How Mavacamten Works for Hypertrophic Cardiomyopathy and Who Qualifies for Treatment

Research-informed explainer — last updated April 12, 2026

Mavacamten (brand name Camzyos) is the first drug approved specifically for obstructive hypertrophic cardiomyopathy that treats the underlying contractile mechanics of the disease rather than just managing symptoms. The EXPLORER-HCM trial demonstrated significant improvements in exercise capacity, symptoms, and outflow obstruction — and the 2024 AHA/ACC guidelines now position it as an early treatment option before considering invasive septal procedures.

This article draws on research from five cardiologists with direct expertise in HCM. Christopher Kramer, MD, Chief of the Cardiovascular Division at the University of Virginia Health System, was an investigator on the pivotal EXPLORER-HCM trial and is a leading expert in cardiac MRI evaluation of HCM. Srihari Naidu, MD, Director of the Hypertrophic Cardiomyopathy Center of Excellence at Westchester Medical Center Health Network, co-authored the 2024 AHA/ACC HCM guidelines and has published specifically on the use of myosin inhibition in patients referred for septal reduction procedures. John Lesser, MD, at Abbott Northwestern Hospital in Minneapolis, has published foundational research on how LVOT obstruction affects clinical outcomes and how cardiac MRI fibrosis detection guides management. Milind Desai, MD, at Cleveland Clinic, has authored comprehensive reviews on HCM diagnosis, evaluation, and management. Euan Ashley, MD, Professor of Genomics and Precision Health at Stanford University, has studied how genetic variants shape the lifetime disease burden in HCM patients.

What is hypertrophic cardiomyopathy?

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease, affecting approximately 1 in 500 people. It is caused by mutations in genes encoding sarcomeric proteins — most commonly myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3). These mutations cause the heart muscle to become abnormally thick, particularly in the ventricular septum.

About 70% of HCM patients have the obstructive form (oHCM), in which the thickened septum partially blocks blood flow out of the left ventricle through the aortic valve — a condition called left ventricular outflow tract (LVOT) obstruction. The remaining 30% have non-obstructive HCM.

A landmark 2003 study by Lesser and colleagues published in the NEJM, analyzing 1,101 patients, established that LVOT obstruction at rest is a strong, independent predictor of progression to severe heart failure symptoms and HCM-related death. Patients with a resting outflow gradient above 30 mmHg had significantly worse prognosis than those without obstruction — making relief of obstruction a primary treatment goal.

How mavacamten works

Conventional HCM treatments — beta-blockers, calcium channel blockers, disopyramide — work by slowing the heart rate, reducing contractility, or blocking calcium signaling. They reduce obstruction and symptoms but do not address the underlying over-contractility of the sarcomere.

Mavacamten takes a fundamentally different approach: it is a selective, reversible inhibitor of cardiac myosin ATPase, the molecular motor that powers heart muscle contraction. By directly modulating the number of myosin heads that enter the force-generating state, mavacamten reduces the hypercontractility that defines HCM. The result is not simply a weaker heart — it is a heart that contracts more normally, with improved relaxation, reduced LVOT gradient, and less mitral valve systolic anterior motion (SAM), a secondary mechanism that worsens obstruction.

Genetic research by Ashley and colleagues at Stanford, published in Circulation in 2018, showed that the specific sarcomeric gene mutation a patient carries predicts not just the presence of HCM but its lifetime burden — including risk of atrial fibrillation, heart failure, and premature death. This work supports the idea that sarcomere-targeted therapy like mavacamten addresses the biological root of the disease rather than downstream consequences.

The EXPLORER-HCM trial: what the evidence shows

The EXPLORER-HCM trial, published in The Lancet in 2020, was a randomized, double-blind, placebo-controlled Phase 3 trial enrolling 251 patients with symptomatic oHCM (NYHA Class II or III) and resting or provoked LVOT gradient of at least 50 mmHg. Participants were already on optimized background therapy (beta-blockers or calcium channel blockers).

