Pathogenesis Of Postoperative Atrial Fibrillation Research Articles

Relationship between platelet-related parameters and new-onset atrial fibrillation after coronary bypass surgery.

Inflammation plays a key role in the pathogenesis of postoperative atrial fibrillation after coronary artery bypass graft surgery. In this study, we aimed to investigate the changes in mean platelet volume and platelet values during the spring and autumn seasons in patients who underwent isolated coronary artery bypass graft surgery and the possible effect of these occurrences on postoperative atrial fibrillation. Consecutive patients who underwent elective isolated coronary bypass surgery at our clinic in the spring and autumn months, between August 2020 and July 2022, were retrospectively included in this study. Variables were evaluated according to the spring and autumn seasons. Patients who did not develop in-hospital postoperative atrial fibrillation were identified as Group 1, and those who did constituted Group 2. A total of 622 patients were included in the study. The patients were divided into two groups: those who were operated on in the spring (n=277, median age=62 years, male gender ratio=77.3%) and those who were operated on in the autumn (n=345, median age=61 years, male gender ratio=81.4%). There was no statistically significant difference between the patients operated on in both seasons in terms of age, gender, hypertension rates, and the frequency of chronic obstructive pulmonary disease. In multivariate analysis, being over 70 years old (OR: 1.934, 95% confidence interval (CI) 1.489-2.995, p<0.001), having a left ventricular ejection fraction below 30% (OR: 1.550, 95%CI 1.190-2.236, p=0.012), and having chronic obstructive pulmonary disease (OR: 1.663, 95%CI 1.339-2.191, p<0.001) were found to be independent predictors in predicting the development of postoperative atrial fibrillation. In this study, we first demonstrated that mean platelet volume and platelet mass index values were higher in patients in the autumn months. Additionally, for the first time in the literature, we showed that there is a significant relationship between platelet mass index value and the development of postoperative atrial fibrillation in patients who underwent isolated coronary artery bypass graft.

Gene modules and genes associated with postoperative atrial fibrillation: weighted gene co-expression network analysis and circRNA-miRNA-mRNA regulatory network analysis.

Atrial fibrillation (AF) is the most common complication in patients undergoing cardiac surgery. However, the pathogenesis of postoperative AF (POAF) is elusive, and research related to this topic is sparse. Our study aimed to identify key gene modules and genes and to conduct a circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory network analysis of POAF on the basis of bioinformatic analysis. The GSE143924 and GSE97455 data sets from the Gene Expression Omnibus (GEO) database were analyzed. Weighted gene co-expression network analysis (WGCNA) was used to identify the key gene modules and genes related to POAF. A circRNA-miRNA-mRNA regulatory network was also built according to differential expression analysis. Functional enrichment analysis was further performed according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. WGCNA identified 2 key gene modules and 44 key genes that were significantly related to POAF. Functional enrichment analysis of these key genes implicated the following important biological processes (BPs): endosomal transport, protein kinase B signaling, and transcription regulation. The circRNA-miRNA-mRNA regulatory network suggested that KLF10 may take critical part in POAF. Moreover, 2 novel circRNAs, hsa_circRNA_001654 and hsa_circRNA_005899, and 2 miRNAs, hsa-miR-19b-3p and hsa-miR-30a-5p, which related with KLF10, were involved in the network. Our study provides foundational expression profiles following POAF based on WGCNA. The circRNA-miRNA-mRNA network offers insights into the BPs and underlying mechanisms of POAF.

Review of the epidemiology, pathogenesis and prevention of atrial fibrillation after pacemaker implantation.

Cardiac pacemaker implantation is an important treatment for symptomatic bradycardia. However, epidemiological data show that the incidence of atrial fibrillation (AF) is significantly higher in patients with implanted pacemakers than in the general population, which may be related to the preoperative presence of multiple risk factors for AF, improvement of diagnostic sensitivity and the pacemaker itself. The pathogenesis of AF after the implantation of pacemaker is related to cardiac electrical remodeling, structural remodeling, inflammation, and autonomic nervous disorder, which are induced by the pacemaker. Moreover, different pacing modes and pacing sites have various effects on the pathogenesis of postoperative AF. Recent studies have reported that reducing the proportion of ventricular pacing, improving the pacing site and setting up special pacing procedures might be highly useful in prevention of AF after pacemaker implantation. This article reviews the epidemiology, pathogenesis, influencing factors, and preventive measures regarding AF after pacemaker surgery.

