Impact of donor benign intimal thickening on cardiac allograft vasculopathy

Background: Epicardial cardiac allograft vasculopathy (CAV) is commonly described as a homogeneous smooth muscle cell (SMC)-rich inward intimal lesion with the SMC oriented circumferentially around the vessel. Recent findings have called this description into question. In this study we aimed to clarify the clinical presentation of epicardial CAV. Methods: Autopsied samples of the 3 major coronaries were analyzed from patients fitting cardiac donor criteria (n = 10) and patients who had undergone cardiac transplantation (n = 34). Histology and immunohistochemistry were performed to identify cellular components of CAV, and image analysis was used to measure the various vascular compartments. Results: Of the 34 cases examined, 28 of the epicardial intimal lesions contained 2 clearly definable layers overlying the media. The layer most adjacent to the media was SMC-rich, with the SMC oriented longitudinally along the vessel length and containing few macrophages, both characteristics of donor-derived benign intimal thickening (BIT). Transplants harvested at 1, 4 or 10 days post-transplant confirmed retention of BIT after transplantation. Image analysis of later transplants supported a hypothesis of carry-over BIT in CAV. The more lumenal CAV layer more closely resembled naturally occurring atherosclerosis. Conclusions: We propose that retention of the SMC-rich BIT layer after transplantation accounts, to a large extent, for the donor-derived, SMC-rich nature of human CAV, and that perturbation of the BIT provides the inflammatory foundation for the development of an accelerated atherosclerosis in the epicardial coronaries of transplant patients. This expanding accelerated atherosclerosis along with the underlying BIT demonstrates the characteristics ascribed to CAV.