Heart Information (Uptodate)

HEART TRANSPLANTATION OVERVIEW

— Cardiac transplantation, also called heart transplantation, has evolved into the treatment of choice for many people with severe heart failure (HF) who have symptoms despite maximum medical therapy. Survival among cardiac transplant recipients has improved as a result of improvements in treatments that suppress the immune system and prevent infection.

Unfortunately, the number of heart donors has reached a plateau despite an increasing number of potential recipients. More than 5000 cardiac transplants occur each year around the world, although it is estimated that up to 50,000 people are candidates for transplantation [1]. This critical organ shortage means that healthcare providers must strictly evaluate who should receive a heart transplant.

REASONS FOR HEART TRANSPLANTATION

— The American Society of Transplantation has published recommendations to guide healthcare providers about which patients should be considered for transplantation [2]. The major reason for cardiac transplantation is to improve survival. A second important reason is to enhance quality of life. (See "Indications and contraindications for cardiac transplantation").

Criteria for heart transplantation — The primary task in selecting candidates for heart transplantation is the person's prognosis. There are many predictors of need for transplantation; the best predictor is the amount of oxygen required by the body, called VO2. This is measured as a person exercises on a treadmill.

The major reason for cardiac transplantation is to improve survival. Thus, being able to predict how a person will do after transplantation is the most important part of the patient selection process.

The benefit of transplantation is clear if a person requires continuous intravenous (IV) medications in the hospital. In unhospitalized patients, the following requirements have been recommended for consideration for cardiac transplantation:
A history of repeated hospitalizations for heart failure
Need for ventricular assist device or artificial heart to support circulation
Increasing types, dosages, and complexity of medications
A reproducible VO2 of less than 14 mL/kg per minute

Patients are stratified into low, medium, and high risk of death without transplant. The final decision about listing a patient for transplant is determined by an established cardiac transplant center.

Deciding who gets a donor heart — To ensure that donor hearts are distributed fairly, an organization known as UNOS (United Network for Organ Sharing) has created a system. This system spells out rules that consider time on the wait list, the severity of illness and the geographic distance between the donor hospital and the transplant center, measured in increasing 500 mile distances from the donor hospital. This system is regularly reviewed and revised with input from a wide variety of interested parties, including transplant professionals, recipients, and donor families.

PRE-HEART TRANSPLANT EVALUATION

— People who meet VO2 requirements must also be evaluated for underlying medical problems, which may prevent a person from being eligible for transplantation. These include:
Fixed pulmonary hypertension
Active infection
Cancer

Other factors will also be considered, including the person's age and the presence of diabetes or lung disease.

Pulmonary hypertension — The major problem that prevents a person from being eligible for cardiac transplantation is fixed pulmonary hypertension. People with fixed pulmonary hypertension have an increased risk of right ventricular failure in the immediate postoperative period; during this time, the right ventricle in the donated heart must work especially hard to provide oxygenated blood to the body.

Fortunately, pulmonary hypertension can often be improved by using medications, including nitroprusside, nesiritide, dobutamine, milrinone, prostaglandin E1, prostacyclin, and inhaled nitric oxide. Milrinone therapy is highly effective, and is often used to determine if pulmonary hypertension is treatable. If pulmonary hypertension is controlled, a patient may be considered for transplantation.

Infection and cancer — Two other reasons transplantation may not be possible are active infection and cancer of any kind. Both of these problems can be worsened by the medications given after heart transplantation. Even without preexisting cancer, the risk of developing cancer is increased following transplantation as a result of anti-rejection medications.

Other concerns — There are a number of other conditions that may affect a patient's ability to receive a cardiac transplantation, depending upon the individual situation.
In the past, many programs routinely excluded people over the age of 55 to 60. However, carefully selected people in this age group (or older) have a survival rate comparable to that of younger patients. As a result, most centers now focus on the patient's "physiologic" age, which emphasizes the health of major organ systems (eg, kidneys, liver) and the number and severity of other underlying medical problems.
Diabetes can interfere with wound healing and increase the risk of infections and vascular (blood vessel) complications. However, people with diabetes who do not have diabetes-associated complications in the kidney, retina, or nerves appear to do as well as people without diabetes who undergo heart transplantation. ("See "Patient information: Preventing complications in diabetes mellitus").
Advanced lung disease can increase the risk of postoperative lung complications, including infection. In addition, recent pulmonary embolism (blood clot) with or without infarction (tissue death) are reasons to delay transplantation. Most centers treat a pulmonary embolism with anticoagulants (blood thinners) for six to eight weeks. (See "Patient information: Pulmonary embolism").

Other conditions that can limit a patient's ability to undergo cardiac transplantation include:
Advanced liver (hepatic) disease. Cirrhosis, for example, can limit survival and increase the risk of death both before and after surgery. (See "Patient information: Cirrhosis").
Renal (kidney) insufficiency. The immunosuppressive drug cyclosporine can be toxic for the kidneys, especially if there is preexisting kidney disease. A combined kidney-heart transplantation may be offered to patients who could require transplantation of both organs within a few years. Over 100 cases of such combined transplantation from single donors have been reported. (See "Patient information: Chronic kidney disease").
A number of other conditions increase the risk of complications, either due to the condition itself or the need for anti-rejection medications after transplantation. These conditions include: advanced peripheral vascular disease (claudication), severe obesity, advanced cardiac cirrhosis (liver disease caused by heart failure), active peptic ulcer disease, gallstones, and diverticulosis.

PSYCHOLOGICAL EVALUATION

— All heart transplantation candidates must have a complete psychological evaluation during the initial screening process. This helps to identify factors in a person's life that could cause difficulty during the waiting period, recovery, and postoperative period. A commitment to and understanding of the importance of anti-rejection medications is critical to the success of heart transplantation.

