Postoperative Atrial Fibrillation Research Articles

Improved Early Outcomes With Off-Pump Coronary Artery Bypass Grafting in Patients With Left Ventricular Dysfunction: A Systematic Review and Meta-Analysis.

The ongoing debate surrounding coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass persists, particularly in individuals with left ventricular dysfunction. The objective of this study was to evaluate the safety and efficacy of these 2 strategies through a comprehensive meta-analysis of existing studies. A systematic search of PubMed, EMBASE, Web of Science, and the Cochrane Central Registry was conducted from inception to July 2023. The primary focus was on studies comparing on-pump versus off-pump CABG as the primary treatment for multivessel coronary artery disease in patients with left ventricular dysfunction (ejection fraction ≤40%), with mortality as the primary outcome. The meta-analysis included 26 studies with a total of 35,863 patients. The results revealed a significant reduction in mortality risk [risk ratio (RR), 0.75; 95% confidence interval (CI), 0.60-0.93; P = 0.009] and other perioperative morbidities associated with off-pump CABG. These included stroke (RR, 0.67; 95% CI, 0.54-0.82; P = 0.0002), myocardial infarction (RR, 0.74; 95% CI, 0.56-0.97; P = 0.03), pulmonary complications (RR, 0.71; 95% CI, 0.55-0.92; P = 0.010), postoperative transfusion (RR, 0.70; 95% CI, 0.55-0.88; P = 0.002), neurological dysfunction (RR, 0.80; 95% CI, 0.64-1.00; P = 0.05), infection (RR, 0.74; 95% CI, 0.56-0.97; P = 0.03), renal failure (RR, 0.79; 95% CI, 0.67-0.95; P = 0.010), and reoperation for bleeding (RR, 0.66; 95% CI, 0.52-0.84; P = 0.0006). However, no significant difference was observed between the 2 groups regarding postoperative atrial fibrillation (RR, 0.97; 95% CI, 0.84-1.12; P = 0.69). In conclusion, off-pump CABG demonstrates a lower perioperative mortality risk and improved overall early outcomes compared with on-pump techniques in individuals with reduced left ventricular function.

Sleep-Disordered Breathing, Advanced Age, and Diabetes Mellitus Are Associated with De Novo Atrial Fibrillation after Cardiac Surgery

Background: Postoperative de novo atrial fibrillation (POAF) is one of the most frequently encountered complications following cardiac surgery. Despite the identification of several risk factors, the link between sleep-disordered breathing (SDB) and POAF has barely been examined. The objective of this prospective observational study was to determine whether severe SDB is associated with POAF in patients after elective coronary artery bypass grafting (CABG) surgery. Study design and methods: The incidence and preoperative predictors of in-hospital POAF were assessed in 272 patients undergoing CABG surgery at the University Medical Center Regensburg (Germany). In-hospital POAF was detected by continuous telemetry-ECG monitoring and 12-lead resting ECGs within the first seven postoperative days. POAF that occurred after hospital discharge within 60 days post CABG surgery was classified as post-hospital POAF and was ascertained by standardized phone interviews together with the patients’ medical files, including routinely performed Holter-ECG monitoring at 60 days post CABG surgery. The night before surgery, portable SDB monitoring was used to assess the presence and type of severe SDB, defined by an apnea–hypopnea index ≥ 30/h. Results: The incidence of in-hospital POAF was significantly higher in patients with severe SDB compared to those without severe SDB (30% vs. 15%, p = 0.009). Patients with severe SDB suffered significantly more often from POAF at 60 days post CABG surgery compared to patients without severe SDB (14% vs. 5%, p = 0.042). Multivariable logistic regression analysis showed that severe SDB (odds ratio, OR [95% confidence interval, CI]: 2.23 [1.08; 4.61], p = 0.030), age ≥ 65 years (2.17 [1.04; 4.53], p = 0.038), and diabetes mellitus (2.27 [1.15; 4.48], p = 0.018) were significantly associated with in-hospital POAF. After additional adjustment for heart failure, the association between sleep apnea and postoperative atrial fibrillation was attenuated (1.99 [0.92; 4.31], p = 0.081). Conclusions: Amongst established risk factors, severe SDB was significantly associated with in-hospital POAF in patients undergoing CABG surgery. Whether SDB contributes to POAF independently of heart failure and whether risk for POAF may be alleviated by proper treatment of SDB merits further investigation.

