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1.  Intravenous magnesium prevents atrial fibrillation after coronary artery bypass grafting: a meta-analysis of 7 double-blind, placebo-controlled, randomized clinical trials 
Trials  2012;13:41.
Postoperative atrial fibrillation (POAF) is the most common complication after coronary artery bypass grafting (CABG). The preventive effect of magnesium on POAF is not well known. This meta-analysis was undertaken to assess the efficacy of intravenous magnesium on the prevention of POAF after CABG.
Eligible studies were identified from electronic databases (Medline, Embase, and the Cochrane Library). The primary outcome measure was the incidence of POAF. The meta-analysis was performed with the fixed-effect model or random-effect model according to heterogeneity.
Seven double-blind, placebo-controlled, randomized clinical trials met the inclusion criteria including 1,028 participants. The pooled results showed that intravenous magnesium reduced the incidence of POAF by 36% (RR 0.64; 95% confidence interval (CI) 0.50-0.83; P = 0.001; with no heterogeneity between trials (heterogeneity P = 0.8, I2 = 0%)).
This meta-analysis indicates that intravenous magnesium significantly reduces the incidence of POAF after CABG. This finding encourages the use of intravenous magnesium as an alternative to prevent POAF after CABG. But more high quality randomized clinical trials are still need to confirm the safety.
PMCID: PMC3359243  PMID: 22520937
2.  Prediction of postoperative atrial fibrillation in a large coronary artery bypass grafting cohort  
The objective of this study was to identify and evaluate predictors of postoperative atrial fibrillation (POAF) in a large coronary artery bypass grafting (CABG) cohort. This was a single centre study of 7115 consecutive patients with preoperative sinus rhythm who underwent isolated CABG between January 1996 and December 2009. Independent risk factors for POAF were identified with multiple logistic regression. The predictive quality of the final model was evaluated by comparing predicted and observed events of POAF, in an effort to find patients at high risk of developing POAF. After CABG, 2270 patients (32%) developed POAF during hospital stay. Independent risk factors of POAF included advancing age (odds ratio, OR 2.0–7.3), preoperative S-creatinine ≥150 µmol/l (OR 1.6), male gender (OR 1.2), New York Heart Association class III/IV (OR, 1.2), smoking (OR 1.1), prior myocardial infarction (OR 1.1) and absence of hyperlipidemia (OR 0.9). The final prediction model was moderate (area under curve, 0.62; 95% confidence interval, 0.61–0.64). Patients with POAF had more postoperative complications, including a higher incidence of stroke and increased length of hospital stay. In conclusion, several risk factors for POAF were identified, but the moderate value of the prediction model confirms the difficulty of identifying patients at high risk of developing POAF after CABG.
PMCID: PMC3329319  PMID: 22314010
Postoperative atrial fibrillation; Coronary artery bypass grafting; Ageing
3.  Postoperative atrial fibrillation predicts long-term survival after aortic-valve surgery but not after mitral-valve surgery: a retrospective study 
BMJ Open  2011;1(2):e000385.
Postoperative atrial fibrillation (POAF) has been reported to be associated with reduced long-term survival after isolated coronary artery bypass grafting surgery. The objective of this study was to determine the impact of POAF on long-term survival after valvular surgery.
The authors retrospectively analysed the preoperative and operative data of 2986 consecutive patients with no preoperative history of atrial fibrillation undergoing first valvular surgery (aortic-valve replacement (AVR), mitral valve replacement or mitral valve repair (MVR/MVRp) with or without coronary artery bypass grafting surgery) in their institution between 1995 and 2008 (median follow-up 5.31 years, range 0.1–15.0). The authors investigated the impact of POAF on survival using multivariable Cox regression.
Patients with POAF were older, and were more likely to have hypertension or renal failure when compared with patients without POAF. The 12-year survival in patients with POAF was 45.7±2.8% versus 61.4±2.1% in patients without POAF (p<0.001). On a multivariable analysis, when adjusting for age and other potential confounding factors, POAF tended to be associated with lower long-term survival (HR for all-cause death (HR)=1.17, 95% CI 1.00 to 1.38, p=0.051). The authors also analysed this association separately in patients with AVR and those with MVR/MVRp. In the multivariable analysis, POAF was a significant predictor of higher long-term mortality in patients with AVR (HR=1.22, CI 1.02 to 1.45, p=0.03) but not in patients with MVR/MVRp (HR=0.87, CI 0.58 to 1.29, p=0.48).
POAF is significantly associated with long-term mortality following AVR but not after MVR/MVRp. The underlying factors involved in the pathogenesis of POAF after MVR/MVRp may partially account for the lack of association between POAF and survival in these patients.
Article summary
Article focus
To investigate if postoperative atrial fibrillation (POAF) may affect long-term survival following heart-valve surgery.
Key messages
POAF is significantly associated with long-term mortality following aortic-valve replacement (AVR).
POAF is not associated with long-term mortality following mitral valve replacement/repair.
Strengths and limitations of this study
This study indicates that POAF is a significant predictor of long-term survival after AVR.
Hence, additional specific intervention, possibly a closer follow-up, should be considered in these patients.
