Mavacamten sharply lowers heart outflow obstruction in real-world Chinese patient cohort

A real-world study from a large Chinese cardiac center reports that mavacamten, the first selective cardiac myosin inhibitor approved for obstructive hypertrophic cardiomyopathy, produced dramatic and sustained reductions in left ventricular outflow tract obstruction over 30 weeks of treatment. In the retrospective analysis, published in Frontiers in Pharmacology, patients who started mavacamten saw their resting outflow tract gradient fall to an average of 23.76 mmHg, while patients on conventional therapy remained severely obstructed at 78.49 mmHg. The provoked gradient, measured during a Valsalva maneuver that stresses the obstruction, dropped to 48.95 mmHg with mavacamten but persisted at 113.59 mmHg with standard drugs. The authors, led by Fang Yuan of Fuwai Hospital of Zhengzhou University, describe the findings as consistent with the mechanism-based promise shown in earlier clinical trials, now reproduced in routine hospital practice.

Hypertrophic cardiomyopathy is a disorder in which the main pumping chamber of the heart thickens abnormally, and roughly two-thirds of affected individuals develop dynamic obstruction of the left ventricular outflow tract, the pathway through which blood exits the heart. Improved genetic testing has pushed estimated prevalence upward from about 0.16 to 0.23 percent toward 0.2 to 0.5 percent, with pathogenic gene variants identified in roughly 60 percent of cases. Traditional drug therapy relies on beta-blockers and non-dihydropyridine calcium channel blockers, which blunt symptoms but do not address the underlying hypercontractility that drives the obstruction. Mavacamten works differently: it selectively inhibits cardiac myosin, directly reducing the excessive contractile force at the root of the disease. China approved the drug on 24 April 2024 for patients in NYHA functional class II or III, marking a shift from purely symptomatic management toward mechanism-based treatment.

The new analysis drew on patients hospitalized at Fuwai Central China Cardiovascular Hospital between January 2024 and May 2025. Of 317 patients initially screened, 57 were excluded for reasons including age under 18, NYHA class I or IV status, severe renal or hepatic dysfunction, incomplete echocardiographic data, or refusal of follow-up. The remaining 260 eligible patients were assigned to groups according to mavacamten availability after its approval, standardized eligibility criteria, and physician judgment: 126 began mavacamten and 134 started conventional pharmacotherapy with beta-blockers, non-dihydropyridine calcium channel blockers, or both. After 30 weeks of follow-up, 38 patients had been lost, leaving 222 patients, 111 in each group, for the final analysis. To qualify, all patients had to meet diagnostic criteria from the 2023 Chinese guidelines, including a resting or Valsalva-provoked outflow tract gradient of at least 30 mmHg together with defined myocardial hypertrophy, and a baseline ejection fraction of at least 55 percent.

Mavacamten was dosed according to a hospital protocol adapted from the EXPLORER-HCM and EXPLORER-CN trials. Patients began at 2.5 mg once daily, with titration at weeks 6, 12 and 18 guided by serial echocardiography. Doses could be increased stepwise to 5, 10 and 15 mg if the resting gradient remained at or above 30 mmHg while the ejection fraction stayed at or above 55 percent. A dose reduction was mandatory if the ejection fraction fell to between 45 and 54 percent, and the drug was stopped immediately if it dropped below 45 percent. Electronic prescription records, outpatient follow-up notes and adverse event documentation were cross-checked to confirm adherence. The control group received conventional therapy prescribed at physician discretion under current American and Chinese guidelines, with dose adjustments at weeks 4 and 12 based on heart rate, blood pressure and symptoms.

The hemodynamic results were striking. By week 30, the resting outflow tract gradient in the mavacamten group had fallen to 23.76 plus or minus 4.09 mmHg against 78.49 plus or minus 13.21 mmHg in controls, a difference the authors report with a t-statistic of 24.074 and a p-value below 0.001. The Valsalva-provoked gradient fell to 48.95 plus or minus 11.10 mmHg versus 113.59 plus or minus 14.92 mmHg, with a t-statistic of 21.147. Longitudinal modeling with linear mixed-effects models confirmed significant group-by-time interactions for both gradients, showing that the mavacamten group improved continuously from baseline to week 30 while the control group initially worsened and then declined modestly, remaining far higher at every time point. Fully adjusted between-group differences at week 30 reached minus 50.96 mmHg for the resting gradient and minus 60.42 mmHg for the provoked gradient, with confidence intervals excluding zero.

