A patient with hypertrophic obstructive cardiomyopathy (HOCM) who is symptomatic despite maximally tolerated doses of beta-blocker is now started on mavacamten. Its mechanism of action is:

• A Blockade of L-type calcium channels, reducing intracellular calcium and decreasing sarcomere contraction force
• B Allosteric inhibition of cardiac myosin ATPase, shifting the myosin head to the super-relaxed (SRX) state and reducing hypercontractility causing dynamic LVOT obstruction ✓
• C Activation of troponin I kinase, increasing troponin I phosphorylation and reducing myofibrillar calcium sensitivity
• D Competitive inhibition of actin-binding sites on myosin, preventing cross-bridge cycling

Explanation

Mavacamten is a first-in-class selective cardiac myosin inhibitor approved for symptomatic obstructive HOCM. It binds allosterically to cardiac myosin (MYH7/MYH6) at a site near the converter domain, stabilising myosin in the super-relaxed (SRX) state — a disordered-relaxed interacting head motif where myosin heads are folded back on the thick filament and ATPase activity is inhibited. By reducing the proportion of myosin heads available for actin interaction, mavacamten reduces excessive cross-bridge cycling and hypercontractility, decreasing dynamic LVOT gradient, improving symptoms and exercise capacity. This is distinct from calcium channel blockade.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.