This is an observational study, hence causality between POAF and long-term survival following AVR cannot be ascertained.
PMCID: PMC3211052  PMID: 22080543
4.  The outcome of thoracic epidural anesthesia in elderly patients undergoing coronary artery bypass graft surgery 
Saudi Journal of Anaesthesia  2012;6(1):16-21.
Thoracic epidural anesthesia (TEA) improves analgesia and outcomes after a cardiac surgery. As aging is a risk factor for postoperative pulmonary complications, TEA is of particular importance in elderly patients undergoing coronary artery bypass graft (CABG).
Fifty patients aged 65–75 years; ASA II and III scheduled for elective CABG were included in the study. Patients were randomized to receive either general anesthesia (GA) group alone or GA combined with TEA group. Heart rate (HR), mean arterial pressure (MAP), and central venous pressure were recorded. Total dose of fentanyl μg/kg, aortic cross clamping, cardiopulmonary bypass (CPB) time, time to first awaking and extubation, arterial blood gases, visual analog scale (VAS) score in intensive care unit were reported. Postoperative pulmonary function tests were done.
TEA showed a significant HR and lower MAP compared with the GA group. The total dose of intraoperative fentanyl and nitroglycerine were significantly lower in the TEA. Patients in TEA group have statistically significantly higher PaO2, lower PaCO2, increase in Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1)
TEA reduced severity of postoperative pulmonary function and restoration was faster in TEA group in elderly patients undergoing CABG. Also, it resulted in earlier extubation and awakening, better analgesia, lower VAS.
PMCID: PMC3299108  PMID: 22412771
Coronary artery bypass graft; elderly; thoracic epidural anesthesia
5.  Efficacy of Combination Therapy of Statin and Vitamin C in Comparison with Statin in the Prevention of Post-CABG Atrial Fibrillation 
Purpose: Atrial fibrillation (AF) is the most frequent arrhythmia that follows coronary artery bypass graft (CABG). Patients developing postoperative AF (POAF) have significantly higher mortality rates. The consistent prophylactic effectiveness of statins and vitamin C are well-accepted; however, no evaluation on combined therapy has been performed. We aimed at assessing the efficacy of combination therapy with statin and vitamin C in comparison with statin alone in the prevention of post CABG-AF.
Methods: In a randomized double blind clinical trial, 120 candidates of CABG were recruited in Tabriz Madani Educational Center in a 15-month period of time. Patients were randomized into two groups of 60 receiving oral atorvastatin (40mg) plus oral vitamin C (2g/d operation day and 1g/d for five consequent days) for intervention group and oral atorvastatin (40mg) for control group. Occurrence of post CABG AF was compared between the two groups.
Results: There were 60 patients, 43 males and 17 females with a mean age of 61.0±11.5 (29-78) years, in the intervention group and sixty patients, 39 males and 21 females with a mean age of 60.5±11.3 (39-81) years, in the control group. The post CABG AF occurred in 6 cases (10%) in the interventional group and 15 patients (25%) in the controls (P=0.03, odds ratio=0.33, 95% confidence interval 0.12-0.93).
Conclusion: Based on our findings, combination prophylaxis against post CABG AF with oral atorvastatin plus vitamin C is significantly more effective than single oral atorvastatin.
PMCID: PMC3885376  PMID: 24409416
Atrial Fibrillation; Atorvastatin; Vitamin C; Coronary Artery Bypass Grafting
6.  Pharmacological and Nonpharmacological Prevention of Atrial Fibrillation after Coronary Artery Bypass Surgery 
Atrial fibrillation (AF) is the most common complication of coronary artery bypass graft surgery (CABG). The reported incidence of AF after CABG varies from 20% to 40%. Postoperative AF (POAF) is associated with increased incidence of hemodynamic instability, thromboembolic events, longer hospital stays, and increased health care costs. A variety of pharmacological and nonpharmacological strategies have been employed to prevent AF after CABG. Preoperative and postoperative beta blockers are recommended in all cardiac surgery patients as the first-line medication to prevent POAF. Sotalol and amiodarone are also effective and can be regarded as appropriate alternatives in high-risk patients. Corticosteroids and biatrial pacing may be considered in selected CABG patients but are associated with risk. Magnesium supplementation should be considered in patients with hypomagnesemia. There are no definitive data to support the treatment with nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, procainamide, and propafenone, or anterior fat pad preservation to reduce POAF.
PMCID: PMC3466882  PMID: 23074627
Atrial fibrillation; Coronary artery bypass; Drug therapy; Cardiac pacing, artificial
7.  N-acetylcysteine supplementation for the prevention of atrial fibrillation after cardiac surgery: a meta-analysis of eight randomized controlled trials 
Atrial fibrillation is the most common type of arrhythmia after cardiac surgery. An increasing body of evidence demonstrates that oxidative stress plays a pivotal role in the pathophysiology of atrial fibrillation. N-acetylcysteine (NAC) is a free radical scavenger, and may attenuate this pathophysiologic response and reduce the incidence of postoperative AF (POAF). However, it is unclear whether NAC could effectively prevent POAF. Therefore, this meta-analysis aims to assess the efficacy of NAC supplementation on the prevention of POAF.