After 30 weeks of treatment with mavacamten:

• 37% of mavacamten patients met the primary endpoint (improvement in peak VO2 plus improvement in functional class, or improvement in peak VO2 plus ≥1.5 NYHA class improvement) versus 17% in the placebo group (P < 0.0001)
• Mean resting LVOT gradient fell from 84 mmHg to 28 mmHg in the mavacamten group
• Significantly more patients improved from NYHA Class III to Class I or II
• The drug also reduced NT-proBNP (a marker of cardiac stress) by roughly 80% — suggesting a broader reduction in myocardial stress beyond obstruction alone

A subsequent study by Naidu and colleagues published in the Journal of the American College of Cardiology evaluated mavacamten specifically in patients who had been referred for septal reduction therapy (SRT) — either surgical myectomy or alcohol septal ablation. After 16 weeks of mavacamten treatment, 82% of these patients no longer met guideline criteria for SRT. This finding has important implications: mavacamten may allow many patients to avoid an invasive procedure entirely, at least for a period.

Who qualifies for mavacamten?

According to the 2024 AHA/ACC HCM guidelines, which Naidu co-authored, mavacamten is indicated for symptomatic patients with obstructive HCM (NYHA Class II–III) who have a resting LVOT gradient of at least 50 mmHg (or provokable to that level) and who remain symptomatic despite beta-blockers or calcium channel blockers. The drug requires enrollment in the CAMZYOS Risk Evaluation and Mitigation Strategy (REMS) program because of a dose-dependent risk of transient reduction in left ventricular ejection fraction.

Key eligibility considerations include:

• Echocardiographic measurement of LVOT gradient both at rest and with provocative maneuvers (Valsalva, exercise)
• Baseline left ventricular ejection fraction should be at least 55%
• Patients must avoid strong CYP2C19 inhibitors and certain other drug interactions
• Echocardiographic monitoring is required at regular intervals to detect any EF decline

Diagnosis and evaluation criteria are detailed in comprehensive reviews by Desai and colleagues published in the Journal of the American College of Cardiology, which describe the multimodality imaging approach — combining echocardiography, stress testing, and cardiac MRI — used to classify patients and assess risk.

The role of cardiac MRI and fibrosis

Cardiac MRI with late gadolinium enhancement (LGE) detects myocardial fibrosis — an important prognostic marker in HCM. Research by Lesser and colleagues in Circulation Heart Failure (2008) and the Journal of the American College of Cardiology (2008) showed that LGE-detected fibrosis independently predicts ventricular arrhythmias and systolic dysfunction. Kramer and colleagues have been central to developing CMR standardization, and the 2013 SCMR task force paper co-authored by Kramer defines how cardiac MRI should be performed and interpreted — relevant to every HCM patient being evaluated for risk stratification.

Patients with extensive fibrosis on CMR may be at higher risk for sudden cardiac death and may need ICD implantation regardless of whether their obstruction is well-controlled.

How mavacamten compares to septal reduction procedures

For patients who do not respond to medications — including mavacamten — two invasive procedures can physically reduce the obstruction:

• Surgical septal myectomy (open-heart surgery to remove part of the thickened septum): the guideline-preferred option when performed at high-volume HCM centers
• Alcohol septal ablation (catheter-based injection of alcohol into the septal artery to cause controlled scar): a less invasive alternative for select patients

Research by Naidu and colleagues in JAMA Cardiology (2016) showed that outcomes after both procedures are strongly volume-dependent: higher-volume centers have significantly lower complication and mortality rates, reinforcing the importance of referral to specialized HCM centers.

Mavacamten does not replace septal procedures for all patients — it adds an important medical option that can provide equivalent relief for many patients while deferring or avoiding surgery.

Questions to ask your doctor

• Has my LVOT gradient been measured both at rest and with provocation (Valsalva), and does it reach the 50 mmHg threshold for mavacamten eligibility?
• Am I on optimal background therapy (beta-blocker or calcium channel blocker) before adding mavacamten?
• Do I have any drug interactions that would make mavacamten unsafe?
• Should I have a cardiac MRI to assess for fibrosis and guide my risk stratification?
• If I do not respond to mavacamten, am I a candidate for surgical myectomy or ablation, and which center should I be referred to?

The bottom line

Mavacamten represents the first disease-targeted therapy for obstructive HCM, directly reducing hypercontractility at the sarcomere level. The EXPLORER-HCM trial demonstrated that it meaningfully improves exercise capacity and symptoms, and a significant proportion of patients referred for septal procedures can avoid surgery after a trial of treatment. Evaluation at a dedicated HCM center with expertise in cardiac imaging, genetic counseling, and the full range of therapeutic options is the standard of care for this condition.