Gut Microbiota in Patients with Postoperative Atrial Fibrillation Undergoing Off-Pump Coronary Bypass Graft Surgery.

Post-operative atrial fibrillation (POAF) is one of the most common complications of cardiac surgery. However, the underlying mechanism is not well understood. Alterations in the gut microbiota are associated with the development of atrial fibrillation (AF). The aim of this study was to explore the relationship between gut microbiota and POAF. Fecal samples were collected before surgery from 45 patients who underwent coronary artery bypass grafting with POAF and 90 matched patients without POAF (1:2). 16S rRNA sequencing was used to detect the microbiome profiles of 45 POAF patients and 89 matched patients (one sample in the no-POAF group was deleted owing to low quality after sequencing). Plasma 25-hydroxy vitamin D level was measured by ELISA. Compared to the patients without POAF, gut microbiota composition was remarkably changed in the patients with POAF, with an increase in Lachnospira, Acinetobacter, Veillonella and Aeromonas, and a decrease in Escherichia-Shigella, Klebsiella, Streptococcus, Brevundimonas and Citrobacter. Furthermore, plasma 25-hydroxy vitamin D levels were decreased in POAF patients and negatively correlated with an abundance of Lachnospira. The gut microbiota composition between patients with and without POAF is significantly different, implying that gut microbiota may play a role in the pathogenesis of POAF. Further studies are needed to fully clarify the role of gut microbiota in the initiation of AF.

Effect of Magnesium Sulfate in Prevention of Postoperative Atrial Fibrillation Arrhythmia among Candidates of CABG Surgery with Abnormal P-wave Duration

Background: Cardiac arrhythmias, especially atrial fibrillation, are among the most common early complications of open-heart surgery. Hypomagnesemia is one of the clinical mechanisms associated with the pathogenesis of postoperative atrial fibrillation. This study aimed to evaluate the effect of magnesium sulfate on the prevention of atrial fibrillation in patients with abnormal P-wave duration who underwent coronary artery bypass graft (CABG)surgery. Methods: In this clinical trial, 150 patients participated who had undergone CABG surgery at Imam Khomeini hospital in Ahvaz in 2014. According to the inclusion criteria, the intervention and control groups were randomly matched. The intervention group, consisting of 57 patients, received 2.4 g of magnesium sulfate daily for three days and 75 patients of the control group received a placebo. Prevention of postoperative atrial fibrillation by magnesium sulfate was evaluated in patients and data were analyzed using SPSS software. Results: The two groups did not have a significant difference in terms of gender, diabetes, hyperlipidemia, and hypertension. Also, mean P-wave duration, length of intensive care unit stay, the total length of hospitalization, left ventricular ejection fraction (LVEF), distribution of creatinine, atrial fibrillation, and aortic clamp time in intervention and control groups were not statistically significant. Only, the total pump duration difference was reported to be statistically significant between groups. Conclusion: The results of our study showed that the administration of magnesium sulfate alone cannot be helpful in the prevention of atrial fibrillation among patients with long P-wave duration. Trial Registration: https://www.irct.ir/, Identifier: IRCT2015092814190N9

Colchicine for prevention of post-operative atrial fibrillation: Meta-analysis of randomized controlled trials.

This study intended to assess the efficacy of colchicine for prevention of post-operative atrial fibrillation (AF). Post-operative AF is a common complication of surgery operations. Inflammation plays a crucial role in the pathogenesis of post-operative AF. Colchicine, a potent anti-inflammatory drug, may have a role in mitigating the incidence of post-operative AF. We searched Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), Database of Chinese sci-tech periodicals (COVIP), and Wanfang Database for randomized controlled trials (RCTs) comparing colchicine versus placebo, or usual care for prevention of post-operative AF. The main outcome was the occurrence of AF post operation, which includes cardiac surgery, lung surgery, or pulmonary vein isolation. The estimated risk ratio (RR) for the occurrence of post-operative AF was evaluated using a random-effects model. The safety end point was the development of any side effects. A total of 12 RCTs with 2274 patients were eventually included in this meta-analysis, where 1141 patients received colchicine and 1133 patients received placebo or usual care. Perioperative colchicine treatment was related to a decreased incidence of post-operative AF (RR: 0.65; 95% confidence interval [CI]: 0.56 to 0.75, p<0.001). Although the incidence of gastrointestinal side effects was increased with colchicine therapy when compared to placebo (RR = 2.49, 95% CI 1.85 to 3.34, p < 0.001), the incidence of major adverse events was not increased (RR = 0.86, 95% CI 0.46 to 1.60, p = 0.64). In conclusion, the results of our meta-analysis suggest that colchicine treatment could lower the incidence of post-operative AF. Further studies are needed to determine the optimal colchicine treatment regime to minimize the incidence of adverse events.

