Atrial Fibrillation Ablation in Patients With Heart Failure and Preserved Ejection Fraction: Faux Pas, Great Absences, and New Hopes

We read with great interest the updated metanalysis by Wani et al. [1] of catheter ablation for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction. The authors include a larger population and more soberly acknowledge the limitations of the findings compared to prior work. Their results provide reassurance to clinicians concerned about worsening left ventricular diastolic dysfunction following AF ablation, as shown by a reduction in heart failure hospitalizations, which aligns with previous observations of transient left atrial dysfunction. Despite these strengths, some conceptual and methodological challenges remain similar to those observed in a previous analysis and merit further consideration. First and foremost, the authors attribute the reduction in stroke incidence solely to the restoration of sinus rhythm. We would like to highlight a different perspective: a mediator exists between the intervention and the outcome. Patients who undergo catheter ablation may be more likely to attend closer follow-up visits that emphasize adherence to oral anticoagulants. Similar adherence differences have been observed in patients undergoing percutaneous coronary intervention, rather than medical therapy alone, for acute coronary syndrome [2]. Post-operative follow-up visits, therefore, may mediate this association. In addition, patients selected for catheter ablation may be more likely to comply with medical recommendations, potentially introducing adherence bias. Thus, the observed reduction in stroke may reflect both rhythm control and differences in follow-up intensity and patient selection. Second, the review does not adequately address procedural safety. Although all-cause hospitalization might be a surrogate marker of post-operative comorbidity, it does not really address the question of how much riskier the ablation is compared to medical management in this population. Although there are discrepancies in the burden and types of complications with medical management, making a direct comparison incongruent, at least three cited articles reported data on safety outcomes [3-5]. While insufficient for pooled analysis, a descriptive summary would have offered a more balanced assessment of both benefits and risks. Third, the analysis of AF recurrence reports results that appear inconsistent with clinical practice. Besides the misinterpretation of the p-value = 0.11 in the paragraph “AF recurrence”, which was then appropriately reworded in the “Discussion”, it is also relevant that 13.2% of the cohort analyzed by Xie et al. was treated with surgical ablation, and 62% of the patients from the same cohort had persistent AF [3]. Furthermore, the study by Patel et al. [6] includes data from 2010 onward, encompassing an era marked by little to no literature on contact force catheters, ablation indices, and second-generation cryoballoons. Our unpublished analysis of the most recent articles on percutaneous catheter ablation [4, 5, 7, 8] shows that AF recurrence is, on average, significantly reduced by 40% over an approximate mean follow-up of 21 months across studies (HR = 0.6, 95% CI: 0.4–0.88; p = 0.01; I2 = 82%: Figure S1). Fourth, the authors included the works by Long et al. [4] and Parkash et al. [9] as sources for analysis. However, these sources are not adequately reported in the References, limiting transparency and reproducibility. Last, an explicit assessment of the quality of the evidence was not presented. Given that nine out of ten studies were not randomized, the overall certainty of evidence is likely low. A formal GRADE evaluation would have clarified the degree of certainty, particularly considering variability in outcomes such as AF recurrence, all-cause mortality, and heart failure hospitalization. We commend the authors for this updated synthesis. Future analyses incorporating pulse-field ablation and ongoing trials such as AMPERE [10] and CABA-HFPEF-DZHK27 [11] will be essential to clarify the role of rhythm control in patients with heart failure and preserved ejection fraction. The authors have nothing to report. The authors have nothing to report. Luigi Di Biase is a consultant for Biosense Webster, Boston Scientific, Stereotaxis, and St Jude Medical and has received speaker honoraria from Medtronic, AtriCure, EPiEP, and Biotronik. The other authors have no conflicts of interest to disclose. Data sharing not applicable to this article as no datasets were generated or analysed during the current study. Figure S1: Forest plot demonstrating the reduction of atrial fibrillation recurrence after percutaneous catheter ablation. The squares represent the effect estimate (mean value) from each study. The bars represent 95% confidence intervals for the effect sizes, while the areas of the squares reflect the weight of the studies. 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