Reply: Hypertrophic Cardiomyopathy With Midventricular Obstruction Is Not Nonobstructive Hypertrophic Cardiomyopathy

The executive committee of the ODYSSEY-HCM (A Study of Mavacamten in Non-Obstructive Hypertrophic Cardiomyopathy; NCT05582395) trial sincerely thanks Dr Seggewiss for his comments and would like to clarify a few points that he raised. As mentioned in our paper, although sponsored by Bristol Myers Squibb, the trial is directed by an independent academic research organization (C5Research, Cleveland, Ohio, USA) and an executive committee. All echocardiographic assessments (including screening eligibility, dose titrations, and safety evaluations) are evaluated in a blinded manner by an imaging core laboratory with appropriate firewalls from the investigators and sponsor. We agree with the observation by Dr Seggewiss that hypertrophic cardiomyopathy (HCM) patients with midcavity obstruction may be hemod ynamically obstructive. However, all the clinical trials of cardiac myosin inhibitors to date for obstructive HCM-EXPLORER HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy), VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HICM Who Are Eligible for Septal Reduction Therapy), and SEQUOIA CM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM)-exclu-sively enrolled patients with left ventricular outflow tract obstruction (LVOTO) and specifically excluded those with midcavity obstruction."* Although patients with midcavity obstruction are a small proportion of the total HCM population,56 this "orphaned" group may benefit from cardiac myosin inhibition and would otherwise not be evaluated in any separate trial nor have access to therapies approved for other HCM patients.