Long-Term Favorable Cardiac Remodeling in Obstructive Hypertrophic Cardiomyopathy Patients Treated With Mavacamten for up to 128 Weeks: Insights From the VALOR-HCM Trial.

Background: In the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy; NCT04349072) trial, patients with severely symptomatic obstructive hypertrophic cardiomyopathy (HCM) treated with mavacamten demonstrated significant improvement in left ventricular outflow tract (LVOT) gradients and echocardiographic indices of cardiac remodeling in the short term.

Objectives: The authors sought to assess whether mavacamten results in sustained favorable long-term cardiac remodeling at 128 weeks (end of trial).

Methods: A total of 112 adult symptomatic obstructive HCM patients (mean age: 60.3 years; 50% men; and 94% NYHA functional class III/IV) who were referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo for 16 weeks. Subsequently, placebo patients transitioned to and received 112 weeks of mavacamten, and the original mavacamten group received 128 weeks of mavacamten. All patients had comprehensive echocardiographic assessments (including LV and left atrial [LA] global longitudinal strain measurements using vendor neutral software [TOMTEC-ARENA TTA2, Philips Healthcare]) at baseline and 128-week follow-up.

Results: At week 128, there was a sustained improvement (mean percentage of change from baseline, all P < 0.05) in LVOT gradients (resting [-61%], post-Valsalva [-72%], and postexercise [-53%]), LV mass index (-11%), septal E/e' (-18%), LV global longitudinal strain (4.5%), LA volume index (-6%), and LA strain (conduit strain [16%], contraction [35%], and reservoir [32%]). In 71 patients with ≥5 point improvement in the Kansas City Cardiomyopathy Questionnaire 23-item Clinical Summary Score (KCCQ-23-CSS), there was a significant and sustained improvement (all P < 0.05), whereas in 25 patients with <5 point improvement in the KCCQ-23-CSS, there was no significant improvement in various LA and LV strain values.

Conclusions: In the VALOR-HCM trial, treatment with mavacamten resulted in sustained favorable cardiac remodeling, including improvement in LVOT gradients, cardiac volumes, cardiac hypertrophy, diastolic function, and markers of LA and LV strain from baseline through week 128, suggesting disease modification. These favorable changes also occurred in association with meaningful improvement in quality of life.