About 30-50% of patients return to work after transplantation, and 80-85% consider themselves to be physically active. One-year survival post-transplantation is about 90% at better centers and the 5-year survival is about 75%. Overall, 90% of patients consider themselves to be normal or have minimal symptoms of disease.
The function of a transplanted heart, however, is not completely normal. Several factors, such as cardiac denervation, altered neurohormonal activity with exercise, organ preservation injury, and differences in the donor and recipient body size, contribute to decreased cardiac function. Thus, while transplant recipients have a better functional capacity than pretransplantation, they are frequently impaired in comparison to normal controls.
What medicines are commonly used for immunosuppression in heart transplant patients?
The combination of cyclosporine, azathioprine, and prednisone has become standard immunosuppressive maintenance therapy in most transplant centers. This combination has been extremely effective in preventing rejection while minimizing the side effects that were associated with dual therapy with high-dose steroids and azathioprine, which had greater side effects. The dose of azathioprine is usually adjusted to maintain a white blood cell count of 4000-6000/mL, while the cyclosporine dose is adjusted by plasma levels depending on the time post-transplantation as well as manifestations of toxicity (e.g., worsening renal function, neurologic symptoms, or biliary stasis). Immediately after transplantation, patients receive methylprednisolone and then are switched to prednisone within 24 hours at a dose of approximately 1 mg/kg/day, which is gradually weaned to a maintenance dose of 0.1 mg/kg/day over the next 6 months. Some centers have discontinued steroids completely in about half of patients, whereas other centers maintain patients on a low dose of prednisone indefinitely.
What are the side effects of the commonly used immunosuppressive medicines? Cyclosporine’s most common side effect is nephrotoxicity, which is believed to be predominantly due to renal arterial vasoconstriction from cyclosporine’s effect on endothelin and prostaglandin production as well as a direct vasoconstrictor effect. Hyperkalemia of hyperuricemia may also develop, but tends to be dose related and reversible with discontinuation or lower doses. Cyclosporine also results in hypertension (in up to 90% of patients). Cholelithiasis is also a common problem among transplant recipients secondary to cyclosporine’s effects on bile metabolism. Hirsutism, often a welcome side effect in men, is quite distressing to women. Many of cyclosporine’s side effects can be avoided by close monitoring of trough cyclosporine levels and adjusting the dose as needed to maintain safe levels.
Bone marrow suppression is the commonest problem with azathioprine but is usually dose-related and responsive to decreasing dosing. A drug-induced hepatitis or cholestasis can also occur with azathioprine.
Steroids at high doses are associated with numerous side effects including osteoporosis, glucose intolerance, and hyperlipidemia.
All these drugs result in an increased susceptibility to infection.
What infections are common in heart transplant patients and when do they usually occur?
Infection remains a major cause of death in the transplant population. In a recent multicenter review, 21% of patients had one or more serious infections within their first year posttransplantation.
Within the first month post transplant, nosocomial bacterial infections with staphylococci or gram-negative organisms tend to predominate. Herpes simplex mucocutaneous infections tend to occur as well within the first several weeks post transplant. After the first month and through the next several months, patients are at higher risk for other viruses such as CMV or opportunistic infections such as fungi, Pneumocystis carinii, or toxoplasmosis.
The lung tends to be the most frequent site of infection in heart transplant patients, and CMV remains the most common single infection. Prophylactic therapy with trimethoprim-sulfamethoxazole appears to be effective in preventing Pneumocystis infection in heart transplant recipients.