Accelerated Graft atherosclerosis following cardiac transplantation: Clinical perspectives

Summary : The advent of effective immunosuppression has made cardiac transplantation a viable treatment option for end‐stage cardiac failure, with marked improvement noted in patient survival expectation in the past decades. However, rejection episodes and infectious complications continue to be of concern in the posttransplant period. A third clinical entity, graft atherosclerosis affecting the coronary arteries, has emerged as another source of significant morbidity and mortality in patients undergoing cardiac transplantation. An early analysis of clinical and laboratory correlates of graft atherosclerosis identified only advanced donor age and elevated plasma levels of triglycerides at 1 year posttransplantation as possible risk factors for the occurrence of coronary vascular disease in the posttransplant period. However, it should be noted that at all other time periods examined, triglyceride levels were not significantly different and that the same held true for virtually all other laboratory determinations. The possible involvement of cytomegalovirus (CMV) in graft atherosclerosis was suggested by clinical observations in renal transplant patients showing that CMV was associated with rejection episodes and with the development of glomerulopathy. An extensive study of 387 cardiac allograft recipients has provided evidence that patients infected with CMV posttransplant are at greater risk for development of graft atherosclerosis and that they die more frequently because of graft atherosclerosis. The precise role played by CMV in the pathogenesis of graft atherosclerosis has yet to be defined. It has been postulated that CMV may facilitate the development of graft atherosclerosis by mediating endothelial/medial cell hyperplasia, by causing direct damage to endothelial cells, by modifying blood vessel wall cell surface antigens, or by inducing cross‐reacting antibodies to sequences of human and CMV genomes. Investigations of these mechanisms to more clearly delineate the role of CMV in the development of graft atherosclerosis are ongoing.