In this episode of In the Thick of It, Dr. Floridian Rader and Dr. Ahmad Masri discuss the transformative results of the MAPLE trial, a head-to-head study comparing aficamten—a cardiac myosin inhibitor—to metoprolol in patients with symptomatic obstructive hypertrophic cardiomyopathy1. The trial utilized a rigorous "double-dummy" design to ensure blinding while testing both medications at therapeutic doses2. Dr. Masri highlights unexpected findings, including the significant reduction in peak $VO_2$ and the worsening of cardiac biomarkers like NT-proBNP in the metoprolol group3. The conversation explores how these results challenge decades of reliance on beta-blockers as a first-line therapy and demonstrate the efficacy of aficamten as a potent upfront monotherapy for improving patient function and cardiac remodeling4.