Efficacy And Safety Of Invasive And Pharmacologic Therapies For Obstructive Hypertrophic Cardiomyopathy: A Systematic Review And Network Meta-analysis Of 8,742 Patients

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Author Block: Shrouk Ramadan¹, Ahmed Farid Gadelmawla², Mohamed Rifai², Amr M. Abou Elezz³, Ahmed Mansour⁴, Ahmed Talkhan⁵, Ahmad Al Othman⁶, Mohammed Sabri Hassanin⁴, Omar Shazly⁷, Rana Mohamed⁸, Imad Samman Tahhan⁹, Mariam Tarek Desouki¹⁰, Abdelrahman Hafez^11,12, Islam Elgendy¹³, Ahmed Sami Abuzaid¹⁴, Shady Abohashem¹⁵. ¹Faculty of Medicine, Ain Shams University, Cairo, Egypt; ²Faculty of Medicine, Menoufia University, Menoufia, Egypt; ³Faculty of Medicine, Tanta University, Tanta, Egypt; ⁴Faculty of Medicine, Al-Azhar University, Cairo, Egypt; ⁵Faculty of Medicine, Mansoura University, Mansoura, Egypt; ⁶Faculty of Medicine,Near East University, Nicosia, Cyprus; ⁷SUNY Upstate Medical University, New York, NY; ⁸Verde valley medical center/Northern Arizona Healthcare, Cottonwood, AZ; ⁹Department of Internal Medicine, Wellington Regional Medical Cenetr, Wellington, FL; ¹⁰The Joseph F. Novogratz Family Heart Rhythm Science Centre, Minneapolis Heart Institute Foundation, Minneapolis, MN; ¹¹Mayo Clinic - Arizona, Phoenix, AZ; ¹²University of Arizona College of Medicine, Phoenix, AZ; ¹³Gill Heart and Vascular Institute, University of Kentucky, Kentucky, KY; ¹⁴Alaska Heart and Vascular Institute, Alaska, AK; ¹⁵Massachusetts General Hospital, Cardiovascular Imaging Research Center, Boston, MA
Disclosure Block: M.T. Desouki: None. A. Hafez: None.

Background: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic left ventricular outflow tract (LVOT) obstruction that drives symptoms and adverse outcomes. This network meta-analysis compared cardiac myosin inhibitors (CMIs), septal reduction therapies, and conventional medical therapy across hemodynamic, functional, and safety outcomes using separate randomized and observational evidence structures.
Objectives: We aim to compare cardiac myosin inhibitors with septal reduction therapies and conventional pharmacologic strategies in obstructive hypertrophic cardiomyopathy using a Bayesian network meta-analysis.
Methods: A PRISMA-NMA systematic review was conducted across PubMed, Scopus, Web of Science, and Cochrane Library through October 2025. Seven randomized controlled trials and 12 observational studies (8,742 adults with oHCM) were included, evaluating mavacamten, aficamten, septal myectomy (SM), alcohol septal ablation (ASA), metoprolol, medical therapy, and placebo. Random-effects frequentist network meta-analyses were performed with P-score ranking, and inconsistency was assessed using node-splitting.
Results: In randomized trials, aficamten (MD −40.95 mmHg, 95% CI −52.46 to −29.43; P-score 0.88) and mavacamten (MD −38.35 mmHg, 95% CI −48.22 to −28.49; P-score 0.79) significantly reduced resting LVOT gradient versus placebo. In the combined network for provoked gradients, SM ranked highest (MD −70.65 mmHg, 95% CI −123.27 to −18.02; P-score 0.90). Both CMIs increased the likelihood of at least 1 NYHA class improvement versus placebo (mavacamten RR 2.33, 95% CI 1.83 to 2.98; aficamten RR 2.32, 95% CI 1.71 to 3.14), and aficamten produced the largest gain in peak VO₂ (MD 1.80 mL/kg/min, 95% CI 1.06 to 2.54; P-score 0.90). In observational analyses, septal reduction therapies were associated with lower long-term mortality compared with medical therapy; however, these findings remain susceptible to residual confounding and heterogenous follow up duration. ASA was associated with lower acute renal failure risk than SM, whereas pacemaker implantation was more frequent after ASA. No significant inconsistency was detected.
Conclusion: Randomized evidence supports CMIs as the most consistent pharmacologic option for short-term LVOT gradient reduction and symptom improvement in oHCM. Septal reduction therapies provided the greatest relief of provoked obstruction and showed favorable longer-term outcome signals versus medical therapy in observational analyses, although survival inferences remain limited by confounding.