Dr. James MacNamara welcomes Dr. Milind Desai from the Cleveland Clinic to dissect the results and implications of the ODYSSEY trial, the largest study ever conducted in hypertrophic cardiomyopathy (HCM). The trial investigated the use of mavacamten in patients with non-obstructive HCM, a population with significant unmet medical needs. While the study did not reach statistical significance for its primary endpoints of KCCQ score and peak VO2, Dr. Desai highlights a powerful "rowing in the same direction" effect seen in secondary data. This includes a 53% reduction in cardiac biomarkers (BNP and troponin) and favorable cardiac remodeling observed on echocardiography. The conversation explores why a strong placebo effect may have impacted the results and identifies a specific "sweet spot" responder group: patients with an ejection fraction above 65% and no history of atrial tachyarrhythmias.

References:
ODYSSEY Subgroup Analysis: https://www.jacc.org/doi/10.1016/j.jacc.2025.12.092

ODYSSEY Exploratory Analyses: https://www.jacc.org/doi/10.1016/j.jacc.2025.12.092

ODYSSEY-HCM Trial: https://www.nejm.org/doi/full/10.1056/NEJMoa2505927