Atrial fibrillation: from pathogenesis to novel treatment options

Abstract The management of atrial fibrillation (AF) is currently undergoing a significant paradigm shift, driven by a deepening understanding of pathophysiology and the urgent need to overcome the inherent safety and durability limitations of conventional thermal catheter ablation. This review provides a comprehensive update on the evolving AF landscape, systematically connecting complex pathogenetic mechanisms, from focal triggers to progressive fibrotic substrate remodeling, with emerging diagnostic and therapeutic innovations. We critically evaluate the expanding spectrum of novel treatment modalities, with an emphasis on pulsed-field ablation (PFA), detailing its biophysical basis of irreversible electroporation, superior myocardium-selective safety profile, and accumulating clinical evidence. Furthermore, the review integrates complementary advancements, including high-resolution electroanatomic mapping systems that refine substrate characterization, hybrid surgical-catheter strategies for refractory cases, and upstream pharmacologic interventions targeting disease progression. By synthesizing contemporary data on procedural workflows and efficacy outcomes from recent randomized trials, we address persisting challenges such as lesion durability and the management of non-pulmonary vein drivers. Finally, we identify critical knowledge gaps regarding long-term comparative effectiveness and propose a phenotype-guided management framework. This approach aims to leverage these diverse emerging technologies to optimize patient selection, thereby advancing the field toward safer, more durable, and truly personalized rhythm control for the growing population of patients with atrial fibrillation.