Prevention of Pathological Atrial Remodeling and Atrial Fibrillation: JACC State-of-the-Art Review

Atrial enlargement in response to pathological stimuli (e.g., hypertension, mitral valve disease) and physiological stimuli (exercise, pregnancy) can be comparable in magnitude, but the diseased enlarged atria is associated with complications such as atrial fibrillation (AF), whereas physiological atrial enlargement is not. Pathological atrial enlargement and AF is also observed in a small percentage of athletes undergoing extreme/intense endurance sport and pregnant women with preeclampsia. Differences between physiological and pathological atrial enlargement and underlying mechanisms are poorly understood. This review describes human and animal studies characterizing atrial enlargement under physiological and pathological conditions and highlights key knowledge gaps and clinical challenges, including: 1) the limited ability of atria to reverse remodel; and 2) distinguishing physiological and pathological enlargement via imaging/biomarkers. Finally, this review discusses how targeting distinct molecular mechanisms underlying physiological and pathological atrial enlargement could provide new therapeutic and diagnostic strategies for preventing or reversing atrial enlargement and AF.