Medline and Embase were systematically reviewed for studies published up to November 2011, in which NAC was compared with controls for adult patients undergoing cardiac surgery. Outcome measures comprised the incidence of POAF and hospital length of stay (LOS). The meta-analysis was performed with the fixed-effect model or random-effect model according to the heterogeneity.
Eight randomized trials incorporating 578 patients provided the best evidence and were included in this meta-analysis. NAC supplementation significantly reduced the incidence of POAF (OR 0.62, 95% CI 0.41 to 0.93; P = 0.021) compared with controls, but had no effect on LOS (WMD -0.07, 95% CI -0.42 to 0.28; P = 0.703).
The prophylactic NAC supplementation may effectively reduce the incidence of POAF. However, the overall quality of current studies is poor and further research should focus on adequately powered randomized controlled trials with POAF incidence as a primary outcome measure.
PMCID: PMC3331849  PMID: 22364379
8.  Predictors of atrial fibrillation following coronary artery bypass surgery 
New-onset atrial fibrillation is the most common form of rhythm disturbance following coronary artery bypass grafting surgery (CABG). It is still unclear which factors have a significant impact on its occurrence after this procedure. The aim of this study was to evaluate clinical predictors of postoperative atrial fibrillation (POAF) after myocardial revascularization.
We performed a retrospective analysis of 322 patients who underwent the first CABG operation without baseline atrial fibrillation. All subjects underwent laboratory blood tests, echocardiography and selective coronarography with ventriculography. Patients were continuously electrocardiographically monitored during the first 48–72h after the operation for the occurrence of POAF.
POAF was diagnosed in 72 (22.4%) of the patients. Multivariate logistic regression analysis was used to identify the following independent clinical predictors of POAF: age ≥65 years (OR 1.78; 95%CI: 1.06–2.76; p=0.043), hypertension (OR 1.97; 95%CI: 1.15–3.21; p=0.018), diabetes mellitus (OR 2.09; 95% CI: 1.31–5.33; p=0.010), obesity (OR 1.51; 95%CI: 1.03–3.87; p=0.031), hypercholesterolemia (OR 2.17, 95%CI: 1.05–4.25; p=0.027), leukocytosis (OR 2.32, 95%CI: 1.45–5.24; p=0.037), and left ventricular segmental kinetic disturbances (OR 3.01; 95%CI: 1.65–4.61, p<0.001).
This study demonstrates that advanced age, hypertension, diabetes, obesity, hypercholesterolemia, leukocytosis, and segmental kinetic disturbances of the left ventricle are powerful risk factors for the occurrence of POAF.
PMCID: PMC3524673  PMID: 21169910
atrial fibrillation; cardiac surgery; risk factors
9.  Perioperative Heart-type Fatty Acid Binding Protein Levels in Atrial Fibrillation after Cardiac Surgery 
Postoperative atrial fibrillation (POAF) is common and associated with poor outcomes. Perioperative ischemia can alter arrhythmic substrate.
To demonstrate an association between perioperative measurement of heart-type fatty acid binding protein (HT-FABP), a sensitive marker of ischemic myocardial injury.
Blood samples from 63 inpatients undergoing coronary artery bypass surgery (CABG), valve surgery or both were obtained before and up to four days after surgery. Continuous telemetry monitoring was used to detect POAF. 59 patients had at least 3 HT-FABP measurements. The relation of ELISA-measured HT-FABP to POAF was assessed using joint logistic regression adjusted for age and surgery type.
Thirty five patients (55%) developed POAF; these were on average older (69.3 ± 10 vs. 60 ± 11 years, p=0.0019), with a higher prevalence of heart failure (43% vs. 17%, p=0.034), chronic obstructive lung disease (26% vs. 4%, p=0.017), preoperative calcium channel blocker use (29% vs. 7%, p=0.031) and more likely to undergo combined surgery (21% vs. 11%, p=0.049). The joint age- and CABG-adjusted model revealed that postoperative but not preoperative HT-FABP levels predicted POAF (coefficient 1.9 ± 0.87, p=0.03). Longer bypass time, prior infarction and worse renal function were all associated with higher postoperative HT-FABP.
A greater rise of HT-FABP is associated with atrial fibrillation after cardiac surgery, suggesting that ischemic myocardial damage is a contributing underlying mechanism. Interventions that decrease perioperative ischemic injury may also decrease the occurrence of POAF.
PMCID: PMC3687792  PMID: 23041578
Atrial Fibrillation; Postoperative; Biomarker; Ischemia; CABG; Valve Surgery
10.  Atrial Fibrillation after Cardiac Surgery: Where are we now? 
To review: 1) Pathophysiology of postoperative atrial fibrillation (POAF); 2) Risk factors for POAF; 3) Prophylaxis of POAF; 4) Treatment of POAF; and 5) Future directions.
We searched the Medline database for articles published between January, 1966 to September, 2008. We used the following keywords: Atrial fibrillation, Postoperative atrial fibrillation, Coronary Artery Bypass, and antiarrhythmic agents. Additionally, we searched references from all relevant articles.
