Donor-Transmitted Atherosclerosis and the Occurrence of Cardiac Antibody-Mediated Rejection Influenced on the Development of Cardiac Allograft Vasculopathy

Abstract

Cardiac allograft vasculopathy (CAV) is still a major cause of mortality in heart transplant (HTx) recipients. Risk stratification for predicting the development of CAV is needed to suppress the development of CAV. Our aim of this study is to clarify the risk factors for the development of CAV. We retrospectively reviewed consecutive 100 HTx recipients who did not have any coronary artery lesions on first coronary angiography at 5 to 12 weeks after transplantation (baseline). Donor-transmitted atherosclerosis (DA) on intravascular ultrasound (IVUS) was defined as a maximal intimal thickness of 0.5 mm or greater at baseline. Pathology diagnosis of cardiac antibody-mediated rejection (pAMR) was pathologically diagnosed on the basis of the 2013 ISHLT working formulation. The development of CAV included the any coronary revascularization, acute myocardial infarction and the coronary artery lesions classified ISHLT CAV 1 or 2. DA on IVUS was observed in 62 recipients regardless of no apparent lesions on angiography. pAMR was diagnosed in six recipients within 1year post-HTx. Sixteen recipients had the development of CAV, including five who underwent revascularization, one who had acute myocardial infarction and three who found the moderate lesions classified ISHLT CAV2. DA and the occurrence of pAMR within 1 year post-HTx significantly influenced on the cumulative incidence of development of CAV at a mean follow up period of 6.7±4.6 years after transplantation [Hazard ratio (HR): 5.2, 95% confidence intervals (CI):1.2-23.0, P=0.029 and HR: 7.3, 95% CI:2.0-26.7, P=0.003, respectively]. Multivariable cox proportional hazard model including DA, the occurrence of pAMR and associated variables with the development of CAV showed that DA and the occurrence of pAMR were independently associated with the development of CAV (HR: 5.4, 95%CI:1.2-24.6, P=0.028 and HR: 6.7, 95%CI:1.5-29.1, P=0.012, respectively). DA and the occurrence of pAMR within 1 year post-HTx independently influenced on the development of CAV.