A 35-year-old athlete has a family history of sudden cardiac death. Echocardiography shows asymmetric interventricular septal hypertrophy (24 mm), systolic anterior motion of the mitral valve, and a peak LVOT gradient of 68 mmHg at rest. He remains symptomatic (NYHA III) despite maximally tolerated metoprolol. Per 2022 ACC/AHA HCM guidelines, the most appropriate next pharmacological addition is:
- A Disopyramide added to a beta-blocker or non-dihydropyridine CCB
- B Mavacamten — cardiac myosin inhibitor specifically approved for obstructive HCM ✓
- C Septal ablation with alcohol is the next step for NYHA III symptoms on maximised medical therapy
- D Surgical myectomy is the only guideline-recommended intervention after beta-blocker failure
Explanation
Mavacamten (cardiac myosin ATPase inhibitor) was evaluated in the EXPLORER-HCM trial (NEJM 2020) and demonstrated significant improvement in LVOT gradient, NYHA class, and exercise capacity in obstructive HCM patients who remained symptomatic despite beta-blockers or CCBs. It received FDA approval (2022) and is now incorporated into 2022 ACC/AHA HCM guidelines as a Class 2a recommendation for symptomatic obstructive HCM inadequately controlled on beta-blockers or verapamil. Disopyramide is an additive option but mavacamten represents a newer mechanism (direct myosin inhibition) with RCT evidence. Septal reduction procedures are indicated for refractory disease failing all medical options.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.