Prophylactic Left Atrial Appendage Ligation During Coronary Artery Bypass Graft Surgery Allows Safe Avoidance of Anticoagulation Regardless of Postoperative Atrial Fibrillation

Prophylactic Left Atrial Appendage Ligation During Coronary Artery Bypass Graft Surgery Allows Safe Avoidance of Anticoagulation Regardless of Postoperative Atrial Fibrillation

Optimal Timing and Duration of Beta-Blocker Therapy for Preventing Postoperative Atrial Fibrillation: A Literature Review

This literature review explores the intricate landscape of postoperative atrial fibrillation (POAF), a common complication that arises following heart surgery. The analysis highlights the significant risks associated with POAF, including stroke, extended hospital stay, and increased healthcare costs. POAF, together with its transient character, indicates an augmented susceptibility to atrial fibrillation in the long run. Despite extensive research on preventive measures, such as beta-blocker medication, uncertainties remain regarding the optimal timing and duration of beta-blocker therapy for preventing POAF. The existing evidence suggests that starting beta-blocker treatment early, ideally within the first 24–48 hours after surgery, may be effective in reducing the occurrence of POAF. Nevertheless, there is a noticeable absence of agreement regarding the optimal length of this therapy. Conflicting viewpoints arise, with certain research calling for brief therapies, while others propose the possible benefits linked to extended treatment. This review highlights the urgent requirement for more research to precisely adjust guidelines, taking into account patient-specific factors and considering the consequences for long-term results. The call to action entails a request for the implementation of uniform definitions, the conduct of prospective randomized controlled trials, and the utilization of larger sample sizes in future investigations. These characteristics are considered critical in providing the medical community with strong evidence, which is crucial for making well-informed therapeutic decisions.

Transdermal bisoprolol for prevention of postoperative atrial fibrillation: A systematic review and meta‐analysis

AbstractBackgroundThe transdermal patch of bisoprolol available in Japan has been reported to demonstrate superior efficacy in preventing postoperative atrial fibrillation, possibly surpassing its oral counterpart. However, there has been no systematic review and meta‐analysis assessing the efficacy of transdermal bisoprolol.MethodsA comprehensive systematic literature search was conducted on PubMed, Embase, and Cochrane to identify all relevant studies assessing the efficacy of transdermal bisoprolol in preventing postoperative atrial fibrillation. The search covered studies from inception up to December 4, 2023. For data analysis, Review Manager (RevMan) 5.4 software was employed, using a random‐effects model to calculate risk ratios (RR) and 95% confidence intervals (CI).ResultsThree studies, comprising a total of 551 patients (transdermal bisoprolol 228 and control 323), were included. There was a decreased risk of postoperative atrial fibrillation or atrial tachyarrhythmias in patients treated with transdermal bisoprolol (RR 0.43, 95% CI 0.27–0.67, p = .0002, I2 = 0%).ConclusionTransdermal administration of bisoprolol has consistently shown efficacy, and this pooled analysis supports its effectiveness. The heterogeneity of the included studies limits certain interpretations. Future randomized clinical trials may elucidate the superiority of transdermal administration over oral administration.

