Abstract-Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an important contributor to population morbidity and mortality. An arrhythmia that is particularly common in the elderly, AF is growing in prevalence with the aging of the population. Our understanding of the basic mechanisms that govern AF occurrence and persistence has been increasing rapidly. This article reviews the basic pathophysiology of AF over a broad range of levels, touching on the tissue mechanisms that maintain the arrhythmia, the relationship between clinical presentation and basic mechanisms, ion channel and transporter abnormalities that lead to ectopic impulse formation, basic models and tissue determinants of reentry, ion channel determinants of reentry, the nature and roles of electric and structural remodeling, autonomic neural components, anatomic factors, interactions between atrial and ventricular functional consequences of AF, and the basic determinants of atrial thromboembolism. We then review the potential implications of the basic pathophysiology of the arrhythmia for its management. We first discuss consequences for improved rhythm control pharmacotherapy: targeting underlying conditions, new atrium-selective drug targets, new targets for focal ectopic source suppression, and upstream therapy aiming to prevent remodeling. We then review the implications of basic mechanistic considerations for rate control therapy, AF ablation, and the prevention of thromboembolic events. We conclude with some thoughts about the future of translational research related to AF mechanisms. (Circulation. 2011; 124:2264-2274.)Key Words: antiarrhythmia agents Ⅲ arrhythmia Ⅲ calcium Ⅲ electrophysiology Ⅲ reentry A trial fibrillation (AF), the most common sustained cardiac arrhythmia, is becoming progressively more prevalent with population aging. 1 Enormous advances in the understanding of AF pathophysiology have occurred over the past 20 years. 2,3 The present article, part of a thematic series in Circulation on AF, provides a broad overview of AF pathophysiology and the potential implications for AF management. In addition, it furnishes background information on basic mechanisms relevant to other articles in the series dealing with AF epidemiology and genetics, stroke prevention, rate control therapy, sinus rhythm maintenance pharmacotherapy, management in structural heart disease, and catheter ablation. For more comprehensive treatment of specific mechanisms, the reader is referred to detailed review articles. [2][3][4][5]
