A 28-year-old man with hypertrophic cardiomyopathy (HCM) has an asymmetric septal hypertrophy of 24 mm (IVS), LVOT gradient 85 mmHg at rest, and syncope with exertion. He is on metoprolol 100 mg/day with partial response. A novel cardiac myosin inhibitor approved in 2022 for symptomatic obstructive HCM is:
- A Disopyramide (sodium channel blocker with negative inotropic effect)
- B Verapamil (L-type calcium channel blocker)
- C Mavacamten (a cardiac myosin ATPase inhibitor reducing hypercontractility) ✓
- D Aficamten (another myosin inhibitor approved earlier for non-obstructive HCM)
Explanation
Mavacamten (Camzyos) is a first-in-class cardiac myosin inhibitor (allosteric inhibitor of cardiac beta-myosin ATPase) approved by FDA in 2022 for adults with symptomatic obstructive HCM (NYHA class II-III) with LVOT gradient ≥50 mmHg. The EXPLORER-HCM trial demonstrated that mavacamten significantly reduced LVOT gradient, improved exercise capacity, and decreased NYHA functional class. Its mechanism is to reduce excessive actin-myosin cross-bridge formation, the fundamental defect in HCM. Disopyramide is an older option for obstructive HCM but has anticholinergic side effects. Verapamil reduces diastolic dysfunction. Aficamten is a second-generation myosin inhibitor (SEQUOIA-HCM trial) but not yet approved.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.