Endothelial Activation and Development of Coronary Artery Disease in Transplanted Human Hearts

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Abstract
Context. —The development of coronary artery disease in heart transplants is often associated with graft failure. Early detection of allografts prone to develop this disease is essential to institute new therapeutic approaches that could prolong allograft function. Objective. —To determine if early activation of arterial/arteriolar endothelium predicts the development of coronary artery disease, graft failure, or both in transplanted human hearts. Design. —Prospective cohort study. Setting. —Heart Transplant Center. Participants. —A total of 121 consecutive adult cardiac allograft recipients who received transplants between 1988 and 1995 and were followed up through 1996. Main Outcome Measures. —Development of coronary artery disease and graft failure. Methods. —Immunocytochemistry was performed on serial endomyocardial biopsy specimens to evaluate endothelial activation markers (intercellular adhesion molecule-1 and histocompatibility antigen HLA-DR) in arteries and arterioles. The presence and progression of coronary artery disease was evaluated by annual coronary angiograms with side-by-side comparisons. Results. —None of the 121 donor hearts showed arterial/arteriolar endothelial activation before transplantation. Arterial/arteriolar endothelial activation was present in 78 and absent in 43 of 121 allografts during the first 3 months after transplantation. The time of appearance and the proportion of biopsy specimens showing endothelial activation during 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 arterial/arteriolar endothelium in transplanted human hearts predicts development of coronary artery disease and increased risk of graft failure.