A 38-year-old woman presents with syncope during exertion and a harsh systolic murmur that increases with the Valsalva manoeuvre and decreases with squatting. Echocardiogram confirms hypertrophic obstructive cardiomyopathy (HOCM) with LVOT gradient 65 mmHg at rest. She remains symptomatic on maximum beta-blocker therapy. Which novel therapy, a cardiac myosin inhibitor, is now FDA-approved for HOCM with persistent symptoms?
- A Vericiguat (soluble guanylate cyclase stimulator)
- B Disopyramide
- C Mavacamten (allosteric cardiac myosin inhibitor) ✓
- D Ivabradine
Explanation
Mavacamten is a first-in-class allosteric inhibitor of cardiac myosin ATPase that reduces the number of myosin heads in the force-producing (actin-binding) state, directly addressing the pathophysiology of HOCM by reducing hypercontractility and LVOT obstruction. The EXPLORER-HCM trial demonstrated significant reduction in LVOT gradient, improvement in functional class, and symptom relief. FDA approved in 2022 for obstructive HOCM with NYHA class II-III symptoms despite beta-blocker or calcium channel blocker therapy. Disopyramide is an older approach for HOCM (class Ia antiarrhythmic with negative inotropic effect) but lacks cardiac specificity.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.