Early onset of heart failure in Japanese ARVC patients with pathogenic desmosomal gene variants

Abstract

Abstract Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy mainly caused by desmosomal gene variants. Although there are a lot of reports regarding to European ARVC patients, the ones in Asian are a few, and the characteristics of Asian ARVC have been still unclear. We have reported that the genetic backgrounds in Japanese ARVC patients were different from those in European ones. In this study, we aimed to examine the phenotype and outcome of Japanese ARVC patients with specific genetic backgrounds. Methods and results This study included 104 Japanese ARVC patients who were diagnosed as definite in the 2010 Task Force Criteria for ARVC and received genetic analysis (79 males [76%]; median age at diagnosis, 40 years [IQR 22–53 years].) Fifty-seven patients carried variants in desmosomal genes classified as pathogenic based on ACMG guideline: 30 in DSG2 (29%), 22 in PKP2 (21%), 2 in DSC2 (2%) and 3 in DSP (3%). The median age of diagnosis was significantly younger in the patients with the pathogenic variants than in those without (37 years [IQR 21–49 years] vs. 46 years [IQR 34–58 years], P=0.01). During a median follow-up of 9.3 years (IQR 3.5–20.9 years), 10 patients died and 2 were received heart transplantation. Sixty-two suffered lethal arrhythmic events including cardiopulmonary arrest, ventricular fibrillation, sustained ventricular tachycardia and appropriate shocks by implantable cardioverter defibrillator. Twenty-two were hospitalized for heart failure. There was no difference in these events rate between the two groups. However, survival analysis revealed that patients with pathogenic variants hospitalized for heart failure significantly earlier in their life than those without (P=0.04, log-rank test, Figure 1). Conclusions The Japanese ARVC patients with pathogenic variants in desmosomal genes are diagnosed and hospitalize for heart failure at younger age than those without. These findings have not been reported in other ethnics. Our study warns that we should be cautious for not only the prevention of lethal arrhythmic events but also the progress of the heart failure in Japanese ARVC patients with pathogenic variants. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Japan Agency for Medical Research and Development Figure 1