The Effects of Propafenone on Postoperative Atrial Fibrillation in Adult Patients Undergoing Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials

Background. Previous research has only conducted a restricted amount of investigations on the effectiveness of propafenone in preventing and treating of atrial fibrillation (AF) after cardiac surgery. Hence, a comprehensive evaluation and meta-analysis were performed to evaluate the effectiveness and safety of propafenone in individuals undergoing cardiac surgery for postoperative atrial fibrillation (POAF). Methods. A meta-analysis of randomized controlled trials was conducted. Until September 15th, 2023, various databases were searched. The main focal points consisted of the presence of POAF, transition from AF to sinus rhythm, and reappearance of AF. The odds ratios (ORs) for treatment effects on dichotomous variables were calculated. Results. The analysis of data included 9 controlled trials that were randomized and had 1014 patients. The findings indicated that propafenone has a significant impact on reducing the occurrence of POAF in adult patients who undergo cardiac surgery (OR, 0.52; 95% CI: 0.30, 0.89; P=0.02). In addition, it was observed that propafenone significantly increase the rate of conversion to sinus rhythm from AF within 20 min (OR, 5.39; 95% CI: 2.25, 12.91; P=0.0002) and 1 hour (OR, 2.89; 95% CI: 1.50, 5.57; P=0.002) after administration. Surprisingly, the administration of propafenone treatment did not have a significant impact on the rate of conversion to sinus rhythm from AF within 24 hours (OR, 0.63; 95% CI: 0.38, 1.04; P=0.07) after administration. Conclusions. The present study suggests that the postoperative administration of propafenone to adult cardiac surgery patients is both safe and effective for preventing and treating POAF.

Pre-operative maintenance of angiotensin-converting enzyme inhibitors is not associated with acute kidney injury in cardiac surgery patients with cardio-pulmonary bypass: a propensity-matched multicentric analysis

Objective: We investigated the effects of the maintenance of angiotensin-converting enzyme inhibitors (ACE inhibitors) the day of the surgery on the incidence of postoperative acute kidney injury (AKI) and cardiac events in patients undergoing cardiac surgery.Methods: We performed a multicentric observational study with propensity matching on 1,072 patients treated with ACE inhibitors. We collected their baseline demographic data, comorbidities, and operative and postoperative outcomes. AKI was defined by KDIGO (Kidney Disease: Improving Global Outcome).Results: Maintenance of an ACE inhibitor was not associated with an increased risk of AKI (OR: 1.215 (CI95%:0.657–2.24), p = 0.843, 71 patients (25.1%) vs. 68 patients (24%)). Multivariate logistic regression and sensitive analysis did not demonstrate any association between ACE inhibitor maintenance and AKI, following cardiac surgery (OR: 1.03 (CI95%:0.81–1.3)). No statistically significant difference occurs in terms of incidence of cardiogenic shock (OR: 1.315 (CI95%:0.620–2.786)), stroke (OR: 3.313 (CI95%:0.356–27.523)), vasoplegia (OR: 0.741 (CI95%:0.419–1.319)), postoperative atrial fibrillation (OR: 1.710 (CI95%:0.936–3.122)), or mortality (OR: 2.989 (CI95%:0.343–26.034)). ICU and hospital length of stays did not differ (3 [2; 5] vs. 3 [2; 5] days, p = 0.963 and 9.5 [8; 12] vs. 10 [8; 14] days, p = 0.638).Conclusion: Our study revealed that maintenance of ACE inhibitors on the day of the surgery was not associated with increased postoperative AKI. ACE inhibitor maintenance was also not associated with an increased rate of postoperative major cardiovascular events (arterial hypotension, cardiogenic shock, vasopressors use, stroke and death).

