Heart Transplantation 

Heart transplantation is the procedure by which the failing heart is replaced with another heart from a suitable donor.^[1] It is generally reserved for patients with end-stage congestive heart failure (CHF) who are estimated to have less than 1 year to live without the transplant and who are not candidates for or have not been helped by conventional medical therapy. In addition, most candidates are excluded from other surgical options because of the poor condition of the heart.

Candidacy determination and evaluation are key components of the process, as are postoperative follow-up care and immunosuppression management. Proper execution of these steps can culminate in an extremely satisfying outcome for both the physician and patient.^[2]

Candidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III (moderate) symptoms or class IV (severe) symptoms.^[3] Evaluation demonstrates ejection fractions of less than 25%. Attempts are made to stabilize the cardiac condition while the evaluation process is undertaken.

Interim therapy can include oral agents as well as inotropic support. Mechanical support with the intra-aortic balloon pump (IABP) or implantable assist devices may be appropriate in some patients as a bridge to transplantation.^{[4, 5, 6]} However, mechanical support does not improve waiting list survival in adult patients with congenital heart disease.^[7]

The annual frequency of heart transplantation is about 1% of the general population with heart failure, both candidates and noncandidates. Improved medical management of CHF has decreased the candidate population; however, organ availability remains an issue.^{[8, 9]} Further information on organ availability and waiting lists is available from the United Network for Organ Sharing.

For patient education resources, see the Heart Center, as well as Heart and Lung Transplant and Congestive Heart Failure.

Disease processes necessitating heart transplantation

The disease processes that necessitate cardiac transplantation can be divided into the following categories:

• Dilated cardiomyopathy (54%) - This often has an unclear origin
• Ischemic cardiomyopathy (45%) - This percentage is rising because of the increase in coronary artery disease (CAD) in younger age groups
• Congenital heart disease and other diseases not amenable to surgical correction (1%)

The pathophysiology of cardiomyopathy that may necessitate cardiac replacement depends on the primary disease process. Chronic ischemic conditions precipitate myocardial cell damage, with progressive enlargement of the myocyte followed by cell death and scarring. The condition can be treated with angioplasty or bypass; however, the small-vessel disease is progressive and thus causes progressive loss of myocardial tissue. This eventually results in significant functional loss and progressive cardiac dilatation.

The pathologic process involved in the functional deterioration of a dilated cardiomyopathy is still unclear. Mechanical dilatation and disruption of energy stores appear to play roles.

The pathophysiology of the transplanted heart is unique. The denervation of the organ makes it dependent on its intrinsic rate. As a result of the lack of neuronal input, some left ventricular hypertrophy results. The right-side function is directly dependent on the ischemic time before reimplantation and the adequacy of preservation. The right ventricle is easily damaged and may initially function as a passive conduit until recovery occurs.

The rejection process that can occur in the allograft has 2 primary forms, cellular and humoral. Cellular rejection is the classic form of rejection and is characterized by perivascular infiltration of lymphocytes with subsequent myocyte damage and necrosis if left untreated.

Humoral rejection is much more difficult to characterize and diagnose. It is thought to be a generalized antibody response initiated by several unknown factors. The antibody deposition into the myocardium results in global cardiac dysfunction. This diagnosis is generally made on the basis of clinical suspicion and exclusion; endomyocardial biopsy is of little value in this context.

CAD is a late pathologic process common to all cardiac allografts, characterized by myointimal hyperplasia of small and medium-sized vessels. The lesions are diffuse and may appear any time from 3 months to several years after implantation. The inciting causes are unclear, though cytomegalovirus (CMV) infection and chronic rejection have been implicated. The mechanism of the process is thought to depend on growth-factor production in the allograft initiated by circulating lymphocytes. Currently, there is no treatment other than retransplantation.

Future and controversies

The future of cardiac transplantation will be determined by the outcomes of several issues. One is the ongoing shortage of donor organs, which has fueled a search for alternative therapies for the failing heart. Such therapies include artificial assist devices, dual-chamber pacing, new drug interventions, and genetic therapy.^[10] These efforts have proven to be successful in reducing the need for transplantation. Research in the area of xenografts continues.^{[11, 12]}

Another issue is the prevention of allograft vascular disease, which remains a paramount challenge. The pathology of allograft vascular disease is clearly multifactorial in origin, making the research and therapy equally complex. Resolution of this issue will prolong graft survival and lives.

A third issue is the question of recipient selection and listing status, which continues to pose medical and ethical dilemmas. If the donor situation were not an issue, then the listing of potential recipients would not be troublesome.

The final issue is financial. In this era of cost containment in health care, the escalating costs of heart transplantation raises the questions of who should pay for the therapy and whether the procedure should be available on demand.

Indications

The general indications for cardiac transplantation include deteriorating cardiac function and a prognosis of less than 1 year to live. Specific indications include the following:

• Dilated cardiomyopathy
• Ischemic cardiomyopathy
• Congenital heart disease for which no conventional therapy exists or for which conventional therapy has failed
• Ejection fraction less than 20%
• Intractable angina or malignant cardiac arrhythmias for which conventional therapy has been exhausted
• Pulmonary vascular resistance of less than 2 Wood units
• Age younger than 65 years
• Ability to comply with medical follow-up care

Contraindications

Contraindications for heart transplantation include the following:

• Age greater than 65 years - This is a relative contraindication; patients who are older than 65 years are evaluated on an individual basis
• Fixed pulmonary vascular resistance of greater than 4 Wood units
• Active systemic infection
• Active systemic disease such as collagen-vascular disease or sickle cell disease
• Active malignancy - Patients with malignancies who have demonstrated a 3- to 5-year disease-free interval may be considered, depending on the tumor type and the evaluating program
• An ongoing history of substance abuse (eg, alcohol, drugs, or tobacco)
• Psychosocial instability
• Inability to comply with medical follow-up care^[13]

Outcomes

The 1-year survival rate after cardiac transplantation is as high as 81.8%, with a 5-year survival rate of 69.8%. A significant number of recipients survive more than 10 years after the procedure. After transplantation, adult patients with congenital heart disease have high 30-day mortality but better late survival.^[7] The functional status of the recipient after the procedure is generally excellent, depending on the his or her level of motivation.

In patients with severe biventricular failure who received pneumatic biventricular assist devices as a bridge to transplant, the 1-year actuarial survival rate was 89%, compared with 92% in patients without a ventricular assist device.^[14]

Arnaoutakis et al found that high-risk patients had better 1-year survival rates at high-volume centers (ie, centers that perform more than 15 procedures per year) than at lower volume centers (79% vs 64%, respectively). These differences dissipated among lower-risk patients. Based on these findings, the authors recommended that all high-risk heart transplantation procedures be performed at higher-volume centers.^[15]