Clinical Course and Predictors of Heart Failure in Asymptomatic Obstructive Hypertrophic Cardiomyopathy

Left ventricular outflow tract obstruction is a major contributor to morbidity in hypertrophic cardiomyopathy and an established therapeutic target. However, the risk factors driving progression to symptomatic heart failure in asymptomatic patients with obstructive hypertrophic cardiomyopathy remain incompletely understood.

We retrospectively identified 341 consecutive asymptomatic patients with obstructive hypertrophic cardiomyopathy (New York Heart Association class I, left ventricular ejection fraction >50%, left ventricular outflow tract gradient ≥30 mm Hg) across 4 centers between 2003 and 2023 (mean±SD age, 48±17 years; 78% men). All underwent transthoracic echocardiography and cardiovascular magnetic resonance. A combined adverse end point included progression to New York Heart Association class II or greater or development of systolic dysfunction (left ventricular ejection fraction <50%). Univariate and multivariable Cox regression analyses were performed.

Over 4.4 (range, 2.4-7.0) years, 98 patients (29%) experienced New York Heart Association progression (6.6%/year). Of these patients, 34 (35%) underwent septal reduction therapy, 4 (4%) developed end-stage heart failure without intervention, and 2 (2%) developed left ventricular ejection fraction <50%. Independent multivariable predictors of the adverse end point were impaired right ventricular stroke volume index, female sex, and prior atrial fibrillation. Patients with progression had lower right ventricular stroke volume index (37±12 versus 42±11 mL/m²; P=0.004; hazard ratio, 1.16 per 5-mL/m² decrease), without significant age interaction (P=0.8). Those in the lowest right ventricular stroke volume index quartile (<34 mL/m²) had 2.5-fold higher progression risk than those in the highest quartile (>49 mL/m²).

Among asymptomatic patients with obstructive hypertrophic cardiomyopathy in a large longitudinal cohort, approximately one-third developed limiting symptoms over 5 years. Impaired right ventricular stroke volume index was a novel, independent predictor of future heart failure and may help identify high-risk patients, with implications for management.