Targeting the Substrate: Mechanism-Based Ablation Strategies for Persistent Atrial Fibrillation

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation, especially effective in patients with paroxysmal AF, where the pulmonary veins (PVs) are the primary triggers. More complex arrhythmogenic mechanisms are involved in persistent AF (PsAF), and PVI alone may not be sufficient. Personalized, substrate-based ablation strategies are increasingly used and can significantly enhance outcomes in PsAF patients. While radiofrequency ablation remains the gold standard, cryoablation provides effective PVI, and pulsed field ablation is emerging as a safer, promising alternative. Advanced mapping techniques may better target scar areas responsible for arrhythmogenesis, optimizing procedural results. While still in development, artificial intelligence and machine learning enable more personalized and precise ablation strategies and may improve long-term outcomes.