before a suitable donor is found. [ citation needed ]


Conditions which may necessitate a heart–lung transplant include:


Candidates for a heart–lung transplant are usually required to be:


Most patients spend several days in  the intensive care unit  after the operation. If there are no complications (e.g.,  infection ,  rejection ), some are able to return home after just two weeks in hospital. Patients will be given  anti-rejection drugs  and  antibiotics  to prevent infection as the anti-rejection drugs weakens the immune system. A schedule of frequent follow up visits is necessary.


The success rate of heart–lung transplants has improved significantly in recent years. The British  National Health Service  states that the survival rate is now around 85%, one year after the transplant was performed. [ 1 ]


In 2004, there were only 39 heart–lung transplants performed in the entire United States and only 75 worldwide. By comparison, in that same year there were 2,016 heart and 1,173 lung transplants. [ 2 ]


Norman Shumway  laid the groundwork for heart lung transplant with his experiments into heart transplant at  Stanford  in the mid-1960s. [ citation needed ]  Shumway conducted the first adult heart transplant in the US in 1968. [ 3 ]


The first successful heart transplant was performed in South Africa in 1967. [ 4 ]  The first successful heart–lung transplant was performed at Stanford in the United States, by  Bruce Reitz  on  Mary Gohlke  in 1981. [ 5 ]


Magdi Yacoub  performed the first heart-lung transplant in the United Kingdom in 1983. [ 6 ]


Australia's first heart-lung transplant was conducted by  Victor Chang  at  St Vincent's Hospital, Sydney  in 1986. [ 7 ]  Iran's first heart-lung transplant was performed in Tehran in 2002. [ 8 ]


Warren C. Jyrch  (June 22, 1921, in  Illinois  – March 2, 1971, in  Chicago ,  Illinois [ 1 ] ) is known for being the first ever  hemophiliac  to ever attempt and survive an  open heart surgery . [ 2 ]  Due to the dangers of being a hemophiliac the surgery to replace Jyrch's  heart valve  was very risky. Another constraint of this surgery was the amount of blood needed, "2,400 pints of blood were necessary for Jyrch’s operation." Jyrch worked as an accountant for  Rock Island Railroad . He died on March 2, 1971, due to a  stroke ; it was later discovered that his death was not related to his surgery months before. Jyrch left behind his wife Helen, and his three daughters, Christine, Eileen, and Paula. [ 3 ]


The  Kawashima procedure  is used for  congenital heart disease  with a single effective ventricle and an  interrupted  inferior vena cava  (IVC).  It was first performed in 1978 and reported in 1984. [ 1 ]


Technically it is very similar to the  bidirectional Glenn procedure  used to direct half the body's venous blood flow into the lungs.  However, in patients with interrupted IVC, most of the blood from the lower body actually joins the blood from the upper body before returning to the heart via the  superior vena cava  (SVC).  Therefore, the redirection of SVC blood to the lungs (as in the Glenn) results in much more than half the venous blood flow  being diverted. [ citation needed ]


After Kawashima, the only de-oxygenated blood returning to the heart is from the abdominal organs (via the  hepatic veins ).  As a result, there is much less  hypoxia  than after Glenn, and the heart is pumping less additional blood than after Glenn.  However, the hypoxia can worsen over time (because of the development of microscopic  AVMs  in the lungs that allow blood to pass through without being oxygenated), [ 2 ]  and therefore these children still may need a complete  Fontan procedure  in the end. [ 3 ] [ 4 ]


The  LeCompte maneuver  is a technique used in  open heart surgery , primarily on infants and children. The maneuver entails cutting the main  pulmonary artery  and moving it  anterior  to the  aorta  before reattaching the pulmonary artery during the following reconstruction of the  great vessels . [ 1 ] [ 2 ]  It allows the surgeon to reconstruct the  right ventricular outflow tract  without needing to connect the proximal and distal sections with a  graft . [ 2 ] [ 3 ]  It also enables the surgeon to avoid compressing the  coronary arteries  and relieves compression of the  bronchi  in cases where the pulmonary artery is severely  dilated  or  aneurysmal . If both pulmonary arteries are not mobilized adequately, they can become stretched, leading to  pulmonic stenosis . [ 2 ]


Commonly, the maneuver is used during an  arterial switch  procedure (in which the pulmonary artery and aorta switch positions) or in surgery to correct  absent pulmonary valve syndrome . [ 1 ] [ 4 ]  It is also used in corrective surgeries for  Tetralogy of Fallot  where the pulmonary valve is anomalous,  persistent truncus arteriosus  with  aortopulmonary window  that affects the  aortic arch , left-to-right shunts, anomalous right pulmonary artery, and  ALCAPA  (anomalous left coronary artery from the pulmonary artery). Other surgeries that regularly employ the LeCompte maneuver include the  Yasui procedure ,  REV procedure , and  Nikaidoh operation , all of which are used to reconstruct hearts with an anomalous left ventricular outflow tract. [ 2 ]


The technique was first used in 1981 and described in 1982. [ 2 ] [ 3 ]


Minimally invasive cardiac surgery , encompasses various aspects of cardiac surgical procedures (aortic valve replacement, mitral valve repair, coronary artery bypass surgery, ascending aorta or aortic root surgery) that can be performed with minimally invasive approach either via mini-thoracotomy or mini-sternotomy. [ 1 ] [ 2 ]   MICS CABG  (Minimally Invasive Cardiac Surgery/Coronary Artery Bypass Grafting) or  the McGinn technique  is  heart surgery  performed through several small incisions instead of the traditional open-heart surgery that requires a  median sternotomy  approach, and can be performed in patients with multivessel coronary artery disease. [ 3 ]  MICS CABG is a beating-heart multi-vessel procedure performed under direct vision through an anterolateral mini-thoracotomy. [ 4 ]


Advantages of minimally invasive heart surgery are less blood loss, reduced post-operative discomfort, faster postoperative recovery and lower risk of infections, reduced duration of mechanical ventilation as well as eliminating the possibility for sternal non-union. This procedure makes heart surgery possible for patients who were previously considered too high risk for traditional surgery due to age or medical history. [ 5 ] [ 6 ]  Patients referred for this procedure may have coronary artery disease (CAD); aortic, mitral or tricuspid valve diseases; or previous unsuccessful stenting.


A recent meta-analysis of randomized controlled trials by Amin et al (2024) showed that minimally invasive mitral valve surgery (MIMVS) reduced the number of days spent in the hospital and demonstrated a trend towards lower postoperative pain scores, but it did not decrease the risk of all-cause mortality or the number of patients needing blood product transfusions. [ 7 ]


MICS CABG is performed through one 5–7 cm incision in the 4th  intercostal  space (ICS). In some cases the  thoracotomy  may be necessary in the 5th ICS instead. A soft tissue refractor is used to allow for greater visibility and access. MICS CABG may be completed in an "anaortic" or no-touch off-pump technique, which has demonstrated reduced postoperative stroke and mortality compared to traditional CABG. [ 8 ]


Two access incisions are also made at the 6th intercostal space and xiphoid process to allow for instruments to position and stabilize the heart. [ 4 ] [ 9 ]


The McGinn proximal technique is performed with the blood pressure lowered to 90-100 systolic which reduces stress to the aorta. A series of tools are used to position and stabilize vessels. The technique uses devices to support the surrounding heart tissues while vital surgery takes place. This is also known as off-pump CABG (OPCAB). OPCAB voids the use of cardiopulmonary bypass (CPB), which requires the heart to be stopped (arrested) with cardioplegia solution. Off-pump is also known as beating heart surgery. [ citation needed ]


Minimally invasive heart surgery has been used as an alternative to traditional surgery for the following procedures:


A cannula with a pump and vacuum action is fed up through an artery in the groin to reduce the stress on the heart so that it may still function during the operation. This pump flows at 2-3 liters per minute to support circulation and eliminates the need for  cardioplegia  to arrest the heart. [ citation needed ]


Hybrid coronary  revascularization  is a common procedure that takes advantage of coronary stenting in combination with CABG. Hybrid coronary bypass is a relatively new procedure and alternative to traditional bypass surgery that is defined by the performance of coronary bypass surgery and coronary stenting of different areas of a patient's heart. MICS CABG allows utilization of the left internal mammary artery (IMA; aka left internal thoracic artery, left ITA) to bypass the left anterior descending artery (LAD), which is termed as left IMA-LAD, as a preferable anastomosis whenever indicated and technically feasible (Loop et al.) and has been proven to benefit in event free survival (Acinapura et al.). The other one or two arteries will be stented, when appropriate, allowing cardiologists and cardiothoracic surgeons to work together. [ 10 ] [ 11 ]


After a minimally invasive procedure, patients recover more quickly than from sternotomy and develop fewer complications. Most patients can expect to resume everyday activities within a few weeks of their operation. After surgery, patients are administered an anaesthetic pain pump and drains that will be removed prior to discharge. Patients are encouraged to move around as much as possible after their operation to recover quickly. Once discharged from hospital, patients require no further post-operative assistance. [ 12 ]


Minimally invasive heart surgery is a safe and broadly applicable technique for performing a wide range of complex heart procedures, including single or multiple heart valve procedures, bypass surgery, and congenital heart repairs.