Relationship between platelet mass index and postoperative atrial fibrillation after elective coronary artery bypass surgery: aretrospective study.

Atrial fibrillation (AF) is the most common complication after cardiac surgery. The pathogenesis of postoperative atrial fibrillation (POAF) is multifactorial and one of the known factors is inflammation. Platelet mass index (PMI) is an indicator of platelet activation and abetter inflammatory marker than mean platelet volume (MPV). In this retrospective study, we investigated the relationship between POAF and PMI. The study included 848 consecutive patients (655male and 193female) who had elective isolated coronary artery by-pass grafting (CABG) or combined CABG and valvular surgery. Platelet count and MPV were measured from preoperative blood samples to calculate PMI. Post-operative atrial fibrillation was defined as irregular and fibrillatory Pwaves occurring 48-96 h after cardiac surgery and lasting at least 30 s. The PMI values in patients who developed POAF were compared with those in patients who did not develop POAF. Patients who developed POAF had higher PMI values (2549.3 ± 1077.1) when compared with patients in sinus rhythm (2248.1 ± 683.4; p < 0.01). In multivariate regression analysis, age (OR: 1.05; 95%CI: 1.02-1.09; p = 0.01), left atrial diameter (OR: 1.05; 95% CI: 1.03-1.09; p = 0.02), hs-CRP (OR: 1.09; 95%CI: 1.05-1.13; p < 0.01), EuroSCOREII (OR: 1.27; 95% CI: 1.14-1.41; p < 0.01), and PMI (OR: 1.01; 95% CI: 1.001-1.02; p < 0.01) were independent predictors of POAF. In ROC analysis, PMI ≥ 2286 predicted POAF development with asensitivity of 69% and aspecificity of 58% (AUC: 0.66; p < 0.01) CONCLUSION: Asignificant relationship was found between preoperatively calculated PMI and POAF. We showed that PMI may be used to predict patients who are at high risk of developing POAF.

Epicardial Adipose Tissue and Postoperative Atrial Fibrillation.

BackgroundAtrial fibrillation (AF) often occurs after cardiac surgery and is associated with increased risk of stroke and mortality. Prior studies support the important role of inflammation in the pathogenesis of postoperative atrial fibrillation (POAF). It is known that an increased volume and a pro-inflammatory phenotype of epicardial adipose tissue (EAT) are both associated with AF onset in non surgical context. In the present study, we aim to evaluate whether also POAF occurrence may be triggered by an increased production of inflammatory mediators from EAT.MethodsThe study population was composed of 105 patients, with no history of paroxysmal or permanent AF, undergoing elective cardiac surgery. After clinical evaluation, all patients performed an echocardiographic study including the measurement of EAT thickness. Serum samples and EAT biopsies were collected before surgery. Levels of 10 inflammatory cytokines were measured in serum and EAT conditioned media. After surgery, cardiac rhythm was monitored for 7 days.ResultsForty-four patients (41.3%) developed POAF. As regard to cardiovascular therapy, only statin use was significantly lower in POAF patients (65.1% vs. 84.7%; p-0.032). Levels of Monocyte Chemoattractant Protein-1 (MCP-1), in both serum and EAT, were significantly higher in POAF patients (130.1 pg/ml vs. 68.7 pg/ml; p = <0.001; 322.4 pg/ml vs. 153.4 pg/ml; p = 0.028 respectively). EAT levels of IL-6 were significantly increased in POAF patients compared to those in sinus rhythm (SR) (126.3 pg/ml vs. 23 pg/ml; p = <0.005).ConclusionHigher EAT levels of IL-6 and MCP-1 are significantly associated with the occurrence of POAF. Statin therapy seems to play a role in preventing POAF. These results might pave the way for a targeted use of these drugs in the perioperative period.

