Lower and Shumway at Stanford University performed the first successful orthotopic heart transplantation in a dog in 1960. Barnard in South Africa unexpectedly performed the first successful human heart transplantation in 1966. This was followed by an explosive interest in heart transplantation but almost uniformly poor results because of organ rejection. Introduction of cyclosporine in 1980 markedly improved the results of adult heart transplantation. This success has extended to pediatric patients, and the first infant cardiac transplantation was carried out by Bailey at Loma Linda University in 1985. Although some ethical and medical issues exist, cardiac transplantation will continue to contribute to the treatment of children with some heart diseases.
Physicians may have a chance to participate in the care of cardiac transplant recipients. Therefore, practitioners should have some basic knowledge on the topic, and that is the aim of this chapter. This chapter is not intended to review up-to-date advances or to provide management guidelines on transplant patients. Cardiac transplantation is done by transplantation centers with multidisciplinary teams of professionals and supporting staff who are primarily responsible for follow-up of their posttransplant patients according to the management protocol established by the center.
Pediatric heart transplantation is a treatment option for children with intractable heart failure or congenital heart defects (CHDs) not amenable to surgical palliation. Several decades ago, when the surgical mortality rate was very high, hypoplastic left heart syndrome (HLHS) was a major indication for heart transplantation. With improved surgical outcome, HLHS is no longer considered a major indication for heart transplantation.
The majority of pediatric transplant patients are those with pre- and postoperative complex CHDs and those with cardiomyopathies. In infants younger than 12 months of age, who account for about 23% of pediatric cardiac transplantation, HLHS is still the most common indication followed by dilated cardiomyopathy. In children, cardiomyopathies (dilated, hypertrophic, and restrictive) account for about 60% of the cases. Most of the other indications for the transplant are patients who had surgical repairs for complex CHDs (e.g., single ventricle, atrioventricular canal defect, truncus arteriosus, L-transposition of the great arteries). Rarely, patients with unresectable cardiac tumor are candidates for transplantation. Significant cardiac allograft vasculopathy and chronic graft dysfunction of a previous heart transplant are rare indications for heart transplantation.
Selection of the Recipient
Careful selection of appropriate recipients remains the most important determinant of a favorable outcome. Multidisciplinary evaluation of the recipient includes assessment of cardiopulmonary, renal, hepatic, neurologic, and infectious disease status and socioeconomic assessment. In general, the recipient should satisfy the following selection criteria:
Terminal heart disease with death expected within 6 to 12 months
The presence of adequate dimension of hilar pulmonary arteries. If the pulmonary vascular resistance (PVR) is high or if severe hypoplasia or stenosis of the pulmonary arteries is present, the patient may be a candidate for heart and lung transplantation.
Other general requirements:
Normal function or reversible dysfunction of the kidneys and liver
Lack of systemic infection
Malignancy under complete remission for longer than 1 year
Lack of systemic disease (e.g., diabetes and degenerative neuromuscular disease) that would limit recovery or survival
Lack of drug addiction
Lack of mental deficiency
Equally important for successful pediatric heart transplantation are a family history of stability, past history of compliance, and evidence of strong motivation for the transplant as assessed by physicians and social workers. The child and parents should demonstrate sufficient responsibility, resources, and psychological strength to cope with multiple outpatient clinic visits, routine endomyocardial biopsy, and a lifetime of vigilance of the immunosuppressed state.
Unique to pediatric transplantation is the requirement of a reliable caregiver for the recipient child. The caregiver identified need not be a parent but must have legal responsibility for total care and be prepared to deal with the strict medical regimen required.
Cardiac transplantation is contraindicated:
If PVR is 6 Wood units/m 2 or greater or
Transpulmonary gradient (TPG = Pulmonary artery [PA] pressure – PA wedge pressure) is 15 mm Hg or greater, which does not respond to vasodilators.
