Heart transplantation

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Heart transplantation
Other names: Cardiac transplant, heart transplant
Heart transplant.jpg
Placement of a donor heart in an orthotopic procedure. Note how the back of the person's left atrium and great vessels are left in place.
SpecialtyCardiothoracic surgery[1]
IndicationsEnd-stage heart failure[1]
ContraindicationsHigh pulmonary vascular resistance, cancer[2]
TypesOrthotopic (usual position)
Heterotopic (unusual position)[1][3]
Steps1) Find compatible donor
2) Bi-caval method (orthotopic)
a) Join the donor left atrium to the recipients atrial cuff
b) Model the pulmonary artery and aorta
c) Release the cross-clamp in donor to complete the remaining joins[1]
SuccessImproves quality and duration of life[2]
ComplicationsRejection, infection, allograft vasculopathy[2]
OutcomeOne year survival > 90%[2]
Five years survival 75%[2]
Frequency5,000 per year[4]
  • Video of the procedure[5]

A heart transplantation is major surgery to remove a seriously diseased heart from a person (recipient) and replace it with a normal one from another person (donor).[1] It is performed when, despite other treatments, the heart fails to pump blood effectively such as in end-stage heart failure or severe coronary artery disease.[1] It is generally an option for a young person with severe irreversible heart failure who has a life expectancy of less than 6 months.[2]

Just over half of recipients have non-ischaemic cardiomyopathy, a third have coronary artery disease, and the rest comprise of valvular heart disease, congenital heart disease and re-transplantations.[1] When performed for heart failure, recipients generally have severe limitation of physical activity, while on optimal treatment, and have undergone other appropriate procedures such as cardiac resynchronisation therapy and have an implantable cardioverter-defibrillator.[1] Scoring systems exist to guide suitability of a recipient.[6] Generally, donors have brainstem death (heart-beating donors); though a few centers have programs using donors following circulatory determined death (non-heart beating donors).[1]

It is not safe to perform a heart transplant if there is high pulmonary vascular resistance or an active cancer.[2] Other reasons for not doing the surgery include active infection, severe kidney or liver failure, recent pulmonary embolism, severe lung disease, or diabetes with complications.[1] Having another serious disease with a poor outcome, recent stroke, drug and alcohol misuse, or obesity can also increase risks.[2] In some centers the surgery is only done in people under the age 60 years.[2] Complications include rejection and allograft vasculopathy.[2] The requirement of immunosuppression may increase the risk of infection, particularly in the first year after surgery.[1] Other problems that might occur include high blood pressurre, high cholesterol and cancer, particularly skin cancer.[2] Better results are achieved if the donor heart is placed within 4 hours of its retrieval, and if the recipient is younger.[1]

Most are performed as a single heart transplant, but it may be combined with a lung, liver or kidney transplant.[1] The donor is fully heparinised before the heart is retrieved and placed in cold saline in an insulated organ transport box.[1] The more common method is bi-caval, a type of orthotopic procedure where the donor heart is placed in the same spot as the persons prior heart.[1][3] It involves joining the donor left atrium to the recipients atrial cuff, and then modelling the pulmonary artery and aorta, before releasing the cross-clamp to complete the remaining joins.[1] A heterotopic (“piggy-backed”) procedure may be done to assist left ventricular function, and involves leaving the prior heart in place while joining the donor heart to its right.[3] Heart transplantation can improve the quality and duration of life, particularly in younger recipients.[2][7] As the donor heart has lost its nerve supply, some of its functions are different.[2] It beats faster and loses the normal blood pressure variation though the day.[2]

As of 2020 more than 120,000 heart transplants have been performed since the first in 1967, by South African cardiac surgeon Christiaan Barnard.[1] More than 5,000 heart transplants are performed each year worldwide.[4] More than half are performed in the US.[8] Expected survival after surgery at one year is greater than 90% and at five years is 75%.[2] In transplants carried out between 1992 and 2001, the greatest risk of death is in the first year after the procedure, and the average survival is 11 years.[1] If another heart transplant is repeated at a later date, the risks of death are higher.[1] Globally, organ donation has limited the number of procedures performed.[1]

Medical uses

A heart transplant is most often performed in a person with a severely weakened heart, when other treatments have not worked.[9] People who are in need of a heart transplant but do not qualify may be candidates for an artificial heart[8] or a left ventricular assist device (LVAD), as a bridge-to-transplantation.[1]

Recipient

Just over half of recipients have non-ischaemic cardiomyopathy, a third have coronary artery disease, and the rest comprise of valvular heart disease, congenital heart disease and re-transplantations.[1] When performed for heart failure, recipients should generally have severe limitation of physical activity, while on optimal treatment and have undergone other appropriate heart procedures such as cardiac resynchronisation therapy and have implantable cardioverter-defibrillator.[1] Composite scoring systems exist to guide suitability of a recipient for heart transplant.[6]

Donor

Generally, donors have been confirmed to have brain stem death (heart-beating donors).[1] A few centres have re-established transplant programs using donors following circulatory determined death (non-heart beating donors).[1] Echocardiography and coronary angiography play a role in assessing suitability of the donor.[1] ABO blood group determines donor and recipient compatibility, and testing for anti-HLA antibodies might be required.[1]

Contraindications

Some people are less suitable for a heart transplant and have an increase chance of complications.[1]

Absolute contraindications:

Relative contraindications:[10]

Complications

Potential complications include:[11]

  • Post-operative complications include infection, sepsis. The surgery death rate was 5–10% in 2011.[12]
  • Acute or chronic graft rejection

Rejection

Since the transplanted heart originates from another organism, the recipient's immune system typically attempts to reject it. The risk of rejection never fully goes away, and the person will be on immunosuppressive drugs for the rest of their life. These drugs may cause unwanted side effects, such as an increased likelihood of infections or the development of certain cancers. 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.[15]