Effects of Omega-3 Polyunsaturated Fatty Acids, Docosahexaenoic Acid and Eicosapentaenoic Acid, on Post-Surgical Complications in Surgical Trauma Patients: Mechanisms, Nutrition, and Challenges

This paper aims to provide an in-depth review of the specific outcomes associated with omega-3 polyunsaturated fatty acids (PUFAs), focusing on their purported effects on post-surgical complications in trauma patients. A comprehensive investigation of omega-3 polyunsaturated fatty acids was conducted until February 2023 using the PubMed database. Surgical trauma is characterized by a disruption in immune response post surgery, known to induce systemic inflammation. Omega-3 PUFAs are believed to offer potential improvements in multiple post-surgical complications because of their anti-inflammatory and antioxidant properties. Inconsistent findings have emerged in the context of cardiac surgeries, with the route of administration playing a mediating role in these outcomes. The effects of omega-3 PUFAs on post-operative atrial fibrillation have exhibited variability across various studies. Omega-3 PUFAs have demonstrated positive effects in liver surgery outcomes and in patients with acute respiratory distress syndrome. Omega-3 is suggested to offer potential benefits, particularly in the perioperative care of patients undergoing traumatic procedures. Incorporating omega-3 in such cases is hypothesized to contribute to a reduction in certain surgical outcomes, such as hospitalization duration and length of stay in the intensive care unit. Therefore, comprehensive assessments of adverse effects can aid in identifying the presence of subtle or inconspicuous side effects associated with omega-3.

The association between low serum calcium level and new-onset atrial fibrillation after coronary artery bypass grafting.

This study aims to investigate the relationship between serum calcium levels and the incidence of postoperative atrial fibrillation in patients undergoing coronary artery bypass graft surgery. This retrospective, observational cohort study consecutively enrolled patients undergoing isolated coronary artery bypass grafting in Beijing Anzhen hospital from January 2018 to December 2021. Patients with a previous history of atrial fibrillation or atrial flutter or requiring concomitant cardiac surgery were excluded. A logistic regression model was used to determine predictors of postoperative atrial fibrillation. Multivariable adjustment, inverse probability of treatment weighting, and propensity score matching were used to adjust for confounders. Moreover, we conducted univariable and multivariable logistic regression analyses on preoperative and postoperative serum calcium and ionized serum calcium levels. The analysis encompassed 12,293 patients. The postoperative atrial fibrillation rate was significantly higher in patients with low serum calcium level than those without (1379 [33.9%] versus 2375 [28.9%], P < 0.001). Low serum calcium level was associated with an increased odds ratio of postoperative atrial fibrillation (odds ratio [95% CI]: 1.27 [1.18-1.37], P < 0.001). Inverse probability of treatment weighting and propensity score matching analyses confirmed the results. The increased postoperative atrial fibrillation rate in low serum calcium level group still existed among subgroup analysis based on different age, sex, body mass index, hypertension, hyperlipidemia, CHA2DS2-VASc and magnesium. Low serum calcium level indicates elevated postoperative atrial fibrillation risk in patients undergoing isolated coronary artery bypass graft surgery even after the adjustment for age, sex, cardiovascular risk factors, echocardiographic parameters and laboratory markers.

Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass.Methods and Results: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Posterior pericardiotomy and the prevention of post-operative atrial fibrillation and cardiac tamponade in isolated coronary artery bypass grafting – A retrospective analysis

BackgroundPost-Operative Atrial Fibrillation (POAF) is the most frequent complication of cardiac surgery and is associated with reduced survival, increased rates of cognitive changes and cerebrovascular accidents, heart failure, renal dysfunction, infection, length of stay and hospital costs. Cardiac tamponade although less common, carries high morbidity and mortality. Shed mediastinal blood in the pericardial space is a major source of intrapericardial oxidative stress and inflammation that triggers POAF. The utilisation of a posterior pericardiotomy (PP) aims to shunt blood from pericardium into the pleural space and have a role in the prevention of POAF as well as cardiac tamponade.Methods2168 patients had undergone isolated Coronary Artery Bypass Grafting at Royal Hobart Hospital from 2008 to 2022. They were divided into PP group vs. control group. Patient baseline demographics, intraoperative data and post-operative outcomes were reviewed retrospectively.ResultsTotal incidence of new POAF and cardiac tamponade was 24% and 0.74% respectively. Primary outcome of both the incidence of POAF (20.2% vs. 26.3%, p < 0.05) and Cardiac Tamponade (0% vs. 1.1%, p < 0.05) were less in the pericardiotomy group. A subgroup analysis of patients with recent myocardial infarction showed reduced incidence of POAF in the PP group (p < 0.05). Increasing age, Body Mass Index, poor left ventricular ejection fraction (EF < 30%) and return to theatre were independent predictors of developing POAF. There were similar rates of return to theatre for bleeding however, no cases of tamponade in the pericardiotomy group. There were no complications attributable to left posterior pericardiotomy and the time added to the duration of surgery was minimal.ConclusionPosterior pericardiotomy is associated with a significant reduction in the incidence of POAF and cardiac tamponade which is safe and efficient.

