ENDOTHELIAL ACTIVATION AND DEVELOPMENT OF CORONARY-ARTERY DISEASE IN TRANSPLANTED HUMAN HEARTS

Context.-The development of coronary artery disease in heart transplan ts is often associated with graft failure, Early detection of allograf ts prone to develop this disease is essential to institute new therape utic approaches that could prolong allograft function. Objective.-To d etermine if early activation of arterial/arteriolar endothelium predic ts the development of coronary artery disease, graft failure, or both in transplanted human hearts. Design.-Prospective cohort study. Settin g.-Heart Transplant Center. Participants.-A total of 121 consecutive a dult cardiac allograft recipients who received transplants between 198 8 and 1995 and were followed up through 1996. Main Outcome Measures.-D evelopment of coronary artery disease and graft failure, Methods.-Immu nocytochemistry was performed on serial endomyocardial biopsy specimen s to evaluate endothelial activation markers (intercellular adhesion m olecule-1 and histocompatibility antigen HLA-DR) in arteries and arter ioles. The presence and progression of coronary artery disease was eva luated by annual coronary angiograms with side-by-side comparisons, Re sults.-None of the 121 donor hearts showed arterial/arteriolar endothe lial activation before transplantation. Arterial/arteriolar endothelia l activation was present in 78 and absent in 43 of 121 allografts duri ng the first 3 months after transplantation. The time of appearance an d the proportion of biopsy specimens showing endothelial activation du ring these first 3 months were significantly associated with the risk of developing coronary artery disease, the progression of the disease, and the time required to develop the disease (P<.001). Significantly more patients with arterial/arteriolar endothelial activation died or received a second transplant (P<.001). Conclusions.-Activation of arte rial/arteriolar endothelium in transplanted human hearts predicts deve lopment of coronary artery disease and increased risk of graft failure .