Biomarkers of cardiac stress moved in the same direction. At week 30, high-sensitivity cardiac troponin I averaged 6.50 ng/L in the mavacamten group versus 13.19 ng/L in controls, and N-terminal pro-B-type natriuretic peptide was lower at a median of 1,082 pg/mL versus 2,361 pg/mL. However, the adjusted analysis complicates this picture: the troponin difference remained robustly significant after adjustment, but the NT-proBNP difference, initially significant in unadjusted comparisons at week 30, became marginally non-significant after full adjustment for baseline structural differences, age, sex and baseline values. The authors attribute this attenuation partly to baseline imbalances in left ventricular end-diastolic diameter, left atrial volume index and end-systolic volume between the groups, which reflect the non-randomized design. Tricuspid annular plane systolic excursion, a marker of right ventricular function, was higher in the mavacamten group at week 30, suggesting preserved right ventricular longitudinal function.

Safety findings deserve careful attention. Although the mean ejection fraction at week 30 did not differ significantly between groups, at 55.12 versus 56.78 percent, the change from baseline told a different story. The mavacamten group experienced progressive ejection fraction declines that peaked at minus 15.76 percent at week 18, compared with essentially stable values in controls, and the decline remained at minus 13.68 percent at week 30. Twelve mavacamten patients, 9.5 percent, saw their ejection fraction fall below 50 percent, versus 2.2 percent of controls, and four patients, 3.2 percent, discontinued the drug because their ejection fraction dropped below 45 percent. Overall adverse event rates were similar between groups, at 19.0 versus 20.9 percent, with serious events rare in both. The authors emphasize that these figures reinforce the necessity of routine echocardiographic surveillance and standardized dose-adjustment protocols, since delayed-onset systolic dysfunction is a recognized risk of myosin inhibition.

Functional and symptomatic outcomes were more nuanced. The six-minute walk distance improved steadily in the mavacamten group, reaching 456.83 meters at week 30 versus 385.47 meters in controls, a highly significant difference. On the Kansas City Cardiomyopathy Questionnaire, the symptom frequency and symptom burden subdomains favored mavacamten significantly, yet the overall clinical summary score did not differ between groups. The authors suggest several explanations: baseline scores in their cohort were higher than in the EXPLORER-HCM trial, leaving less room for improvement, the Chinese-language questionnaire may incompletely capture exertional breathlessness in these patients, and 30 weeks may be too short for symptomatic gains to catch up with hemodynamic improvement. Subgroup analyses found no significant heterogeneity by age, sex or clinical strata for the summary score.

Background medication use shifted in ways that may have influenced the comparison. In the mavacamten group, beta-blocker use fell from 70.6 percent at baseline to 55.6 percent at week 30, with some patients discontinuing background therapy entirely after their gradient dropped below 30 mmHg, likely reflecting physician caution about the combined negative inotropic effects. In the control group, beta-blocker use intensified from 76.1 to 86.6 percent, with higher equivalent metoprolol doses at week 30. The authors note that this dynamic, in which the intervention group de-escalates while the control group optimizes, introduces a form of performance bias that may underestimate mavacamten’s true incremental benefit. They also cite the PIONEER-HCM trial, where concomitant beta-blocker use attenuated the gradient reduction from 89.5 mmHg to 25 mmHg, and note that the absence of disopyramide at their institution means the control arm did not represent the full pharmacological arsenal available elsewhere.

The authors are careful about what the study can and cannot establish. As a retrospective, single-center observational study with physician-driven, non-randomized treatment allocation, the findings are associative rather than causal, and residual confounding from unmeasured factors such as myocardial fibrosis burden, specific sarcomere variants or prior treatment intensity cannot be excluded. No CYP2C19 metabolizer phenotyping or systematic genetic testing was performed. The 30-week follow-up also precludes conclusions about long-term durability, late-onset systolic dysfunction, or effects on septal reduction therapy, hospitalization and mortality. Within those limits, the study offers some of the first post-marketing Chinese real-world data on a drug that transforms the hemodynamics of obstructive hypertrophic cardiomyopathy, and it supports the growing case that mechanism-targeted myosin inhibition can deliver profound, sustained obstruction relief, provided that vigilant monitoring of cardiac function accompanies every step of dose titration.

Subject of Research: Real-world clinical effectiveness of mavacamten in obstructive hypertrophic cardiomyopathy

Article Title: Clinical effectiveness of mavacamten on cardiac function and disease-related indicators in patients with obstructive hypertrophic cardiomyopathy

Article References: Shi, Y.-N., Huang, J.-J., Liu, H.-Z., Xu, Y., & Yuan, F. (2026). Clinical effectiveness of mavacamten on cardiac function and disease-related indicators in patients with obstructive hypertrophic cardiomyopathy. Frontiers in Pharmacology, 17, Article 1861248. https://doi.org/10.3389/fphar.2026.1861248

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1861248

Keywords: mavacamten, obstructive hypertrophic cardiomyopathy, cardiac myosin inhibitor, left ventricular outflow tract gradient, LVEF, NT-proBNP, high-sensitivity troponin I, beta-blockers, echocardiography, retrospective study, drug safety, real-world evidence