The Development of Cardiac Allograft Vasculopathy Occurs in Early Intimal Thickening and Constrictive Remodeling in Long-Term Period; Long-Term Serial Intravascular Ultrasound Study

Abstract

The development of cardiac allograft vasculopathy (CAV) is known to be induced by a biphasic process involving early intimal thickening and late constrictive remodeling. However, change of intimal thickening long-term period post heart transplantation (HTx) is still unknown. Our aim of this study was to investigate the change of intimal thickening of CAV long-term period post-HTx. Intravascular ultrasound (IVUS) of coronary arteries were performed at 5 to 12 weeks after HTx (baseline) and repeated annually in all HTx recipients. And we reviewed the medical records of consecutive 102 HTx recipients who underwent serial intravascular ultrasounds from baseline to at least 1-year post HTx. 'Progressive intimal thickening on IVUS' was defined as an annual increase in maximal intimal thickness (MIT) of 0.3 mm or greater. The development of CAV included the any coronary revascularization, acute myocardial infarction and the coronary artery lesions classified ISHLT CAV 1 or 2. The progressive intimal thickening on IVUS was high incidence by 3 years post-HTx, however, was low after 3 years post-HTx (Figure 1). Also, similar trends were shown regardless of initiation of everolimus. The incidence of progressive intimal thickening on IVUS was higher in the early period than in the mid-term period (92.3% vs 25.0%, P<0.001). While, cumulative event free rate of the development of CAV was linearly decreasing until 10 years after HTx (Figure 2). This long-term serial IVUS study supported that lumen loss on CAV occurred in a biphasic process consisting of the early intimal thickening and late constrictive remodeling. These results suggest that interventions to suppress an increase in intimal thickening is earlier needed within 3 years post-HTx, and also further treatment strategy to suppress the late constrictive remodeling on CAV are required.