The importance of mean platelet volume to lymphocyte ratio in predicting atrial fibrillation after coronary bypass operations

Background/Aim: The rate of postoperative atrial fibrillation (PoAF) after coronary artery bypass graft (CABG) operations ranges between 25-40%. Inflammation plays an important role in the pathogenesis of PoAF, and mean platelet volume and lymphocyte count are important inflammatory parameters. This study aimed to investigate the importance of the mean platelet to lymphocyte ratio (MPVLR) in predicting PoAF after CABG operations. Methods: Three hundred and eighty consecutive patients who underwent on-pump CABG in our clinic between August 2016 and August 2020 were included in this retrospective observational cohort study. Patients with a known history of atrial fibrillation, reoperations, emergency operations, patients who had acute coronary syndrome within the last month, combined surgeries, those with systemic inflammatory disease, chronic autoimmune disease, chronic liver/kidney disease, and hematological diseases, and patients under steroid therapy were excluded from the study. Patients who did not develop postoperative PoAF were included in Group 1, while those who did were included in Group 2. Results: There were 319 patients in Group 1 with a median age of 59 (32-83) years, and 61 patients in Group 2, with a median age of 66 (38-86) years (P<0.001). There was no difference between the groups in terms of gender distribution, hypertension (HT), diabetes mellitus (DM), smoking, body mass index, hyperlipidemia, ejection fraction, and current medical treatments (such as Angiotensin-converting enzyme inhibitor and beta-blocker therapy). The rate of chronic obstructive pulmonary disease (P=0.017), as well as MPV, MPVLR, intensive care unit stay and total hospitalization times were significantly higher (P<0.001 for all) in Group 2, while lymphocyte levels were significantly lower (P=0.006). Based on multivariate analysis, being over 70 years old (OR: 2.432, CI 95%: 1.966-3.723, P<0.001), having an ejection fraction below 35% (OR: 1.325, CI 95%: 1.190-1.1894, P=0.021) and MPVLR (OR: 1.821, 95%CI: 1.645-2.1592, P<0.001) were independent predictors of PoAF. Conclusion: We found that the preoperative MPVLR value, which can be obtained from a simple hemogram test, is an important predictor of PoAF in patients who underwent CABG. MPVLR value can be a marker in determining risky groups preoperatively.

Atrial fibrillation and alteration of heart rate variability after video-assisted pulmonary lobectomy versus thoracotomy pulmonary lobectomy

ObjectiveTo compare the incidence of atrial fibrillation (AF) and alteration of heart rate variability (HRV) after pulmonary lobectomy through video assisted thoracic surgery or thoracotomy, and to explore the role of autonomic nerves in the pathogenesis of atrial fibrillation after pulmonary lobectomy.MethodsIn a single institution, 224 patients (age > 60) with normal sinus rhythm were enrolled in the study. Experienced surgeons and anesthetists carried out operation and anesthesia according to the same procedure. The hearts were monitored using Holter for more than 96 h. Any new-onset AF was recorded and HRV was analyzed at different time intervals.ResultsOne hundred twelve patients undergoing video-assisted thoracic surgery (VATS) and 112 patients undergoing thoracotomy (THOR) were matched for age and gender. Atrial fibrillation occurred in 39 patients, with a similar incidence between the two groups (VATS: 19/112, 16.9% and THOR: 20/112, 17.9%, P = 0.82). The post-operational heart variability at different time intervals was comparable between the two groups.ConclusionPulmonary lobectomy through video assisted thoracic surgery does not reduce the postoperative atrial fibrillation. Autonomic nerve mechanism may be involved in the pathogenesis of postoperative atrial fibrillation.

CD8+CD28null T Lymphocytes are Associated with the Development of Atrial Fibrillation after Elective Cardiac Surgery.

