Practical Takeaways in oHCM from Contemporary Data

Closing out this discussion of atrial fibrillation (AFib) and cardiac myosin inhibitor (CMI) safety in obstructive hypertrophic cardiomyopathy (oHCM), Mariko Harper, MD, MS, FACC, director of the Hypertrophic Cardiomyopathy Center of Excellence at Virginia Mason Franciscan Health, and James MacNamara, MD, a non-invasive cardiologist and hypertrophic cardiomyopathy (HCM) specialist at UVA Health, translate the data into practical counseling and monitoring guidance for community cardiologists.

Harper asks MacNamara what he would tell a community cardiologist counseling a patient about AFib risk before starting a CMI. MacNamara emphasizes leading with the therapy's overall benefit, improved fitness, quality of life, obstruction relief, and favorable cardiac remodeling, so the AFib conversation does not overshadow the broader picture. He notes that while a meaningful proportion of patients with baseline AFib will experience recurrence, new AFib incidence remains low in general use, and there is no data suggesting worse hard outcomes like stroke, so AFib risk alone is not a reason to withhold these therapies.

MacNamara frames counseling around treatment phase: the titration phase is more dynamic, with possible transient ejection fraction (EF) drops and a longer runway before symptoms fully resolve, while the maintenance phase is comparatively stable. If a patient develops new symptoms or an unexplained EF drop during maintenance, he says AFib should be near the top of the differential.

Harper adds that clinicians should use every clinic visit as an opportunity to screen for AFib, particularly when an unexplained EF change appears, and notes that a full echocardiogram, capturing atrial function, is more informative than a limited study. She and MacNamara then walk through practical management: MacNamara typically holds the CMI when EF is low, given the long half-life of both approved agents that allows time before restarting, and proceeds to cardioversion when feasible. He starts every patient with new AFib on anticoagulation regardless of symptom status, explicitly avoiding the CHA2DS2-VASc score, which he says underestimates stroke risk in HCM. Management occurs entirely in the outpatient setting; MacNamara notes that in his career, the only CMI patients who have required emergency department visits, a small number overall, presented specifically with an atrial arrhythmia.

Asked to name the single point that should most change how a community cardiologist approaches this conversation, MacNamara stresses that CMIs remain good options within the broader oHCM treatment landscape, that clinicians should be vigilant and honest with patients about the unknowns, and that he does not currently differentiate AFib risk counseling between mavacamten and aficamten as a class, since neither agent's causal role has been established. Harper closes with 4 take-home points: CMIs remain highly effective for symptomatic oHCM; AFib is common in this population, with baseline prevalence likely higher than previously understood; routine periodic AFib screening should continue regardless of CMI status, with additional monitoring touchpoints created by CMI surveillance; and when a transient EF drop occurs, AFib should be assumed to be a possible driver and managed aggressively even without overt symptoms.