A patient with hypertrophic obstructive cardiomyopathy (HOCM) presents with drug-refractory left ventricular outflow tract obstruction. Mavacamten has recently been approved for this indication. Its mechanism of action is:
- A Allosteric inhibitor of cardiac myosin ATPase, reducing the number of force-generating actin-myosin cross-bridges and decreasing hypercontractility ✓
- B Negative chronotrope reducing heart rate and filling time, thus reducing outflow tract gradient
- C L-type calcium channel blocker reducing calcium influx and sarcomere shortening
- D Selective cardiac beta-1 blocker reducing inotropy and the Venturi effect in the LVOT
Explanation
Mavacamten (a cardiac myosin inhibitor) selectively inhibits cardiac myosin ATPase by binding to a specific allosteric site on the myosin S1 domain, reducing the proportion of myosin heads in the force-generating (dihydropyridine-sensitive, detached-to-force transition) state. This directly reduces the number of active actin-myosin cross-bridges per sarcomere, decreasing hypercontractility without significantly altering heart rate. In HOCM, the pathological hypercontractility causes dynamic LVOT obstruction; mavacamten reduces the gradient by addressing the root cause — myosin hyperactivation driven by MYH7/MYBPC3 mutations.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.