Catheter Ablation Versus Medical Therapy in Persistent Atrial Fibrillation Across the Spectrum from Pre–Heart Failure to Symptomatic Heart Failure: A Systematic Review and Meta-Analysis

Abstract Background Catheter ablation is increasingly used for rhythm control in atrial fibrillation (AF) with heart failure (HF), but its effects on ventricular function, functional status, and clinical outcomes remain incompletely defined for non-paroxysmal AF specifically. We aimed to quantify the effects of catheter ablation versus medical therapy in patients with persistent or long-standing persistent AF and concomitant HF. We searched PubMed, Scopus, ScienceDirect, EBSCO, and the Cochrane Library through May 2026 for randomised controlled trials and peer-reviewed subgroup analyses enrolling adults with non-paroxysmal AF and HF at least Stage B ACC/AHA. Outcomes were pooled as mean differences (MDs) or risk ratios (RRs) using random-effects meta-analysis. Risk of bias was assessed with RoB 2 and certainty of evidence with GRADE. Results Ten randomised controlled trials and two extended follow-up studies, comprising 2853 participants, were included. Catheter ablation improved left ventricular ejection fraction (MD 6.28%, 95% CI 2.45 to 10.11), disease-specific quality of life (MD -6.97), and New York Heart Association functional class (MD -0.70), increased freedom from AF (RR 1.84), and reduced unplanned rehospitalisation (RR 0.54). All-cause mortality did not differ significantly in the primary analysis (RR 0.72; P = 0.13) but showed a directional reduction approaching significance on long-term follow-up (P = 0.05). Six-minute walk distance and stroke or transient ischaemic attack did not differ between groups. An exploratory subgroup analysis suggested that the magnitude of structural benefit may vary by medical comparator strategy. Conclusions In persistent and long-standing persistent AF spanning pre-heart failure to symptomatic HF, catheter ablation improves ventricular function, quality of life, functional class, and arrhythmia-free survival, and reduces rehospitalisation, with a directional but not definitive reduction in long-term mortality. These findings support catheter ablation as a disease-modifying rather than purely symptomatic strategy in this population.