Natural History and Clinical Outcomes of Patients With Variant-Related Arrhythmogenic Right Ventricular Cardiomyopathy

Background: Genetic variants in desmosomal cadherins, desmoglein 2 () and desmocollin 2 (), cause a distinct form of arrhythmogenic right ventricular cardiomyopathy (ARVC), which remains poorly reported. In this study, we aimed to provide a comprehensive description of the phenotypic expression, natural history, and clinical outcomes of patients with this ARVC subset. Methods: Genetic and clinical data of and variant carriers were collected from 5 countries in Europe and Asia. We assessed the phenotypic profile of these patients and their clinical outcomes, focusing on heart failure and ventricular arrhythmia events. Conclusions: ARVC attributable to variants in desmosomal cadherins mostly present with right ventricular or biventricular disease. Multiple variants are common in these patients and are associated with more frequent clinical penetrance, earlier onset of disease, and adverse clinical outcomes.