Catheter Ablation for Persistent Atrial Fibrillation: Rationale, Evidence, and Contemporary Strategies Beyond Pulmonary Veins

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial morbidity and mortality due to increased risks of stroke, heart failure, and death. Catheter ablation is now firmly established as a first-line or early rhythm control strategy in selected patients with paroxysmal AF and as a Class I indication in symptomatic patients with persistent AF refractory to antiarrhythmic drug therapy. However, outcomes remain more variable in persistent and long-standing persistent AF, reflecting greater atrial substrate complexity, procedural challenges, and ongoing uncertainty regarding optimal ablation strategies. This review provides a structured, evidence-based overview of contemporary catheter ablation approaches for AF, with particular emphasis on persistent disease. We discuss the anatomical and mechanistic rationale underlying pulmonary vein isolation and adjunctive lesion sets, summarize current clinical evidence supporting various strategies, and highlight differences in efficacy, safety, and reproducibility. In addition, we address the importance of patient selection, shared decision making, procedural expertise, and comprehensive risk factor modification as integral components of successful long-term rhythm control. By integrating guideline recommendations with mechanistic insights and clinical trial data, this review aims to clarify the current best practices and identify remaining knowledge gaps in the catheter ablation of atrial fibrillation.