7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Atrial fibrillation and flutter after cardiac surgery : Richard Lee, MD, MBA : Gabriel S Aldea, MD, Bradley P Knight, MD, FACC, John Pepper, MA, MChir, FRCS, FESC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 28, 2022. INTRODUCTION Atrial fibrillation (AF) and atrial flutter occur frequently after cardiac surgery. The development of these atrial arrhythmias prolongs hospital stay and is associated with worse long-term prognosis. Other supraventricular arrhythmias, including atrial arrhythmias such as atrioventricular nodal re-entrant tachycardia, are not common in this setting. (See "Atrioventricular nodal reentrant tachycardia".) This topic will review the pathogenesis, predictors, clinical course, prevention, and management of AF and atrial flutter occurring after cardiac surgery. Most of the observations on atrial arrhythmias come from patients who developed atrial fibrillation. Our approach to patients with atrial flutter is similar, unless otherwise specified. Ventricular tachyarrhythmias after cardiac surgery and arrhythmias after cardiac transplantation are discussed separately. (See "Early cardiac complications of coronary artery bypass graft surgery", section on 'Ventricular tachyarrhythmias' and "Heart transplantation in adults: Arrhythmias".) PATHOGENESIS Atrial fibrillation (AF) and atrial flutter can occur early in the postoperative period or as a late complication of cardiac surgery. A discussion of the mechanisms of AF in the general population is found elsewhere. (See "Mechanisms of atrial fibrillation".) https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 1/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Postoperative AF is likely related to a combination of perioperative factors. These include pre- existing degenerative changes in the atrial myocardium and perioperative conditions that result in abnormalities of several electrophysiologic parameters that promote the development of AF, such as dispersion of atrial refractoriness, increase in phase 3 depolarization, enhanced automaticity, increased interatrial conduction time, and decreased conduction velocity, atrial transmembrane potentials, and fluid and electrolyte shifts [1-5]. (See "The electrocardiogram in atrial fibrillation".) RISK FACTORS Although some patients develop atrial fibrillation (AF) after cardiac surgery without any apparent predisposing factors, most patients have at least one clinical predictor. Preoperative risk factors include [2,6-17]: Increasing age [6-12]. Previous history of AF. Mitral valvular disease, particularly mitral stenosis. Increased left atrial size or cardiomegaly. Previous cardiac surgery. Chronic obstructive pulmonary disease (COPD). Elevated preoperative hemoglobin A1c [18]. Low-intensity physical activity in the year prior to surgery [19]. Being a White person [20]. Obesity [17,21]. Absence of beta blocker or angiotensin converting enzyme inhibitor (ACE inhibitor) treatment or withdrawal of previous treatment. (See 'Prevention of atrial fibrillation and complications' below.) Preoperative digoxin use in some [7,13] but not all studies [14]. Higher preoperative plasma concentration of brain natriuretic peptide (BNP) [15]. (See "Natriuretic peptide measurement in heart failure".) https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 2/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Low-dose dopamine [22]. Severe right coronary artery stenosis [12]. Preoperative increase in P wave duration on surface (>116 msec) [16] or on signal averaged (>140 msec) ECG ( figure 1) [9,23]. (See "Signal-averaged electrocardiogram: Overview of technical aspects and clinical applications".) Hypokalemia and hypomagnesemia. (See 'Pathogenesis' above.) Alcohol use disorder. (See "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Alcohol'.) PERIOPERATIVE RISK FACTORS Perioperative factors that have been implicated in the creation of atrial susceptibility to atrial fibrillation (AF) or atrial flutter include: Atrial injury from surgical handling, or cannulation, atrial suture lines. Acute atrial enlargement from pressure or volume overload. Inadequate myocardial protection during cardiopulmonary bypass. Atrial ischemia. Long bypass and aortic cross-clamp times. Hyperadrenergic state (eg, use of postoperative inotropic medications). Pulmonary complications, hypoxemia. Inflammation [24,25]. (See "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Inflammation and infection'.) Hypokalemia and hypomagnesemia [26-29]. Pericardial effusion and pericarditis. Oxidative stress [30]. While mechanisms specific to late AF have not been identified, atrial flutter in these patients is re-entrant and may involve atypical isthmuses between natural barriers, atrial incisions, and scar https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 3/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate as well as the cavotricuspid isthmus [31-33]. Two potential negative risk factors are off-pump coronary artery bypass graft surgery (CABG) and preservation of the anterior fat pad: Off-pump CABG off-pump CABG is associated with a lower rate of postoperative AF than