Transcriptome analysis from human epicardial adipose tissue biopsies analyzed according to postoperative atrial fibrillation occurrence after cardiac surgery. Transcriptome analysis from human epicardial adipose tissue biopsies analyzed according to postoperative atrial fibrillation occurrence after cardiac surgery

Introduction: Post-operative atrial fibrillation (POAF) is a frequent complication after cardiac surgery, but its pathophysiology remains incompletely understood. Considering that epicardial adipose tissue (EAT) is in close vicinity with the atrial myocardium, we hypothesized that a specific pre-operative EAT phenotype would be associated to POAF onset following surgery. Methods: Patients undergoing cardiac surgery prospectively enrolled in the POMI-AF cohort between February 2016 and June 2017 were studied. EAT samples were collected at the beginning of surgery. Whole-tissue gene expression patterns and the stromal and vascular fraction (SVF) cellular composition were explored. Patients were followed after surgery by continuous ECG to detect POAF onset. Results: Among the 60 patients included in the cohort, 15 POAF and 15 non-POAF patients were matched based on pre-operative characteristics. Gene set enrichment analysis of transcriptomic data from pre-operative EAT samples revealed 40 enriched biological processes in POAF vs non-POAF patients. Most of these processes were related to cellular immune response. Leukocytes (63±15% of total cells), and more specifically lymphocytes (56±13% of total CD45+ cells), represented the major cell subset in the preoperative EAT SVF, with no quantitative differences between POAF and SR patients (76 [52; 84]% vs 56 [50; 64]%, p=0.22). However, POAF patients presented a significantly higher cytotoxic CD8+/helper CD4+ T lymphocyte ratio than SR patients (respectively, 0.69[0.55; 1.19] vs 0.50 [0.31; 0.54], p=0.03) suggesting a cytotoxic shift prior to surgery. Conclusion: Epicardial fat from patients who develop POAF displays a specific pre-operative transcriptome signature characteristic of cellular immune response and cytotoxic lymphocyte enrichment. Overall design: 30 matched samples analyzed (15 POAF vs 15 SR patients)