Finally, all patients are screened for the use and abuse of alcohol and other recreational drugs (marijuana, cocaine, heroin). Anyone who abuses drugs or alcohol currently or in the recent past is not a good candidate for transplantation since post-transplant drug or alcohol abuse occurs frequently.

Potential heart transplant recipients are advised stop smoking. Many centers will not list active smokers, and will check urine nicotine levels to ensure that the person has truly quit smoking. Recreational drugs, alcohol, and cigarette smoking are known to be harmful to the heart. Because the supply of donor hearts is limited and the demand is great, preference must be given to people who are likely to benefit the most and survive longest as a result of their transplant.

OUTCOME AFTER FIRST HEART TRANSPLANT

Survival — Approximately 85 to 90 percent of heart transplant patients are living one year after their surgery, with an annual death rate of approximately 4 percent thereafter. The three-year survival approaches 75 percent. (See "Prognosis after cardiac transplantation").

The outcome of patients undergoing heart transplantation for complex congenital (from birth) heart disease is similar to that of patients with other forms of heart disease. The one-year survival rate in people with congenital heart disease is 79 percent; at five years, the survival rate is 60 percent.

Prognosis — There are a number of factors in both the recipient and the donor that are associated with poor outcomes after transplantation.

Recipient factors — Factors associated with an increased risk of death up to one year after transplantation include:
Preoperative need for artificial breathing support (ventilator)
If the heart transplantation is the second
Heart conditions other than coronary artery disease or cardiomyopathy
Preoperative need for heart function assistance with a ventricular assist device
Being female
Being underweight or obese

Donor factors — A variety of donor factors affect the early outcomes:
A female donor is associated with increased one-year mortality.
The age of the donor heart does not affect long-term survival, although coronary artery disease is increased in hearts from donors over 63 years of age due to the presence of narrowing in the coronary arteries.
Thickening of the left ventricle (left ventricular hypertrophy) in the donor heart is associated with poorer outcomes compared to a heart without thickening.
Elevated blood levels of troponin I and T in the donor, which are markers of heart muscle damage, increase the risk of early heart failure.

Causes of death — There are four major causes of death after cardiac transplantation, which occur at different times:
Sudden (acute) rejection
Infections other than cytomegalovirus (CMV)
Artery disease in the transplanted heart vessels (allograft vasculopathy)
Lymphoma and other malignancies

Early mortality — Cardiac transplant recipients have an average of one to three episodes of rejection in the first year after transplantation. Between 50 and 80 percent of people experience at least one rejection episode. Acute rejection is most likely to occur in the first three to six months, with the incidence declining significantly after this time.

In the first year, most deaths are due either to acute rejection (18 percent) or infections (22 percent). Infections often develop as a result of the anti-rejection medications and weakened immune system that are required to prevent rejection.

Late mortality — Rejection is less common after the first year, and by four to five years after transplantation, less than 10 percent of deaths are the result of rejection.

However, development of rapidly progressing coronary artery disease in the arteries of the transplanted heart (called allograft vasculopathy), becomes the most common cause of death by five years. The number of fatal cancers increases over time as well. (See "Prevention and treatment of cardiac transplant vasculopathy").

Infections remain a significant cause of death after the first year. These infections are the result of a weakened immune system, and can develop from common bacteria and viruses in the community or from uncommon infections.

Posttransplant lymphoproliferative disease (PTLD) is a type of cancer that occurs in patients who use immunosuppressive medications. PTLD includes non-Hodgkin lymphoma (NHL). Most cases of PTLD occur in the first year after transplant. Among patients who develop lymphoma, the overall survival rates are between 25 to 35 percent at five years. (See "Patient information: Diffuse large B-cell lymphoma in adults" and see "Lymphoproliferative disorders following solid organ transplantation").

OUTCOME AFTER REPEAT HEART TRANSPLANTATION

— Some people must consider a second heart transplant if rejection or allograft vasculopathy develops. Slightly more than 2 percent of heart transplant cases are retransplants every year.

Survival after heart retransplantation is related to the time interval between the first transplant and the retransplant; a person is less likely to survive when this interval is short (ie, less than two years). When the interval between the first transplant and retransplantation is more than two years, the one-year survival is similar to that of a first transplantation (75 percent).

WHERE TO GET MORE INFORMATION

— Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:
Patient Level Information:

Patient information: Preventing complications in diabetes mellitus
Patient information: Pulmonary embolism
Patient information: Cirrhosis
Patient information: Chronic kidney disease
Patient information: Diffuse large B-cell lymphoma in adults
Professional Level Information:

Indications and contraindications for cardiac transplantation
Prognosis after cardiac transplantation
Prevention and treatment of cardiac transplant vasculopathy
Lymphoproliferative disorders following solid organ transplantation
Acute cardiac allograft rejection: Diagnosis
Acute cardiac allograft rejection: Treatment
Arrhythmias following cardiac transplantation
Left ventricular dysfunction after orthotopic cardiac transplantation
Lipid abnormalities after cardiac transplantation
Natural history and diagnosis of cardiac transplant vasculopathy
Rehabilitation after cardiac transplantation

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.
National Library of Medicine

(www.nlm.nih.gov/medlineplus/hearttransplantation.html, available in Spanish)
National Heart, Lung, and Blood Institute

(www.nhlbi.nih.gov/health/dci/Diseases/ht/ht_whatis.html)
American Heart Association

(www.americanheart.org)
European Society of Cardiology

(www.heartfailurematters.org)
United Network for Organ Sharing (UNOS)

(www.transplantliving.org)