Variation in Combined Cardiopulmonary Exercise Test and Stress Echocardiography Findings in Patients With Obstructive Hypertrophyc Cardiomyopathy Treated With Mavacamten: A Prospective Observational Multicenter Study

Background Mavacamten, a selective cardiac myosin inhibitor, improves left ventricular outflow tract (LVOT) obstruction and symptoms in obstructive hypertrophic cardiomyopathy (HCM). However, real–world data integrating cardiopulmonary exercise testing (CPET) and echocardiography remain limited. Methods In this prospective multicenter study, 28 patients with symptomatic obstructive HCM underwent transthoracic echocardiography and symptom–limited CPET at baseline and after 6 months of mavacamten therapy. The primary endpoint was the change in echocardiographic and CPET parameters. An exploratory secondary endpoint was the identification of baseline predictors of functional response, defined as a ≥5 percentage point increase in predicted peak oxygen consumption (%pred pVO₂). Results After 6 months of treatment, resting LVOT gradient decreased from 30.5 [19.2–40.0] to 7.0 [6.0–8.2] mmHg (p = 0.001), and peak LVOT gradient from 75.5 [60.0–106.2] to 34.0 [17.8–51.2] mmHg (p = 0.001) (Figure 1). Left atrial volume index and diastolic function indices significantly improved, with reductions in E/e′ at rest (12.6 [9.4–17.2] to 10.6 [8.3–12.7]; p=0.001) and at peak (14.1 [13.1–17.1] to 11.2 [9.3–13.8]; p = 0.001) (Figure 2). Peak pVO₂ increased from 1213 [918–1598] to 1352 [1039–1992] ml/min (p= 0.001), pVO₂ ml/min/kg from 16.0 [13.5–17.8] to 16.4 [14.6–21.0] (p=0.004), and %pred pVO₂ from 68.0 [63.0–78.0] to 77.0 [69.5–86.0] (p=0.008) (Figure 3). PETCO₂ at peak exercise increased (34.1 [31.2–35.6] to 35.4 [33.1–37.6]; p=0.002), and VE/VCO₂ slope decreased significantly (35.0 [32.7–37.0] to 31.6 [28.7–35.0]; p=0.007), indicating enhanced ventilatory efficiency. Overall, 46% of patients achieved a functional response (Δ%pred pVO₂ ≥+5). Lower baseline %pred pVO₂ (OR 0.58 [0.36–0.91]; p=0.021) and higher VE/VCO₂ slope (OR 1.56 [1.02–2.42]; p=0.041) independently predicted response, with fair model discrimination (AUC=0.73). Conclusions Mavacamten significantly reduced LVOT gradients and improved diastolic, ventilatory, and functional parameters in obstructive HCM. Nearly half of patients experienced a clinically relevant improvement in exercise capacity, with baseline ventilatory inefficiency and lower aerobic performance identifying those most likely to benefit.