Aldosterone-Mediated Atrial Remodeling and Atrial Fibrillation: Molecular Mechanisms, Translational Insights and Implications for Cardiac Surgery

Atrial fibrillation (AF) has heterogeneous mechanisms, including structural atrial cardiomyopathy, electrical remodeling and primary ion-channel abnormalities. Aldosterone–mineralcorticoid receptor (MR) signaling may contribute to an arrhythmogenic atrial substrate through redox-sensitive, inflammatory, profibrotic and electrophysiological pathways; however, their direct demonstration in human atria varies. Primary aldosteronism is associated with excess AF risk, but circulating aldosterone, renin-independent secretion, tissue MR activation and MR-antagonist exposure are not interchangeable biological measures. This narrative review critically distinguishes evidence from human atrial tissue, atrial experimental systems and extrapolation from other cardiovascular models, with particular emphasis on the cardiac surgical setting. Preoperative aldosterone has been associated with postoperative atrial fibrillation (POAF), whereas perioperative MR-antagonist studies have reported discordant findings and observational analyses remain susceptible to confounding. We propose a testable, rather than established, two-hit framework in which a pre-existing endocrine-associated atrial substrate may interact with perioperative inflammation and hemodynamic stress. The review identifies gaps in endocrine phenotyping and the need for adequately powered prospective and interventional studies before aldosterone-directed POAF prevention can be recommended.