Prevalence of Post-operative Atrial Fibrillation Following Cardiac Surgery among Asian Population and Preferred Treatment Modalities- A Systematic Review

Background: Postoperative atrial fibrillation is a common complication following cardiac surgery. Despite numerous studies, the true prevalence and optimal management strategies remain unclear. This systematic review investigates the prevalence and management techniques followed anmongst Asian population post-cardiac surgery. Methods: A comprehensive search was conducted across multiple databases between 2000 and 2023. Data on study characteristics, prevalence, and treatment modalities were extracted and assessed for quality using standardized tools. Results: Out of 1849 identified studies, 23 met the eligibility criteria, all conducted in Asian countries. The prevalence of POAF ranged from 10 % to 58 % among cardiac surgery patients in individual studies, translating to a calculated mean value of 24.46 % POAF cases in all accumulated eligible studies for prevalence in the Asian population. The prevalence of POAF in the Asian population was calculated to be 20.95%. Treatment modalities such as antiarrhythmics and anticoagulants showed varying efficacy, with dexmedetomidine demonstrating potential preventive effects. Studies highlighted the higher recurrence rates in cardiac surgery compared to non-cardiac surgery patients. Additionally, the association between POAF and adverse outcomes such as stroke and mortality underscores the importance of effective management strategies. Conclusion: Despite limitations in study design and sample sizes, this review provides insights into POAF in Asian cardiac surgery patients. Tailored approaches incorporating antiarrhythmics, anticoagulation, and lifestyle modifications may help mitigate the burden of POAF and improve patient outcomes. Further research is warranted to elucidate optimal management strategies and address existing gaps in knowledge.

Letter to the Editor "Machine learning to develop a novel model for predicting new-onset postoperative atrial fibrillation after coronary artery bypass grafting".

Letter to the Editor "Machine learning to develop a novel model for predicting new-onset postoperative atrial fibrillation after coronary artery bypass grafting".

Comparison of Del Nido (a different application) and crystalloid blood cardioplegia on arrhythmia and early results.

The results of the use of del-Nido(DN) solution using a different method or crystalloid blood cardioplegia in coronary bypass patients were compared. We aimed to investigate the effects on intraoperative and postoperative arrhythmias, arrhythmia durations and early results. The study included 175 patients using crystalloid blood cardioplegia (Group 1) and 150 patients using DN solution(Group 2). In the DN group, 75% of the calculated plegia dose was given first. the remaining part was applied by giving from grafts. Intraoperative/postoperative data were compared. There was no significant difference between the groups in terms of demographic characteristics. Preop troponin level was similar.(p = 0.190) However, there was a statistical difference between the postoperative 6th hour.(p = 0.001) There was no difference in troponin values at the postoperative 24th hour. (p = 0.631) Spontaneous rhythm occurred at the cardiopulmonary by pass (CPB) weaning stage in most of the patients in Group 2 (95.3%). Although the need for temporary pacing was less in Group 2, it was not significant.(p = 0.282) No patient required permanent pacing. CPB duration, cross clamp times and intraoperative glucose levels, intensive care follow-up times and hospitalization times were found to be shorter in Group 2. Although the postoperative atrial fibrillation frequency was similar (p = 0.261), the time to return to sinus was lower in Group 2.(p = 0.001). The use of DN cardioplegia solution provides significant positive contributions to avoid arrhythmias compared to crystalloid blood cardioplegia. DN solution applied with this method may contribute to reducing the anxieties associated with its use in isolated coronary artery bypass surgery.

