Heart transplantation

(Diagram illustrating the placement of a donor heart in an orthotopic procedure. Notice how the back of the patient's left atrium and great vessels are left in place).

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Editor(s)-in-Chief: C. Michael Gibson, M.S., M.D.; Juan A. Sanchez, M.D., M.P.A., [1], Chairman, The Stanley J. Dudrick Department of Surgery, Saint Mary's Hospital, Waterbury, CT; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

Heart transplantation or cardiac transplantation, is a surgical transplant procedure performed on patients with end-stage heart failure or severe coronary artery disease to prolong life. The most common procedure is to take a working heart from a recently deceased organ donor (allograft) and implant it into the patient. The patient's own heart may either be removed (orthotopic procedure) or, less commonly, left in to support the donor heart (heterotopic procedure). It is also possible to take a heart from another species (xenograft), or implant a man-made artificial one, although the outcome of these two procedures has been less successful in comparison to the far more commonly performed allografts.

Cardiac transplantation is reserved for patients with end-stage congestive heart failure despite all interventions. 1 year survival is 80%, and 5 year survival is 60%. Lifelong immunosuppressive therapy is used to prevent (or postpone) rejection, but increases the risk for opportunistic infections and malignancies.

The indications for heart transplantation include severe hemodynamic compromise due to heart failure which equires IV inotropic support to maintain adequate organ perfusion; a peak Vo2 <10 ml/kg/min; NYHA Class IV symptoms not amenable to any other intervention; or recurrence of symptomatic ventricular arrhythmias refractory to all therapeutic intervention.

History

The first heart transplanted into a human occurred in 1964 at the University of Mississippi Medical Center in Jackson, Mississippi when a team led by Dr. James Hardy transplanted a chimpanzee heart into a dying patient. The heart beat 90 minutes before stopping. Dr. James Hardy had performed the first human lung transplant the previous year.

The first human to human heart transplant was performed by Professor Christiaan Barnard at Groote Schuur Hospital in December 1967. The patient was a Louis Washkansky of Cape Town, South Africa, who lived for 18 days after the procedure before dying of pneumonia. The donor was Denise Darvall, who was rendered brain dead in a car accident.

The first successful United States heart transplant was done at St. Lukes hospital in Houston Texas by Denton Cooley, M. D. in June 1968. The donor was a teenage suicide victim (who had had an aortic coarctation repaired as a young child, also by Dr. Cooley) and the recipient, Mr. Thomas, had terminal severe cardiomyopathy. He survived 8 months before dying of rejection of the transplanted heart.

A series of five subsequent heart transplants was done that month by Dr. Cooley followed by a number of transplants in Houston that year before the program was canceled leaving only Norman Shumway at Stanford University at San Francisco doing heart transplants and research on the rejection phenomenon.

1970 - Recipient selection criteria standardized

1973 - Surveillance endocardial biopsy

1977 - Distant donor heart procurement

1980 - Cyclosporine A

Epidemiology and Demographics

Reporting of transplant statistics to the Registry of the International Society for Heart and Lung Transplantation (ISHLT) is required in the US, but not other countries. According to ISHLT:

• 5000 heart transplants are performed per year worldwide
• 10-20 heart transplants per year are performed at each center
• 50-59 years is the average age of heart transplant recipients
• 10:1 is the ratio of awaiting recipients to donors
• 207 hospitals performed heart transplants in 207
• 51% of heart transplants are performed for non-ischemic cardiomyopathy and 38% are performed for ischemic heart disease

Indications

In order for a patient to be recommended for a heart transplant they will generally have advanced, irreversible heart failure with a severely limited life expectancy. It is important to note that the life expectancy of heart failure has improved over the past two decades due to improvements in both medical therapy (ACE Inhibition, beta-blockers, aldosterone antagonists and device therapy such as automatic implantable cardiac defibrillators AICDs and cardiac resynchronization. Thus, patients should not be considered for cardiac transplantation unless they have failed aggressive medical and device therapy .

