Abstract 9337: The Association of Echo Parameters With Health Status in Patients With Obstructive Hypertrophic Cardiomyopathy. Insights From the Explorer-HCM Trial

Introduction: The EXPLORER-HCM trial showed mavacamten, a direct cardiac myosin inhibitor, improved the health status of patients with obstructive hypertrophic cardiomyopathy (HCM). To explore physiologic mechanisms for this improvement, we examined cross-sectional and longitudinal associations of echocardiographic parameters with health status. Methods: EXPLORER-HCM was a 13-country, double-blind randomized trial of mavacamten or placebo for 30 weeks in symptomatic patients with obstructive HCM and peak LVOT gradient ≥50 mmHg. Health status was assessed with the Kansas City Cardiomyopathy Questionnaire-overall summary score (KCCQ-OS, range 0-100, higher=better). Using a series of multivariable linear regression models, we examined the association of 1) echo parameters with KCCQ-OS at baseline and 2) change in echo parameters with change in KCCQ-OS. Nonlinear associations were explored with cubic splines. As this was a mechanistic analysis, treatment was not included. Results: Among 196 patients (mean age 58±12 years, 39% women), mean KCCQ-OS was 67±18 at baseline and 76±19 at 30 weeks; mean change of 10±16 points. At baseline, only interventricular septal thickness (IVST) was significantly associated with KCCQ-OS in adjusted analyses (1.2-point decrease in KCCQ-OS per 1 mm higher IVST; 95% CI -2.2 to -0.2, p=0.015). However, when comparing changes in echo parameters with changes in KCCQ-os, decreases in LVOT gradient at rest, LVOT gradient post-exercise, LVOT gradient with Valsalva, LV mass, posterior wall thickness, and IVST were each associated with significant improvements in KCCQ-OS (FIGURE). Measures of diastolic function were not associated with KCCQ-OS, either cross-sectionally or longitudinally. Conclusions: Among patients with obstructive HCM, reductions in LVOT gradients, LV mass, and wall thickness (IVST>posterior wall) were associated with significant improvements in patients’ symptoms, function, and quality of life.