Distinct phenotypes of cardiac allograft vasculopathy after heart transplantation: A histopathological study

Abstract

Introduction: Long-term survival after heart transplantation (HTx) is hampered by cardiac allograft vasculopathy (CAV). Better understanding of the pathophysiological mechanisms of CAV might have considerable consequences for therapeutic approaches in the future. The aim of the present study was to investigate the histological phenotypes of CAV in relation with clinical patient characteristics. Methods and results: Coronary cross-sections from 51 HTx patients were obtained at autopsy. CAV was observed in 42 patients (82%). Three histological CAV phenotypes were identified (H-CAV 1-3). No CAV (H-CAV 0) is as seen in normal coronary arteries; intimal thickening consisting of a layer of longitudinal oriented smooth muscle cells. In H-CAV 1 to 3 a second intimal layer is formed, on top of the longitudinal oriented smooth muscle cell layer, with predominantly mononuclear inflammatory infiltrate in loose connective tissue (H-CAV 1), smooth muscle cells in different orientation (H-CAV 2), or a fibrotic intimal lesion (H-CAV 3). H-CAV type was significantly related with time after transplantation, age at transplantation, the amount of atherosclerotic disease and the occurrence of infection. In addition, morphometric analysis revealed that higher H-CAV types have a relatively larger intimal area, that is compensated for by expansive arterial remodeling of the artery. Conclusion: CAV in an ongoing process that can be classified into three different phenotypes; inflammatory lesions, lesions rich of smooth muscle cells and fibrotic lesions. Our results suggest that these phenotypes are related to time after transplantation, age at transplantation, the amount of atherosclerotic disease and the occurrence of infection.