What malignancies are common in heart transplant patients and what predisposes patients to them?

Skin and lip cancers are fairly common post-transplantation and are believed to be secondary to a metabolite of azathioprine which causes increased photosensitivity. Unlike non-transplant patients, in transplant patients squamous cell tumors are more frequent than basal cell tumors by a ratio of 2:1. These tumors tend to be more aggressive and metastasize more quickly in transplant patients. Other tumors which are substantially more common are non-Hodgkin’s lymphomas, Kaposi’s sarcoma, and uterine, cervical, vulvar, and perineal tumors. Common tumors such as those of the lung, breast, and colon fortunately do not seem to be markedly increased in the transplant population.

A special form of lymphoma known as post-transplant lymphoproliferative disease is a common tumor that has been associated with cyclosporine-based immunosuppression. This tumor is usually of B-cell origin and is believed to be induced by the Epstein-Barr virus. Patients with this disease will often respond to decreased levels of immunosuppression and possibly antiviral therapy, suggesting a relationship to intensity of immunosuppression. Use of OKT3 and other antilymphocyte antibodies has also been implicated in increasing the risk of this disease.

What is the leading cause of death in heart transplantation after the first year?

Coronary artery disease (graft atherosclerosis) remains the leading cause of death in patients after their first transplant year. Graft atherosclerosis can develop within months of transplantation but usually appears gradually, so that 5 years post transplantation 30-50% of patients have

angiographic evidence of disease. Detection of graft atherosclerosis is a difficult clinical problem since cardiac transplant patients do not usually have angina due to cardiac denervation from the surgical procedure. In addition, noninvasive tests such as exercise testing and radionuclide scans are less reliable in the cardiac transplant patient. Thus yearly coronary angiography is still routinely employed in these patients. Patients with severe disease usually present with sudden death or congestive heart failure secondary to a myocardial infarction. The etiology of this accelerated graft atherosclerosis is unknown but it is believed to be secondary to immune mediated endothelial injury.

Histopathologically, arteries with graft atherosclerosis usually have diffuse concentric lesions that involve the length of the vessel in comparison to typical coronary artery disease, where lesions tend to be more focal and nonconcentric. This usually makes heart transplant patients poor candidates for revascularization by angioplasty or surgery and leaves retransplantation as the only definitive therapy for this life-threatening process.

What predisposes heart transplant patients to coronary artery disease?

Although the exact mechanism of graft atherosclerosis remains unclear, certain variables strongly correlate with its development. Humoral rejection, circulating HLA antibodies, HLA mismatch at the DR locus, hyperlipidemia, and CMV infection all have been variably associated with its development. Medical attempts to prevent or slow this process, such as exercise, lipid-lowering agents, and blood pressure control, have not met with success. The calcium channel blocker diltiazem may result in modest slowing of this disease process.

What noninvasive tests are useful for the diagnosis of coronary artery disease in heart transplant patients?

Unfortunately, routine exercise testing, nuclear myocardial blood flow scans with thallium and sestamibi, as well as dobutamine stress echocardiography all lack the sensitivity to be useful tests in screening for graft atherosclerosis. The reason is likely the diffuse nature of graft coronary artery disease, which complicates interpretation of results. Surveillance angiography is the gold standard for screening for graft atherosclerosis, and noninvasive tests are used predominantly to assess functional capacity as well as clarify the significance of certain lesions.

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