JACC Heart Fail. 2026 Jun 8:103149. doi: 10.1016/j.jchf.2026.103149. Online ahead of print.
ABSTRACT
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a myocardial disorder characterized by left ventricular hypertrophy and progression to heart failure (HF). Approximately 40% of cases are caused by variants in genes encoding sarcomere proteins.
OBJECTIVES: This study sought to determine the relationship between genotype and other clinical predictors of HF outcomes in HCM patients.
METHODS: This observational, single-center cohort comprised 505 genotyped HCM patients (52 years of age [Q1-Q3: 41-62 years], 33% women). Patients were stratified into gene-positive (G+) and gene-elusive (G-) groups. The primary endpoint was HF-related death or cardiac transplantation. Secondary endpoints included cardiac death, arrhythmic events, and all-cause mortality. Proportional hazards models were used to evaluate predictors of outcomes, including genetic status, log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, peak VO, and left ventricular ejection fraction (LVEF).
RESULTS: During a median follow-up of 10.6 years (Q1-Q3: 4.6-15.0 years), 34 patients (6.7%) experienced the primary outcome (HF-related death: 22 [4.4%] and heart transplantation: 12 [2.4%]). The HF endpoint occurred in 12.8% (28 of 219) of the G+ group compared with 2.1% (6 of 286) of the G- group. In multivariable Cox analysis, G+ status (HR: 5.86; 95% CI: 2.26-15.25; P < 0.001), log NT-proBNP (HR: 2.46; 95% CI: 1.59-3.80; P < 0.001), peak VO (HR: 0.90; 95% CI: 0.82-0.98; P < 0.001), and LVEF (HR: 0.74 per 5% increment; 95% CI: 0.63-0.86; P < 0.001) were independently associated with HF outcomes. For secondary endpoints, 60 patients (11.9%) died of cardiac causes, 34 (6.7%) experienced arrhythmic events, and 115 (22.8%) died of any cause.
CONCLUSIONS: Genetic status, peak VO, log NT-proBNP, and LVEF independently predict HF outcomes in HCM. Combining genotype with HF biomarkers and functional capacity measures identifies patients at increased risk of HF-related death or transplant and may support targeted monitoring and selection for disease-modifying trials.
PMID:42268168 | DOI:10.1016/j.jchf.2026.103149