Mineralocorticoid Receptor Antagonism Reduces Atrial Arrhythmias Post‐Cardiac Surgery and Attenuates Atrial Stress Responses to Cardioplegic Arrest

作者：Sina Danesh, Fazal Khan, Trevor C. Chopko, Aurora Lee, Ran Huo, Lu Shuyang, Vincy Tam, Wenbin Gao, Austin Todd, Joseph J. Maleszewski, Francis D. Pagani, Hartzell V. Schaff, Y. Eugene Chen, Paul A. Friedman, Hakan Oral, Marco Metra, Bertram Pitt, Ienglam Lei, Paul C. Tang · 发表于：Journal of the American Heart Association · 年份：2025 · DOI：10.1161/jaha.125.043661 · 被引用次数：3 · 研究领域：Hormonal Regulation and Hypertension、Atrial Fibrillation Management and Outcomes、Adrenal Hormones and Disorders

BACKGROUND: Postoperative atrial fibrillation occurs in ~40% after cardiac surgery. Mineralocorticoid receptor antagonists (MRA) are known to reduce chronic atrial fibrillation (AF) development and burden. We evaluated the association of preoperative MRA use with postoperative atrial fibrillation and investigated atrial cell types modulated by MRAs during cold preservation. METHODS: We studied 19 042 cardiac surgery patients at Mayo Clinic. Propensity 1:3 matching identified 298 MRA users and 894 non-users. A subgroup analysis of patients on any preoperative diuretic was performed to isolate cardiac-specific effects of MRAs, matching 298 MRA users to 894 non-MRA diuretic users. AF recurrence was assessed for up to 6-years. Single-nucleus RNA sequencing (snRNA-seq) was performed on human donor atria exposed to canrenone (a water-soluble MRA) during cold preservation with ex-vivo reperfusion, and expression profiles were compared with atria from patients with AF. RESULTS: <0.001). MRA use was associated with a reduced incidence of paroxysmal and chronic AF at 6-years. snRNA-seq identified a cardiomyocyte subpopulation, CM2, with high mineralocorticoid receptor expression where canrenone suppressed cold preservation-induced mineralocorticoid receptor target gene expression, which was conversely elevated in chronic AF. Canrenone also attenuated stress-response in atrial macrophages and pericytes. CONCLUSIONS: Preoperative MRAs were associated with reduced postoperative and long-t...