Eliminating the need for median sternotomy greatly reduces the trauma and pain associated with open-chest surgery and improves quality of life for patients. In the hospital, reduced post-operative discomfort enables patients to quickly begin a shorter recovery process. Most patients ambulate more easily and participate more actively in their personal care. Additionally, this approach lowers risk of complications such as bleeding, infection and eliminates the risk of sternal non-union. [ 13 ]


Minimally invasive heart surgery improves cosmetic results. Rather than a prominent 10-inch scar down the middle of the chest, patients are left with smaller marks to the side of the ribs. For women, in many cases, this scar is completely unnoticeable as it sits below the breast. [ 13 ]


Benefits Include:


At the 2014 International Society for Minimally Invasive Cardiothoracic Surgery Annual Meeting in Boston, Dr. Joseph T McGinn presented a study titled "Minimally Invasive CABG is Safe and Reproducible: Report on the First Thousand Cases," which found a low rate of conversion to sternotomy and low rate of complications. Assessing survival and adverse cardiac events up to 8.0 years (average 2.9±2.0 years), MICS CABG is a safe, reproducible operation that yields survival (96.1±0.9%) and durability comparable to conventional CABG. [ 14 ] [ 15 ]


The Journal of Thoracic and Cardiovascular Surgery published a study on November 1, 2013, that confirmed MICS CABG as safe, feasible, and associated with excellent graft patency rates at 6 months post surgery, with graft patency of 92% for all grafts and 100% for left internal thoracic artery grafts. Coronary artery bypass graft patency was studied through computed tomography angiography. 92% of patients were free from angina and none of the participants experienced any aortic complications, repeat revascularizations, cerebrovascular accidents, myocardial infarctions or death. The two-year study included 91 participants between the ages 48 and 79, averaging a hospital stay of 4 days (range, 3–9 days). Clinical Trial Registration Unique identifier: NCT01334866. [10] [ 16 ]


At 2012 American Heart Association's Scientific Sessions and Resuscitation Science Symposium, a study titled "Minimally Invasive CABG: Results to 6 Years" was presented, demonstrating MICS CABG feasibility and established alternative for multivessel sternotomy CABG. It was also noted that the procedure is associated with a short hospital length of stay, no deep wound infections and is safe. The study also proved survival and durability on par with sternotomy. [ 17 ]


At the 2010 International Society for Minimally Invasive Cardiothoracic Surgery Annual Meeting in Berlin, Germany, duel center data was presented the standardization of MICS CABG in performance and reproducibility of its results. Its safety and effective alternative for performing surgical myocardial revascularization on the beating heart (OPCAB) is emphasized. "Shortened hospital stay is starting to be realized and its application to high risk and complex patients is now being done." [ 18 ]


A 2009 publication in Circulation, titled "Minimally Invasive Coronary Artery Bypass Grafting: Dual-Center Experience in 450 Consecutive Patients" concluded MICS CABG as a feasible procedure with excellent short-term outcomes. At that time the study noted, "this operation could potentially make multivessel MICS CABG safe, effective and more widely available." [ 9 ]


Minimally invasive cardiac surgery was pioneered by Dr Joseph T McGinn, Jr. The first minimally invasive heart cardiac surgery was performed in the United States on January 21, 2005, at The Heart Institute at Staten Island University Hospital in Staten Island, New York by a team led by Dr. Joseph T. McGinn. This technique is an off-pump coronary artery bypass surgery. The procedure is much less invasive than traditional bypass surgery because it is performed through three small incisions rather than the traditional sternotomy. Since its first procedure, over 1000 MICS CABG procedures have been performed at The Heart Institute and elsewhere around the world. [ 6 ]  Other centers that utilize the MICS CABG technique for coronary heart disease are the University of Ottawa Heart Center (ON, Canada), Houston Methodist DeBakey Heart Center (Houston, TX), and Vanderbilt University Medical Center (Nashville, TN). [ 19 ] [ 20 ] [ 21 ]


Minimally invasive direct coronary artery bypass (MIDCAB)  is a surgical treatment for  coronary heart disease  that is a less invasive method of  coronary artery bypass surgery  (CABG). [ 1 ]  MIDCAB gains surgical access to the heart with a smaller  incision  than other types of CABG. MIDCAB is sometimes referred to as "keyhole"  heart surgery  because the operation is analogous to operating through a  keyhole .


MIDCAB is a form of  off-pump coronary artery bypass surgery  (OPCAB), performed "off-pump" – without the use of  cardiopulmonary bypass  (the heart-lung machine).  MIDCAB differs from OPCAB in the type of incision used for the surgery; with traditional CABG and OPCAB a  median sternotomy  (dividing the  breastbone ) provides access to the heart; with MIDCAB, the surgeon enters the chest cavity through a  mini-thoracotomy  (a 2-to-3 inch incision between the ribs).


MIDCAB surgery is no longer reserved for only anteriorly placed single- or double-vessel diseases, because such lesions are usually managed with  angioplasty . The surgery has recently begun to be used in multi-vessel coronary disease.


People with multi-vessel coronary disease, who desire a minimally invasive approach to surgery may be eligible for  hybrid bypass .  A hybrid approach combines coronary bypass (using the MIDCAB approach) and coronary  stenting .


Minimized extracorporeal circulation  ( MECC ) is a kind of  cardiopulmonary  bypass ( heart-lung machine ), a part of  heart surgery . [ 1 ]  The introduction of extracorporeal circulation has facilitated  open heart surgery . The development of modern techniques in extracorporeal circulation is the result of the combined efforts of physiologists, physicians, and engineers. During the first half of the 20th century scientists refined their methods in the development of extracorporeal circulation so that it could be used in humans.


In 1937 Gibbon reports the first successful use of extracorporeal circulation in animals (in this case, cats). On May 6, 1953 Gibbon performed his first successful operation using an extracorporeal circuit in an 18-year-old woman who had a large  atrial septum defect  with a large  left-to-right shunt . It was Lillehei  who one year later introduced the bubble oxygenator, simple and inexpensive, opening the doors of open heart surgery to all surgeons around the world.


The first commercial minimized extracorporeal circulation was the CorX System from Cardiovention, a start-up company from the USA. This system included an integrated  centrifugal pump  – polypropylene  oxygenator , a complete  heparin -coated surface and a low priming volume. One of the most effective Mini-Systems (MECC Maquet) was introduced almost at the same time (1999). The increasing application in clinical practice explains this machine's success. The benefits of this type of extracorporeal circulation are that a lower consumption of blood and blood products is observed in the  peri-operative  and post-operative phase and that a lower  inflammatory response  is being measured in peri-operative blood samples in comparison to conventional  cardiopulmonary bypass .


Mitral valve annuloplasty  is a surgical technique for the repair of leaking  mitral valves . Due to various factors, the two leaflets normally involved in sealing the mitral valve to retrograde flow may not  coapt  properly. Surgical repair typically involves the implantation of a device surrounding the mitral valve, called an annuloplasty device, which pulls the leaflets together to facilitate coaptation and aids to re-establish mitral valve function.


Mitral regurgitation  is the most common form of mitral valve dysfunction. Today more than 2.5 million Americans are estimated to be affected by mitral regurgitation. This number is expected to double by the year 2030. Every year, 300,000 people worldwide undergo open heart surgery for  mitral valve repair , 44,000 people in the US alone. [ 1 ]


Since it was initially established 40 years ago by Professor  Alain Carpentier , mitral valve annuloplasty has been continuously improved and is considered the gold standard for the treatment of most etiologies of mitral valve dysfunction today. [ 2 ]


The goal of mitral valve annuloplasty is to regain mitral valve competence by restoring the physiological form and function of the normal mitral valve apparatus. [ 3 ]  Under normal conditions the mitral valve undergoes significant dynamic changes in shape and size throughout the  cardiac cycle . These changes are primarily due to the dynamic motion of the surrounding mitral valve annulus, a collageneous structure which attaches the mitral leaflets and the left  atrium  to the  ostium  of the left ventricle and the  aortic root . [ citation needed ]


Throughout the cardiac cycle, the annulus undergoes a sphincter motion, narrowing down the orifice area during  systole  to facilitate coaptation of the two leaflets and widens during  diastole  to allow for easy diastolic filling of the left ventricle. This motion is further enhanced by a pronounced three-dimensional configuration during systole, the characteristic saddle shape. These changes throughout the cycle are believed to be key to optimize leaflet coaptation and to minimize tissue stresses. The challenge of mitral valve annuloplasty is to improve the diseased and distorted shape of the mitral valve and to reestablish the physiological configuration, while preserving normal annular dynamics. Today, cardiac surgeons can select from a variety of annuloplasty devices, flexible, semi-rigid, or rigid, incomplete or complete, planar or saddle-shaped, adjustable and non-adjustable. While the general goal of all devices is the same, namely to increase leaflet coaptation and to support the posterior annulus against dilation, flexible bands are designed to maintain the three-dimensional contour of the native annulus and some of its natural dynamics. The goal of semi-rigid rings is to maintain coaptation and valve integrity during systole, while allowing for good hemodynamics during diastole. Rigid rings are designed to provide rigid support in large dilation and under high-pressure. [ citation needed ]


Annuloplasty devices usually come in different sizes. The surgeon can estimate the dimensions of the patient’s mitral valve and decide on an appropriate ring size. Depending on the disease etiology, different approaches are taken. Surgeons can decide to "undersize" the device, "truesize" the device, or "oversize" it. [ 4 ]


Annuloplasty devices are classified by the U.S.  Food and Drug Administration  (FDA) as  class II  medical devices. [ 5 ]


Mitral valve repair  is a  cardiac surgery  procedure performed by  cardiac surgeons  to treat  stenosis  (narrowing) or  regurgitation  (leakage) of the  mitral valve . The mitral valve is the "inflow valve" for the left side of the  heart .  Blood  flows from the  lungs , where it picks up oxygen, through the  pulmonary veins , to the  left atrium  of the heart. After the left atrium fills with blood, the mitral valve allows blood to flow from the left atrium into the heart's main pumping chamber called the left  ventricle . It then closes to keep blood from leaking back into the left atrium or lungs when the ventricle contracts (squeezes) to push blood out to the body. It has two flaps, or leaflets, known as cusps.


