How Real-World Registries inform oHCM Management

Real-world registries offer a window into how obstructive hypertrophic cardiomyopathy (oHCM) patients treated with mavacamten fare outside the controlled setting of a clinical trial, particularly around atrial fibrillation (AFib) and ejection fraction (EF). In this segment, James MacNamara, MD, a non-invasive cardiologist and hypertrophic cardiomyopathy (HCM) specialist at UVA Health, and Mariko Harper, MD, MS, FACC, director of the Hypertrophic Cardiomyopathy Center of Excellence at Virginia Mason Franciscan Health, discuss what the MARVEL registry showed. MacNamara turns to Harper, noting her involvement in the MARVEL registry, and asks her to describe the study's key findings. Harper explains that MARVEL evaluated 465 patients across 8 HCM and academic centers in the United States over approximately 16.5 months of real-world observational follow-up. The registry found a background AFib prevalence of about 27%, higher than earlier randomized trials or historical estimates, while new-incident AFib was notably lower, at about 2.7%. She notes these patients tended to carry high-risk profiles on AFib risk scores based on age and comorbidities, which is in line with what would be expected for new AFib incidence in this population. Harper highlights that mean EF remained preserved above 60% across the full cohort, regardless of AFib status, a reassuring finding given the field's ongoing attention to cardiac myosin inhibitor (CMI)-associated EF changes. She frames the overall takeaway as 2-fold: background AFib is common in this population independent of therapy, so screening should be routine regardless of CMI use, and most patients with AFib who are treated with a CMI do well, with preserved EF and improved symptoms. Harper adds an important caveat from the small subset of patients who experienced a transient EF drop: recurrence of AFib was disproportionately common in that group. She frames this as the clearest emerging signal from the data, that among the minority of patients who see their EF dip, AFib appears to be one of the most consistent associated variables, reinforcing the value of actively screening for arrhythmia whenever an unexplained EF change occurs.