Therapeutic Response to Myosin Inhibitor Therapy in Noonan Syndrome-Associated Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND

Myosin inhibitor therapy is a novel option for hypertrophic cardiomyopathy (HCM) with left ventricular outflow tract obstruction. Noonan syndrome (NS), a RASopathy, can mimic HCM but was excluded from myosin inhibitor trials.

CASE SUMMARY: A 60-year-old woman with obstructive HCM (HOCM) presented with progressive dyspnea (NYHA functional class III). Echocardiography showed severe septal hypertrophy (19 mm) and persistent left ventricular outflow tract obstruction (peak gradient: 51 mm Hg during Valsalva) despite beta-blocker therapy. Mavacamten, a myosin ATPase inhibitor, was initiated. After 6 months, symptoms improved (NYHA functional class II), the gradient decreased to 11 mm Hg, and N-terminal pro-B-type natriuretic peptide levels normalized. Genetic testing later confirmed NS.

DISCUSSION: This is to our knowledge the first reported case of myosin inhibitor efficacy in NS-associated HOCM. Although NS-related hypertrophy stems from RAS/MAPK pathway dysregulation, the patient responded similarly to those with sarcomeric mutations. This suggests downstream hypercontractility may be a shared therapeutic target.

TAKE-HOME MESSAGES: Myosin inhibitors may benefit syndromic HOCM. Further research is warranted.