Real-world experience and structural remodeling with cardiac myosin inhibitors in hypertrophic obstructive cardiomyopathy: Insights from a Heart Failure Network Registry

Background Randomized controlled trials have established cardiac myosin inhibitors (CMIs) as a cornerstone therapy for hypertrophic obstructive cardiomyopathy (HOCM). However, longitudinal real-world data regarding referral patterns, disease trajectories, and structural remodeling in routine clinical care remain limited. This study evaluates the impact of mavacamten within a specialized Heart Failure (HF) network. Methods A retrospective analysis was conducted on all HOCM patients evaluated since 2007. Since 2020, patients receiving pharmacological therapy were tracked to examine referral pathways between outpatient cardiologists and a central HF hub. Clinical, functional, and laboratory parameters were assessed at baseline (BL) and follow-up (FU) for all patients initiated on CMIs. Results At our tertiary care center, septal reduction therapy (SRT) and alcohol septal ablation (TASH) represented the primary treatment strategy for symptomatic HOCM before the approval and clinical availability of mavacamten in Germany. Historical SRT comprised 24 surgical myectomies (2007-2021) and 17 TASH (2007-2025). Since 2020, 73 patients received medical therapy alone: 37 on optimized beta-blockers and 36 on mavacamten. Following the approval of mavacamten in Germany, interventional SRT markedly declined, with only 1 TASH performed and no further surgical myectomies undertaken at our center. Efficient network integration allowed 22.2% (n=8) of CMI patients to return to routine outpatient care immediately following successful titration. The CMI cohort (n=36; mean age 56.8±13.5 years; 56% female) exhibited high-risk features: 25% had sarcomere mutations, 11% had prior ICDs and fibrosis in 63%. Mean HCM-SCD risk score was 2.9±1.4. 94% were on betablockers (39% on maximum dose). Following a mean FU of 288.8 days (range 92–752), mavacamten induced significant remodeling and symptomatic improvement:Hemodynamics: Left ventricular outflow tract gradient at rest decreased from 55.7±43.3 to 14.9±6.5mmHg; Valsalva gradient from 123.0±53.6 to 29.8±17.4 mmHg.Structural Remodeling: Mean septal thickness was reduced by 4.3mm (BL 21.2±3.7 vs. FU 17.3±3.5mm), while LVEF remained stable (BL 57.3±4.2% vs. FU 55.3±3.3%).Functional Status: 77.8% of patients improved to NYHA Class I. NT-proBNP levels fell from 1559.3±1823.0 to 354.5±489.7 pg/ml. Safety was favorable with no deaths or rehospitalizations. One patient discontinued CMI due to suspected depressive side effects; five patients required intensification of antihypertensive therapy during titration. Conclusion In a real-world setting, there is a clear transition toward guideline-directed pharmacological disease-modifying therapy, reserving invasive SRTfor selected patients with persistent symptoms or contraindications to medical treatment. A collaborative HF network model facilitates safe drug initiation and enables the transition of stable patients back to routine outpatient care.