In this opening segment, Martin (Marty) Maron, MD, and Ahmed Masri, MD, PA-C, introduce the discussion and frame obstructive hypertrophic cardiomyopathy (HCM) as the central focus, emphasizing outflow tract gradients as the key driver of symptoms.

Maron and Masri review decades of experience with beta-blockers, calcium channel blockers, disopyramide, and septal reduction therapies, underscoring persistent under-treatment and the unmet need that set the stage for myosin inhibitors.

Maron and Masri introduce cardiac myosin inhibitors—mavacamten and aficamten—explaining their sarcomere-level mechanism and the rationale for targeting hypercontractility in obstructive HCM.

Maron and Masri review pivotal phase 3 trials of mavacamten and aficamten and explain how efficacy and systolic function monitoring shaped their respective REMS programs.

Maron and Masri discuss whether myosin inhibitors, particularly aficamten, should be considered first-line therapy for symptomatic obstructive HCM in treatment-naive patients, in light of data from trials like MAPLE-HCM.

Maron and Masri define the ongoing role of surgical myectomy and alcohol septal ablation in the myosin inhibitor era and preview emerging trials of aficamten in nonobstructive HCM.