Major Cardiac Events in Patients and Relatives With Hereditary Hypertrophic Cardiomyopathy

Area of Science:

• Cardiovascular Genetics
• Genetic Cardiology
• Molecular Cardiology

Background:

• Limited data exists on hypertrophic cardiomyopathy (HCM) disease expression in relatives of affected individuals.
• Understanding familial disease patterns is vital for effective family screening, genetic counseling, and patient management.
• Implications for family screening, genetic counseling, and management of HCM families are significant.

Purpose of the Study:

• To investigate disease expression and penetrance in relatives of index patients with hypertrophic cardiomyopathy (HCM).
• To analyze relatives carrying pathogenic/likely pathogenic (P/LP) variants in known HCM genes.
• To assess clinical characteristics and major adverse cardiac events (MACE) in affected relatives.

Main Methods:

• Clinical and genetic investigations were performed on 453 HCM index patients.
• 903 relatives of genotype-positive index patients were invited for clinical and genetic testing.
• Penetrance, disease expression, and MACE incidence rates were evaluated in P/LP variant carriers.

Main Results:

• Forty percent of index patients carried a P/LP variant; 54% of relatives tested carried a P/LP variant.
• HCM penetrance among relatives was 39%.
• No significant differences in age at diagnosis, clinical characteristics, or MACE incidence were observed between index patients and affected relatives.

Conclusions:

• Disease expression in hypertrophic cardiomyopathy (HCM) is similar between index patients and relatives carrying P/LP variants.
• Affected relatives and index patients have an equal risk of major adverse cardiac events (MACE).
• Findings support family screening and follow-up for genotype-positive HCM families to improve management and reduce complications.