Postoperative atrial fibrillation (POAF) is assumed as a complex and multifactorial interaction of different pathogenic factors. Data suggests an inflammatory process as the main trigger of this specific type of atrial fibrillation. CD8+ T lymphocytes that lack the surface protein CD28 were found to be crucially involved in chronic inflammatory processes within the cardiovascular system. Of utmost interest, these so-called CD8+CD28null T cells are known to present with autoaggressive behavior and deleterious cytotoxic effects on human tissue. A total of 129 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were enrolled. Fluorescence-activated cell sorting was performed to investigate lymphocyte subsets. Patients were stratified in two subgroups according to patients developing POAF (n = 60) and individuals free of POAF (n = 69). Comparing patients developing POAF to individuals free of POAF, the fraction of CD8+ lymphocytes was significantly higher in individuals developing POAF (30.5% [POAF] vs. 25.7% [no-POAF]; p = 0.021). Interestingly, also the fraction of CD8+CD28null T lymphocytes was significantly higher in the POAF subgroup (66.7% [POAF] vs. 61.6% [non-POAF]; p = 0.043). Multivariate logistic regression proved that the fraction of CD8+CD28null cells is a strong and independent prognosticator for the development of POAF with an adjusted odds ratio per 1 standard deviation of 3.21 (95% confidence interval 1.01-10.18; p = 0.048). We found that cytotoxic CD8+CD28null T lymphocytes proved to be a strong and independent predictor for the development of POAF after elective cardiac surgery. Our results potentially indicate an autoimmune impact of this preexisting, highly cytotoxic T cell subset in the pathogenesis of POAF.

Temporary autonomic modulation with botulinum toxin type A to reduce atrial fibrillation after cardiac surgery

Postoperative atrial fibrillation (POAF) frequently complicates cardiac surgery and is associated with worse outcomes. The cardiac autonomic nervous system is implicated in the pathogenesis of POAF. The purpose of this study was to determine the efficacy and safety of selective cardiac autonomic modulation in preventing POAF. In this randomized, double-blind, placebo-controlled trial, adults undergoing cardiac surgery were randomized 1:1 to intraoperative injection of 250 units onabotulinumtoxinA (botulinum toxin type A [BoNTA]) or placebo into epicardial fat pads. The study was powered to detect a 40% reduction in relative risk of POAF. Time to first episode of in-hospital POAF was the primary outcome, evaluated in patients receiving injection. Additionally, incidence of POAF, length of stay (LOS), and adverse events were examined. The trial assigned 145 patients to injection, 15 of whom were dropped before treatment, leaving 130 patients for analysis. Overall, 36.5% (23/63) of BoNTA-treated patients developed POAF compared with 47.8% (32/67) of placebo-treated patients. The time-to-event analysis revealed a hazard ratio of 0.69 (95% confidence interval 0.41-1.19; P = .18) for the BoNTA vs placebo arm. There were no significant differences in postoperative hospital LOS (median [interquartile range] 6.0 [3.4] vs 6.2 [3.7] days; P=.51) or adverse events prolonging LOS (27/63 [42.9%] vs 30/67 [44.8%]; P = .83) in patients receiving BoNTA vs placebo. Epicardial injection of onabotulinumtoxinA was without discernible adverse effects, but we failed to detect a significant difference in risk of POAF. Future large-scale studies of epicardial onabotulinumtoxinA injection as a potential POAF prevention strategy should be designed to study smaller, but clinically meaningful, treatment effects.

CD4+CD28null T Lymphocytes are Associated with the Development of Atrial Fibrillation after Elective Cardiac Surgery

Post-operative atrial fibrillation (POAF) is postulated as a complex interaction of different pathogenic factors, suggesting inflammatory processes as a main trigger of this particular type of atrial fibrillation. Therefore, the study sought to assess the impact of cellular immunity on the development of POAF. Comparing patients developing POAF to individuals free of POAF the fraction of CD4+CD28null T Lymphocytes was significantly higher in individuals developing POAF (11.1% [POAF] vs. 1.9% [non-POAF]; p < 0.001). CD4+CD28null cells were independently associated with the development of POAF with an adjusted odds ratio per one standard deviation of 4.89 (95% CI: 2.68–8.97; p < 0.001). Compared to N-terminal Pro-Brain Natriuretic Peptide, the fraction of CD4+CD28null cells demonstrated an increased discriminatory power for the development of POAF (NRI: 87.9%, p < 0.001; IDI: 30.9%, p < 0.001). Interestingly, a pre-operative statin-therapy was associated with a lower fraction of CD4+CD28null cells (p < 0.001) and showed an inverse association with POAF (p < 0.001). CD4+CD28null cells proved to be predictive for the development of POAF after cardiac surgery. Our results potentially indicate an auto-immune impact of this preexisting, highly cytotoxic T cell subset in the pathogenesis of POAF, which might be modified via the anti-inflammatory potential of a pre-operative statin-therapy.