New-onset atrial fibrillation is a red flag to microvascular free tissue transfer failure in head and neck cancer patients.

Background Postoperative new-onset atrial fibrillation (AF) has been shown to be associated with increased surgical morbidity and mortality following cancer ablation surgery. However, evidence on new-onset AF's impact on surgical outcomes in head and neck cancer patients undergoing tumor ablation and microvascular free tissue transfer remains scarce. This study aims to evaluate the association between AF and surgical outcomes in these patients. Methods We enrolled head and neck cancer patients who underwent tumor ablation reconstructed with microvascular free tissue transfer from the National Health Insurance Research Database (NHIRD). Patients were grouped into (1) without AF, (2) new-onset AF, and (3) preexisting AF. The groups were matched by propensity score based on age, gender, cancer stage, and comorbidities. The primary outcome was postoperative complications, whereas all-cause mortality was the secondary outcome. Results Total 26,817 patients were included in this study. After matching, we identified 2,176 (79.24%) patients without AF, 285 (10.37%) with preexisting AF, and 285 (10.37%) with new-onset AF. Our results demonstrated that the free flap failure rate was twofold escalated in patients with new-onset AF (9.8%) compared to those without AF (5.4%) or preexisting AF (5.3%) (p = 0.01). However, we did not identify significant differences among other postoperative complications across groups. Additionally, we found that the risk of all-cause mortality was significantly elevated in patients with preexisting AF (p<0.001) compared to those without AF or new-onset AF. Conclusion Our study demonstrated that new-onset AF is associated with an increased risk of flap failure and could serve as a predictor. On the other hand, all-cause mortality in patients with preexisting AF was significantly elevated. Close postoperative monitoring in patients with new-onset and preexisting AF is crucial to identify any potential adverse effects.

Outcomes of coronary artery bypass grafting (CABG) in patients with OSA-COPD overlap syndrome versus COPD alone: an analysis of US Nationwide Inpatient Sample.

Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are associated with unfavorable outcomes following coronary artery bypass grafting (CABG). The purpose of this study was to compare in-hospital outcomes of patients with COPD alone versus OSA-COPD overlap after CABG. Data of adults ≥ 18 years old with COPD who received elective CABG between 2005 and 2018 were extracted from the US Nationwide Inpatient Sample (NIS). Patients were divided into two groups: with OSA-COPD overlap and COPD alone. Propensity score matching (PSM) was employed to balance the between-group characteristics. Logistic and linear regression analyses determined the associations between study variables and inpatient outcomes. After PSM, data of 2,439 patients with OSA-COPD overlap and 9,756 with COPD alone were analyzed. After adjustment, OSA-COPD overlap was associated with a significantly increased risk of overall postoperative complications (adjusted odd ratio [aOR] = 1.12, 95% confidence interval [CI]: 95% CI: 1.01-1.24), respiratory failure/prolonged mechanical ventilation (aOR = 1.27, 95%CI: 1.14-1.41), and non-routine discharge (aOR = 1.16, 95%CI: 1.03-1.29), and AKI (aOR = 1.14, 95% CI: 1.00-1.29). Patients with OSA-COPD overlap had a lower risk of in-hospital mortality (adjusted odd ratio [aOR] = 0.53, 95% CI: 0.35-0.81) than those with COPD only. Pneumonia or postoperative atrial fibrillation (AF) risks were not significantly different between the 2 groups. Stratified analyses revealed that, compared to COPD alone, OSA-COPD overlap was associated with increased respiratory failure/prolonged mechanical ventilation risks among patients ≥ 60 years, and both obese and non-obese subgroups. In addition, OSA-COPD overlap was associated with increased risk of AKI among the older and obese subgroups. In US adults who undergo CABG, compared to COPD alone, those with OSA-COPD are at higher risks of non-routine discharge, AKI, and respiratory failure/prolonged mechanical ventilation, but a lower in-hospital mortality. No increased risk of AF was noted.