Systolic heart failure with a left ventricular ejection fraction < 35%

Due to either:

• Ischemic cardiomyopathy
• Dilated cardiomyopathy
• Valvular heart disease
• Hypertensive heart disease
• Etiologies which are excluded are amyloid, HIV, and cardiac sarcoma

Ischemic coronary artery disease with refractory angina

Ischemia which is not amenable to coronary artery bypass graft surgery (CABG) and is refractory to maximally tolerated medical therapy

Intractable life-threatening arrhythmias

• Ventricular arrhythmias which are not controlled by an implantable cardioverter-defibrillator
• Ventricular arrhythmias that are refractory or not amenable to electrophysiologic guided single or combination medical therapy
• Patients that are not a candidate for ablative therapy

Hypertrophic obstructive cardiomyopathy (HOCM)

Class IV heart failure symptoms persist despite maximal therapy, myomectomy, alcohol septal ablation, mitral valve replacement

Congenital heart disease

• Fixed pulmonary hypertension must not be present

Additional Considerations

• The patient should have a stable psychosocial situation

Contraindications

Underlying myocardial disease

Underlying etiologies of myocardial disease which are contraindications are:

• Amyloid
• HIV
• Cardiac sarcoma.

Co-morbid or associated conditions

Some patients are less suitable for a heart transplant, especially if they suffer from other circulatory conditions unrelated to the heart. The following conditions in a patient would increase the chances of complications occurring during the operation:

• Kidney, lung, or liver disease
• Insulin-dependent diabetes with other organ dysfunction
• Life-threatening diseases unrelated to heart failure such as cancer that would severely limit life expectancy
• Vascular disease of the neck and leg arteries.
• No ongoing acute infections
• No recurrent pulmonary infections
• No alcohol, tobacco or drug abuse
• Severe lung disease such as chronic obstructive pulmonary disease
• Morbid obesity
• ABO incompatibility

Donor Criteria

1. Brain death declared
2. Age <45 (special exceptions)
3. No pre-existent heart disease
4. Few coronary artery disease risk factors
5. No untreated acute infections
6. No systemic malignancy
7. No cardiac trauma
8. Normal ECG
9. Normal echocardiogram
10. Negative HIV and Hepatitis screen

Equitable Distribution of Donor Hearts to those Awaiting Transplantation and the Process of Being Listed for a Transplant

In order to assure that access to donor hearts is equitably distributed, the United Network for Organ Sharing (UNOS), was created. In general, patients who are hospitalized and require ongoing administration of parenteral inotropic agents are at highest risk of death, and are placed at the highest priority on the list of potential recipients. The following factors are used in assigning the priority for transplantation:

• The level of acuity of the patient's condition (sicker patients are higher on the list)
• The time the patient has waited on the list (patients who have waited longer are higher on the list)
• Duration of ischemic time anticipated when a donor heart does become available (assessed in increments of 500 miles between donor and recipient hospitals)(patients who are located closer to the donor heart are higher on the list)

Some patients may be moved down the list or they may be taken off of the list (delisted). About 5% of patients are delisted because they improve with medical therapy. The prognosis of patients who have been delisted is controversial. The largest study to date of 100 patients indicates that delisted patients may have a slightly poorer long-term prognosis than those patients who are transplanted. While early survival was better among those patients who were delisted, survival after 30 months tended to be better among patients who were transplanted. Among delisted patients, the mean duration of survival was 7.7 years, and 94%, 55% and 28% of patients were event-free at 1, 5, and 10 years respectively. Although data is lacking, it has been hypothesized that survival could be further improved among delisted patients to 45% at 10 years if a defibrillator or AICD was implanted.

The predictors of death within two months of being placed on a transplant list among status 1 candidates include :

1. Inotropic and intra-aortic balloon pump support
2. Pulmonary capillary wedge pressure >20 mm Hg
3. UNOS status 1A
4. Mechanical ventilation
5. Serum creatinine >1.5 mg/dl
6. Failed cardiac transplant
7. Valvular cardiomyopathy
8. Age >60 years
9. Caucasian ethnicity
10. Weight ≤70 kg
11. Lack of an AICD on the day of listing

The mortality among children and young adults < 18 years of age who are awaiting transplant was 17% between 1999 and 2006 and is higher than adults. The majority of the deaths occurred in those children who weighed 10-15 Kg.

Criteria for Cardiac Transplantation

While assessment of the indications and contraindications are important first steps in evaluating the appropriateness for cardiac transplantation, the prognosis of a patient with and without transplantation is critical in making the final determination as to whether a patient is suitable for cardiac transplantation. Discussed below are criteria that are used based upon the estimation of the patient's prognosis.

