Mavacamten in Hypertrophic Cardiomyopathy (HCM)

Role of Mavacamten in Hypertrophic Cardiomyopathy (HCM)

Mavacamten is a first-in-class cardiac myosin inhibitor used in the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM). It targets the underlying pathophysiology of the disease rather than only treating symptoms.

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Mechanism of Action

In HCM, excessive interaction between actin and myosin leads to hypercontractility and impaired relaxation of the myocardium.

Mavacamten works by:

• Inhibiting cardiac myosin ATPase activity

• Reducing actin–myosin cross-bridge formation

• Decreasing hypercontractility of the left ventricle

This leads to:

• Reduction in LV outflow tract (LVOT) obstruction

• Improvement in diastolic relaxation

• Decrease in myocardial energy consumption

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Clinical Effects

Mavacamten has been shown to:

• Reduce LVOT gradient

• Improve NYHA functional class

• Improve exercise capacity (peak VO₂)

• Reduce symptoms such as dyspnea and chest pain

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Key Clinical Trial

The EXPLORER‑HCM trial demonstrated that mavacamten significantly improved symptoms and functional capacity in patients with symptomatic obstructive HCM compared with placebo.

Major findings:

• Significant reduction in post-exercise LVOT gradient

• Improved KCCQ clinical summary score

• Higher proportion of patients achieving functional improvement

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Guideline Position

According to the American College of Cardiology and American Heart Association updates:

Mavacamten is recommended for:

• Symptomatic obstructive HCM (NYHA II–III)

• Patients with persistent LVOT obstruction despite beta-blockers or non-dihydropyridine calcium channel blockers

It may delay or reduce the need for septal reduction therapy (surgical myectomy or alcohol septal ablation).

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Monitoring

Because excessive contractility reduction may cause systolic dysfunction, echocardiographic monitoring of LVEF is required.

Treatment should be held if LVEF < 50%.

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Practical Clinical Role

Mavacamten is particularly useful in patients with:

• Symptomatic obstructive HCM

• Significant LVOT gradient ≥50 mmHg

• Inadequate response to beta-blockers or verapamil

• Patients being considered for septal reduction therapy

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Key Take-Home Points

• First disease-specific pharmacologic therapy for obstructive HCM

• Reduces LVOT obstruction and symptoms

• Can delay need for invasive septal reduction procedures

• Requires regular echo monitoring for LVEF

Comments

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