Baseline and postoperative levels of C-reactive protein and interleukins as inflammatory predictors of atrial fibrillation following cardiac surgery: a systematic review and meta-analysis.

Postoperative atrial fibrillation (POAF) is a leading arrhythmia with high incidence and serious clinical implications after cardiac surgery. Cardiac surgery is associated with systemic inflammatory response including increase in cytokines and activation of endothelial and leukocyte responses. This systematic review and meta-analysis aimed to determine the strength of evidence for evaluating the association of inflammatory markers, such as C-reactive protein (CRP) and interleukins (IL), with POAF following isolated coronary artery bypass grafting (CABG), isolated valvular surgery, or a combination of these procedures. We conducted a meta-analysis of studies evaluating measured baseline (from one week before surgical procedures) and postoperative levels (until one week after surgical procedures) of inflammatory markers in patients with POAF. A compre-hensive search was performed in electronic medical databases (Medline/PubMed, Web of Science, Embase, Science Direct, and Google Scholar) from their inception through May 2017 to identify relevant studies. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. A literature search of all major databases retrieved 1014 studies. After screening, 42 studies were analysed including a total of 8398 patients. Pooled analysis showed baseline levels of CRP (standard mean difference [SMD] 0.457 mg/L, p < 0.001), baseline levels of IL-6 (SMD 0.398 pg/mL, p < 0.001), postoperative levels of CRP (SMD 0.576 mg/L, p < 0.001), postoperative levels of IL-6 (SMD 1.66 pg/mL, p < 0.001), postoperative levels of IL-8 (SMD 0.839 pg/mL, p < 0.001), and postoperative levels of IL-10 (SMD 0.590 pg/mL, p < 0.001) to be relevant inflammatory parameters significantly associated with POAF. Perioperative inflammation is proposed to be involved in the pathogenesis of POAF. Therefore, perioperative assessment of CRP, IL-6, IL-8, and IL-10 can help clinicians in terms of predicting and monitoring for POAF.

Inflammation, oxidative stress and postoperative atrial fibrillation in cardiac surgery.

Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery that occurs in up to 60% of patients. POAF is associated with increased risk of cardiovascular mortality, stroke and other arrhythmias that can impact on early and long term clinical outcomes and health economics. Many factors such as disease-induced cardiac remodelling, operative trauma, changes in atrial pressure and chemical stimulation and reflex sympathetic/parasympathetic activation have been implicated in the development of POAF. There is mounting evidence to support a major role for inflammation and oxidative stress in the pathogenesis of POAF. Both are consequences of using cardiopulmonary bypass and reperfusion following ischaemic cardioplegic arrest. Subsequently, several anti-inflammatory and antioxidant drugs have been tested in an attempt to reduce the incidence of POAF. However, prevention remains suboptimal and thus far none of the tested drugs has provided sufficient efficacy to be widely introduced in clinical practice. A better understanding of the cellular and molecular mechanisms responsible for the onset and persistence of POAF is needed to develop more effective prediction and interventions.

The effect of oxidative stress related with ischemia-reperfusion damage on the pathogenesis of atrial fibrillation developing after coronary artery bypass graft surgery.

We aimed to investigate the role of oxidative stress related with ischemia- reperfusion damage on the pathogenesis of atrial fibrillation (AF) developing after coronary artery bypass graft (CABG) surgery. In our prospective, single-center study, 118 patients who underwent elective isolated on-pump CABG surgery were included. Patients were divided into two groups according to the development of postoperative atrial fibrillation (POAF) as Group 1: Patients who developed POAF, and Group 2: Patients who remained in sinus rhythm. In addition to preoperative demographic, laboratory, echocardiographic, intraoperative, and postoperative clinical characteristics, levels of plasma total oxidative status (TOS) after placement and removal of aortic cross clamp (ACC) were compared between the two groups. Predictors of POAF were also investigated by multivariate logistic regression analysis. A comparison of preoperative demographic, laboratory, echocardiographic, and postoperative clinical characteristics between the two groups showed that patients in Group 1 were significantly older (65.6±7.20 vs. 59.6±9.07, p<0.001), had a lower hematocrit level (37.5±5.16 vs. 39.7±5.28; p=0.034), and an enlarged left atrium diameter (39±0.45 vs. 3.6±0.48; p=0.006). Changes in plasma TOS levels after placement and removal of ACC were statistically significant in Group 1 [13 (8.6-23), 30 (18.1-47.3); p=0.001 vs. 14 (8.8-22.2), 24 (21.4-42.7); p=0.060]. Length of stay in the intensive care unit [3 (2-14) vs. 2 (1-58); p=0.001] and length of stay in hospital [7 (6-85) vs. 7 (5-58); p=0.001] were prolonged in Group 1. In multivariate logistic regression analysis, aging (odds ratio (OR): 1.088, 95% confidence interval (CI): 1.005-1.177; p=0.036), hematocrit level (OR: 0.718, 95% CI: 0.538-0.958; p=0.025), pump temperature (OR: 1.445, 95% CI: 1.059-1.972; p=0.020), and plasma TOS level (OR: 1.040, 95% CI: 1.020-1.050; p=0.040) were found to be independent predictors of POAF. Ischemia-reperfusion damage related with ACC placement may be an important factor on the pathogenesis of POAF. Minimizing the oxidative stress occurring intraoperatively should be targeted for preventing mortality and morbidity due to POAF.