The techniques of mitral valve repair include inserting a cloth-covered ring around the valve to bring the leaflets into contact with each other ( annuloplasty ), removal of redundant/loose segments of the leaflets (quadrangular resection), and re-suspension of the leaflets with artificial ( Gore-Tex ) cords.


Procedures on the mitral valve usually require a  median sternotomy , but advances in non-invasive methods (such as  keyhole surgery ) allow surgery without a sternotomy (and resulting pain and scar).   Minimally invasive mitral valve surgery  is much more technically demanding and may involve higher risk.


Occasionally, the mitral valve is abnormal from birth ( congenital ). More often the mitral valve becomes abnormal with age ( degenerative ) or as a result of  rheumatic fever . In rare instances the mitral valve can be destroyed by infection or a bacterial  endocarditis . Mitral regurgitation may also occur as a result of  ischemic heart disease  (coronary artery disease) or non-ischemic heart disease (dilated cardiomyopathy).


In 1923 Dr.  Elliott Cutler  of the  Peter Bent Brigham Hospital  performed the world’s first successful heart valve surgery – a mitral valve  repair . The patient was a 12-year-old  comatose  girl with  rheumatic mitral stenosis . [ 1 ]


The development of the heart-lung machine in the 1950s paved the way for  replacement  of the mitral valve with an  artificial valve  in the 1960s. For decades after,  mitral valve replacement  was the only surgical option for patients with a severely diseased mitral valve. However, there are some significant downsides to a  prosthetic mitral valve . Infection of the valve can occur, which is dangerous and difficult to treat. Patients with mechanical heart valves are required to take  blood thinners  for the rest of their lives, which presents a risk of bleeding complications. The artificial mitral valve has an elevated risk of stroke. Patients with mechanical heart valves who use warfarin for anticoagulation have to be on long-term anticoagulation therapy.  This means they must go to the clinic and have a lab blood draw done, typically once a month but more frequently if the level needs to be closely monitored until it is in the therapeutic range.  The therapeutic range for most adults with a mechanical valve is an  INR  of 2.5–3.5. [ 2 ]  Finally, artificial tissue valves will wear out – on average lasting between 10 and 15 years, requiring further surgery at an advanced age.


In the past two decades, some surgeons have embraced surgical techniques to repair the damaged native valve, rather than replace it. These techniques were pioneered by a French heart surgeon,  Dr. Alain F. Carpentier . A repair still involves major cardiac surgery but for many patients presents the significant advantage of avoiding  blood thinners  and may provide a more durable result. However, some studies suggest that blood thinners like Warfarin can reduce a “composite of bleeding and  thromboembolic complications ” and potentially postoperative complications, as those taking Warfarin have shown “superior long-term survival estimates.” [ 3 ]   Not all damaged valves are suitable for repair; in some, the state of valve disease is too advanced and replacement is necessary.  Often, a surgeon must decide during the operation itself whether a  repair  or a  replacement  is the best course of action.  For patients with the most common type of mitral valve disease, termed "degenerative" or "myxomatous" mitral valve disease, repair rates are very high and long term durability is excellent. [ 4 ]


There has been great debate about timing of surgery in patients with asymptomatic mitral valve regurgitation.


The traditional surgical approach to a mitral valve repair is a full or partial  sternotomy , in which the surgeon cuts through the breastbone at the center of the chest to access the heart.  There are  minimally invasive  (port access) options available pioneered by Hugo Vanerman in Belgium.  The minimally invasive approach does not involve cutting the breastbone, but instead uses multiple incisions in the side of the chest and the leg. Cardiac surgeons are not unanimous about the relative merits of sternotomy versus the minimally invasive approach. The minimally invasive approach can produce a less prominent scar, is beneficial for very obese patients, and may allow the patient to return to their normal activity sooner than a sternotomy. But some cardiac surgeons argue that unless performed by the most experienced cardiac centers, minimally invasive surgery can involve a longer time on a bypass machine, a lower repair rate, and higher (although still low) risk of stroke. One cardiac surgery professor said, "I think the only benefit is for  cosmesis  for the patient and the benefit is for marketing and growing our practices for ourselves because it’s a good way to grow one's practice." [ 5 ]


Robotic mitral valve repair operations are also being utilized throughout the United States.


In the 2000s there have been several trials of a newer strategy of mitral valve repair that does not require major cardiac surgery. Through a catheter inserted in the groin, the valve leaflets are clipped together. This technique –  percutaneous  mitral valve repair – is available in Europe but still in clinical trial in the United States. It is a highly specialized technique only available at select hospitals. Early trial results suggest that it may be a beneficial approach for patients who are at high risk from conventional surgery. [ 6 ] [ 7 ]


As early as January 2000 a team of doctors [ 8 ]  at the  Instituto de Cardiología y Cirugía Cardiovascular  in  La Habana ,  Cuba  have performed beating heart mitral valve repair or replacement. The beating heart mitral valve replacement technique is as safe as the arrested heart technique, and is the recommended alternative to arrested heart technique. [ 9 ]


Mitral valve replacement  is a procedure whereby the diseased  mitral valve  of a patient's heart is  replaced  by either a mechanical or tissue (bioprosthetic) valve.


The mitral valve may need to be replaced because: [ citation needed ]


Causes of mitral valve disease include  infection ,  calcification  and inherited  collagen disease . Current mitral valve replacement approaches include  open heart surgery  and  minimally invasive cardiac surgery  (MICS).


The mitral valve is a bileaflet valve sited between the left  atrium  and left  ventricle , responsible for preventing blood flowing from the ventricle to the atrium when the heart contracts. It is elliptical, and its area varies from 5.0 to 11.4 cm 2 . The valve leaflets are separated by two  commissures , and each leaflet of the valve (anterior leaflet, the large one, and posterior leaflet, the small one) has three sections (p1, p2, p3). Histologically, each leaflet is composed of the solid fibrosa, the spongiosa at the atrial surface and another fibroelastic layer covering the leaflets. [ 1 ]  Two  papillary muscles  originating from the base of the left ventricle hold the mitral leaflets in place through  chordae tendinae , which insert the edge of the leaflets, preventing them from leaking during left ventricle  systole . [ 2 ]


During normal mitral valve function fluid jets from the  left atrium  through the mitral valve into the  left ventricle . The  vortex  created from this jetting travels towards the apex of the left ventricle because of the  asymmetric  shape of the mitral valve leaflets. This vortex rotates clockwise until the isovolumetric contraction of the left ventricle opens the aortic valve and redirects the fluid flow from the apex of the left ventricle to the  systemic circulation  and the rest of the body. [ citation needed ]


The asymmetry of the mitral valve is very important in the diastolic flow patterns of transmitral flow. Additionally the entire systems; the mitral annulus, papillary muscles and the chordae tendinea all play a vital role in forming a sophisticated vortex that optimizes the fluid flow in the left heart. Simulations have been performed showing how all of these aspects of the mitral valve contribute to the normal vortex formation in the left heart. [ 3 ] [ 4 ]


The most common cause of mitral stenosis is rheumatic fever, seen mostly in the developing world. Other causes are mitral degenerative disease, severe calcification (elderly), congenital deformities, malignant carcinoid syndrome,  neoplasm , left atrial appendage  thrombus , endocarditic vegetations, certain inherited metabolic diseases, or complications of previous procedures at the aortic valve. [ 5 ]  Mitral stenosis causes left atrial pressure to increase, which, if left untreated, can lead to ventricular dilation,  hypertrophy ,  atrial fibrillation , and  thrombus  creation. Symptoms include shortness of breath ( dyspnea ) on exertion, when lying flat ( orthopnea ) or during the night ( paroxysmal nocturnal dyspnea ), and fatigue. [ 6 ]


If mitral leaflets don't coapt (close) effectively, blood flows backwards (regurgitation) from the left ventricle towards the left atrium during systole. The most common causes are myxomatous degeneration (Barlow disease), ischemic heart disease, dilated cardiomyopathy, rheumatic valve disease, mitral annular calcification, infective endocarditis, congenital anomalies, endocardial fibrosis, myocarditis, and collagen-vascular disorders. [ 7 ]  The most used system to classify mitral valve regurgitation is Carpentier's classification, which separates mitral regurgitation into three types, depending on the leaflet motion in relation to the mitral annular plane: [ citation needed ]


There are two main types of artificial mitral valve: mechanical valves and tissue (bioprosthetic) valves. [ 8 ]  They come in various sizes (commonly starting from an external diameter of 19 mm and increasing by 2 mm per model). [ 9 ]


