Long-Term Favorable Cardiac Remodeling in Obstructive Hypertrophic Cardiomyopathy Patients Treated With Mavacamten
Milind Y Desai1, Yuichiro Okushi2, Kathy Wolski3
1Hypertrophic Cardiomyopathy Center, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Coordinating Center for Clinical Research, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Insights
Mavacamten significantly improved cardiac remodeling and reduced LVOT gradients in hypertrophic cardiomyopathy (HCM) patients over 128 weeks. These long-term benefits suggest disease modification and improved quality of life.
Area of Science:
- Cardiology
- Pharmacology
- Medical Imaging
Background:
- The VALOR-HCM trial investigated mavacamten for symptomatic obstructive hypertrophic cardiomyopathy (HCM).
- Short-term mavacamten treatment showed improvements in LVOT gradients and cardiac remodeling.
Purpose of the Study:
- To assess long-term cardiac remodeling effects of mavacamten over 128 weeks.
- Evaluate sustained improvements in hypertrophic cardiomyopathy (HCM) patients.
Main Methods:
- 112 adult obstructive HCM patients were randomized to mavacamten or placebo.
- Echocardiography, including LV and LA strain, was performed at baseline and 128 weeks.
Main Results:
- Sustained improvements observed in LVOT gradients, LV mass index, septal E/e', LV global longitudinal strain, and LA strain.
- Significant improvements in quality of life (KCCQ-23-CSS) correlated with favorable cardiac remodeling.
Conclusions:
- Mavacamten demonstrated sustained favorable cardiac remodeling and disease modification in HCM.
- Long-term treatment with mavacamten improved cardiac function and patient quality of life.
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.
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