Preoperative serum levels of interleukin-6 and interleukin-8 as predictors of the development of postoperative atrial fibrillation among patients undergoing coronary artery bypass grafting surgery

Objectives The aim of the study was to evaluate the ability of preoperative estimation of serum interleukins (IL-6 and IL-8) for predicting the possibility of development of postoperative atrial fibrillation (POAF) among patients who have undergone coronary artery bypass grafting (CABG) surgery. Patients and methods The study included 90 patients who underwent CABG, with a mean age of 63.8 ± 4.7 years. All patients underwent on-pump surgery with a mean aortic cross-clamping time of 65.9 ± 14.6 min and a mean cardiopulmonary bypass (CPB) time of 99.1 ± 19.7 min. Preoperative blood samples were collected for enzyme-linked immunosorbent assay estimation of serum IL-6 and IL-8 levels. Results After CABG surgery, 24 patients developed POAF (26.7%); five were female and 19 were male with a mean age of 64.1 ± 5.2 years. Four patients had a history of previous atrial fibrillation (AF), whereas 20 patients had no history of preoperative AF. Mean aortic clamping and CPB times were significantly longer in POAF patients compared with AF-free patients. Mean preoperative serum IL-6 and IL-8 levels were significantly higher in patients compared with controls, with significantly higher levels in POAF patients compared with AF-free patients. There was a positive significant correlation between the occurrence of POAF and history of preoperative AF, preoperative serum levels of IL-6 and IL-8, and aortic clamping and CPB times. Regression analysis defined elevated serum levels of IL-6 and IL-8, prolonged aortic clamping and CPB times, and history of preoperative AF as predictors of the occurrence of POAF among patients undergoing CABG in decreasing order of significance. Conclusion Inflammatory factors play a prominent role in the pathogenesis of POAF; high preoperative serum levels of IL-6 and IL-8 could aid in identification of patients liable to develop POAF, especially when associated with prolonged clamping time or preoperative history of AF.

The occurrence of postoperative atrial fibrillation according to different surgical settings in cardiac surgery patients

Atrial fibrillation is the most common arrhythmia after cardiac surgery. The pathogenesis of postoperative atrial fibrillation is multifactorial. The aim of the study was to analyse preoperative, intraoperative and postoperative factors and their relationships with the occurrence and duration of atrial fibrillation. One hundred and ninety-six patients with coronary heart disease (152 men, age 62.7 ± 10.1 years) underwent surgical revascularization. Extracorporeal circulation was used in 64 patients and minimal extracorporeal circulation was used in 75 patients. Fifty-seven patients underwent surgery without extracorporeal circulation. During the first three postoperative days, subjects were monitored for the duration and incidence of atrial fibrillation, laboratory markers of inflammation (C-reactive protein, leucocytes) and serum potassium. Demographic data and associated cardiovascular diseases in the groups were not statistically different. The overall incidence of atrial fibrillation was 56% (110 patients). The highest incidence of atrial fibrillation was found in the extracorporeal circulation subgroup, with a significantly lower incidence using minimal extracorporeal circulation, and in patients operated on without extracorporeal circulation (75 vs 47 vs 46%, P <0.001). The longest duration of atrial fibrillation was found in patients operated on with extracorporeal circulation compared with minimal extracorporeal circulation, and without extracorporeal circulation (9.7 ± 11.6 vs 4.9 ± 8.3 vs 3.1 ± 5.2, P ≤0.001). The incidence of postoperative atrial fibrillation significantly correlated with elevation of inflammatory markers (C-reactive protein, leucocytes) compared with patients who were free of atrial fibrillation (P ≤0.001, P ≤0.05). The values of serum potassium were not significantly different. The relationship between postoperative atrial fibrillation and echocardiographic parameters was not confirmed. The use of extracorporeal circulation leads to a higher incidence of postoperative atrial fibrillation compared with the use of minimal extracorporeal circulation or with surgery without extracorporeal circulation, probably due to enhanced systemic inflammatory response.

