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August 31, 2026Journal of the American College of Cardiology

Effects of Mavacamten on Cardiac Biomarkers in Nonobstructive Hypertrophic Cardiomyopathy

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Why the study?

No therapy is approved for symptomatic nonobstructive hypertrophic cardiomyopathy, and the role and response of cardiac biomarkers with mavacamten needed evaluation.

Does mavacamten reduce cardiac biomarkers in symptomatic adults with nonobstructive hypertrophic cardiomyopathy?

Population

580 symptomatic nHCM patients

Comparison

Mavacamten vs placebo

Design

Exploratory analysis of a randomized trial

Follow-up

48 weeks

Key result

Mavacamten treatment for 48 weeks in symptomatic nonobstructive hypertrophic cardiomyopathy significantly reduced NT-proBNP by 58% (geometric mean ratio 0.42; 95% CI 0.37-0.47; P<0.001) versus placebo.

Authors

MDMilind Y. DesaiIOIacopo OlivottoTATheodore P. Abraham

Discussion

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Overview

In symptomatic nonobstructive hypertrophic cardiomyopathy, mavacamten significantly reduced NT-proBNP and hs-cTnI over 48 weeks compared to placebo, despite the main trial not meeting its primary clinical endpoints.

Key Points

  • To evaluate baseline determinants of cardiac biomarkers and determine the 48-week effects of mavacamten versus placebo on NT-proBNP and hs-cTnI levels in symptomatic nonobstructive hypertrophic cardiomyopathy.
  • Randomized, placebo-controlled trial (ODYSSEY-HCM; NCT05582395) evaluating 580 symptomatic adult patients with nonobstructive hypertrophic cardiomyopathy (mean age 56 ± 15 years, 45.9% women).
  • Patients were randomized to receive mavacamten (titrated from 5 mg/d to 1–15 mg/d based on left ventricular ejection fraction) or placebo for 48 weeks.
  • Changes from baseline to week 48 in NT-proBNP and high-sensitivity cardiac troponin I (hs-cTnI) concentrations were measured alongside echocardiographic parameters.
  • At baseline, median biomarker levels were elevated across the cohort (NT-proBNP: 917.5 ng/L, IQR: 463–1,725 ng/L; hs-cTnI: 29.1 ng/L, IQR: 14.4–91.7 ng/L).
  • At week 48, the mavacamten arm achieved a 58% reduction in NT-proBNP (geometric mean ratio: 0.42; 95% CI: 0.37–0.47; P < 0.001) and a 51% reduction in hs-cTnI (geometric mean ratio: 0.49; 95% CI: 0.45–0.53; P < 0.001).
  • No significant change in either biomarker occurred in the placebo group, with reductions in the mavacamten group appearing early and persisting through 48 weeks.

Study Design

Type

RCT (n=580)

Randomization

randomized

Structured PICO

Does mavacamten reduce cardiac biomarkers in symptomatic adults with nonobstructive hypertrophic cardiomyopathy?

P
Population
580 symptomatic adults with nonobstructive hypertrophic cardiomyopathy, mean age 56 years, followed for 48 weeks.
I
Intervention
Mavacamten (starting at 5 mg/d, with titration ranging from 1 to 15 mg, based on left ventricular ejection fraction) for 48 weeks
C
Comparator
Placebo
O
Outcome
Changes in NT-proBNP and hs-cTnI from baseline to week 48surrogate

Main Result

Effect estimate: Geometric mean ratio 0.42 (95% CI 0.37-0.47)

p-value: p=<0.001

In symptomatic nonobstructive hypertrophic cardiomyopathy, mavacamten significantly reduced NT-proBNP and hs-cTnI over 48 weeks compared to placebo, despite the main trial not meeting its primary clinical endpoints.

Limitations

  • Whether these changes translate into longer-term adaptive remodeling and improvements in patient-reported health status, exercise capacity, and outcomes remain to be ascertained.

Cite This Study

Desai et al. (2025) conducted an RCT in symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM) (n=580). Mavacamten vs. placebo was evaluated on Change in NT-proBNP from baseline to week 48 (Geometric mean ratio 0.42, 95% CI 0.37-0.47, p=<0.001). Mavacamten treatment for 48 weeks in symptomatic nonobstructive hypertrophic cardiomyopathy significantly reduced NT-proBNP by 58% (geometric mean ratio 0.42; 95% CI 0.37-0.47; P<0.001) versus placebo.

synapsesocial.com/papers/6a952d67a36a2b91f4f443a5https://doi.org/10.1016/j.jacc.2025.08.017
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