POAF occurs in 25-60% of patients depending on the type of cardiac surgery performed. POAF generally occurs on postoperative day 2 or 3. POAF is associated with an increased risk of morbidity and mortality, and longer hospital stay. Prophylactic treatments reduce the likelihood of POAF. In patients who experience POAF, rhythm strategies should be used in those who are symptomatic and hemodynamically unstable. All other patients should be managed with rate strategies.
PMCID: PMC2572025  PMID: 18982137
Atrial fibrillation; postoperative atrial fibrillation; coronary artery bypass; antiarrhythmic agents
11.  Preoperative Angiotensin Blocking Drug Therapy Is not Associated with Atrial Fibrillation after Cardiac Surgery 
American heart journal  2010;160(2):329-336.e1.
Preoperative use of angiotensin blocking drug therapy (ABDT) with ACE-inhibitors or Angiotensin II receptor blockers (ARBs) and its link to occurrence of postoperative atrial fibrillation (POAF), a common marker of poor outcomes after cardiac surgery, remains controversial.
From 1997-2003 10,552 patients underwent coronary artery bypass grafting (CABG) with or without valve surgery. To adjust for differences of clinical characteristics between patients receiving ABDT within 24 hours prior to surgery compared to those who did not, propensity score analyses were conducted.
ABDT was prescribed in 4,795 (45%) prior to surgery of which 1,725 (36%) developed POAF prior to discharge vs. 1908 (33%) of 5,757 patients who have not received ABDT (unadjusted odds ratio [OR] of 1.13 (95% Confidence Interval [CI] 1.05-1.25, p<0.01). In 6744 propensity score matched patients with well balanced co-morbidity profiles, ABDT was not associated with POAF (OR 1.05, CI 0.95-1.16, p=0.38). Stratified analysis within quintiles of propensity score and propensity-adjusted logistic multivariable regression confirmed these findings.
In this large observational study we found no evidence of an association between preoperative angiotensin blockade and the occurrence of postoperative atrial fibrillation. Adequately powered randomized studies are needed to clarify the best strategy of perioperative angiotensin blocking drug therapy in patients with and without guideline-based indications.
PMCID: PMC2919305  PMID: 20691840
12.  Postoperative Atrial Fibrillation 
ISRN Cardiology  2011;2011:203179.
Postoperative atrial fibrillation (POAF) is common among surgical patients and associated with a worse outcome. Pathophysiology of POAF is not fully disclosed, and several perioperative factors could be involved. Direct cardiac stimulation from perioperative use of catecholamines or increased sympathetic outflow from volume loss/anaemia/pain may play a role. Metabolic alterations, such as hypo-/hyperglycaemia and electrolyte disturbances, may also contribute to POAF. Moreover, inflammation, both systemic and local, may play a role in its pathogenesis. Strategies to prevent POAF aim at reducing its incidence and ameliorate global outcome of surgical patients. Nonpharmacological prophylaxis includes an adequate control of postoperative pain, the use of thoracic epidural analgesia, optimization of perioperative oxygen delivery, and, possibly, modulation of surgery-associated inflammatory response with immunonutrition and antioxidants. Perioperative potassium and magnesium depletion should be corrected. The impact of those interventions on patients outcome needs to be further investigated.
PMCID: PMC3262508  PMID: 22347631
13.  Epidural anesthesia and postoperative analgesia with ropivacaine and fentanyl in off-pump coronary artery bypass grafting: a randomized, controlled study 
BMC Anesthesiology  2011;11:17.
Our aim was to assess the efficacy of thoracic epidural anesthesia (EA) followed by postoperative epidural infusion (EI) and patient-controlled epidural analgesia (PCEA) with ropivacaine/fentanyl in off-pump coronary artery bypass grafting (OPCAB).
In a prospective study, 93 patients were scheduled for OPCAB under propofol/fentanyl anesthesia and randomized to three postoperative analgesia regimens aiming at a visual analog scale (VAS) score < 30 mm at rest. The control group (n = 31) received intravenous fentanyl 10 μg/ml postoperatively 3-8 mL/h. After placement of an epidural catheter at the level of Th2-Th4 before OPCAB, a thoracic EI group (n = 31) received EA intraoperatively with ropivacaine 0.75% 1 mg/kg and fentanyl 1 μg/kg followed by continuous EI of ropivacaine 0.2% 3-8 mL/h and fentanyl 2 μg/mL postoperatively. The PCEA group (n = 31), in addition to EA and EI, received PCEA (ropivacaine/fentanyl bolus 1 mL, lock-out interval 12 min) postoperatively. Hemodynamics and blood gases were measured throughout 24 h after OPCAB.
During OPCAB, EA decreased arterial pressure transiently, counteracted changes in global ejection fraction and accumulation of extravascular lung water, and reduced the consumption of propofol by 15%, fentanyl by 50% and nitroglycerin by a 7-fold, but increased the requirements in colloids and vasopressors by 2- and 3-fold, respectively (P < 0.05). After OPCAB, PCEA increased PaO2/FiO2 at 18 h and decreased the duration of mechanical ventilation by 32% compared with the control group (P < 0.05).
In OPCAB, EA with ropivacaine/fentanyl decreases arterial pressure transiently, optimizes myocardial performance and influences the perioperative fluid and vasoactive therapy. Postoperative EI combined with PCEA improves lung function and reduces time to extubation.