conventional CABG in some [34-36], but not all [37], studies. (See "Off-pump and minimally invasive direct coronary artery bypass graft surgery: Clinical use".) Preservation of the anterior fat pad Some [38], but not all [39], studies have found lower rate of postoperative AF with preservation of the anterior fat pad. However, none of these risk factors has adequate predictive accuracy to identify the individual patient at risk for postoperative atrial arrhythmia. As a result, risk models that use several factors have been created [6,40]. In one study, a multivariable risk model was derived in a cohort of 3093 patients, and then tested in a validation cohort of 1564 patients [6]. Predictors were identified for any postoperative AF as well as for recurrent AF. The risk score for any postoperative AF successfully stratified patients into groups at low risk (AF incidence <17 percent), medium risk (AF incidence 17 to 52 percent), and high risk (AF incidence >52 percent) ( table 1). While we do not routinely use any of these risk models, they highlight the individual risks. INCIDENCE AND TIME COURSE Atrial fibrillation (AF) occurs in 15 to 40 percent of patients in the early postoperative period following coronary artery bypass graft surgery (CABG) [1,6,41,42]. In a 2018 post-hoc analysis of 1812 patients without prior AF in the EXCEL trial, which compared CABG with percutaneous coronary intervention (PCI) for left main coronary artery disease, perioperative AF developed in 18.0 percent of those undergoing CABG (and 0.1 percent of those who received PCI). The incidence increases with increasing age [6-12,43]. (See "Left main coronary artery disease", section on 'Randomized trials' and 'Adverse outcomes following atrial fibrillation' below.) AF occurs in 37 to 50 percent after valve surgery [1,7,8], and in as many as 60 percent undergoing valve replacement plus CABG [1,7]. Atrial arrhythmias occur most often within the first few days after surgery [1,6,9,11]. In a prospective, multicenter study of 4657 patients undergoing surgery, the majority of first episodes of AF occurred by day two, while the majority of recurrent episodes occurred by day three. Forty-three percent of patients with AF had more than one episode [6]. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 4/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Among patients with postoperative AF who have no prior history of atrial arrhythmias, the AF is usually self-limited, as 15 to 30 percent convert within two hours and up to 80 percent in 24 hours [1,44,45]. The mean duration of AF in one report was 11 to 12 hours [45] and more than 90 percent are in sinus rhythm six to eight weeks following surgery [1,45-47]. In one report, for example, only 3 of 116 patients who developed AF after CABG were still in AF at six weeks [46]. AF may also occur late after cardiac surgery and the incidence is likely higher than appreciated because many patients may have continued asymptomatic episodes of AF. In a study of over 2000 patients enrolled in cardiac rehabilitation programs after cardiac surgery, 11 percent of patients developed AF (4.4 percent new-onset AF) [48]. Late postoperative AF was associated with adverse outcomes, including heart failure and rehospitalization. Atrial flutter is relatively uncommon compared to atrial fibrillation. CLINICAL MANIFESTATIONS AND DIAGNOSIS The development of atrial fibrillation or flutter after cardiac surgery may or may not lead to symptoms, such as palpitations, or to a change in the hemodynamic status of the patient. In some individuals with rapid ventricular rates, the blood pressure may fall and potentially be associated with a decline in the urine output. We are not aware of any studies that have systematically characterized the clinical manifestations of postoperative atrial fibrillation (AF) in coronary artery bypass graft surgery patients. In our experience, about 90 percent of these individuals are symptomatic and about 15 percent are hemodynamically unstable. The diagnosis of AF in the hospital is usually not difficult as most patients are on continuous monitoring. All patients should have documentation of the rhythm with a 12-lead electrocardiogram. (See "The electrocardiogram in atrial fibrillation".) Longer-term continuous AF screening may detect more episodes in postoperative cardiac surgery patients who are discharged from the hospital, but more studies are needed before we can recommend this as routine practice (see "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Screening'). In a randomized trial of 336 cardiac surgical patients with risk factors for stroke, use of continuous cardiac rhythm monitoring with wearable sensors increased the rate of AF detection within 30 days of discharge. In the intent-to-treat analysis, the primary end point of AF for at least six minutes occurred in 32 patients in the intervention group versus 3 patients in the usual care group (absolute difference, 17.9 percent 95% CI 11.5-24.3 percent) [49]. