James MacNamara, MD

Atrial fibrillation (AFib) is common in patients with hypertrophic cardiomyopathy (HCM) and, once identified, raises immediate questions about how aggressively to pursue rhythm control. In this segment, 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 HCM specialist at UVA Health, compare their screening habits and management philosophies before turning to what the pivotal cardiac myosin inhibitor (CMI) trials showed about AFib risk.

Screening and Management Approaches for AFib in HCM

Harper opens by asking what data shows about AFib as a driver of morbidity and mortality, noting that longer time spent in AFib appears to carry independent risk in older studies, which is why detection remains the first step toward treatment. She then turns the conversation to management style, asking MacNamara whether he favors early rhythm control or a more conservative beta-blocker-first approach.

MacNamara describes himself as an aggressive early rhythm control adopter. His practice pursues initial cardioversion to restore sinus rhythm and works closely with electrophysiology colleagues, not only for defibrillator placement but for catheter ablation. Pharmacologic rhythm control is used less often than procedural options in his experience. MacNamara says he does everything possible to avoid leaving a patient with HCM in persistent AFib, since prolonged AFib becomes progressively harder to reverse.

Harper agrees, noting that before CMI therapy existed, there was little favorable atrial remodeling to counterbalance the progressive enlargement of the left atrium and accumulating atrial fibrosis seen in HCM. She observes that AFib compounds those structural changes, driving both symptoms and worse prognosis. With pulsed field ablation now available and offering a faster, safer procedural option, Harper says she encourages early electrophysiology consultation and shared decision-making, adding that she rarely encounters a truly asymptomatic AFib patient who does not feel better after ablation or cardioversion.

The discussion then shifts to the first cardiac myosin inhibitor approved, mavacamten, and roughly 5 years of accumulated long-term data. Harper asks MacNamara for his interpretation of the AFib signal seen in the pivotal EXPLORER-HCM and VALOR-HCM trials. MacNamara recalls that AFib was not viewed as a major concern in those earlier randomized trials since some background AFib would be expected in any HCM population. EXPLORER-HCM showed no increased incidence of AFib relative to placebo, at about 8% over the trial course, while VALOR-HCM saw AFib in about 10% of patients over a longer follow-up period, again with no significant difference between the treatment and placebo arms.

Harper notes that real-world data carries its own caveats since patients seen in clinical practice do not always mirror trial populations. She points out that the VALOR-HCM cohort was exclusively New York Heart Association (NYHA) class III and IV patients already being considered for septal reduction therapy, a sicker population that would be expected to carry higher background AFib rates.

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Videos

Atrial fibrillation (AFib) has long shadowed hypertrophic cardiomyopathy (HCM), but the arrival of cardiac myosin inhibitor (CMI) therapy has sharpened the question of what that relationship really means. As real-world experience with mavacamten and aficamten accumulates alongside pivotal trial data and new adolescent findings from SCOUT-HCM, clinicians are working to reconcile a safety signal that looks different depending on where they look.

AFib and HCM: Setting the Stage for Safety

This is the first installment of a 9-part video series in which 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 HCM specialist at UVA Health, unpack how the AFib safety signal reported with CMI therapy compares against pivotal trial data, adolescent findings, and the latest real-world evidence, including data presented at the American College of Cardiology (ACC) meeting.

Harper and MacNamara open by grounding the discussion in how common AFib already is in HCM, independent of any specific therapy. MacNamara notes that reported incidence varies widely by study, ranging as high as 20% and, in some series, as high as 50%. He adds that the more clinicians look for AFib in this population, the more they find it, a theme that recurs throughout the conversation.

Harper points out that background AFib rates in more recent literature have climbed well past the historical range of roughly 15% to 20%, and that AFib and HCM appear closely linked, with AFib often poorly tolerated in these patients. MacNamara underscores the clinical stakes: patients with HCM who develop AFib do not fit standard population-level stroke risk classification systems, meaning many are committed to long-term anticoagulation, and most AFib studies evaluating de-escalation of anticoagulation exclude patients with HCM altogether.

The 2 also discuss how overlapping symptoms complicate detection. HCM itself produces vague symptoms, chest pain, dyspnea, dizziness, and palpitations, that mirror those of AFib, making it difficult to know which condition is driving a given complaint without active surveillance. Both report aggressive annual rhythm monitoring in their own practices, particularly in older patients, specifically to catch paroxysmal AFib that would otherwise go undetected between visits. Harper notes that many referred patients have never had a monitor placed despite guideline recommendations, underscoring a persistent gap in screening consistency across practices.

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James MacNamara, MD

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