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Myosin Inhibitors in Hypertrophic Obstructive Cardiomyopathy: Experience with Mavacamten in a National Referral Center

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© The Author(s). This work is open access and is licensed under CC-BY-NC 4.0. Users may copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

Background: Hypertrophic cardiomyopathy (HCM) is defined by left ventricular wall thickening not attributable to other causes, with an estimated prevalence of 1 in 200–500 individuals. HCM is classified as obstructive (HOCM) when the left ventricular outflow tract (LVOT) gradient exceeds 30 mmHg.1 Symptom presence correlates with worse prognosis.2 First-line treatment includes beta-blockers, non-dihydropyridine calcium channel blockers, and disopyramide to reduce LVOT obstruction and managing arrhythmias, atrial fibrillation, or embolic risk. Despite medical therapy, up to 50% of patients remain symptomatic and/or exhibit significant LVOT obstruction.3 Septal reduction therapies such as surgical myectomy or alcohol septal ablation are in those cases required – procedures carrying risks even in experienced centers.4

Recently, European cardiomyopathies guidelines incorporated myosin ATPase inhibitors, such as mavacamten, as a novel alternative therapy.

Objective: To describe the initial experience of a national referral centre for familial cardiomyopathies using mavacamten in the treatment of HOCM.

Methods: A retrospective, single-centre study was conducted including patients with HOCM treated with mavacamten. Clinical and demographic data were collected at baseline and during follow-up, including left ventricular ejection fraction (LVEF), peak LVOT gradient, NT-proBNP, high-sensitivity troponin T, NYHA functional class, and 6-minute walk test. Adherence and tolerance to therapy were assessed. Follow-up occurred at 4, 8, and 12 weeks, with extended data at 18 and 24 weeks for some patients.

Results: 8 patients were included. All started mavacamten at 5 mg/day. None required dose reduction due to LVEF deterioration, and the drug was well tolerated without significant adverse effects. All patients experienced marked clinical and functional improvement, with a reduction in LVOT gradients and NT-proBNP levels. Notably, all reached NYHA class I-II, and none required invasive septal reduction therapy (see table). The cohort was clinically and genetically heterogeneous, supporting the efficacy of the new treatment.

Conclusion: This case series demonstrates that mavacamten is a safe and effective non-invasive treatment option for symptomatic HOCM patients in a real-world setting. The observed improvements in clinical status, biomarkers, and echocardiographic parameters align with findings from clinical trials. Mavacamten may reduce the need for invasive septal reduction in appropriately selected patients.

References

  1. Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC guidelines for the management of cardiomyopathies. Eur Heart J 2023;44:3503–626. 
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  2. Maron BJ, Desai MY, Nishimura RA. et al. Diagnosis and evaluation of hypertrophic cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol 2022;79:372–89. 
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  3. Sherrid MV, Shetty A, Winson G, et al. Treatment of Obstructive Hypertrophic Cardiomyopathy symptoms and gradient resistant to first-line therapy with β-blockade or verapamil. Circ Heart Fail 2013;6:694–702. 
    Crossref | PubMed
  4. Smedira NG, Lytle BW, Lever HM, et al. Current effectiveness and risks of isolated septal myectomy for hypertrophic obstructive cardiomyopathy. Ann Thorac Surg 2008;85:127–33. 
    Crossref | PubMed