Atrial Fibrosis and Inflammation inPostoperative Atrial Fibrillation: Comparative Effects of Amiodarone, Colchicine, or Exosomes.

Extracellular vesicles (EVs) isolated from human heart-derived cells have shown promise in suppressing inflammation and fibroblast proliferation. However, their precise benefits in atrial fibrillation (AF) prevention and the role of their antifibrotic/anti-inflammatory properties remain unclear. The purpose of this study was to conduct a head-to-head comparison of antiarrhythmic strategies to prevent postoperative AF using a rat model of sterile pericarditis. Specifically, we aimed to assess the efficacy of amiodarone (a classic antiarrhythmic drug), colchicine (an anti-inflammatory agent), and EVs derived from human heart-derived cells, which possess anti-inflammatory and antifibrotic properties, on AF induction, inflammation, and fibrosis progression. Heart-derived cells were cultured from human atrial appendages under serum-free xenogen-free conditions. Middle-aged Sprague Dawley rats were randomized into different groups, including sham operation, sterile pericarditis with amiodarone treatment, sterile pericarditis with colchicine treatment (2 dose levels), and sterile pericarditis with intra-atrial injection of EVs or vehicle. Invasive electrophysiological testing was performed 3days after surgery before sacrifice. Sterile pericarditis increased the likelihood of inducing AF. Colchicine and EVs exhibited anti-inflammatory effects, but only EV treatment significantly reduced AF probability, whereas colchicine showed a positive trend without statistical significance. EVs and high-dose colchicine reduced atrial fibrosis by 46 ± 2% and 26 ± 2%, respectively. Amiodarone prevented AF induction but had no effect on inflammation or fibrosis. In this study, both amiodarone and EVs prevented AF, whereas treatment with colchicine was ineffective. The additional anti-inflammatory and antifibrotic effects of EVs suggest their potential as a comprehensive therapeutic approach for AF prevention, surpassing the effects of amiodarone or colchicine.

Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation.

Postoperative atrial fibrillation (POAF) is associated with increased morbidity and mortality. Epicardial injection of botulinum toxin may suppress POAF. This study sought to assess the safety and efficacy of AGN-151607 for the prevention of POAF after cardiac surgery. This phase 2, randomized, placebo-controlled trial assessed the safety and efficacy of AGN-151607, 125 U and 250 U vs placebo (1:1:1), for the prevention of POAF after cardiac surgery. Randomization was stratified by age (<65,≥65 years) and type of surgery (nonvalvular/valve surgery). The primary endpoint was the occurrence of continuous AF≥30 seconds. Among 312 modified intention-to-treat participants (placebo, n=102; 125 U, n=104; and 250 U, n=106), the mean age was 66.9 ± 6.8 years; 17% were female; and 64% had coronary artery bypass graft (CABG) only, 12% had CABG+ valve, and 24% had valve surgery. The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125-U group (relative risk [RR] vs placebo: 0.80; 95%CI: 0.58-1.10; P=0.16), and 47.2% of the 250-U group (RR vs placebo: 1.04; 95%CI: 0.79-1.37; P=0.78). The primary endpoint was reduced in the 125-U group in those≥65 years (RR: 0.64; 95%CI: 0.43-0.94; P=0.02) with a greater reduction in CABG-only participants≥65 years (RR: 0.49; 95%CI: 0.27-0.87; P=0.01). Rehospitalization and rates of adverse events were similar across the 3 groups. There were no significant differences in the rate of POAF with either dose compared with placebo; however, there was a lower rate of POAF in participants≥65 years undergoing CABG only and receiving 125 U of AGN-151607. These hypothesis-generating findings require investigation in a larger, adequately powered randomized clinical trial. (Botulinum Toxin Type A [AGN-151607] for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery [NOVA]; NCT03779841); A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of Botulinum Toxin Type A [AGN 151607] Injections into the Epicardial Fat Pads to Prevent Post-Operative Atrial Fibrillation in Patients Undergoing Open-Chest Cardiac Surgery; 2017-004399-68).

