Key result
Mavacamten reduces maximal LV wall thickness by ~2.1 mm vs placebo in symptomatic nonobstructive HCM.
Why the study?
Symptomatic nonobstructive hypertrophic cardiomyopathy lacks approved therapies, and this exploratory analysis evaluated echocardiographic changes with mavacamten.
Does mavacamten improve echocardiographic markers of left ventricular and left atrial function in symptomatic adults with nonobstructive hypertrophic cardiomyopathy?
RCT (n=580)
Double-blind
randomized
Yes
Does mavacamten improve echocardiographic markers of left ventricular and left atrial function in symptomatic adults with nonobstructive hypertrophic cardiomyopathy?
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“In nHCM, it drives biochemical and structural remodelling without conferring meaningful symptomatic benefit, while potentially posing a considerably elevated risk of clinically relevant systolic dysfunction. These findings support phenotype-guided precision therapy, urging stringent echocardiographic surveillance and caution regarding off-label use in non-obstructive disease.”
“A secondary analysis of the ODYSSEY-HCM data published in the Journal of the American College of Cardiology revealed that mavacamten was associated with improvements in cardiac biomarkers and favourable cardiac remodelling compared with placebo; these findings warrant further investigation into the efficacy of mavacamten in this patient cohort.”
“This case provides compelling support for a similar effect of mavacamten in some patients with nonobstructive HCM. We demonstrate novel insight into ECG changes, which have never been reported in nHCM, complemented by improvements in left ventricular diastolic function as also reported in recently published literature.”
In symptomatic nonobstructive hypertrophic cardiomyopathy, mavacamten improved echocardiographic markers of LV diastolic and LA function and induced modest regression of LV hypertrophy, though it caused a reversible drop in LVEF <50% in 21.5% of patients.
BACKGROUND Symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM) lacks approved therapies. The ODYSSEY-HCM trial (A Study of Mavacamten in Non-Obstructive Hypertrophic Cardiomyopathy; NCT05582395), the largest to date in HCM patients, evaluating the efficacy of mavacamten in symptomatic adults with nHCM, did not demonstrate improvements in its primary endpoints (functional capacity and patient-reported health status). OBJECTIVES This exploratory analysis of the phase 3, randomized, placebo-controlled trial evaluated echocardiographic changes in nHCM patients from baseline to week 48. METHODS Symptomatic nHCM patients were randomized to placebo or mavacamten (5 mg/d, titrated between 1 and 15 mg based on left ventricular ejection fraction [LVEF]). Echocardiographic assessments of LV systolic/diastolic function and left atrial (LA) function were performed at baseline and week 48. RESULTS Among 580 randomized patients (mean age 56 ± 15 years, 45.9% women), baseline measures included LVEF (65.8 ± 4%), maximal LV wall thickness (20.8 ± 4 mm), LV mass index (122.3 ± 31 g/m2), average E/e' (13.3 ± 6), and LV-global longitudinal strain (-13.2 ± 4%). LA parameters included volume index (43.5 ± 16 mL/m2), reservoir strain (19.1 ± 9%), and conduit strain (-11.6 ± 6%). At week 48, there was significant placebo-corrected treatment difference with patients on mavacamten demonstrating significant reduction in maximal LV wall thickness (-2.1 mm [95% CI: -2.5 to -1.7 mm]), LV mass index (-3.8 g/m2 [95% CI: -7.1 to -0.5 g/m2]), and E/e' (-1.3 [95% CI: -2.0 to -0.7]), with a -5.3% [95% CI: -5.9% to -4.1%]; P < 0.01) reduction in LVEF. A reduction in LVEF <50% occurred in 62 patients (21.5%) in the mavacamten arm vs 5 (1.7%) in the placebo arm and recovered following drug interruption. Patients in the mavacamten group maintaining LVEF ≥50% throughout the study (n = 212) demonstrated an improvement in LV-global longitudinal strain at week 48 (-0.4% [95% CI: -0.8% to -0.05%]; P < 0.05). LA functional parameters including contractile (-1.1% [95% CI: -1.8% to -0.4%]) and conduit (-1.4% [95% CI: -0.6% to -2.3%]) strain also improved significantly at week 48 (P < 0.05), whereas LA volume was significantly reduced in patients without atrial fibrillation (-2.6 mL/m2 [95% CI: -4.7 to -1.11 mL/m2]; P = 0.009). CONCLUSIONS Symptomatic nHCM patients treated with mavacamten demonstrated directional improvements in markers of LV diastolic and LA function, modest regression in LV hypertrophy-related parameters, but 1 in 5 demonstrated an LVEF <50%, which reversed following therapy interruption.
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Desai et al. (2025) conducted an RCT in Nonobstructive hypertrophic cardiomyopathy (n=580). Mavacamten vs. Placebo was evaluated on Change in maximal LV wall thickness from baseline to week 48 (MD -2.1 mm, 95% CI -2.5 to -1.7, p=<0.0001). Mavacamten significantly reduced maximal left ventricular wall thickness by 2.1 mm compared to placebo at 48 weeks in patients with symptomatic nonobstructive hypertrophic cardiomyopathy.
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