Mechanical valves are made from metal and/or pyrolitic carbon, [ 10 ]  and can last 20–30 years. [ 11 ]  The risk of blood clots forming is higher with mechanical valves than with bioprosthetic valves. As a result, patients with mechanical valves must take blood-thinning medication (anticoagulants) for the rest of their lives, making them more prone to bleeding. [ 11 ]


There are three types of mechanical valves:


Bileaflet valves are the most common type of mechanical valve, offering desirable haemodynamics. [ 12 ]  The two leaflets of a bileaflet disc valve open during  diastole  and close during  systole . [ citation needed ]


Bioprosthetic valves are made from animal tissues. Most people with bioprosthetic valves don’t need to take anticoagulants long term. However, bioprosthetic valves may only last 10–15 years. [ 11 ]  They tend to deteriorate more quickly in younger patients. [ 11 ]  Valve failure prevalence at 10 years is 30%, increasing to 35–65% at 15 years. [ 13 ]  New tissue preservation technologies are being studied to try to increase the durability of bioprosthetic valves. [ 14 ]


The choice of valve depends upon the patient's age, medical condition, preferences, and lifestyle. [ 11 ]  Typically, patients younger than 65 years old will receive a mechanical valve unless they are unable to take long-term anticoagulation, and patients older than 70 years will receive a bioprosthetic valve. [ 8 ]


The most common approach for surgeons to reach the heart is a  median sternotomy  (vertically cutting the breastbone), but other incisions can be employed, such as a left or right thoracotomy. [ 15 ]  After the heart is exposed, the patient is put on a  cardiopulmonary bypass  machine, also known as a heart–lung machine. This machine breathes for the patient and pumps their blood around their body – bypassing the heart – while the surgeon replaces the heart valve. Next, an aortic clamp is placed on the aorta, and the heart is stopped ( cardioplegia ). [ 15 ]  Depending on the pathology of the mitral valve and surgeon's preference, various approaches can be used to access the mitral valve. The interatrial groove approach involves incising the left atrium posterior to the interatrial groove. The transatrial oblique approach is utilized when the left atrium is small. In this approach, the right atrium is opened and another incision is made at the interatrial septum. [ 16 ]


The valve is excised 4–5 mm from the annulus, leaving intact the attached chordae unless they are calcified or otherwise diseased. The valve is replaced by a mechanical or bioprosthetic valve. The replacement valve is sewn into the annulus with interrupted or horizontal mattress sutures with the pledgets on the atrial side. [ 17 ]  The atrial walls are closed, taking care not to trap air within the chambers of the heart. [ 18 ]  The heart is restarted, and the patient is taken off the heart–lung machine. [ citation needed ]


Following surgery, patients are typically taken to an  intensive care unit  for monitoring. They may need a  respirator  to help them breathe for the first few hours or days after surgery. The patient should be able to sit up in bed within 24 hours. After two days, the patient may be moved out of the intensive care unit. Patients are usually discharged after 7–10 days. If the mitral valve replacement is successful, patients can expect their symptoms to improve significantly. [ 19 ]


Some scarring occurs after surgery. After median sternotomy, the patient will have a vertical scar on their chest above their breastbone. If the heart is accessed from under the left breast there will be a smaller scar in this location. [ 20 ]


Patients with a bioprosthetic mitral valve are prescribed anticoagulants, such as  warfarin , for 6 weeks to 3 months after their operation, while patients with mechanical valves are prescribed anticoagulants for the rest of their lives. Anticoagulants are taken to prevent blood clots, which can move to other parts of the body and cause serious medical problems, such as a  heart attack . Anticoagulants will not dissolve a blood clot but they do prevent other clots from forming or prevent clots from becoming larger. [ 21 ]


Once their wounds have healed, patients should have few, if any, restrictions from daily activities. People are advised to walk or undertake other physical activities gradually to regain strength. Patients who have physically demanding jobs will have to wait a little longer than those who don’t. Patients are also restricted from driving a car for six weeks after the surgery. [ citation needed ]


As with other cardiac procedures, mitral valve replacement is associated with risks, such as bleeding, infection, thromboembolism, renal shutdown,  cardiac tamponade ,  stroke , or reaction to anesthesia. [ 22 ]  The risk of death is about 1%. [ 23 ]  Risks depend on a patient’s age, general health, specific medical conditions, and heart function. [ 24 ]


Pedrizetti  et al. [ 25 ]  studied the fluid mechanics in the left heart in 40 randomized patients with mechanical and tissue artificial heart valves. Using  echocardiography  they quantitatively analyzed the velocity field in the left heart and found that the patients with artificial mitral valves had a consistent counterclockwise  circulation , as opposed to the normal clockwise circulation that is characteristic of normal transmitral flow. [ citation needed ]


To further characterize this counterclockwise circulation a  numerical simulation  was performed which backed up the data taken from the echocardiograph study. [ citation needed ]


This flipped vortex circulation could lead to further complications in the patient who had mitral valve replacement surgery as it was observed to cause stagnation points, crossed flows, increased energy requirements and pressure shifts from the lateral to the septal wall in the left heart. [ citation needed ]


Since the 1990s, surgeons have been working on less invasive approaches to mitral valve surgery, known as minimally invasive cardiac surgery (MICS). Minimally invasive mitral valve replacement involves a small incision (5–8 cm) just below the right breast. The benefits of MICS over conventional surgery include reduced hospital stay and blood transfusion requirements, and a smaller scar. [ 26 ]


Rather than removing the existing valve, transcatheter mitral valve replacement [ 27 ]  involves wedging a new valve into the site of the existing valve. The replacement valve is delivered to the site of the existing valve through a tube called a catheter. The catheter may be inserted through the femoral artery in the thigh, or through a small incision in the chest. [ 28 ]  Once the replacement valve is in place, it is expanded, pushing the old valve’s leaflets (the sections that open and close) out of the way. [ 29 ] [ 30 ] [ 31 ]


Many mitral valves can be repaired instead of replaced. In fact,  mitral valve repair  is recommended by international guidelines wherever possible. [ 32 ] [ 33 ]  Advantages of mitral valve repair over replacement include lower surgical mortality (~1% for repair  vs  ~5% for replacement [ 34 ] ), lower rates of  stroke  and  endocarditis  (an infection of the heart’s inner lining), equivalent or better long‑term durability, [ 35 ] [ 36 ] [ 37 ]  and improved long-term survival. [ 35 ]  Patients who have their valve repaired have a similar life expectancy to the general population. [ 38 ]  In addition, patients may not need to take anticoagulants long term following mitral valve repair. [ 39 ]


For individuals with few symptoms, or those with contraindications to surgery, options exist for medical treatment in both  mitral insufficiency  and  mitral valve stenosis , although they won't cure the conditions. Such medical treatments include  diuretics , [ 40 ] [ 41 ]   vasodilators , [ 41 ] [ 40 ]  and  ACE inhibitors . [ 40 ] [ 42 ] [ 43 ]


The  Mustard procedure  was developed in 1963 by Dr.  William Mustard  at the  Hospital for Sick Children . It is similar to the previous  atrial   baffle  used with a  Senning procedure , the primary difference being that the Mustard uses a graft made of  Dacron  or  pericardium , while the Senning uses native heart tissue.


The procedure was developed to treat  transposition of the great vessels , eponymously known as  blue baby syndrome . This is a condition in which the  aorta  and  pulmonary artery  are attached to the heart in an opposite order from what is usually present at birth, resulting in the aorta being the outflow tract for the  right ventricle  and the pulmonary artery serving as the outgoing path for blood from the  left ventricle . [ 1 ]  The technique was adopted by other surgeons and became the standard operation for the dextro variant of transposition. [ 2 ]


The procedure was developed with support from the  Heart and Stroke Foundation of Canada .


In his autobiography,  South African  cardiac surgeon  Christiaan Barnard  claims to have been the first to perform the operation, with Mustard only following 'several years later'. [ 3 ]


Prior to the development of the  Senning procedure  in the 1950s,  blue baby syndrome  from transposition was usually fatal.  The defect causes blood from the  lungs  to flow back to the lungs and blood from the body to flow back to the body.  As a result, the babies are   blue  at birth because of  insufficient blood oxygen . [ 2 ]


In a normal heart, the sequence of blood is from  vena cava  to right ventricle, then to the lungs and finally from lungs to the left ventricle to be circulated throughout the body. In patients with transposition, the order is from cava to left atrium and ventricle, then to the lungs and finally to the right side of the heart to be pumped out to systemic circulation. [ 2 ]


The Mustard Procedure allows total correction of transposition of the great vessels. It creates a baffle to redirect deoxygenated caval blood to the left atrium, which then pumps blood to the left ventricle, which in turn delivers this deoxygenated blood to the lungs. The effect is that the left ventricle is a functional right, and the right ventricle a functional left.


