Pre-operative inflammation and post-operative atrial fibrillation in coronary artery bypass surgery.

Post-operative atrial fibrillation (POAF) is the most common complication following coronary artery bypass surgery (CABG) with new onset in approximately 30% of the patients [1]. Accumulating data suggest that there is a close link between AF and inflammation. Several studies have shown that patientswithAF have increased levels of various inflammatory markers such as CRP (C-reactive protein), IL-6 (interleukin-6) and TNF-α (tumor necrosis factor alpha) [2]. Interestingly CRP levels of the patientswith AFare higher compared to thosewith sinus rhythm and in those with persistent AF compared with patients with paroxysmal AF [2]. Although systemic inflammation has been implicated in thedevelopmentof paroxysmal atrialfibrillation, it is unclearwhichkey inflammatory biomarkers have a clinical predictive value that could be used in clinical practice to stratify these patients. In this study we examined the predictive value of circulating levels of monocyte chemoattractant protein 1 (MCP-1), IL-6 and CRP on the development of POAF in patients undergoing CABG. MCP-1 is a chemokine expressed mainly by inflammatory cells and its expression is up-regulated with tissue injury and proinflammatory stimuli [3,4]. The study population consisted of 184 patients undergoing elective CABG. The participants were recruited preoperatively and exclusion criteria were any inflammatory, infective liver or renal disease or malignancy. We also excluded patients receiving non-steroid antiinflammatory drugs and patients who were in sinus rhythm but were under any anti-arrhythmic medication. The patients included to the study were in sinus rhythm and had no history of atrial fibrillation in the past. The demographic characteristics of the participants are demonstrated in Table 1. Blood samples were collected from all the patients the morning before surgery following an 8-hour fasting period. MCP-1 and interleukin-6 (IL-6) levels were determined using ELISA (ELISA kits R&D systems,Wiesbaden–Nordenstadt, Germany). CRP levelsweredeterminedby immunonephelometry (NLatex, Dade-Behring Marburg, Marburg, Germany). The patients were continuously monitored with surface electrocardiography (ECG) for the first 48 h after surgery during their stay in the cardiac intensive care unit (CICU). After their discharge from the CICU and their transfer to the wards, heart rhythm was evaluated every 4 h with ECG or whenever a relevant sign or symptom was reported, until the day of their discharge from the hospital and every incident of POAF was recorded. Normally distributed variables are presented as means ± SEM. Comparisons across 2 groups were performed by unpaired t-test. The predictive value of the measured biomarkers on the development of POAFwas evaluated by plotting the Kaplan–Meier curves and by running a log-rank test. All p-values are two-tailed and SPSS 21.0 was used for all statistical analyses. During follow-up, 37 of the patients developed POAF (20% of the study population). Patients were separated into 3 groups (lower, mid and higher) based on their MCP-1, IL6 and hsCRP values, and Kaplan– Meier curves were generated. Groups with mid and higher values of MCP-1 had significantly less incidents of postoperative AF comparing with the low value group, p b 0.05 (Fig. 1A). The differences between the groups stratified by IL6 and hsCRP levels were not statistically significant, p = NS (Fig. 1B–C). When we compared the group of patients who developed POAF with those who remained in SR throughout their hospital stay, we observed significantly lower preoperative levels of MCP-1 in those who developed POAF compared to those who did not, p b 0.05 (Fig. 2A). Preoperative levels of IL6 and hsCRP were similar between the two groups, p = NS (Fig. 2B–C). Myocardial inflammation especially the inflammation of the right atrium during cardiac surgery causes structural and electrical remodeling to the myocardium, leading to the impairment of the conduction of the electrical stimulus. It has been previously reported that anti-inflammatory therapy has significantly lowered the incidence of POAF [5]. The exact mechanism in which myocardial inflammation causes this heterogeneity of the electrical stimulus conduction, further leading to the development of POAF has not yet been clarified. CRP levels, the most commonly used inflammatory biomarker, have been associated with the development of POAF in patients undergoing CABG [6]. The association of CRP levels with the development of AF was originally believed to be due to the fact that CRP detected in the myocardial cells of the atrium leads to the consequent activation of complement and causes further myocardial injury [7–9]. Moreover, endothelial cells and cardiomyocytes responding to the oxidative stress produce a variety of inflammatory mediators such as MCP-1, which in turn attract further inflammatory molecules into the damaged zone [10,11]. MCP-1 is one of the best studied chemokines. It is produced by many cell types including