A patient is scheduled for a heart transplant. What is a major cause of death beyond the first year after transplantation?

• A. Infection
• B. Acute rejection
• C. Immunosuppression
• D. Cardiac vasculopathy

Answer: (D)

Late after a heart transplant, the major cause of death is cardiac allograft vasculopathy, a form of chronic rejection that produces diffuse narrowing of the coronary arteries. This progressive, immune- and non-immune–injury-driven thickening of the vessel walls limits blood flow to the transplanted heart, leading to ischemia, graft dysfunction, and eventual death despite ongoing immunosuppressive therapy. Infections and acute rejection are today more common earlier after transplant when immunosuppression is highest; they account for early risk but not the late, dominant threat. Immunosuppression itself is necessary to prevent rejection and doesn’t directly cause the late death—its side effects, like infection, are more relevant early on. Thus, late death after transplant is most often due to the development of cardiac vasculopathy.