Functional Capacity and Peak V02 (V02 Max)

This objective metric is listed by the ACC/AHA heart failure guidelines as a critical measure in determining when to list someone for transplantation . A normal peak V02 is > 20 ml/kg/min. Older data from 1986 through 1989 identified and peak V02 of 14 ml/kg/min as a threshold for listing a patient . Those patients with a peak V02 > 14 ml/kg/min who were considered too stable for cardiac transplantation had a survival that was similar to that of patients with a peak V02 < 14 ml/kg/min who were transplanted. It should be noted that peak V02 is variable, and should be re assessed periodically. It should also be noted that gender, age, comorbidities, and a patient's level of conditioning should be taken into account when interpreting the peak V02. If a patient is consistently in the peak V02 range of 10-12 ml/kg/min, then transplantation should be considered.

ACC / AHA Transplant Criteria

The ACC / AHA criteria are as follows :

Absolute Indications

• For hemodynamic compromise due to severe heart failure

• Refractory cardiogenic shock
• Documented dependence on intravenous inotropic support to maintain adequate organ perfusion
• Peak VO2 less than 10 mL/kg per min with achievement of anaerobic metabolism

• Severe symptoms of ischemia that consistently limit routine activity and are not amenable to coronary artery bypass surgery or percutaneous coronary intervention.
• Recurrent symptomatic ventricular arrhythmias refractory to all therapeutic modalities

Relative indications

1. Peak V02 of 11 to 14 mL/kg per minute (or 55 percent predicted) and major limitation of the patient's daily activities
2. Recurrent unstable ischemia not amenable to other intervention
3. Recurrent instability of fluid balance/renal function not due to patient noncompliance with medical regimen

"Insufficient" indications

1. Low left ventricular ejection fraction
2. History of functional class II or IV symptoms of HF
3. Peak VO2 greater than 15 mL/kg per minute (or greater than 55 percent predicted) without other indications

Surgical Procedure

Pre-operative

A typical heart transplantation begins with a suitable donor heart being located from a recently deceased or brain dead donor. The transplant patient is contacted by a nurse coordinator and instructed to attend the hospital in order to be evaluated for the operation and given pre-surgical medication. At the same time, the heart is removed from the donor and inspected by a team of surgeons to see if it is in a suitable condition to be transplanted. Occasionally it will be deemed unsuitable. This can often be a very distressing experience for an already emotionally unstable patient, and they will usually require emotional support before being sent home.

Operative

Once the donor heart has passed its inspection, the patient is taken into the operating theatre and given a general anesthetic. Either an orthotopic or a heterotopic procedure is followed, depending on the condition of the patient and the donor heart.

Orthotopic procedure

The orthotopic procedure begins with the surgeons performing a median sternotomy to expose the mediastinum. The pericardium is opened, the great vessels are dissected and patient is attached to cardiopulmonary bypass. The failing heart is removed by transecting the great vessels and a portion of the left atrium. The pulmonary veins are not transected; rather a circular portion of the left atrium containing the pulmonary veins is left in place. The donor heart is trimmed to fit onto the patients remaining left atrium and great vessels and sutured in place. The new heart is restarted, the patient is weaned from cardiopulmonary bypass and the chest cavity is closed.

Heterotopic procedure

In the heterotopic procedure, the patient's own heart is not removed before implanting the donor heart. The new heart is positioned so that the chambers and blood vessels of both hearts can be connected to form what is effectively a 'double heart'. The procedure can give the patients original heart a chance to recover, and if the donor's heart happens to fail (eg. through rejection), it may be removed, allowing the patients original heart to start working again. Heterotopic procedures are only used in cases where the donor heart is not strong enough to function by itself (due to either the patients body being considerably larger than the donor's, the donor having a weak heart, or the patient suffering from pulmonary hypertension).

Post-operative

The patient is taken into ICU to recover. When they wake up, they will be transferred to a special recovery unit in order to be rehabilitated. How long they remain in hospital post-transplant depends on the patient's general health, how well the new heart is working, and their ability to look after their new heart. Once the patient is released, they will have to return to the hospital for regular check-ups and rehabilitation sessions. They may also require emotional support. The number of visits to the hospital will decrease over time, as the patient adjusts to their transplant. The patient will have to remain on lifetime immunosuppressant medication to avoid the possibility of rejection. Since the vagus nerve is severed during the operation, the new heart will beat at around 100 bpm until nerve regrowth occurs.