The Mustard procedure was largely replaced in the late 1980s by the  Jatene procedure  (arterial switch), in which the native arteries were switched back to normal flow, so that the RV (right ventricle) would be connected to the pulmonary artery and the LV (left ventricle) would be connected to the aorta.  This surgery had not been possible prior to 1975 because of difficulty with re-implanting  coronary arteries  which perfuse the actual heart muscle itself ( myocardium ), and even after it was first performed the excellent results from the Mustard operation meant that it was a long time before the Jatene procedure took over. [ citation needed ]


The Mustard procedure improved an 80%  mortality rate  in the first year of life to an 80% survival at age 20. Long-term follow-up studies now extend to more than 40 years post-operation [ 4 ]  and there are numerous patients thriving in their 50s. A Facebook group, Mustard or Senning Survivors, [ 5 ]  gathers several hundred global survivors in their 20s to 50s into a single community, supporting adults born with TGA that have had a Mustard, Senning, Rastelli or Nikaidoh heart procedure. [ citation needed ]


The  Norwood procedure  is the first of three palliative surgeries for patients with  hypoplastic left heart syndrome  (HLHS) and other complex heart defects with  single ventricle  physiology intended to create a new functional single ventricle system. [ 1 ]  The first successful Norwood procedure involving the use of a cardiopulmonary bypass was reported by Dr.  William Imon Norwood , Jr. and colleagues in 1981. [ 2 ] [ 3 ]


Variations of the Norwood procedure, or Stage 1 palliation, have been proposed and adopted over the last 30 years; however, its basic components have remained unchanged. The purpose of the procedure is to utilize the right ventricle as the main chamber pumping blood to the body and lungs. A connection between left and right atria (collecting chambers of the heart) is established via atrial septectomy, allowing blood arriving from the lungs to travel to the right ventricle. Next a connection between the right ventricle and aorta is created using a tissue graft from the main pulmonary artery. [ 4 ]  Lastly, an aortopulmonary shunt is created to provide blood flow to the lungs from the systemic circulation. The most common shunts are the  Modified Blalock Taussig  shunt (MBTS) or right ventricle- to pulmonary artery shunt (RVPA or  Sano shunt ).


Most patients who undergo a Norwood procedure will proceed to further stages of single ventricle palliation. A second surgery, also known as the  Glenn procedure , occurs at 4–6 months of age. The third surgery is the  Fontan procedure , occurring when patients are 3–5 years of age. [ 5 ]


Norwood procedure is most commonly performed to treat  hypoplastic left heart syndrome , double outlet right ventricle,  double inlet left ventricle , and other single ventricle congenital heart defects. [ 5 ]  Variations are also used for palliation of  mitral  and  tricuspid atresia [ 6 ]  and subsets of  transposition of great arteries  (TGA). [ 7 ]


Without surgical repair, infants born with a single ventricle cardiac defect face almost certain mortality in the first year of life. [ 8 ] [ 9 ] [ 10 ]  In these conditions, the most urgent problem is that the heart is unable to pump blood to the systemic circulation (i.e. to the body). The goal of these three surgeries is to ultimately connect the single ventricle to the systemic circulation. To accomplish this, blood flow to the lungs is disrupted, and therefore an alternative path must be created to provide blood flow to the lungs. [ 11 ]


There are numerous factors that increase the risk of the Norwood procedure and are relative contraindications. Those factors include  Low birth weight , extremely premature delivery, poor ventricular function,  Intraventricular hemorrhage , severe non-cardiac congenital defects, and genetic syndromes with poor prognosis. [ 5 ]


While the Norwood procedure is the standard of care for single ventricle cardiac defects, there are other treatment options for patients depending on their unique anatomy. [ 12 ]  One option is the Hybrid procedure which is done via cardiac catheterization and surgery. [ 13 ] [ 14 ]  A stent is placed in the  ductus arteriosus  to keep it patent and bands are placed over both the left and right pulmonary arteries to limit pressure and over-circulation to the lungs. [ 15 ]  Another option is cardiac transplantation, although this is uncommon due to the limited availability of neonatal donor hearts. [ 16 ] [ 17 ]  Families can also elect to pursue comfort care for their newborns, especially if there are concomitant anatomic defects or genetic syndromes with poor prognosis. [ 9 ] [ 18 ]


Entry to the body cavity for the Norwood procedure is gained by a vertical incision above the  sternum . Separation of the sternum is necessary.  This surgery is complex and may vary slightly depending on the  diagnosis  and overall condition of the  heart . The surgery on the heart can be divided into two main steps. [ 19 ]


The main  pulmonary artery  is separated from the left and right portions of the pulmonary artery and joined with the upper portion of the  aorta .  Widening of the  pulmonary artery  is often necessary, and may be accomplished by using the patient's existing  biological tissue , or appropriate animal tissue.  This allows the  blood , a mixture of  oxygenated  and deoxygenated, to be pumped to the body via the morphologic right ventricle, through the  pulmonary valve . At this point in the surgery, the right ventricle is directly connected to systemic circulation through the Neoaorta or the reconstructed aortic outflow track. Second step of the procedure establishes blood flow to the lungs. [ 20 ]


Variations to this step have been proposed over the years, however only two have been adapted in general practice over the last 20 years. In both cases a conduit is used to direct blood flow into the lungs, however anatomic anchoring varies. There are two different types of shunts used during the procedure:  Modified Blalock Taussig  or (MBTS) and right ventricle- to pulmonary artery shunt (RVPA or  Sano shunt ). MBTS shunt provides connection from the pulmonary artery to  brachiocephalic artery  or  subclavian artery , while the RVPA conduit provides connection from right ventricle to pulmonary artery. [ 21 ] [ 5 ]


The Single Ventricle Reconstruction trial conducted in 2005 compared the two conduits at one, three and five year intervals. Although RVPA shunts performed better at the one and three year end points, five year follow up demonstrated no difference between survival or improvement in freedom from transplantation. [ 22 ] [ 23 ]


After Norwood procedure infants enter the interstage which typically lasts up to 5 months. During this period the patients are medically optimized using diuretics and vasodilators. [ 24 ]


The Norwood procedure is a complex and high-risk surgery with high rates of morbidity and mortality despite advancements in surgical technique, perioperative care, and postoperative monitoring. [ 25 ]


Immediate post surgical complications have been reported by multiple studies to involve hemorrhage, vocal cord paralysis due to close proximity of the recurrent laryngeal nerve to the cardiac sack, cardiac arrhythmias as a result of potential cardiac tissue manipulation and damage, and protein-losing enteropathy. [ 26 ] [ 5 ]  Other surgical complications include low cardiac output syndrome, atrioventricular valve regurgitation, aortic valve insufficiency, ventricular dysfunction, seizures, stroke, shunt thrombosis, infection, cardiac arrest, and death. [ 5 ] [ 27 ]


The interstage period is the period after the Norwood procedure and before stage II pallation (Glenn procedure, typically 4–6 months of age). This time is very high-risk for infants because the single ventricle must pump to both the systemic and pulmonary circulations, with mortality rates ranging from 2%-20%. [ 25 ] [ 28 ]


Due to the balance required to maintain adequate blood flow to the systemic and pulmonary circulations, infants in the interstage period face multiple risks:


Long-term survival rates for children with single ventricle physiology are improving as medical and surgical advancements continue. In the major SVR trial (Single Ventricle Reconstruction) the transplant-free survival rate was only 54-59% amongst patients who underwent the Norwood procedure. [ 32 ]  These patients experience ongoing health challenges and require lifelong cardiology follow-up. [ 12 ]


Children with single-ventricle physiology who undergo the Norwood procedure often experience neurodevelopmental impairment. [ 33 ]  Neurodevelopmental and behavioral impairments are the most common long-term morbidity for children with single ventricle cardiac defects. [ 34 ]  Children's hospitals have begun to implement multidisciplinary neurodevelopmental care teams as part of the standard of care for this population. [ 35 ]  The impact of these interventional programs remains an active area of research. [ 35 ]


Factors affecting neurodevelopment in these children include: [ 33 ] [ 36 ]


Children who undergo the Norwood procedure may experience a range of neurodevelopmental issues, such as:


First ever series of documented Norwood procedures were performed by Dr. William Imon Norwood between 1979 and 1981. [ 41 ]  Dr. Norwood was an American physician who completed his fellowship in cardiothoracic pediatric surgery at Boston Children's Medical Center (BCMC), Boston Massachusetts. [ 42 ]  During his time at BCMC he became interested in the most complex congenital heart defects, particularly HLHS. Under direct supervision of his program mentor Dr. Aldo Castanedo, he performed and later perfected what would become the three stage Norwood palliation. After successful publication of his work in 1981, Dr. Norwood joined the Project Hope stationed in Krakow, Poland. There, he continued to develop and refine his work: he was responsible for Poland's first ever Fontan procedure in a patient with single ventricle pathology. [ 43 ]


Off-pump coronary artery bypass  ( OPCAB ),  or  beating-heart surgery , is a form of  coronary artery bypass graft  (CABG) surgery performed without  cardiopulmonary bypass  (heart-lung machine) as a treatment for  coronary heart disease . It was primarily developed in the early 1990s by Dr. Amano Atsushi. Historically, during bypass surgeries, the heart is stopped and a heart-lung machine takes over the work of the heart and lungs. When a  cardiac surgeon  chooses to perform the CABG procedure off-pump (OPCAB) the heart is still beating while the graft attachments are made to bypass a blockage.


Off-pump coronary artery bypass was developed partly to avoid the complications of cardiopulmonary bypass during cardiac surgery. It had been believed that cardiopulmonary bypass causes a post-operative cognitive decline known as a  postperfusion syndrome  (informally called "pumphead"), but research has shown no long-term difference between on and off pump coronary artery bypass [ 1 ]  in patients of lower risk. This is probably because the pump is not the main cause of brain damage but is due to  the formation of a  clot  or  embolus .


