Work

Genetic Yield and Imaging Characteristics in Apical-Dominant Hypertrophic Cardiomyopathy

Year: 2026

Type: article

Abstract: ypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, characterized by unexplained left ventricular (LV) hypertrophy, with pathogenic (P) or likely pathogenic (LP) variants in sarcomeric genes identified in 30% to 60% of patients.1 Apical HCM, a distinct morphological subtype predominantly affecting the LV apex, is significantly more prevalent in Asian populations (up to 40% of cases) compared with Western cohorts (approximately 8%).2,3 However, genetic testing yield in apical HCM has historically been lower than in classic forms, with prior studies reporting yields of only 14% to 25% using targeted gene panels.4-6 Wholeexome sequencing (WES) may improve diagnostic sensitivity by enabling comprehensive analysis of all protein-coding regions.7 We aimed to evaluate the diagnostic yield of WES and genotypephenotype associations, including cardiac magnetic resonance (CMR)-defined myocardial fibrosis, in a Korean HCM cohort with a high prevalence of apical morphology.Understanding the genetic landscape of apical HCM is important for informing family screening strategies and risk stratification in Asian populations.We prospectively enrolled 116 unrelated, consecutive HCM patients (LV wall thickness $15 mm by echocardiography) from Soonchunhyang University Bucheon Hospital between December 2021 and May 2024.Patients with uncontrolled hypertension, severe valvular disease, or concomitant systemic disease were excluded.All patients underwent WES; genomic DNA was extracted from peripheral blood and sequenced on an Illumina platform.Variants were classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines 8 ; patients harboring P/LP variants were classified as genotype-positive.Apical HCM was defined as hypertrophy predominantly involving the LV apex, including both pure apical and mixed (apical with midventricular involvement) types.3 A subset of patients (n = 57) underwent CMR.Late gadolinium enhancement (LGE) extent and extracellular volume (ECV) fraction were quantified using validated automated deeplearning software (Myomics, Phantomics Inc).9Continuous variables were compared using the Student's t-test or Wilcoxon rank-sum test, and categorical variables were compared using the chi-square or Fisher exact test.This study was approved by the Soonchunhyang University Bucheon Hospital Institutional Review Board (SCHBC 2021-10-003-001), and all participants provided written informed consent.

Source: JACC Asia

DOI: 10.1016/j.jacasi.2026.08.004