Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea

Abstract

AbstractObstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL‐6], C‐reactive protein [CRP], von Willebrand factor [vWF], N‐terminal pro‐brain natriuretic peptide [NT‐proBNP], high‐sensitivity Troponin T [hs‐TnT], and Galectin‐3 [Gal‐3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription‐polymerase chain reaction (RT‐PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty‐six patients (15 with OSA and 41 non‐OSA) were included in this hypothesis‐generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01–12.92), and had significantly higher baseline levels of NT‐proBNP (p = .044), vWF (p = .049), Gal‐3 (p = .009), IL‐6 (p = .002), and CRP (p = .003). This group presented lower levels of miR‐21 and miR‐208 (both p < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk.