Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy - VALOR-HCM

Contribution To Literature:

Highlighted text has been updated as of August 28, 2023.

The VALOR-HCM trial showed that mavacamten improved symptoms and significantly reduced eligibility for needing septal reduction therapy (SRT) among symptomatic patients with obstructive HCM who were considering SRT and on maximally tolerated medical therapy.


The goal of the trial was to assess the safety and efficacy of adding mavacamten to maximally tolerated medical therapy among patients with obstructive hypertrophic cardiomyopathy (HCM).

Study Design

Eligible patients were randomized in a 1:1 fashion to mavacamten (n = 56) or placebo (n = 52). Mavacamten was started at a dose of 5 mg, and titrated using core laboratory measured left ventricular ejection fraction (LVEF) and left ventricular outflow tract (LVOT) gradient at rest and with Valsalva provocation. After 16 weeks, patients originally randomized to placebo were crossed over to 5 mg of mavacamten daily.

  • Total number of enrollees: 108
  • Duration of follow-up: 16 weeks
  • Mean patient age: 60 years
  • Percentage female: 49%

Inclusion criteria:

  • Age ≥18 years
  • Documented HCM with maximum septal wall thickness ≥15 mm or ≥13 mm with family history of HCM (determined by a core echocardiography laboratory)
  • Severe symptoms despite maximally tolerated medical therapy
  • New York Heart Association (NYHA) functional class III/IV or class II with exertional syncope or near syncope
  • Maximal medical HCM therapy could include disopyramide and/or combination beta-blockers and calcium channel blockers
  • Dynamic LVOT gradient at rest or with provocation (Valsalva maneuver or exercise) ≥50 mm Hg
  • Documented LVEF ≥60%
  • Must have been referred within the past 12 months for SRT and actively considering scheduling the procedure

Other salient features/characteristics:

  • Baseline medical therapy: beta-blockers (45%), calcium channel blockers (15%), combination (32%)
  • Resting LVOT gradient: 49 mm Hg
  • Post-exercise gradient: 84 mm Hg
  • NYHA class III/IV: 93%

Principal Findings:

The primary endpoint, decision to proceed with SRT or guideline eligible at week 16, for mavacamten vs. placebo, was 17.9% vs. 76.8% (p < 0.0001).

  • Proceeded with SRT: 3.6% vs. 3.6%
  • Guideline eligible for SRT but did not proceed: 14.3% vs. 69.6%

Secondary outcomes for mavacamten vs. placebo:

  • Improvement in NYHA class ≥I class: 63% vs. 21% (p < 0.05)
  • Change from baseline in resting LVOT gradient at 16 weeks: -36 vs. -1.5 mm Hg (p < 0.05)
  • Change from baseline in Valsalva LVOT gradient at 16 weeks: -45.2 vs. 0.4 mm Hg (p < 0.05)
  • Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 clinical summary score at 16 weeks: 10.4 vs. 1.9 (p < 0.05)
  • Change from baseline in EF: -3.4 vs. 0.3%

Safety outcomes for mavacamten vs. placebo:

  • Nonsustained ventricular tachycardia: 0% vs. 9.1%
  • Nausea: 7.1% vs. 1.8%
  • No patients had chronic heart failure, syncope, or sudden cardiac death

Outcomes at 56 weeks: After 16 weeks, placebo patients crossed over to mavacamten in a blinded fashion. Primary endpoint for mavacamten 56 weeks vs. mavacamtem 40 weeks exposure: 8.9% vs. 19.2%; SRT-eligible based on guideline criteria: 1.8% vs. 7.7%. At least 1 grade improvement in NYHA class: 93% vs. 73%. Efficacy was similar in men and women.


The results of this trial indicate that mavacamten for 16 weeks improved symptoms and significantly reduced eligibility for needing SRT among symptomatic patients with obstructive HCM who were considering SRT. The cross-over study confirms the efficacy of mavacamten at 56 weeks.

Mavacamten is a targeted inhibitor of cardiac myosin. It decreases the number of myosin-actin cross-bridges and reduces excessive contractility characteristic of HCM. In the EXPLORER-HCM trial too, mavacamten was superior to placebo in improving patient-centered outcomes. The current findings are thus complementary to that trial. Long-term data on both safety and efficacy with mavacamten, as well as any impact on clinical outcomes, are needed.


Presented by Dr. Milind Desai at the European Society of Cardiology Congress, Amsterdam, Netherlands, August 28, 2023.

Desai MY, Owens A, Geske JB, et al. Dose-Blinded Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy: Outcomes Through 32 Weeks. Circulation 2023;147:850-63.

Editorial: Rakowski H, Bataiosu R. Can Novel Myosin Inhibitors Defer Septal Reduction Therapy in HCM? At What Risk and at What Cost? Circulation 2023;147:864-6.

Presented by Dr. Milind Y. Desai at the American College of Cardiology Annual Scientific Session (ACC 2022), Washington, DC, April 2, 2022.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, SCD/Ventricular Arrhythmias, Acute Heart Failure

Keywords: ACC22, ACC Annual Scientific Session, Adrenergic beta-Antagonists, Calcium Channel Blockers, Cardiac Myosins, Cardiomyopathy, Hypertrophic, Cardiomyopathies, Death, Sudden, Cardiac, Disopyramide, ESC Congress, ESC23, Heart Failure, Stroke Volume, Syncope, Tachycardia, Ventricular, Valsalva Maneuver, Ventricular Function, Left

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