Genotype Predicts Heart Failure Independent of LVEF, Peak VO2, and NT-proBNP Levels in Hypertrophic Cardiomyopathy.

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 VO2, 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 VO2 (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 VO2, 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.