Integrating Myosin Inhibitors With Septal Reduction and Future Directions in Nonobstructive HCM

To close the discussion, Dr Maron and Dr Masri address how surgical myectomy and alcohol septal ablation fit into a therapeutic ecosystem that now includes potent sarcomere-directed drugs. Masri stresses that clinicians have an obligation to present all reasonable options—medical and invasive—and to individualize decisions through shared decision-making. Although cardiac myosin inhibitors offer a noninvasive, reversible approach that can be maintained long term, patients must understand that therapy is generally chronic, and gradients and symptoms recur when treatment is discontinued. By contrast, septal reduction, particularly surgical myectomy, can offer a more definitive “one-and-done” solution, albeit with higher upfront procedural risk and recovery.

Maron underscores that a subset of patients with complex LVOT and mitral valve anatomy may have residual obstruction and symptoms despite optimal myosin inhibition. For these individuals, structural intervention remains essential to address anatomic contributors that pharmacologic modulation cannot fully overcome. Younger patients, women planning pregnancy, and individuals strongly averse to lifelong pharmacotherapy and monitoring may also reasonably favor septal reduction, provided they understand and accept procedural risks. The experts agree that myosin inhibitors are unlikely to obviate the need for expert septal reduction centers but will instead complement and refine referral patterns.

Finally, the discussion looks ahead to nonobstructive HCM. Masri cites the neutral ODYSSEY-HCM trial of mavacamten in nonobstructive disease but expresses optimism regarding the ongoing ACACIA-HCM trial evaluating aficamten in this population. Both clinicians regard nonobstructive HCM as a major remaining unmet need, given the lack of targeted therapies that reliably improve exercise capacity and symptoms. Maron concludes that results from trials like ACACIA-HCM will be pivotal in determining whether the benefits of myosin inhibition can extend beyond obstructive physiology, potentially redefining care for an even broader spectrum of patients with HCM.