Clinical features and prognosis according to genotype variation in hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac condition with many identified disease-causing genetic variants. However, little is known about the clinical course based on the genotype. This study investigates the relationship between the genotype and clinical outcome in patients with HCM. Method A total of 127 patients diagnosed with HCM and underwent genetic testing using a next-generation sequencing panel included ≥30 cardiomyopathy-related genes at two tertiary hospitals. The genotype-positive group (N=51) with pathogenic/likely-pathogenic variants and the genotype-negative group (N=76) were compared in terms of imaging phenotypes and clinical outcomes. The primary outcome was a composite of sudden cardiac death (SCD) and ventricular arrhythmia. Result Among the genotype-positive group, MYBPC3 (37%), MYH7 (29%) and TNNI3 (16%) variants were predominantly identified. The genotype-positive group was diagnosed at a younger age (51.1 ± 14.0 vs 59.7 ± 11.7, p0.001), showed a higher maximal ventricular wall thickness (17.2 ± 5.1 vs 14.2 ± 4.0, p0.001), and a higher prevalence of late gadolinium enhancement on cardiac magnetic resonance imaging (86.5% vs 54.4%, p=0.003) compared to the genotype-negative group. The genotype-positive group had a higher incidence of the primary outcome (39.2% vs 9.2%, p0.001). Conclusion The patients with pathogenic/likely pathogenic variants exhibited morphological characteristics associated with a high risk of SCD, and experienced worse clinical outcomes.