Genotype-phenotype correlations in hypertrophic cardiomyopathy: Insights from an HCM Center of Excellence

Authors

Muddasir Ashraf, Advocate Health - MidwestFollow
M Fuad Jan, Advocate Health - MidwestFollow
Arshad Jahangir, Advocate Health - MidwestFollow
Stacie Kroboth, Advocate Health - MidwestFollow
Zaid Abood, Advocate Health - MidwestFollow
Sara Walczak, Advocate Health - MidwestFollow
Heather Sanders, Advocate Health - MidwestFollow
A Jamil Tajik, Advocate Health - MidwestFollow

Recommended Citation

Ashraf M, Jan MF, Jahangir A, et al. Genotype-phenotype correlations in hypertrophic cardiomyopathy: Insights from an HCM Center of Excellence. Curr Probl Cardiol. 2025;50(4):102996. doi:10.1016/j.cpcardiol.2025.102996

Affiliations

Aurora Sinai/Aurora St. Luke's Medical Centers

Abstract

Background:Owing to the recognition of previously unknown pathogenic gene variants and reclassification of longer-known variants, gene distribution in patients with hypertrophic cardiomyopathy (HCM) is ever-changing. Conflicting data make the role of genotype in risk stratification unclear.

Methods:We evaluated genotype distribution and genotype-phenotype correlations in all adult patients with HCM seen at our HCM Center of Excellence from March 31, 2010, to April 30, 2023. We also evaluated a composite outcome, including all-cause mortality, stroke, implantable cardioverter-defibrillator placement, heart failure hospitalization, left ventricular assist device implantation, heart transplantation, septal myectomy, and alcohol septal ablation, based on genotype status. All-cause mortality was separately analyzed.

Results:Of 827 patients with HCM, genotyping was completed in 754 (91.2%). We identified 202 (27%) genotype-positive (Gen-P), 163 (22%) variant of unknown significance (VUS), and 389 (51%) genotype-negative (Gen-N) patients. Mean age was 47, 57, and 58 years, respectively. The most common gene implicated was MYBPC3 (63%). More patients were on optimal medical treatment after following up with our HCM Center. Electrocardiographic, Holter, echocardiographic, and cardiac magnetic resonance imaging characteristics differed based on genotype status. The composite outcome was worse in Gen-P than Gen-N (HR 1.84, p

Conclusion:MYBPC3 was the most common gene implicated. Outcomes were worse in Gen-P patients. Centers of Excellence play an important role in the optimal medical management of patients with HCM.

Type

Article

PubMed ID

39890042