Why the study?
Postoperative atrial fibrillation occurs in ~40% after cardiac surgery, and while MRAs reduce chronic AF, their association with postoperative AF and specific atrial cell-type modulation remained to be evaluated.
Does preoperative mineralocorticoid receptor antagonist use reduce the incidence of postoperative and long-term atrial fibrillation in adults undergoing cardiac surgery?
Does preoperative mineralocorticoid receptor antagonist use reduce the incidence of postoperative and long-term atrial fibrillation in adults undergoing cardiac surgery?
Preoperative mineralocorticoid receptor antagonist use is associated with a significant reduction in both early and long-term postoperative atrial fibrillation after cardiac surgery, likely by suppressing atrial stress responses in cardiomyocytes.
Should not yet change practice; leaves open a role for preoperative MRAs in preventing long-term AF after cardiac surgery.
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. 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-term AF after cardiac surgery. Mechanistically, our ex-vivo human atrial model revealed that MRAs suppress mineralocorticoid receptor -driven atrial stress responses, particularly in conduction-relevant cardiomyocytes.
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Danesh et al. (2025) studied this question.
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