TY - JOUR
T1 - Genotype-phenotype correlations in hypertrophic cardiomyopathy: Insights from an HCM Center of Excellence
AU - Ashraf, Muddasir
AU - Jan, M Fuad
AU - Jahangir, Arshad
AU - Kroboth, Stacie
AU - Abood, Zaid
AU - Walczak, Sara
AU - Sanders, Heather
AU - Tajik, A Jamil
PY - 2025/1/29
Y1 - 2025/1/29
N2 - 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 ages were 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
AB - 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 ages were 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
U2 - 10.1016/j.cpcardiol.2025.102996
DO - 10.1016/j.cpcardiol.2025.102996
M3 - Article
C2 - 39890042
JO - Aurora GME
JF - Aurora GME
ER -