Prevention of Postoperative Atrial Fibrillation: Novel and Safe Strategy Based on the Modulation of the Antioxidant System

Postoperative atrial fibrillation (AF) is the most common arrhythmia following cardiac surgery with extracorporeal circulation. The pathogenesis of postoperative AF is multifactorial. Oxidative stress, caused by the unavoidable ischemia–reperfusion event occurring in this setting, is a major contributory factor. Reactive oxygen species (ROS)-derived effects could result in lipid peroxidation, protein carbonylation, or DNA oxidation of cardiac tissue, thus leading to functional and structural myocardial remodeling. The vulnerability of myocardial tissue to the oxidative challenge is also dependent on the activity of the antioxidant system. High ROS levels, overwhelming this system, should result in deleterious cellular effects, such as the induction of necrosis, apoptosis, or autophagy. Nevertheless, tissue exposure to low to moderate ROS levels could trigger a survival response with a trend to reinforce the antioxidant defense system. Administration of n−3 polyunsaturated fatty acids (PUFA), known to involve a moderate ROS production, is consistent with a diminished vulnerability to the development of postoperative AF. Accordingly, supplementation of n−3 PUFA successfully reduced the incidence of postoperative AF after coronary bypass grafting. This response is due to an up-regulation of antioxidant enzymes, as shown in experimental models. In turn, non-enzymatic antioxidant reinforcement through vitamin C administration prior to cardiac surgery has also reduced the postoperative AF incidence. Therefore, it should be expected that a mixed therapy result in an improvement of the cardioprotective effect by modulating both components of the antioxidant system. We present novel available evidence supporting the hypothesis of an effective prevention of postoperative AF including a two-step therapeutic strategy: n−3 PUFA followed by vitamin C supplementation to patients scheduled for cardiac surgery with extracorporeal circulation. The present study should encourage the design of clinical trials aimed to test the efficacy of this strategy to offer new therapeutic opportunities to patients challenged by ischemia–reperfusion events not solely in heart, but also in other organs such as kidney or liver in transplantation surgeries.

Intracardiac expression of markers of endothelial damage/dysfunction, inflammation, thrombosis, and tissue remodeling, and the development of postoperative atrial fibrillation

Atrial fibrillation (AF) is a common complication of coronary artery bypass grafting (CABG), and may have an inflammatory and/or thrombotic etiology. We sought to determine the expression of inflammatory (interleukin [IL]-6), thrombotic (tissue factor and von Willebrand factor [VWF]) and remodeling (matrix metalloproteinase [MMP]-9 and tissue inhibitor of metalloproteinase [TIMP]-1) markers by left atrial appendage (LAA) and right atrial appendage (RAA) tissue in the prediction of postoperative AF. We determined whether the tissue expression of markers of certain different pathophysiologic mechanisms predicted the development of AF after CABG. LAA and RAA tissue was excised during CABG in 100 patients free of AF and inflammation. Tissue marker expression was quantified by immunohistochemistry and was related to 30-day postoperative AF. Overall, there were no significant differences in staining intensity of any marker between LAA tissue and RAA tissue. However, more intense expression of VWF by LAA tissue predicted the 30 patients with postoperative AF as compared with those free of AF (P = 0.006). IL-6, MMP-9 and TIMP-1 expression by RAA and LAA epicardial tissue was stronger than expression by endocardium or cardiomyocytes (all P < 0.025) but failed to predict AF. In this study, one of the largest to investigate tissue expression of pathophysiologic markers in relation to postoperative AF, we show that more intense expression of VWF by LAA tissue is a significant predictor of postoperative AF. This points towards a possible role of endothelial damage/dysfunction (as reflected by VWF changes) in the pathogenesis of postoperative AF.