Trial Registration
PMCID: PMC3182129  PMID: 21923942
epidural anesthesia; analgesia; patient-controlled analgesia; off-pump coronary artery bypass grafting
14.  Atrial pacing for the prevention of atrial fibrillation after coronary artery bypass graft surgery: a review of the literature 
Heart  2004;90(2):129-133.
Atrial fibrillation (AF) occurs in 20–40% of patients after coronary artery bypass graft surgery (CABG) and contributes to increased morbidity and expenditure after CABG. The limited efficacy of pharmacological treatment to prevent post-CABG AF has stimulated research into alternative prophylactic strategies for the arrhythmia. This article critically reviews the trial evidence in the literature regarding the efficacy of epicardial atrial pacing to prevent post-CABG AF. Thirteen randomised controlled trials of either right, left, or biatrial pacing to prevent post-CABG AF were identified. Overall, prophylactic biatrial epicardial pacing appears to be effective prophylaxis against post-CABG AF and to reduce postoperative hospital stay. The efficacy of single site right or left atrial pacing is less clear. Further data are required to determine both the efficacy of single site atrial pacing and the cost effectiveness of pacing strategies to prevent AF after CABG.
PMCID: PMC1768083  PMID: 14729772
atrial pacing; atrial fibrillation; coronary artery bypass graft
15.  Effects of high thoracic epidural anesthesia on mixed venous oxygen saturation in coronary artery bypass grafting surgery 
To investigate possible effects of high thoracic epidural anesthesia (HTEA) on mixed venous oxygen saturation (SvO2) in coronary artery bypass grafting surgery (CABGS).
Sixty-four patients scheduled for CABGS were randomly assigned to either test (HTEA) or control group. Standard balanced general anesthesia was applied in both groups. Mean arterial blood pressure (MAP), heart rate (HR), oxygen saturation (SpO2), central venous pressure (CVP), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), pulmonary compliance (C), bispectral index (BIS), body temperature, SvO2, hematocrit values were recorded before induction. Postoperative hemodynamic changes, inotropic agent, need for vasodilatation, transfusion and additional analgesics, recovery score, extubation time, visual analogue scale (VAS) values, duration of stay in intensive care unit (ICU) and hospital were recorded.
Study groups were similar in SpO2, CVP, PCWP, PAP, C, body temperature, BIS values, development of intraoperative bradycardia. In HTEA group, intraoperative MAP, SVR, PVR, need for transfusion were lower, whereas CO, CI, SvO2, hematocrit values were higher (p<0.05). Postoperative MAP, HR, hypertension development, need for vasodilatator, transfusion, analgesics, extubation time, recovery data, duration of stay in ICU, hospital were lower in HTEA group (p<0.05). VAS score decreased in 30 minutes and 12 hours following extubation in HTEA and control group, respectively.
HTEA may improve balance between oxygen presentation and usage by suppressing neuroendocrin stress response; provide efficient postoperative analgesia, more stabile hemodynamic, respiratory conditions, lower duration of stay in ICU, hospital.
PMCID: PMC3628587  PMID: 23531633
coronary arteries bypass grafting surgery; mixed venous oxygen saturation; thoracic epidural anesthesia
16.  Atrial fibrillation following cardiac surgery: risk analysis and long-term survival 
We studied potential risk factors for postoperative atrial fibrillation (POAF) in a large cohort of patients who underwent open-heart surgery, evaluating short- and long-term outcome, and we developed a risk-assessment model of POAF.
A retrospective study of 744 patients without prior history of AF who underwent CABG (n = 513), OPCAB (n = 207), and/or AVR (n = 156) at Landspitali Hospital in 2002–2006. Logistic regression analysis was used to study risk factors for POAF, comparing patients with and without POAF.
The rate of POAF was 44%, and was higher following AVR (74%) than after CABG (44%) or OPCAB (35%). In general, patients with POAF were significantly older, were more often female, were less likely to be smokers, had a lower EF, and had a higher EuroSCORE. The use of antiarrythmics was similar in the groups but patients who experienced POAF were less likely to be taking statins. POAF patients also had longer hospital stay, higher rates of complications, and operative mortality (5% vs. 0.7%). In multivariate analysis, AVR (OR 4.4), a preoperative history of cardiac failure (OR 1.8), higher EuroSCORE (OR 1.1), and advanced age (OR 1.1) were independent prognostic factors for POAF. Overall five-year survival was 83% and 93% for patients with and without POAF (p <0.001).
POAF was detected in 44% of patients, which is high compared to other studies. In the future, our assessment score will hopefully be of use in identifying patients at high risk of POAF and lower complications related to POAF.
PMCID: PMC3515503  PMID: 22992266
Postoperative atrial fibrillation; Coronary artery bypass surgery; Atrial valve replacement; Risk factors; Risk assessment; Prophylaxis; Survival
17.  Carvedilol for Prevention of Atrial Fibrillation after Cardiac Surgery: A Meta-Analysis 
PLoS ONE  2014;9(4):e94005.
