Are we clear about the mechanisms by which biopsy evidence of interstitial fibrosis following cardiac transplantation helps predict late post-transplant coronary artery disease?

Transplant-associated coronary artery disease (TxCAD), or coronary vasculopathy, is the leading cause of death after the first year of transplantation and, once diagnosed, is associated with a mortality rate of 40% at two years (1). Though coronary vasculopathy is widely believed to represent some form of chronic humoral and cellular rejection, some nonimmune risk factors such as older donor age, ischemia time, dyslipidemia, preexisting donor coronary artery disease (CAD) and post-transplantation cytomegalovirus infection have also been identified (2,3). These risk factors suggest that both immune and nonimmune causes probably interact to lead to coronary vasculopathy, although the precise mechanisms involved remain poorly understood.