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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𝘼𝙣𝙩𝙞𝙘𝙤𝙖𝙜𝙪𝙡𝙖𝙩𝙞𝙤𝙣 𝘼𝙛𝙩𝙚𝙧 𝙎𝙩𝙧𝙤𝙠𝙚 in Patient with AF and acute IS/TIA European Heart Association Guideline recommends: • 1 days after TIA • 3 days after mild stroke • 6 days after moderate stroke • 12 days after severe stroke Early anticoagulation can decrease a risk of recurrent stroke and embolic events but may increase a risk of secondary hemorrhagic transformation of brain infarcts. The 1-3-6-12-day rule is a known consensus with graded increase in delay of anticoagulation between 1 and 12 days after onset of ischemic stroke or transient ischemic attack(TIA), according to neurological severity based on European expert opinions. However, this rule might be somewhat later than currently used in a real-world practical setting.

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