Postoperative atrial fibrillation (POAF) remains the most common complication after cardiac surgery. Current guidelines recommend β-blockers to prevent POAF. Carvedilol is a non-selective β-adrenergic blocker with anti-inflammatory, antioxidant, and multiple cationic channel blocking properties. These unique properties of carvedilol have generated interest in its use as a prophylaxis for POAF.
To investigate the efficacy of carvedilol in preventing POAF.
PubMed from the inception to September 2013 was searched for studies assessing the effect of carvedilol on POAF occurrence. Pooled relative risk (RR) with 95% confidence interval (CI) was calculated using random- or fixed-effect models when appropriate. Six comparative trials (three randomized controlled trials and three nonrandomized controlled trials) including 765 participants met the inclusion criteria.
Carvedilol was associated with a significant reduction in POAF (relative risk [RR] 0.49, 95% confidence interval [CI] 0.37 to 0.64, p<0.001). Subgroup analyses yielded similar results. In a subgroup analysis, carvedilol appeared to be superior to metoprolol for the prevention of POAF (RR 0.51, 95% CI 0.37 to 0.70, p<0.001). No evidence of heterogeneity was observed.
In conclusion, carvedilol may effectively reduce the incidence of POAF in patients undergoing cardiac surgery. It appeared to be superior to metoprolol. A large-scale, well-designed randomized controlled trial is needed to conclusively answer the question regarding the utility of carvedilol in the prevention of POAF.
PMCID: PMC3976381  PMID: 24705913
18.  Fish Oil and Atrial Fibrillation after Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials 
PLoS ONE  2013;8(9):e72913.
Influence of fish oil supplementation on postoperative atrial fibrillation (POAF) was inconsistent according to published clinical trials. The aim of the meta-analysis was to evaluate the effects of perioperative fish oil supplementation on the incidence of POAF after cardiac surgery.
Pubmed, Embase and the Cochrane Library databases were searched. Randomized controlled trials (RCTs) assessing perioperative fish oil supplementation for patients undergoing cardiac surgery were identified. Data concerning study design, patient characteristics, and outcomes were extracted. Risk ratio (RR) and weighted mean differences (WMD) were calculated using fixed or random effects models.
Eight RCTs involving 2687 patients were included. Perioperative supplementation of fish oil did not significantly reduce the incidence of POAF (RR = 0.86, 95%CI 0.71 to 1.03, p = 0.11) or length of hospitalization after surgery (WMD = 0.10 days, 95% CI: 0.48 to 0.67 days, p = 0.75). Fish oil supplementation also did not affect the perioperative mortality, incidence of major bleeding or the length of stay in the intensive care unit. Meta-regression and subgroup analyses indicated mean DHA dose in the supplements may be a potential modifier for the effects of fish oil for POAF. For supplements with DHA >1 g/d, fish oil significantly reduced the incidence of POAF; while it did not for the supplements with a lower dose of DHA.
Current evidence did not support a preventative role of fish oil for POAF. However, relative amounts of DHA and EPA in fish oil may be important for the prevention of POAF.
PMCID: PMC3769383  PMID: 24039820
19.  Preoperative atrial fibrillation is an independent risk factor for mid-term mortality after concomitant aortic valve replacement and coronary artery bypass graft surgery 
Preoperative atrial fibrillation (PAF) has been associated with poorer early and mid-term outcomes after isolated valvular or coronary artery bypass graft surgery. Few studies, however, have evaluated the impact of PAF on early and mid-term outcomes after concomitant aortic valve replacement and coronary aortic bypass graft (AVR-CABG) surgery.
Data obtained prospectively between June 2001 and December 2009 by the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database Program was retrospectively analysed. Patients who underwent concomitant atrial arrhythmia surgery/ablation were excluded. Demographic and operative data were compared between patients undergoing concomitant AVR-CABG who presented with PAF and those who did not using chi-square and t-tests. The independent impact of PAF on 12 short-term complications and mid-term mortality was determined using binary logistic and Cox regression, respectively.
Concomitant AVR-CABG surgery was performed in 2563 patients; 322 (12.6%) presented with PAF. PAF patients were generally older (mean age 76 vs 74 years; P < 0.001) and presented more often with comorbidities including congestive heart failure, chronic pulmonary disease and cerebrovascular disease (all P < 0.05). PAF was associated with 30-day mortality on univariate analysis (P = 0.019) but not multivariate analysis (P = 0.53). The incidence of early complications was not significantly higher in the PAF group. PAF was independently associated with reduced mid-term survival (HR, 1.58; 95% CI, 1.14–2.19; P = 0.006).
PAF is associated with reduced mid-term survival after concomitant AVR-CABG surgery. Patients with PAF undergoing AVR-CABG should be considered for a concomitant surgical ablation procedure.
PMCID: PMC3598038  PMID: 23287590
Cardiac surgery; Coronary artery bypass graft; CABG; Aortic valve replacement; Preoperative atrial fibrillation; Mortality; Morbidity; Survival
20.  Renal effects of dexmedetomidine during coronary artery bypass surgery: a randomized placebo-controlled study 
BMC Anesthesiology  2011;11:9.