Sometimes, the fatty type materials that collects to form a blockage or line on the walls of an artery may break loose during CABG procedure manipulation.  This debris can result in clots, or emboli, that may interrupt the flow of blood to the brain, causing neurological damage or even stroke.  Data analysis from beating-heart surgery patients shows a significant reduction in the release of this debris with correspondingly lower stroke rates.


The fatty emboli which cause brain damage are generated when the large artery from the heart (aorta) is manipulated and although these are reduced in most off-pump coronary bypass surgeries they are not eliminated because the aorta is still used as a site to attach some of the grafts. A growing number of OPCAB surgeons, however, are avoiding the aorta completely, known as "anaortic" or no-touch coronary bypass surgery, by taking all their grafts from sites other than the aorta (e.g. the internal mammary arteries.). [ 2 ] [ 3 ]  This results in a very low risk of stroke, actually less than occurs during  percutaneous coronary intervention . [ 4 ]


In addition to off-pump surgery being associated with the clinical benefits of a reduced risk of stroke or memory problems, patients also typically have a faster recovery and shorter hospital stay, fewer  blood transfusions , and fewer unwanted inflammatory/immune response issues.


Minimally invasive direct coronary artery bypass surgery  (MIDCAB) is a form of OPCAB that involves an incision rather than cutting into the sternum. [ 5 ]  An advanced form of this is  totally endoscopic coronary artery bypass surgery   (TECAB) that uses  robotic surgery . [ 6 ]


Off-pump surgery can be more technically challenging. The technique has a steep  learning curve , but with adequate training and experience,  the quality of the  anastomoses  has been shown to be similar to on-pump results in surgeons with comparable experience


On February 18, 2012, Amano Atsushi performed a successful off-pump coronary artery bypass operation on  Emperor Akihito . [ 7 ]


The  Onassio Cardiac Surgery Centre  ( Greek :  Ωνάσειο Καρδιοχειρουργικό Κέντρο ) or simply  Onassio  ( Ωνάσειο ) is a model hospital, specialized in adult and pediatric heart diseases, and is a donation of the non-profit  Alexander S. Onassis Foundation  to the Greek State. [ 1 ]  It is a non-profit legal entity under private law and operates under the supervision of the Greek Ministry of Health and Social Insurance. It is located in Kallithea, Athens, at the end of  Syngrou Avenue  (Syngrou 356). [ 1 ]


The Onassio Cardiac Surgery Center was the scene where the last act of the active political life of  Andreas Papandreou , prime minister of Greece and protagonist of its public life for decades, took place. For 4 months, from 29 November 1995 to 21 March 1996, Papandreou was hospitalized at Onassio [ citation needed ] , submitting his resignation as prime minister on 15 January 1996.


One of the goals of the "Alexander S. Onassis" Charitable Foundation (which was founded in 1975 by the daughter of  Aristotle Onassis ,  Christina ) was the creation of a modern cardiac surgery center in Athens, since, while cardiac surgeries had already begun to be performed in Greece, the capabilities of state hospitals could not meet the needs of the Greek population, resulting in the ever-increasing exodus of a large number of heart patients abroad. [ 2 ]


Construction work began in October 1987 (the foundation stone was laid on October 8, 1987, by the then Prime Minister Andreas Papandreou, who was to become the most famous patient of Onassios) and was completed in September 1992. On October 6, 1992, the official opening of the operation took place of the center. [ 2 ]


Onassio cost a total of 75 million dollars (at the exchange rate prevailing in 1992) and is located on an area of 8,000 sq.m. A large part of the total cost was allocated to furnishing the center with the most advanced technical means of operation and the most modern scientific instruments. [ 2 ]


Henry Opitek  (January 6, 1911 – March 13, 1981 [ 1 ] ) became the first patient to survive open heart surgery in 1952.


On July 3, 1952, Opitek, a 41-year-old male suffering from shortness of breath, made medical history at  Harper University Hospital  in  Michigan . The  Dodrill-GMR  heart machine, considered by some to be the first operational  mechanical heart  was successfully used while performing heart surgery on Opitek.  Forest Dewey Dodrill , a surgeon at Wayne State University's Harper Hospital in Detroit, used the machine to bypass 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." [ 2 ]


A  cardiovascular perfusionist ,  clinical perfusionist  or  perfusiologist , and occasionally a  cardiopulmonary bypass doctor [ 1 ] [ 2 ]  or  clinical perfusion scientist , [ 3 ]  is a  healthcare professional  who operates the  cardiopulmonary bypass  machine (heart–lung machine) during  cardiac surgery  and other surgeries that require cardiopulmonary bypass to manage the patient's physiological status. [ 4 ]  As a member of the cardiovascular surgical team, the perfusionist also known as the clinical perfusionist helps maintain  blood flow  to the body's tissues as well as regulate levels of  oxygen  and  carbon dioxide  in the blood, using a heart–lung machine. [ 4 ]


Perfusionists form part of the wider cardiovascular surgical team which includes  cardiac surgeons ,  anesthesiologists , and  residents . [ 5 ]  Their role is to conduct  extracorporeal circulation  as well as ensure the management of physiologic functions by monitoring the necessary variables. The perfusionist provides consultation to the physician in selecting appropriate equipment and techniques to be used. [ 6 ]


Other responsibilities include administering blood products, administering  anesthetic agents  or drugs, measuring selected laboratory values (such as  blood cell count ), monitoring  circulation , monitoring  blood gases , surveil  anticoagulation , induction of  hypothermia , and hemodilution. [ 4 ] [ 6 ]  Sometimes, perfusionists are granted administrative tasks such as purchasing supplies or equipment, as well as personnel and departmental management. [ 6 ]


Perfusionists can be involved in a number of cardiac surgical procedures, select vascular procedures and a few other surgical procedures in an ancillary role. [ 4 ]


Perfusionists  may participate in curative or staged palliative procedures to treat the following pediatric pathologies:


Adult surgical procedures may include:


Select ancillary procedures in which perfusion techniques and/or perfusionists may be involved include  isolated limb perfusion ,  intraperitoneal hyperthermic chemoperfusion  and  tracheal resection/repair .


In the  United States , a four-year  bachelor's degree  is a prerequisite for admission into an accredited perfusion program, typically with a concentration in  biology ,  chemistry ,  anatomy  and  physiology , varying depending on specific perfusion program. [ 7 ]  As of 2022, there are 18 accredited perfusion training programs, of which ten are  master's degrees , seven are  certificate programs , and one is a bachelor's degree. [ 8 ]  Training typically consists of two years of academic and clinical education. [ 9 ]  A perfusion student will typically begin his or her training in a  didactic fashion  in which the student will closely follow instructions from a certified clinical perfusionist in the confines of a cardiac surgery procedure. Academic coursework may be concurrent or precede this clinical instruction. Early in their clinical training, the perfusion student may have little involvement outside of an observational role. However, as time progresses, more tasks may be incrementally delegated to them. Upon graduating from a perfusion program, the graduate must begin the certification process. In the interim, the perfusion graduate is typically referred to as board-eligible, which is sufficient for employment in cardiac surgery with the understanding that achieving certified status is required for long-term employment. Most employers have stipulations on the duration of board-eligible status.


To become certified as a certified clinical perfusionist, a perfusionist must undergo a two-part exam administered by the  American Board of Cardiovascular Perfusion . The first part is the Perfusion Basic Science Exam and the second part the Clinical Applications in Perfusion Exam. The exam process is open to a perfusion student that has graduated or about to graduate from an accredited perfusion education program. In addition, a perfusion student must have participated in a minimum of 75 perfusions during the course of their training before sitting for the Perfusion Basic Science Exam and performed 40 independent perfusions after graduation before sitting for the Clinical Applications in Perfusion Exam. [ 10 ]  Upon passing the Clinical Applications in Perfusion Exam, the perfusionist is designated a certified clinical perfusionist.


Following certification, perfusionists must be recertified every year by attaining minimum clinical and educational requirements. [ 11 ]  Proof of fulfillment of these recertification requirements must be submitted to the American Board of Cardiovascular Perfusion and are mandatory to maintain certified status to use the designation.


As of February 2010, there were 3,766 certified perfusionists in the United States and approximately 300 certified perfusionists in Canada. [ 12 ]


In  Canada , there are three training programs:  Burnaby  in  Western Canada ,  Toronto  and  Montreal  in  Eastern Canada .  British Columbia Institute of Technology  in Burnaby offers an advanced specialty certificate in cardiovascular perfusion to graduates of its two-year program. Applicants must be certified respiratory therapists, critical care nurses, or cardiac professionals with two years or more of current experience in cardiac critical care. Applicants to the  Michener Institute  program in Toronto must have a  bachelor's degree  at minimum, with or without respiratory therapy, nursing or other clinical certification. The master's program is two years. The perfusion program of the  Université de Montréal  is a three-year bachelor's degree of 90 credits in biomedical science of which 27 credits are specific to clinical perfusion and in addition a diplôme d’études supérieurs spécialisées (DESS) of 30 credits in clinical perfusion of one-year at the master level.


