Mitral regurgitation and atrial fibrillation recurrence in hypertrophic cardiomyopathy: association or modifiable substrate?

I read with great interest the article by Zhang et al., examining the long-term effectiveness of radiofrequency catheter ablation (RFCA) in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) (1). The authors demonstrated symptomatic improvement and identified predictors of AF recurrence, including left atrial diameter, female sex, and moderate-to-severe mitral regurgitation. Several concerns warrant discussion.

First, the retrospective design and relatively small sample size (n=129) raise concerns regarding residual confounding and selection bias (1). While multivariable analysis was performed, important determinants of AF recurrence in HCM—such as atrial fibrosis burden, genetic background (e.g., sarcomeric mutations), and left atrial functional parameters—were not incorporated (2). These factors are mechanistically linked to arrhythmogenic substrate and may substantially influence ablation outcomes. Incorporation of cardiac magnetic resonance or electro-anatomical mapping data would strengthen causal inference.

Second, the definition and assessment of arrhythmia recurrence warrant clarification. Although recurrence was defined as arrhythmic episodes ≥30 seconds after a 3-month blanking period, the intensity and uniformity of rhythm monitoring may influence detection sensitivity (3). Under-detection of asymptomatic AF could bias comparisons between the sinus rhythm and recurrence groups, particularly when evaluating downstream outcomes such as thromboembolism and heart failure hospitalization.

Third, the reported association between RFCA and improved clinical outcomes—including reduced HCM-related mortality and heart failure hospitalization—should be interpreted cautiously (1). Given the observational nature of the study, these differences may reflect baseline risk stratification rather than a direct causal effect of rhythm control. Patients maintaining sinus rhythm likely had more favorable structural and functional profiles. Propensity score adjustment or time-dependent analyses could help disentangle the treatment effect from patient selection.

Fourth, the identification of moderate-to-severe mitral regurgitation as an independent predictor of recurrence is intriguing and clinically relevant (1). However, the mechanistic relationship between mitral regurgitation and AF recurrence remains incompletely explored. It would be valuable to distinguish functional mitral regurgitation driven by left atrial and ventricular remodeling from structural mitral valve abnormalities, as these entities may have different implications for reversibility after rhythm control (4). Longitudinal assessment of mitral regurgitation severity following RFCA could provide insight into bidirectional interactions between valvular dysfunction and atrial remodeling.

While the CAAP-AF score demonstrated reasonable predictive performance (C-statistic of 0.768) (1), its incremental value over HCM-specific parameters is unclear. Given the unique pathophysiology of HCM, the development of a disease-specific risk model incorporating myocardial hypertrophy, diastolic dysfunction, and fibrosis markers may offer superior discrimination.

Acknowledgments

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Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2026-0229/coif). The author has no conflicts of interest to declare.

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References

1. Zhang Z, Li S, Ma L, et al. Effectiveness of radiofrequency catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy: long-term outcomes and predictors of recurrence. Cardiovasc Diagn Ther 2026;16:1. [Crossref] [PubMed]
2. Rowin EJ, Hausvater A, Link MS, et al. Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy. Circulation 2017;136:2420-36. [Crossref] [PubMed]
3. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021;42:373-498. [Crossref] [PubMed]
4. Okazaki RA, Flashner LC, Kinlay S, et al. Catheter ablation for atrial fibrillation in patients with significant mitral regurgitation: A systematic review and meta-analysis. Heart Rhythm 2025;22:637-46. [Crossref] [PubMed]