Genotype-Phenotype Relationship in Hypertrophic Cardiomyopathy.

BACKGROUND/

OBJECTIVES

Hypertrophic cardiomyopathy (HCM) is an inherited disease with genetic and phenotypic variability and an unclear genotype-clinical course relationship. The aim of our study was to assess the phenotypic and molecular characteristics of patients with HCM.

METHODS

Clinical and genetic data from adult HCM patients treated at a university hospital between 2005 and 2024 were analysed. A comparative analysis of probands with a single pathogenic/likely pathogenic (P/LP) variant and without a P/LP variant was performed.

RESULTS

The analysis involved 214 individuals with HCM, 42.1% being females. The median age at HCM diagnosis was 52 (38-62) years. P/LP variants were identified in 92 (43.0%) individuals. Compared to patients without an identified genetic cause, individuals with P/LP variants had a significantly earlier HCM diagnosis (43.5 (32.3-58.0) vs. 54.0 (45.8-65.0) years, p < 0.001) and higher maximal thickness on cardiac imaging (17.5 (15.0-21.0) vs. 17.0 (15.0-19.0) mm, p = 0.009 on transthoracic echocardiography and 21.0 (18.0-23.0) vs. 18.0 (16.0-20.0) mm, p < 0.001 on cardiac magnetic resonance imaging). During the median follow-up of 4.2 (1.6-6.8) years, individuals with P/LP HCM variants had earlier onset of atrial fibrillation (p = 0.021), ventricular tachycardia (p = 0.004), heart failure composite (p = 0.006), and overall composite outcome (p = 0.002). No difference between the groups was observed when hazard ratios for clinical outcomes were adjusted by age at HCM diagnosis and gender.

CONCLUSIONS

Genotype influences HCM phenotype, as patients with P/LP variants experience earlier onset and more pronounced hypertrophy. However, once diagnosed, genotype may not predict the outcomes of HCM.