In the  United Kingdom  and  Ireland , a bachelor's degree in a science subject (usually life or clinical sciences) is a prerequisite to enrolment on the two-year perfusion training course. Trainees must complete a two-year MSc program at the  University of Bristol  while employed as a trainee perfusionist by a sponsoring hospital trust. This post is paid as an annex U AfC band 7. They complete academic assessments (essays and exams), while in the workplace moving from a purely observational role to one in which they are capable of managing the patient while they are on cardiopulmonary system with minimal supervision. Once a trainee has been the primary perfusionist in 150 clinical procedures, they must undertake a practical exam. For this exam, the candidate is observed by two external examiners whilst building and priming a cardiopulmonary circuit, then using it during a surgical operation. After the practical exam, trainees must complete a 40-minute  viva voce  exam, which tests their academic knowledge. After this is successfully completed, they are awarded an MSc in Clinical Perfusion Science and the status of accredited clinical perfusion scientist. They must maintain this by performing a minimum of 40 clinical procedures per year.


In some states of  Australia  and  New Zealand , a perfusionist must have at least a science degree (usually in health sciences) as an entry requirement before training. Further didactic training is in a practical format at a hospital whilst doing a three-year course via correspondence and e-learning, with the Australian and New Zealand College of Perfusionists (ANZCP). The final examination for a clinical perfusionist is administered by the ANZCP over two days. This involves three hours of written assessment, two hours of multiple choice questions, and four half-hour  viva voce . Perfusion training is determined by the hospital at which the perfusionist is employed and may involve a hospital accredited training program which is determined by the health department to be the equivalent of ANZCP certification program.


In Australia perfusion can also be provided by a medically trained  physician  who has undertaken additional subspecialty training. [ 13 ]


In  India , there are different programs for educating perfusionists. A three-year bachelor's degree program (most common) with one-year internship, a two-year post-graduate diploma  are available. Bachelor's and master's degree in some reputed institutions (i.e. PGI Chandigarh, AIIMS New Delhi, jipmer,  Gandhi Medical College, Bhopal , naryana groups Bangalore, Sawai Mansingh Medical College Jaipur, Sher-e-Kashmir Institute of Medical Sciences, Srinagar). Recently, the Board of Cardiovascular Perfusion of India introduced certification. [ clarification needed ]


In  China ,  Egypt , and some South American countries, a clinical perfusionist is a medical doctor who has completed subspecialty training. [ citation needed ]
In  Argentina , a perfusionist is a medical doctor, usually a  cardiologist , who has undertaken additional sub-specialty training. They are often referred to as  hemodinamistas  (hemodynamics specialists).


In  Europe , perfusionist education standards are set by the European organisation of perfusion, EBCP (The European Board of Cardiovascular Perfusion) and has been implemented in many European countries. The length of the eduacation and training varies between 1 and 4 years, depending on requirements for entering the program. [ 14 ]
In the northern countries of Europe,  Scandinavia  including  Sweden ,  Denmark  and  Norway , perfusionists are educated at  Aarhus University  at the Scandinavian School of Cardiopulmonary Technology. [ 15 ]  Most perfusionist candidates are educated intensive care nurses/anaesthetic nurses and the education includes a Master Thesis in Cardiopulmonary Technology. [ 16 ]


The  pericardial heart valve  was invented by  Marian Ionescu , a British surgeon working at the General Infirmary in Leeds, England. [ 1 ]  He created this artificial bioprosthetic  heart valve  as a three-cusp structure made of chemically treated bovine  pericardium  attached to a  Dacron  cloth-covered  titanium  frame. [ 2 ]


The experimental and  in vitro  testing of this novel device took place in 1970, and in March 1971, Ionescu began, for the first time, the implantation of the pericardial valve in all three  cardiac  positions in humans. Between 1971 and 1976 the valves had been made in Ionescu's own hospital laboratory. Throughout these five years of usage in 212 patients the performance of the pericardial valve was thoroughly evaluated. The results showed that this original valve exhibited the best  haemodynamic  performance, at rest and during exercise, [ 3 ]  when compared with the reported results of all other artificial valves in existence. It demonstrated a very low risk of embolisation even in the absence of long term  anticoagulation  treatment of the patients. [ 2 ]  There were no cases of valve  thrombosis , intra-vascular  haemolysis  or sudden, unexpected valve failure. The durability of the valve was good at 5 years of follow-up. [ 2 ]


Based on these results, the Shiley Laboratory in Irvine, California, began to manufacture this valve and to distribute it worldwide under the name of the 'Ionescu - Shiley Pericardial Xenograft.'


From 1976 onwards a series of modifications were made in order to improve the qualities and the performance of the pericardial xenograft. The selection and preparation of the bovine  pericardium  were standardised and rigorously controlled. For tissue fixation at zero pressure a solution of 0.5% purified glutaraldehyde was used. It contained an optimal proportion of  monomers  and  polymers  and an ideal cross-link density was obtained by controlling the concentration and the  pH  of the solution as well as its temperature and exposure time of the tissue to its action. The thickness and pliability of the pericardium were standardized and the direction of macroscopically visible fibres matched for each three cusps of a particular valve. The supporting stent was changed. The titanium was replaced with machined  Delrin  which is an acetyl  homopolymer  with low 'creep' properties due to a stable  molecular memory . It is flexible and shock absorbent, essential qualities for a tissue heart valve support.
This new stent contained a radio-opaque marker at its base for easy identification. The contour of the scalloped posts was modified and the height of the stent reduced. The entire Delrin structure was covered with seamless Dacron velour and at a later stage, the margins of the scalloped edges were covered with a thin layer of pericardium in an attempt to prevent or reduce the abrasion of the leaflets when in contact with this margin during valve closure. The sewing rim was bolstered for better and safer attachment to the heart annuli and its shape was anatomically contoured into two different configurations to better fit in the aortic and the atrio-ventricular positions. Two other additions were made: an integral valve holder which prevents the touching of the valve's cusps, and a 'freeze-watch' indicator as a safe—guard against exposing the valves during transportation or storage at temperatures below 4 degrees Celsius. [ 4 ]


The geometry of the valve was slightly modified due to changes in the shape of the stent and by removing the outside pledgets around the posts. This gave a more streamlined shape of the whole structure. These modifications had been progressively introduced and all of them were incorporated in the 'Ionescu - Shiley Low Profile Pericardial Xenograft' valve, which became available in 1983.


Approximately 200,000 pericardial valves manufactured by Shiley Laboratories were distributed around the world between 1976 and 1987 and it is presumed that most of them were implanted in patients. [ 5 ]  The use of this valve generated a lot of interest expressed in several specialist symposia, academic meetings, and numerous scientific articles published over the years.


The appropriation and organisation of this enormous material and the classification and interpretation of data has been a very difficult and complex task, especially because - contrary to what it is claimed - there remains a great deal of variation in standards of reporting in all essential chapters of a scientific work. In some cases it is quite impossible to follow such standards as it will be described later. Despite all these difficulties and impediments, a general view of the performance of the pericardial valve as close to reality as possible could be obtained.


One should however keep in mind that any single investigator should resist the temptation to write a review of such a complex matter as tissue heart valves, and to cover the subject completely and fairly. One should also remember that if we study complex and variable conditions, averages must be rejected because they confuse while aiming to unify, and distort while aiming to simplify.


From the material available it is evident that the reported hospital mortality and, up to a certain point, late mortality are similar among the various publications of different authors, and do not directly reflect on the quality of the valve used.


The Ionescu pericardial valve had a large central opening almost equal with the inner surface area of the supporting stent. This, plus the pliability of the pericardial tissue, confer this valve exceptional  hydraulic  qualities. Haemodynamic studies by several authors [ 3 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ]  investigating patients with pericardial valves demonstrated that in all respects the haemodynamic function of this valve is superior to that reported for the porcine valves and, generally speaking, equal to that of the best mechanical prostheses. The haemodynamic results reported by other investigators are very similar to those by Tandon's group. Some authors stressed the advantage of very low  pressure gradients  across small pericardial valves (viz: 17, 19 and 21mm diameter) for implantation in small aortic roots without the need of complex surgical techniques for root enlargement. [ 7 ] [ 8 ] [ 9 ]


Tandon and associates [ 10 ] [ 11 ]  performed pre- and postoperative haemodynamic investigations at rest and during exercise in 110 patients. There were 51 with  aortic valve  replacement, 44 with  mitral  replacement, 3 with  tricuspid  and 12 who received multiple valve replacement. Following a technique and protocol developed at  Leeds General Infirmary , from the group of 110 patients investigated, 13 patients with aortic and 6 with mitral valve replacement were subjected to multiple, sequential haemodynamic studies at rest and during exercise at the following intervals: aortic: preoperatively and at 9.9, 42.2 and 68.3 months postoperatively; mitral: preoperatively and at 11.2, 42.3 and 68.7 months postoperatively. The results obtained showed that the considerable improvement recorded at the first postoperative investigation was maintained up to 68 months following valve replacement. [ 3 ]


In order to demonstrate visually the reasons for the great haemodynamic difference between the pericardial and porcine valves, Ionescu recorded in a ' pulse duplicator ' the opening characteristics of two porcine valves (Hancock Modified Orifice and the recently modified Edwards valve) and two pericardial valves ( the Standard and the Low-Profile Shiley valves).


