Reevaluating exercise intolerance in hypertrophic cardiomyopathy: the role of stress echocardiography combined with cardiopulmonary exercise testing

Abstract

Background: Dynamic left ventricular outflow tract obstruction (LVOTO) defines obstructive hypertrophic cardiomyopathy (oHCM), while mechanisms of exercise intolerance in non-obstructive hypertrophic cardiomyopathy (noHCM) remain unclear. Cardiopulmonary exercise testing combined with stress echocardiography (CPETecho) enables simultaneous assessment of LVOTO and cardiopulmonary function, providing insights into exercise limitation determinants across hypertrophic cardiomyopathy phenotypes. Objectives: To assess CPETecho diagnostic yield for dynamic LVOTO detection and identify distinct exercise intolerance determinants in oHCM versus noHCM. Methods: In this multicenter cohort, 195 hypertrophic cardiomyopathy patients underwent maximal semi-supine CPETecho with serial LVOT gradient, pulmonary pressure, and cardiopulmonary evaluations. Exercise intolerance (peak VO₂ <80% predicted) was analyzed via logistic regression for contributing factors. Results: Among 195 patients (mean age 61 years, 71% male), 57% was labeled as oHCM while 43% was noHCM. Highest LVOTO gradients occurred post-exercise recovery (p<0.001 versus mid/peak). Exercise intolerance affected 52% overall (65% oHCM vs 35% noHCM, p<0.001). In oHCM, LVOTO gradient was the primary determinant; in noHCM, mid-exercise E/e′ ratio (diastolic dysfunction) correlated most strongly. Chronotropic incompetence was common (61%), partly due to beta-blocker use (46%). Conclusions: CPETecho unmasks distinct exercise intolerance mechanisms-LVOTO in oHCM, diastolic dysfunction in noHCM-supporting a personalized diagnostic approach.