People who have had heart transplants are monitored in various ways to test for the development of rejection.[16]

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.[17]

Procedure

There are generally two types of procedure; orthotopic, involving removing the recipient's heart and implanting the donor's heart in the chest of the recipient, and heterotopic, involving leaving the recipient's heart where it is and attaching the donor heart to it.[18] Equipment required includes carefully selected recipient and donor, cardiopulmonary bypass, surgical instruments and qualified personnel.[18]

Donor retrieval

A beating donor heart awaiting transplant

The donor is fully heparinised before the heart is retrieved and placed in cold saline in an insulated organ transport box.[1] Ischemic time is ideally limited to around 4 hours or less.[19]

Organ implantation

The orthotopic procedure is when the donor heart is placed in the same spot as the persons prior heart.[1] It can biatrial or bicaval.[1] An alternative less commonly performed method is heterotopic.[1] There is also the domino transplant.[20] A heart transplant may be combined with a lung, liver or kidney transplant.[1]

Bicaval

The more common method is bi-caval.[1]

Biatrial

Domino

The explanted heart from the recipient of a combined heart-lung recipient is used as a donor heart for a second recipient.[20]

Heterotopic

A heterotopic (“piggy-backed”) procedure may be done to assist left ventricular function, and involves leaving the prior heart in place while joining the donor heart to its right.[3]

Post-procedure

Outcome

Expected survival after surgery at one year is greater than 90% and at five years is 75%.[2] In transplants carried out between 1992 and 2001, the greatest risk of death is in the first year after the procedure, and the average survival is 11 years.[1] If a person survives the first year, the average survival increases to 13 years.[1] If the another heart transplant is repeated at a later date, the risks of death are higher.[1]

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.[21]

Frequency

As of 2020 more than 120,000 heart transplants have been performed since the first in 1967.[1] More than 5,000 heart transplants are performed each year worldwide.[4] More than half are performed in the US.[8]

History

In 1907, Simon Flexner wrote the paper "Tendencies in Pathology," in which he said that it would be possible one day by surgery to replace diseased human organs – including arteries, stomach, kidneys and heart.[22]

Early heart transplantations

The world's first human-to-human heart transplant was performed on Louis Washkansky on 3 December 1967 at Groote Schuur Hospital, South Africa, by Christiaan Barnard, utilizing the techniques developed by American surgeons Norman Shumway and Richard Lower.[23][24] Washkansky, however, died 18 days later from pneumonia.[25][26] Barnard later modified the orthotropic biatrial method to preserve the sino-atrial node.[27]

On 6 December 1967, at Maimonides Hospital in Brooklyn, New York, Adrian Kantrowitz performed the world's first heart transplant in a baby.[28][29] 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.[30] Norman Shumway performed the first adult heart transplant in the US on 6 January 1968, at the Stanford University Hospital.[31] The fourth surgeon in the world to attempt the surgery was P. K. Sen, who performed the world's sixth human heart transplant in India on 16 February 1968.[31] A team led by Donald Ross performed the first heart transplant in the United Kingdom on 3 May 1968.[32] Worldwide, more than 100 transplants were performed by various doctors during 1968.[33] Only a third of these patients lived longer than three months.[34] In response to the poor results in most units around the world during the years following Barnard's first transplant, the UK announced a clinical moratorium on heart transplants in 1973. It was felt at the time that cardiac transplantation required more research into the management of rejection, more donors and a change in public opinion. Shumway's and Barnard's units continued.[35]

Later years

The introduction cyclosporine in 1983 allowed much smaller amounts of corticosteroids to be used to prevent many cases of rejection (the "corticosteroid-sparing" effect of cyclosporine).[36]

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 Eric Rose of the New York–Presbyterian Hospital. Reemtsma and Fred Bowman were also members of the team for the six-hour operation.[37]

In 1988, the first "domino" heart transplant was performed, in which a patient in need of a lung transplant with a healthy heart will receive a heart-lung transplant, and their original heart will be transplanted into someone else.[38]

Sri Lanka's first heart transplant was successfully performed at the Kandy General Hospital on 7 July 2017.[39]

Cross-species transplantation

In 1963, American surgeon James Hardy, who had carried out the first human lung transplantation, visited Keith Reemtsma and was impressed by the outcome of his chimpanzee kidney transplantations.[40] On 24 January 1964, Hardy became the first to transplant a heart into a human when he transplanted a chimpanzee heart into the chest of dying Boyd Rush.[41][42] Hardy used a defibrillator to shock the heart to restart beating, but he survived less than 2 hours.[40] Author Donald McRae states that Hardy could feel the "icy disdain" from fellow surgeons at the Sixth International Transplantation Conference several weeks after this attempt with the chimpanzee heart.[43] The consent form Hardy asked Rush's stepsister to sign did not include the possibility that a chimpanzee heart might be used, although Hardy stated that he did include this in verbal discussions.[42][44]

The great disparity between the number of people 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.[45]

In 1997 Dhaniram Baruah of Assam, India was arrested for transplanting a pig's heart into a 32-year old man, who died on the eighth day after surgery.[46] On 7 January 2022, with a one-off approval by the United States Food and Drug Administration on grounds of compassionate use in a person who had no other option, David Bennett, aged 57, of Maryland became the first person to receive a gene-edited pig heart in a transplant led by Bartley P. Griffith at the University of Maryland Medical Center.[47]

Research directions

Ex vivo machine perfusion is an emerging technology under investigation to create a similar environment around a beating donor heart while simultaneously keeping it warm.[48] It is being trialled in Australia,[49] the UK,[50] and others.[51]

References

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