All four valves were manufactured for clinical use and all had an implantation diameter of 25mm. The valves were tested under identical conditions in the mitral compartment of the pulse duplicator and photographs were taken at the peak of  diastole . The flow rates were for each frame, from left to right: 0, 100, 200, 300 and 400 ml per second. The opening of the cusps of both types of pericardial valves is synchronous and regular, without three-dimensional flexure and the low-profile pericardial valve shows an even larger opening when compared with the standard pericardial valve. There are no crevices or dead spaces behind the open cusps of the pericardial valves. The difference between the porcine and the pericardial valves is flagrant in all respects. (Fig )


Many authors had studied, in-vitro, the hydrodynamic performance of the pericardial valve and found that it possesses better functional characteristics than the porcine valves and similar to those of the best prostheses. [ 13 ] [ 14 ] [ 15 ]  In summary, the excellent haemodynamic function of the pericardial valve is one of its great advantages and sets it aside from all other tissue valves.


While dealing with a very large number of reports from different hospitals with various numbers of patients who received pericardial valves and were followed up for differing durations of time, from five to ten years, and especially because the reporting did not follow an 'established' albeit loose 'standard' of identification, description and grading of the events, it is better to enumerate the results from some of the more representative series reported and draw only general conclusions.


The following data show the results as given in actuarial percentages of freedom from embolism.


TABLE I. Freedom from embolism


From perusing innumerable publications on the results of heart valve replacement with pericardial valves concerning the rate of embolic complications, one may formulate several conclusions.


A clear picture concerning the exactitude of thrombotic and embolic complications of artificial heart valves, and especially of pericardial valves, seems to be very difficult. The knowledge at present is superficial and incomplete concerning the real causes and the risk and contributing factors to this complex phenomenon. Consequently, it has never been practical to try to standardise definitions, and even more complicated to establish lines of treatment. Everyone talks of 'causes' and 'risk factors' but no-one possesses any scientific evidence to this effect.


The so-called 'risk factors' for embolisation, with the exception of  atrial fibrillation , can be called, at best, 'scientific illusions'. Consequently, any scientific, logical way of establishing a therapeutic means for preventing such phenomena due to unknown or incompletely understood causes is doomed to remain empirical, and the end results uncertain. [ 18 ] [ 19 ] [ 20 ] [ 21 ] [ 24 ]  There are myriads of reports for and against anticoagulant treatment for patients with tissue heart valve replacement. In addition, heart valve replacement patients are followed-up by a 'committee' made up successively by the  surgeon , the  cardiologist , the  general practitioner  in this or another town, etc. The impression of knowledge or our acceptance of ignorance compound this matter further. The only solution, for patients and doctors alike, would be an artificial heart valve which carries a very low risk of clotting, and therefore would not require, in the majority of cases, anticoagulant treatment.


One main drawback in the recent 'scientific' literature on pericardial valves is that the essential data for arriving at an intelligent interpretation of results is missing. There is no description of the pre-operative condition of the patients concerning cardiac rhythm, various arrhythmias, atrial fibrillation, anticoagulant treatment, previous systemic emboli, etc., and scant information about the post-operative condition: cardiac rhythm, the nature and duration of anticoagulation, the time of occurrence of embolic phenomena and the magnitude and sequelae, if any.


All this is already in the past, now, for practical purposes, one can conclude that the pericardial valve carries a very small risk of embolisation, much smaller than that of the porcine valves even in the absence of anticoagulant treatment. The risk of pericardial valve thrombosis is exceedingly remote. The very few cases reported have not been thoroughly investigated as far as the cause or the contributing factors, related or not to the valve, are concerned. Anticoagulant related haemorrhage was extremely rarely reported because few patients received  prothrombin  depressants for long periods of time (Sublata Causa Tollitur Effectus).


There are several reports on tissue valves stating that the incidence of emboli was higher among patients receiving anticoagulation. In addition, it was observed that the rate of embolisation appears to be decreasing with the passage of time with the pericardial valves, unlike the experience with porcine valves in the mitral position where the risk remained constant during the whole period of follow-up in spite of different schemes of long-term anticoagulation. [ 20 ]


The favourable embolic rate and virtual lack of valve thrombosis of the pericardial valve appears to be due to the quality of the tissue, and especially to the design of the valve with a smooth and synchronous movement of the three cusps and the streamlined structure conferring the valve optimal hydrodynamic characteristics even at low flow rates. [ 14 ] [ 18 ] [ 20 ]


Infective endocarditis is a severe condition which occurs on native as well as on artificial valves. Both mechanical prosthetic devices and tissue heart valves are affected. The incidence of endocarditis, in western countries, ranges from 1.5 to 6.2 cases per 100,000 people per annum. The cumulative rate of prosthetic valve endocarditis is 1.5 to 3.0% at one year following valve replacement and 3 to 6% at five years, the risk being the greatest during the first six months after valve replacement.


Prosthetic valve endocarditis arising within two months of valve surgery is generally the result of intra-operative contamination of the prosthesis or a bacteraemic post-operative complication. The nosocomial nature of these infections is reflected in their primary microbial causes: coagulase-negative staphylococci, S. aureus, facultative gram negative bacilli, diphtheroids and fungi.


Epidemiologic evidence suggests that prosthetic valve endocarditis due to coagulase negative staphylococci that presents between 2 and 12 months after surgery is often nosocomial in origin but with a delayed onset. [ 25 ]


This short introduction may help to reflect on the various and sometimes opposing view-points concerning the 'origin' of prosthetic valve endocarditis. As in most recent scientific reports, some descriptions of tissue valve endocarditis suffer from the same lack of clarity and standardization in the presentation of facts and do not give all relevant details for a better understanding of events and their causes. From eight published articles of large series of patients with Ionescu-Shiley Pericardial valves, only one report presents a higher than average number of valvular bacterial infections. [ 26 ]  The other seven publications describe the rate of infection with figures of similar magnitude.


TABLE II. Freedom from infective endocarditis


Footnotes to the table:


(A):  The authors make a remark: Prior to heart valve replacement 86 patients suffered from infective endocarditis but only 9 of these patients developed recurrent infection following pericardial valve replacement.


(B):  Of the 17 cases of infection, 15 occurred between 1976 and 1981 and only 2 cases between 1981 and 1985. Ionescu's group took draconian measures in trying to jugulate post-operative infections which they considered to be, in great part, nosocomial in origin. Those measures were directed at systematic pre-operative dental examination and treatment, search for any hidden, potential foci of infection - urological, upper and lower respiratory tract, judicious selection of antibiotic cover of the patient before, during and following heart valve replacement operations and strict monitoring of all signs of infection in the post-operative period. It appears that these measures had borne fruit.


(C):  On two occasions, Holden successfully implanted pericardial valves in patients with infective endocarditis and he advocates the use of such valves in similar situations because the pericardial valves are considered to be more resistant to infection than other devices. [ 17 ]


(D):  This group considers that in its hands the pericardial valves were more prone to infection than the porcine valves, and also when compared to the results with pericardial valves published by other surgeons.


In conclusion, it is obvious that the risk of infective endocarditis in pericardial valves is not dissimilar from that encountered in porcine valves at least up to ten years after valve insertion. It can also be considered that the minor variations occurring in the published reports are due to local hospital differences, surgical technique, general handling of the valves and other factors.


One rarely finds a patient who was treated medically for proven endocarditis on his own valve who does not require valve replacement sooner or later. There is no fundamental reason why any pericardial valve should become infected more frequently than another one except if the patient becomes septicaemic and the infecting organisms will reach the valve area. It appears illogical to claim that because one surgeon reported a higher incidence of infective endocarditis with one type of valve, that there could be any significant differences between 'his' valves and those implanted by other surgeons. The difference is in the number of patients with circulating infecting micro-organisms capable of infecting the valve area.


Most authors do not consider infective endocarditis as a valve-related failure and do not include cases of infection in such statistics. The pericardial valve does not behave in a different way from other tissue valves as far as infection is concerned, with probably one exception. In the impression of some surgeons, the pericardium itself seems to be more resistant to infection than the porcine valve.


The durability of the pericardial valve, like that of all other artificial heart valves, depends on multiple factors, one of the most important being the environment in which the artificial valves function.


Primary or intrinsic tissue failure occurred with pericardial valves and it has been reported in several publications. Unfortunately, many reports do not contain some of the essential data and details necessary for building a clear image of this crucial aspect of valve performance. Table III tabulates some of the available data on primary tissue failure.


TABLE III. Primary tissue failure


Remarks for primary tissue failure


(A):  The ages of the patients range from 8 to 90 years (mean 57). 74% were over 70 years of age. The age of the two patients with valve failure (calcification) was not mentioned.


(B):  The most important element in this large series is the demonstration that one of the most important factors in valve calcification is the age of the patient at the time of valve implantation.


(C):  In this series, the authors mention, in addition, 4 cases of entanglement of sutures around the struts. These 4 patients were re-operated upon at between one week and 50 months following the first valve operation.


(D):  The authors stated that all 8 failures were due to valve calcification and that 2 of them had additional tears. They find that their results with 'calcification' in all failed valves are contrary to Gabbay's results  [ 34 ]  where failures occurred mainly through cusp tears.


This table is only an attempt to give a general impression and to provide a basis for a more detailed interpretation of results. However, several conclusions can be formulated on the complex, varied, and in some cases controversial results published. As very often, a good amount of significant data is missing and this complicates the task of being precise and fair in interpreting the results.


It appears that the great majority of pericardial valves function correctly until about 6 to 7 years post implantation. Beyond seven years of follow-up, the actuarial figures for freedom from valve failure start to decrease. In the table, the risk of valve failure seems to be greater in the aortic position as reported by some authors. In reality, the general consensus among surgeons, in various presentations and formal discussions, shows the contrary.