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August 31, 2026Journal of the American College of CardiologyOpen Access

Echocardiographic Changes With Mavacamten in Nonobstructive Hypertrophic Cardiomyopathy

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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 LV and LA function in symptomatic adults with nonobstructive hypertrophic cardiomyopathy?

Population

580 symptomatic patients with nonobstructive hypertrophic cardiomyopathy

Comparison

Mavacamten titrated between 1 and 15 mg vs placebo

Design

Phase 3 randomized placebo-controlled trial exploratory analysis

Follow-up

48 weeks

Key result

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.

Authors

MDMilind Y. DesaiYOYuichiro OkushiSJShada Jadam

Discussion

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Overview

Mavacamten improves echocardiographic markers of LV diastolic and LA function and modestly regresses LV hypertrophy in symptomatic nonobstructive HCM, though it carries a risk of reversible LVEF reduction.

Key Points

  • Evaluate echocardiographic changes in left ventricular and left atrial structure and function from baseline to week 48 in patients with symptomatic nonobstructive hypertrophic cardiomyopathy receiving mavacamten.
  • Exploratory analysis of the phase 3, randomized, placebo-controlled ODYSSEY-HCM trial (NCT05582395) including 580 symptomatic nHCM patients (mean age 56 ± 15 years, 45.9% women).
  • Participants were randomized to receive placebo or mavacamten (5 mg daily titrated between 1 and 15 mg based on left ventricular ejection fraction [LVEF]) with echocardiograms evaluated at baseline and week 48.
  • At week 48, mavacamten showed significant placebo-corrected reductions 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]), E/e' (-1.3 [95% CI: -2.0 to -0.7]), and LVEF (-5.3% [95% CI: -5.9% to -4.1%]; P < 0.01).
  • An LVEF reduction below 50% occurred in 21.5% (n = 62) of patients in the mavacamten group versus 1.7% (n = 5) in the placebo group, which recovered following temporary drug interruption.
  • Among mavacamten-treated patients maintaining LVEF ≥50% (n = 212), LV global longitudinal strain improved (-0.4% [95% CI: -0.8% to -0.05%]; P < 0.05), with concurrent significant improvements in left atrial contractile and conduit strain.

Study Design

Type

RCT (n=580)

Blinding

Double-blind

Randomization

randomized

Multicenter

Yes

Structured PICO

Does mavacamten improve echocardiographic markers of LV and LA function in symptomatic adults with nonobstructive hypertrophic cardiomyopathy?

P
Population
580 symptomatic adults with nonobstructive hypertrophic cardiomyopathy and preserved ejection fraction, followed for 48 weeks.
I
Intervention
Mavacamten (5 mg/d, titrated between 1 and 15 mg based on left ventricular ejection fraction [LVEF])
C
Comparator
Placebo
O
Outcome
Echocardiographic changes in LV systolic/diastolic function and left atrial (LA) function from baseline to week 48surrogate

Main Result

Mean Difference: -2.1 (95% CI -2.5–-1.7)

Absolute Event Rate: 18.9% vs 20.7%

p-value: p=<0.0001

Mavacamten improves echocardiographic markers of LV diastolic and LA function and modestly regresses LV hypertrophy in symptomatic nonobstructive HCM, though it carries a risk of reversible LVEF reduction.

Limitations

  • Exploratory and post hoc nature of the analysis
  • No correction for multiple comparisons, meaning nominal P values should be interpreted cautiously
  • Clinical implications of structural changes remain uncertain given the lack of symptom improvement in the primary trial

Cite This Study

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.

synapsesocial.com/papers/6a952d67a36a2b91f4f443a6https://doi.org/10.1016/j.jacc.2025.08.019
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Effects of Mavacamten on Cardiac Biomarkers in Nonobstructive Hypertrophic Cardiomyopathy2025 · 12 citations
  2. 2Echocardiographic changes with mavacamten in patients with obstructive hypertrophic cardiomyopathy: early experience from a referral center2026
  3. 3Mavacamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy2025 · 68 citations
  4. 4Effect of Mavacamten on Echocardiographic Features in Chinese Patients with Obstructive Hypertrophic Cardiomyopathy: Results from the EXPLORER-CN Study2025 · 9 citations
  5. 5Systematic evaluation of serial electrocardiographic changes in patients treated with mavacamten2025