Partial CArdiac Denervation to prevent PostOperative Atrial Fibrillation after coronary artery bypass grafting (pCAD-POAF): study protocol for a randomized controlled trial

Postoperative atrial fibrillation (POAF) is commonly seen in patients undergoing coronary artery bypass grafting (CABG), increasing the risk of morbidity, mortality and hospital expenses. This study is aimed to evaluate the effect of partial cardiac denervation, which is achieved by cutting off the ligament of Marshall and resecting the fat pad along the Waterston groove, on the prevention of POAF after CABG. Patients planned for CABG at our center will be screened for eligibility for this study. A total of 430 patients will be randomized into intervention (partial cardiac denervation) group and control group. Intraoperative high-frequency electrical stimulation and further histologic analysis will be performed among certain number of patients to confirm the existence of ganglia. All of the patients will be continuously monitored for the incidence of POAF through electrophysiologic device until the 6th day postoperatively, and required to complete a 30-day follow-up (twelve lead electrocardiogram and echocardiogram assesment) after discharge. The primary endpoint is the incidence of POAF, while the secondary endpoints are the cost-effectiveness and safety outcomes. In conclusion, this trial will evaluate whether partial cardiac denervation through cutting off the ligament of Marshall and resecting the fat pad along the Waterston groove can reduce the incidence of POAF after CABG. If this procedure is revealed to be effective and safe, it may provide a potential therapeutic approach to prevent POAF in this group of patients.

Circulating BMP10 Levels Associate With Late Postoperative Atrial Fibrillation and Left Atrial Endomysial Fibrosis

BackgroundSerum bone morphogenetic protein 10 (BMP10) blood levels are a marker for history of atrial fibrillation (AF) and for major adverse cardiovascular events in patients with AF, including stroke, AF recurrences after catheter ablations, and mortality. The predictive value of BMP10 in patients undergoing cardiac surgery and association with morphologic properties of atrial tissues are unknown. ObjectivesThis study sought to study the correlation between BMP10 levels and preoperative clinical traits, occurrence of early and late postoperative atrial fibrillation (POAF), and atrial fibrosis in patients undergoing cardiac surgery. MethodsPatients with and without preoperative AF history undergoing first cardiac surgery were included (RACE V, n = 147). Preoperative blood biomarkers were analyzed, left (n = 114) and right (n = 125) atrial appendage biopsy specimens were histologically investigated after WGA staining, and postoperative rhythm was monitored continuously with implantable loop recorders (n = 133, 2.5 years). ResultsAdjusted multinomial logistic regression indicated that BMP10 accurately reflected a history of persistent AF (OR: 1.24, 95% CI: 1.10-1.40, P = 0.001), similar to NT-pro-BNP. BMP10 levels were associated with increased late POAF90 occurrence after adjustment for age, sex, AF history, and early POAF occurrence (HR: 1.07 [per 0.1 ng/mL increase], 95% CI: 1.00-1.14, P = 0.041). Left atrial endomysial fibrosis (standardized β = 0.22, P = 0.041) but not overall fibrosis (standardized Β = 0.12, P = 0.261) correlated with circulating BMP10 after adjustment for age, sex, AF history, reduced LVF, and valvular surgery indication. ConclusionsIncreased BMP10 levels were associated with persistent AF history, increased late POAF incidence, and LAA endomysial fibrosis in a diverse sample of patients undergoing cardiac surgery.