Dexmedetomidine, an alpha2-adrenoceptor agonist, has been evaluated as an adjunct to anesthesia and for the delivery of sedation and perioperative hemodynamic stability. It provokes dose-dependent and centrally-mediated sympatholysis. Coronary artery bypass grafting (CABG) with extracorporeal circulation is a stressful procedure increasing sympathetic nervous system activity which could attenuate renal function due the interrelation of sympathetic nervous system, hemodynamics and renal function. We tested the hypothesis that dexmetomidine would improve kidney function in patients undergoing elective CABG during the first two postoperative days.
This was a double-blind, randomized, parallel-group study. Patients with normal renal function and scheduled for elective CABG were randomized to placebo or to infusion of dexmedetomidine to achieve a pseudo steady-state plasma concentration of 0.60 ng/ml. The infusion was started after anesthesia induction and continued until 4 h after surgery. The primary endpoint was creatinine clearance. Other variables included urinary creatinine and output, fractional sodium and potassium excretion, urinary potassium, sodium and glucose, serum and urinary osmolality and plasma catecholamine concentrations. The data were analyzed with repeated-measures ANOVA or Cochran-Mantel-Haenszel test.
Sixty-six of 87 randomized patients were evaluable for analysis. No significant between-group differences were recorded for any indices of renal function except for a mean 74% increase in urinary output with dexmedetomidine in the first 4 h after insertion of a urinary catheter (p < 0.001). Confidence interval examination revealed that the sample size was large enough for the no-difference statement for creatinine clearance.
Use of intravenous dexmedetomidine did not alter renal function in this cohort of relatively low-risk elective CABG patients but was associated with an increase in urinary output.
This study was carried out in 1994-1997 and was thus not registered.
PMCID: PMC3123640  PMID: 21605394
21.  The Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Trial – Rationale and Design 
American heart journal  2011;162(1):56-63.e3.
Post-operative atrial fibrillation/flutter (PoAF) commonly complicates cardiac surgery, occurring in 25–60% of patients. PoAF is associated with significant morbidity, higher long-term mortality, and increased healthcare costs. Novel preventive therapies are clearly needed. In experiments and short-term trials, seafood-derived long-chain omega-3 polyunsaturated fatty acids (PUFA) influence several risk factors that might reduce risk of PoAF. A few small and generally underpowered trials have evaluated effects of omega-3-PUFA supplementation on PoAF, with mixed results. The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) trial is an appropriately powered, investigator-initiated, randomized, double-blind, placebo-controlled, multinational trial to determine whether peri-operative oral omega-3-PUFA reduces occurrence of PoAF in 1,516 patients undergoing cardiac surgery. Additional aims include evaluation of resource utilization, biologic pathways and mechanisms, postoperative cognitive decline, and safety. Broad inclusion criteria encompass a real-world population of outpatients and inpatients scheduled for cardiac surgery. Treatment comprises a total pre-operative loading dose of 8–10 g of omega-3-PUFA or placebo divided over 2–5 days, followed by 2 g/d until hospital discharge or post-operative day 10, whichever first. Based on anticipated 30% event rate in controls, total enrollment of 1,516 patients (758 per treatment arm) will provide 90% power to detect 25% reduction in PoAF. OPERA will provide invaluable evidence to inform biologic pathways, proof-of-concept that omega-3-PUFA influence cardiac arrhythmias, and potential regulatory standards and clinical use of this simple, inexpensive, and low-risk intervention to prevent PoAF.
PMCID: PMC3134828  PMID: 21742090
22.  Does Off-pump Coronary Artery Bypass Reduce the Prevalence ofAtrial Fibrillation? 
Introduction: To examine whether or not off-pump CABG (Coronary Artery Bypass Reduce) reduces the incidence of AF after cardiac surgery. Methods: The study was carried out in 939 consecutive coronary artery disease patients with sinus rhythm from which 383 patients underwent off-pump CABG, and 556 patients were operated through on-pump CABG. All patients were monitored postoperatively during intensive care unit (ICU) stay. Then, the incidence and predictive risk factors of post operative AF (POAF) in two groups were determined and compared with each other. Results: Overall, the mean age of the patients was 56.0±12.8 years with 234 patients (24.9%) being older than 65 years. POAF developed in 38 patients (9.9%) of the off-pump and in 93 patients (16.7%) of the on-pump CABG. There was significant difference between two groups when considering the incidence of POAF (P=0.002). Among preoperative risk factors, age>65 years had a significant association with the incidence of AF in both groups. This study also showed that most of the POAF cases converted to sinus rhythm after treatment. Moreover, these finding demonstrated that conversion to sinus rhythm is significantly more probable in off-pump group (P=0.006). Conclusion: A reduced prevalence of POAF could be observed in patients with off-pump as compared with on-pump techniques. Furthermore, conversion to sinus rhythm in off-pump group was significantly more probable than on-pump group.
PMCID: PMC3825388  PMID: 24251010
Off-pump CABG; On-pump CABG; Postoperative Atrial Fibrillation; Risk Factor
23.  A Randomized, Placebo-Controlled Trial of Omega-3 Fatty Acids for Inhibition of Supraventricular Arrhythmias After Cardiac Surgery: The FISH Trial 
Omega-3 polyunsaturated fatty acids (n3-PUFAs) might have antiarrhythmic properties, but data conflict on whether n3-PUFAs reduce rates of atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG). We hypothesized that n3-PUFAs would reduce post-CABG AF, and we tested this hypothesis in a well-powered, randomized, double-blind, placebo-controlled, multicenter clinical trial.
