The main problem in managing heart transplant recipients is to maintain the subtle equilibrium between acute rejection and infection. Acute rejection is the main cause of morbidity in the first postoperative year. Its outcome and management were transformed by the introduction of cyclosporine, a selective inhibitor of lymphocyte activation. Although many noninvasive procedures have been developed, serial endomyocardial biopsy remains the gold standard for close surveillance of rejection episodes.
The management of infection is based on strict clinical vigilance, prophylaxis against the most common and dangerous opportunistic infections (sulfamethoxazole-trimethoprim for Pneumocystis carinii, etc), and preemptive therapy against cytomegalovirus (CMV) infection, based on laboratory surveillance. CMV is a major cause of morbidity in heart transplant recipients. It causes a flu-like or specific organ-related syndrome and is directly cytotoxic, with indirect effects on host tolerance of the graft, predisposing to acute rejection and vascular disease in the graft.
After the first year, allograft vasculopathy and tumors become the main mid- and long-term problems in transplant recipient management. Allograft vasculopathy is a specific coronary vasculopathy characterized by diffuse and concentric intimal hyperplasia associated with low-grade vascular inflammation and smooth muscle cell proliferation, ultimately resulting in coronary graft lumen loss. Since the graft is denervated, even severe allograft vasculopathy can be asymptomatic. Periodic coronary angiography or the far more sensitive technique of intravascular ultrasound (IVUS) are therefore used to test for vasculopathy. Patients may have a normal angiogram, but if IVUS shows intimal hyperplasia >0.5 mm, their prognosis is poorer. Other noninvasive techniques recently confirmed as reliable and cost-effective in monitoring graft vascular disease are myocardial perfusion single photon emission computed tomography (SPECT), or myocardial perfusion scintigraphy, and dobutamine stress echocardiography.
Vasculopathy risk factors may be immunologic (acute rejection, CMV infection, and HLA donor-recipient mismatch) and/or nonimmunologic (hypercholesterolemia, hypertension, diabetes). fS-HydroxyfS-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the only medical treatment proven to prevent allograft vasculopathy progression and improve survival. Diltiazem may also help, but its interference with cyclosporine metabolism has decreased its use.
Long-term immunosuppression significantly increases the risk of solid cancers. The most frequent tumors in heart transplant recipients involve the immune system and are linked to viral infections. Kaposi’s sarcoma and Epstein-Barr virus-related lymphomas are quite common, as in HIV patients. Skin cancers, melanoma, and epithelial cell tumors are also related to the immunosuppressive burden. Other cancers that are common in the general population, such as lung, breast, and colon cancer, are no more frequent in transplant recipients. However, immunosuppression may increase malignancy and progression since some neoplasms that were undetected at pretransplant screening have become clinically apparent after only a few months of immunosuppression. Heart transplant recipients with cancer need a weaker immunosuppressive regimen with closer rejection surveillance and may benefit from conventional therapy. However, their prognosis is generally poorer than that of the general population.