After the decision has been made for heart transplantation and after complete multidisciplinary evaluation, the patient is placed on the cardiac transplantation waiting list (to the United Network of Organ Sharing [UNOS] and the Regional Organ Bank). Each listing is specific for ABO blood type and the recipient’s weight.
Evaluation and Management of the Cardiac Donor
The cardiac donor must meet the legal definition of brain death. Most neonatal donors are victims of sudden infant death syndrome or birth asphyxia. Most older children donors are victims of car accidents or violence.
The screening of donor is accomplished in three phases.
Primary screening is done by organ procurement specialists to obtain information on body size, ABO blood type, serologic data on hepatitis B and human immunodeficiency virus (HIV), cause of death, clinical course, and routine laboratory data.
Secondary screening is performed by cardiac surgeons or cardiologists, who pay attention to the extent of other (especially thoracic) injuries, the extent of treatment required to sustain acceptable hemodynamic status, electrocardiogram (ECG), chest radiographs, arterial blood gas analysis, and echocardiogram.
Tertiary screening is inspection of the heart by a “harvesting” surgeon to ensure that there is no evidence of a palpable thrill over the heart and great arteries, obvious arteriosclerotic heart disease, or myocardial contusion.
Donor heart should have:
No evidence of cardiac abnormalities by echocardiography, ECG, or myocardial enzyme tests
Left ventricular fractional shortening greater than 28%, regardless of inotropic support
Specific compatibility should exist between the donor and recipient in three aspects
ABO blood group compatibility
The donor’s body weight should be within 20% of the recipient’s weight; a larger donor heart is better tolerated than a smaller one.
The donor should be within close geographic range so that the donor heart can be harvested, transported, and implanted within 4 hours (up to 9 hours for infants).
Medical management of donor heart before transplantation: The donor should be managed in the intensive care unit with routine monitoring. The systolic blood pressure should be maintained in the normal range (>100 mg Hg for adults). Inotropic support and fluid resuscitation may be necessary. Normal serum electrolyte levels, acid–base balance, and oxygenation should be maintained. The hematocrit should be above 30%.
Informed Consent from the Family and Recipient
The public often misunderstands what transplantation can accomplish. The recipient and parents must fully understand the short- and long-term implications of transplantation by knowing the following facts, which are not well publicized:
Unlike most cardiac surgeries, cardiac transplantation is not a cure for the condition for which it is being considered. It can be viewed as another medical problem that will require lifelong medical attention, including frequent hospital visits or admissions for noninvasive and invasive procedures, frequent adjustments of immunosuppressive and antibiotic medications, varying degrees of limitations in activity, and adjustments in lifestyle.
There is always a threat of rejection and infection throughout the patient’s life. Even with full compliance, rejection can occur, resulting in death or a need for retransplantation.
The heart received will not last for an indefinite period; it will eventually develop allograft coronary artery disease (CAD), requiring consideration of retransplantation.
Immunosuppressive therapy may cause malignancies (especially lymphoma in children) and an increased risk of infection.
Lifelong medical attention will place a tremendous financial, emotional, and social burden on the family. A dysfunctional family could result.
There are currently two surgical techniques used in cardiac transplantation: the right atrial (RA) technique and the bicaval technique. The latter is a more recent technique and has become more popular than the former.
In the RA cardiac transplantation, when the native heart is explanted, the posterior walls of both atria of the recipient heart are left in place and are anastomosed to the donor heart. End-to-end anastomoses are also made between the donor and recipient aortas and pulmonary arteries ( Fig. 35-1 ). This technique is similar to those described by Lower and Shumway in 1960. The hospital mortality rate is 10% to 15%.
A modification of the above, called “bicaval” cardiac transplantation, has become popular in some institutions ( Fig. 35-2 ). In this technique, the RA is also explanted from the recipient, leaving only the posterior wall of the left atrium (LA) with four pulmonary veins attached. Anastomoses are made between the venae cavae, the aorta, the PA, and the LA.