Background: This study aimed to investigate the causal relationship between coronary artery bypass grafting (CABG) and atrial fibrillation (AF) using Mendelian Randomization (MR) and a retrospective cohort from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Methods: We performed two-sample MR analysis using GWAS summary statistics (UK Biobank and EBI) to identify genetic instruments for CABG, followed by sensitivity analyses (MR-Egger, weighted median) to validate causality. Concurrently, 1,835 ICU patients from MIMIC-IV were analyzed via multivariable logistic regression to assess CABG-AF association, stratified by age, hemodynamic, and coagulation profiles. Results: MR analysis demonstrated a robust causal effect of CABG on AF (IVW OR=1.8, P=2.33×10??), corroborated by cohort data showing doubled AF risk post-CABG (OR=2.1, 95% CI:1.4–3.1, P<0.001). Subgroups with autonomic instability (low heart/respiratory rates) or coagulopathy (INR>2.5) exhibited heightened susceptibility. Conclusion: CABG independently elevates AF risk via autonomic, inflammatory, and hemostatic pathways, necessitating tailored perioperative monitoring and prophylactic interventions.

The authors have declared no competing interest.

The author(s) received no specific funding for this work.

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The data utilized in this study is de-identified to ensure patient confidentiality and compliance with ethical standards. One of the authors, Li Li, has successfully completed the necessary ethical training and certification to access and extract the data. The certification for data access was granted under the authorization number 13369960, ensuring that all procedures followed were in accordance with institutional and regulatory guidelines for the use of medical data in research.

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