Methods and Results
Patients undergoing CABG were randomized to pharmaceutical-grade n3-PUFAs 2 g orally twice daily (minimum of 6 g) or a matched placebo ≥24 hours before surgery. Gas chromatography was used to assess plasma fatty acid composition of samples collected on the day of screening, day of surgery, and postoperative day 4. Treatment continued either until the primary end point, clinically significant AF requiring treatment, occurred or for a maximum of 2 weeks after surgery. Two hundred sixty patients were enrolled and randomized. Before surgery, n3-PUFA dosing increased plasma n3-PUFA levels from 2.9% to 4% and reduced the n6:n3-PUFA ratio from 9.1 to 6.4 (both P<0.001). Similar changes were noted on postoperative day 4. There were no lipid changes in the placebo group. The rate of post-CABG AF was similar in both groups (30% n3-PUFAs versus 33% placebo, P=0.67). The post-CABG AF odds ratio for n3-PUFAs relative to placebo was 0.89 (95% confidence interval 0.52–1.53). There were no differences in any secondary end points.
Oral n3-PUFA supplementation begun 2 days before CABG did not reduce AF or other complications after surgery.
Clinical Trial Registration
url: Unique identifier: NCT00446966. (J Am Heart Assoc. 2012;1:e000547 doi: 10.1161/JAHA.111.000547.)
PMCID: PMC3487324  PMID: 23130134
fatty acids; coronary artery bypass graft surgery; atrial fibrillation
24.  Secondary Prevention following CABG: Findings of a National Randomized Controlled Trial and Sustained Society-Led Incorporation into Practice 
Circulation  2010;123(1):39-45.
Despite evidence supporting the use of aspirin, B-blockers, ACE inhibitors, and lipid-lowering therapies in eligible patients, adoption of these secondary prevention measures following coronary artery bypass grafting (CABG) has been inconsistent. We sought to rigorously test on a national scale whether low-intensity continuous quality improvement (CQI) interventions can be used to speed secondary prevention adherence following CABG.
Methods and Results
A total of 458 hospitals participating in the Society of Thoracic Surgeons National Cardiac Database and treating 361,328 patients undergoing isolated CABG were randomized to either a control or an intervention group. The intervention group received CQI materials designed to influence the prescription of the secondary prevention medications at discharge. The primary outcome measure was discharge prescription rates of the targeted secondary prevention medications at intervention vs. control sites, assessed by measuring pre-intervention and post-intervention site differences. Pre-randomization treatment patterns and baseline data were similar in the control (N=234) and treatment (N=224) groups. Individual medication use as well as composite adherence increased over 24 months in both groups, with a markedly more rapid rate of adherence uptake among the intervention hospitals and a statistically significant therapy hazard ratio in the intervention vs. control group for all 4 secondary prevention medications.
Provider-led, low-intensity CQI efforts can improve the adoption of care processes into national practice within the context of a medical specialty society infrastructure. The findings of the present trial have led to the incorporation of study outcome metrics into a medical society rating system for ongoing quality improvement.
PMCID: PMC3683243  PMID: 21173357
CV surgery: coronary artery disease; Health policy and outcomes research; Compliance/adherence; Secondary prevention
25.  Short-Term Complications and Resource Utilization in Matched Subjects After On-Pump or Off-Pump Primary Isolated Coronary Artery Bypass 
Studies suggest that patients who undergo off-pump coronary artery bypass grafting (OPCABG) have fewer short-term complications and use fewer inpatient resources than do patients who undergo standard coronary artery bypass grafting (CABG) with extracorporeal circulation. However, dissimilarity between groups in risk factors for complications has hindered interpretation of results.
To compare the prevalence of selected complications (atrial fibrillation, stroke, reoperation, and bleeding) and inpatient resource utilization (length of stay, discharge disposition, total charges) between subjects undergoing primary isolated CABG or OPCABG who were matched with respect to key risk factors.
Retrospective, causal-comparative survey conducted in 1 center for 18 months. Patients who underwent primary isolated CABG or OPCABG were matched for sex, age (within 2 years), left ventricular ejection fraction (within 0.05), and graft-patient ratio (exact match) and compared for prevalence of new-onset atrial fibrillation, stroke, reoperation within 24 hours, and bleeding. Statistical analysis included Wilcoxon and t tests for paired comparisons.
The sample (107 matched pairs) was 63% male, with a mean age of 66 (SD 9.5) years, a mean left ventricular ejection fraction of 0.51 (SD 0.13), and a mean graft-patient ratio of 3.41 (SD 0.74). The 2 groups did not differ significantly in New York Heart Association class (P=.43), Acute Physiology and Chronic Health Evaluation III score (P=.22), postoperative β-blocker use (P=.73), or comorbid conditions. None of the complications examined differed significantly between pairs.
Patients with comparable risk profiles have similar prevalences of selected complications after CABG and OPCABG.
PMCID: PMC3655795  PMID: 15568655

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