AF Management in oHCM in Era of Cardiac Myosin Inhibitors

With cardiac myosin inhibitors (CMIs) now established as first-line therapy for obstructive hypertrophic cardiomyopathy (oHCM), clinicians are reassessing how atrial fibrillation (AFib) fits into an evolving treatment landscape, including an unresolved paradox in the cardiac remodeling data. In this segment, Mariko Harper, MD, MS, FACC, director of the Hypertrophic Cardiomyopathy Center of Excellence at Virginia Mason Franciscan Health, and James MacNamara, MD, a non-invasive cardiologist and hypertrophic cardiomyopathy (HCM) specialist at UVA Health, work through both issues.

Harper asks MacNamara how AFib management has evolved now that CMIs are an established treatment class, specifically whether he still reaches for beta-blockers, disopyramide, or other antiarrhythmics. MacNamara says his practice remains focused on procedural management, cardioversion followed by catheter ablation, while using antiarrhythmics cautiously given toxicity and cardiomyopathy-related contraindications. He notes dofetilide remains a tool he uses to maintain sinus rhythm, and that his patients with HCM are likely the group he pursues sinus rhythm most aggressively for compared with his general cardiology practice.

Harper notes that disopyramide remains guideline-supported for obstructive symptom control, separate from any AFib indication, but says she rarely reaches for it given how effective CMIs have become, and would not favor it simply because a patient also has AFib. She describes her approach as early electrophysiology referral for procedural options such as pulsed field ablation. MacNamara agrees, adding that reassessment should be ongoing rather than a one-time decision, noting that CMI therapy offers more flexibility than permanent interventions like myectomy or alcohol septal ablation. He points out that AFib is not unique to CMI therapy either, with septal reduction procedures reporting 20% to 40% AFib incidence in less rigorous but longer-standing datasets, reinforcing that AFib simply complicates CMI management rather than uniquely causing it.

The discussion then turns to a paradox in the remodeling data. Harper notes that multiple studies, including long-term mavacamten extension data, show persistent favorable remodeling with CMI therapy: a smaller left atrium, improved diastolic function, near-complete resolution of systolic anterior motion, and reduced mitral regurgitation, changes traditionally associated with lower long-term AFib risk. MacNamara agrees this creates a paradox, since nearly every structural marker improves except AFib itself, which remained no worse than placebo in the pivotal trials but did not improve either. He notes biologic plausibility for a direct atrial effect, since atrial tissue also contains sarcomeres, but stresses this mechanistic link has not been established. MacNamara adds that left atrial size and left ventricular remodeling data have been consistent across both approved agents, though he flags that his own center has observed a reduction in left atrial strain in preliminary, unpublished data that runs counter to the broader trial literature, suggesting the atrial story may be more complex than currently understood.