"Living organ" transplant

Doctors made medical history in February 2006, at Bad Oeynhausen Clinic for Thorax and Cardiovascular Surgery, Germany, when they successfully transplanted a 'beating heart' into a patient. Normally, potassium chloride injected donor's heart (in order to stop it beating, before being removed from the body) packed in ice in to preserve it. The ice can usually keep the heart fresh for up to four to six hours, depending on its condition to start with. Rather than cooling the heart, this new procedure involves keeping it at body temperature and hooking it up to a special machine called an Organ Care System that allows it to continue beating with warm, oxygenated blood flowing through it. This can maintain the heart in a suitable condition for much longer than the traditional method.

Immunosuppressive Therapy

A. Cyclosporine A

B. Adrenocortical steroids

C. Azathioprine

D. OKT3

E. Anti-thymocyte globulin (ATG)

EKG Findings Following Transplantation

12 lead EKG shows accessory atrial activity (better seen in lead II at the end of the first complex in the middle between the second and third complex and after the third complex) due to some of the original sinus node still remains in addition to the donor sinus node after a cardiac transplant. Because of a suture line in the right atrium the ectopic atrial rhythm rarely conducts to the AV node. Right axis deviation and a rSR' which might suggest volume overload RVH also shown.

Prognosis

After the first 6 months, the mortality rates is approximately 3.5% per year. The prognosis for heart transplant patients following the orthotopic procedure has greatly increased over the past 20 years, and as of Aug. 11, 2006, the survival rates were as follows.

• 1 year: 86.1% (males), 83.9% (females)
• 3 years: 78.3% (males), 74.9% (females)
• 5 years: 71.2% (males), 66.9% (females)

The "half-life" of patient survival has likewise improved as follows :

• 1982-1991: 8.9 years
• 1992-2001: 10.5 years
• 2002-2007: 11.0 years

As of 2006, Tony Huesman is the world's longest living heart transplant patient, having survived for 28 years with a transplanted heart. Huesman received a heart in 1978 at the age of 20 after viral pneumonia severely weakened his heart. The operation was performed at Stanford University under American heart transplant pioneer Dr. Norman Shumway, who continued to perform the operation in the U.S. after others abandoned it due to poor results.

Causes of Death after Transplantation

• Rejection
• Infection
• Technical problems
• CNS events
• Malignancy

ACC / AHA Guidelines- Recommendations for Pacing After Cardiac Transplantation (DO NOT EDIT)

“

Class I 1. Permanent pacing is indicated for persistent inappropriate or symptomatic bradycardia not expected to resolve and for other Class I indications for permanent pacing. (Level of Evidence: C) Class IIb 1. Permanent pacing may be considered when relative bradycardia is prolonged or recurrent, which limits rehabilitation or discharge after postoperative recovery from cardiac transplantation. (Level of Evidence: C) 2. Permanent pacing may be considered for syncope after cardiac transplantation even when bradyarrhythmia has not been documented. (Level of Evidence: C)

”

Guideline Resources

• The ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities

Additional Resources

• Western Cape Government Website, South Africa (21 February 2005). "Chris Barnard Performs World's First Heart Transplant". Cape Gateway. Retrieved 2007-01-10.
• Department of Cardiothoracic Surgery. "Patient's Guide to Heart Transplant Surgery". University of Southern California. Retrieved 2007-01-10.
• Nancy Reid (September 22, 2005). "Heart transplant: How is it performed?". Healthwise. Retrieved 2007-01-10.
• Jeffrey Everett (10/29/2003). "Heart Transplant: Indications". AllRefer.com. Retrieved 2007-01-10.
• "Hartford Hospital Heart Transplant Program". Hartford Hospital, Connecticut, United States. Retrieved 2007-01-10.

External links

Official Heart Transplant Museum - Heart Of Cape Town

References

de:Herztransplantation hu:Szívátültetés nl:Harttransplantatie simple:Heart transplant uk:Трансплантація серця

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