Abstract 12176: Outcomes and Genetic Characteristics of Hypertrophic Cardiomyopathy With Severe Right Ventricular Hypertrophy

Abstract

Introduction: Severe right ventricular hypertrophy (SRVH) is extremely rare in hypertrophic cardiomyopathy (HCM). Hypothesis: We assessed the hypothesis that patients with HCM with SRVH may have multiple mutations and poor prognosis. Methods: We performed a retrospective cohort study involving 2415 HCM patients. Patients with HCM with a maximum right ventricular wall thickness ≥10 mm, either with or without a pressure gradient at the RV outflow tract (RVOT) exceeding 25 mmHg, were enrolled. Deep (30X) whole-genome sequencing was performed in 11 patients using the Illumina HiSeq X platform. The patients'clinical features, cardiovascular mortality and morbidity were analyzed. The survival estimates were calculated using the Kaplan-Meier method, and risk of either cardiovascular death or event was determined using a multivariate Cox hazards regression model. Results: Of the 2415 HCM patients, 43 patients (1.6%) with SRVH were identified and 12 of them demonstrated isolated RVOT obstruction. The mean age at diagnosis was 31.1 ± 16.3 years, and 24 (55.8%) of them were women. The maximum average RV wall thickness was 13.3 ± 2.4 mm. The multivariate Cox regression analysis identified 2 independent predictors of cardiovascular death, including NYHA class ≥III, with a hazard ratio of 8.6 (95% CI: 1.70-43.38, p = 0.009), and a left ventricular end-diastolic diameter ≥50 mm, with a hazard ratio of 6.0 (95% CI: 1.67-21.92, p = 0.006). Age ≤18 years was with a 3-fold increased risk cardiovascular events (95% CI: 1.14-7.16, p = 0.002). At least one variant in a specific sarcomere gene was identified in 10 patients (90.9%), of which the MYH7 mutation was the most common (n = 6, 54.5%), and 10 novel locations were detected. Double mutations involving HCM-related genes were observed in 8 (73%) patients. All patients exhibited either double or multiple mutations, either in arrhythmogenic right ventricular, dilated cardiomyopathy or ion-channel disease genes. Conclusions: HCM with SRVH was characterized by an early onset of disease and increased cardiovascular mortality and morbidity. Double or multiple sarcomere gene mutations might be responsible for this phenotype with multiple mutations in other forms of cardiomyopathy and ion-channel disease associated genes.