Clinical features and prognosis according to genotype variation in hypertrophic cardiomyopathy

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.

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.

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, p<0.001), showed a higher maximal ventricular wall thickness (17.2 ± 5.1 vs 14.2 ± 4.0, p<0.001), 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%, p<0.001).

The patients with pathogenic/likely pathogenic variants exhibited morphological characteristics associated with a high risk of SCD, and experienced worse clinical outcomes.