A 45-year-old man presents with progressive dyspnoea and syncope. Echo shows asymmetric septal hypertrophy (IVS 22 mm, posterior wall 10 mm), SAM of mitral valve, and peak LVOT gradient 80 mmHg at rest (>110 mmHg with Valsalva). Which drug is the MOST recently approved pharmacological option specifically reducing LVOT gradient through a novel mechanism?
- A Disopyramide (class IA antiarrhythmic with negative inotropic effect)
- B Verapamil (L-type calcium channel blocker improving diastolic function)
- C Mavacamten (cardiac myosin inhibitor, FDA-approved 2022) ✓
- D Propranolol (non-selective beta blocker reducing heart rate and LVOT gradient)
Explanation
Mavacamten is a first-in-class selective allosteric inhibitor of cardiac myosin ATPase (sarcomere inhibitor) that reduces excessive cross-bridge cycling and hypercontractility in obstructive HCM. Approved by FDA in 2022 (EXPLORER-HCM trial, Phase 3), it significantly reduces LVOT gradient, symptoms, and exercise capacity in symptomatic obstructive HCM. This represents the first disease-specific pharmacotherapy targeting the molecular defect (sarcomere hyperfunction). Beta blockers, verapamil, and disopyramide are established negative inotropic agents but do not specifically target the myosin mechanism and are less efficacious for severe obstruction.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.