Natural History and Clinical Outcomes of Patients With DSG2/DSC2 Variant-Related Arrhythmogenic Right Ventricular Cardiomyopathy

作者：Liang Chen, Yuxiao Hu, Ardan M. Saguner, Barbara Bauce, Yaxin Liu, Anteng Shi, Fu Guan, Zhongli Chen, Maria Bueno Marinas, Lingmin Wu, Déborah Foltran, Alexis Hermida, Véronique Fressart, Serena Pinci, Rudy Celeghin, Zixian Chen, Baowei Zhang, Yubi Lin, Xiaorui Liu, Marco Cason, Marika Martini, Ilaria Rigato, Corinna Brunckhorst, Ruth Biller, Cristina Basso, Bing Yang, Xiaoyan Zhao, Julia Cadrin‐Tourigny, Alessio Gasperetti, Cynthia A. James, Xianliang Zhou, Estelle Gandjbakhch, Kalliopi Pilichou, Fırat Duru, Shengshou Hu · 发表于：Circulation · 年份：2025 · DOI：10.1161/circulationaha.124.072226 · 被引用次数：24 · 研究领域：Cardiovascular Effects of Exercise、Cardiomyopathy and Myosin Studies、Eosinophilic Disorders and Syndromes

BACKGROUND: Genetic variants in desmosomal cadherins, desmoglein 2 ( DSG2 ) and desmocollin 2 ( DSC2 ), 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 DSG2 and DSC2 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. RESULTS: Overall, 271 subjects, 254 with DSG2 variants, were included in this study (median age, 38 years [interquartile range, 25–52]; 62.7% male). Of these, 165 were probands, and 200 were diagnosed with definite ARVC. A total of 181 (66.8%) individuals carried missense variants, mainly distributed in the extracellular domains. Notably, we included 78 (28.8%) individuals with multiple variants. Of the 200 cases with diagnosed ARVC, 41 (20.5%) experienced premature cardiac death before the age of 65. Among the 81 individuals for whom both left ventricular ejection fraction and right ventricular fractional area change data were available at presentation, 29 (35.8%) had isolated right ventricular dysfunction, and 16 (19.8%) had biventricular dysfunction. Single-variant carriers who engaged in intense physical exercise were younger at disease ...