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 5/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate ADVERSE OUTCOMES FOLLOWING ATRIAL FIBRILLATION Potential adverse outcomes after the development of postoperative atrial fibrillation (AF) include stroke, death, and prolongation of hospital stay: Postoperative AF has been associated with an increased risk of in-hospital stroke in some [7,41,50-55] but not all series [56,57]. In some of these studies, it is possible that underlying comorbidities, such as older age, cerebrovascular or peripheral artery disease, and cardiopulmonary bypass time, are related to in-hospital stroke rather than the arrhythmia itself [43,52,56-59]. At least three studies with differing designs have evaluated the long-term thromboembolic risk of patients with new onset AF after coronary artery bypass graft surgery (CABG) and reached somewhat different conclusions: In the EXCEL trial of patients with left main coronary artery disease, new onset AF was an independent predictor of stroke at three years with a rate of 6.6 percent compared with 2.4 percent in patients without AF [43]. (See 'Incidence and time course' above.) In a cohort study of 2108 patients who developed postoperative AF and 8432 patients with nonvalvular AF, the risk of thromboembolism was lower in the former group (18.3 versus 29.7 events per 1000 person-years; adjusted hazard ratio 0.67, 95% CI 0.55-0.81) [60]. In addition, the risk was similar between the groups of patients with and without postoperative AF. In a post-hoc analysis of the ART randomized trial (see "Coronary artery bypass graft surgery: Graft choices", section on 'Two arterial grafts') comparing bilateral with single internal thoracic artery grafts, the cumulative incidence of cerebrovascular accident was higher in those with postoperative AF relative to those without (6.3 versus 3.7 percent; hazard ratio 1.53, 95% CI 1.06-2.23) [61]. Postoperative AF may identify a subset of patients with increased in-hospital and long-term mortality [6,25,41,42,62,63]. This was suggested by a retrospective study of 6475 patients undergoing CABG at a single institution, 994 (15 percent) of whom developed AF [41]. Patients with AF had significantly greater mortality in-hospital (7.4 versus 3.4 percent) and at four years (26 versus 13 percent). In a case-matched subset of 390 patients, the mortality at five years was significantly higher in those with AF (20 versus 7 percent). On multivariate analysis, postoperative AF was a predictor of long-term mortality in both the retrospective cohort (adjusted odds ratio 1.5) and the case-matched population (odds ratio 3.4). https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 6/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate In the EXCEL trial of patients with left main coronary artery disease, new onset AF was an independent predictor of all-cause death at three years with a rate of 11.4 percent compared with 4.3 percent in patients without AF [43]. (See 'Incidence and time course' above.) In another study of 1832 patients who underwent CABG, patients with postoperative AF had a higher long-term mortality (2.99 versus 1.34 per 100 person-years; adjusted hazard ratio 2.13, 95% CI 1.45-3.15) during a median follow-up of 51 months [42]. Patients with AF were at higher risk of dying from systemic embolism (adjusted hazard ratio 4.33, 95% CI 1.78-10.52), but not from other causes. Postoperative AF is associated with prolongation of the duration of hospitalization, with an increased length of stay between one and six days [7,11,43,50,51,64,65]. New onset AF added approximately six days to the hospital duration in the EXCEL trial of patients with left main coronary artery disease [43]. (See 'Incidence and time course' above.) PREVENTION OF ATRIAL FIBRILLATION AND COMPLICATIONS We recommend therapies to prevent the development of postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery in an attempt to decrease the duration of hospitalization, to possibly decrease the risk of in-hospital stroke and death, and to decrease the need for anticoagulation in some patients. Prevention of atrial fibrillation The use of beta blockers, sotalol, amiodarone, atrial pacing, or antioxidant vitamins lowers the risk of postoperative AF [66]. Beta blockers are the best studied of these therapies and we prefer beta blockers to sotalol or amiodarone based on their ease of use and better safety profile. We do not recommend atrial pacing in most cases. There have been no studies comparing the relative efficacy and safety of the traditional antiarrhythmic drugs to antioxidant vitamins. Beta blockers Beta blocker administration is the most widely used prophylactic strategy based on numerous studies showing benefit, ease of use, and cost considerations [1,6,10,14,64,67-70]. Meta-analyses of randomized trials from 2002 and 2004 found that they reduced the risk of AF compared to placebo or no therapy (odds ratios of 0.35, 95% CI 0.26-0.49 and 0.39, 95% CI 0.28-0.52) [64,71]. However, a larger 2006 meta-analysis of 31 trials including 4452 patients performed separate analyses based on whether non-study beta blocker was allowed to be continued or not [72]. When trials confounded by postoperative non-study beta blocker withdrawal were excluded, the effect of beta blockers, although still significant, was less (OR 0.69, 95% CI 0.54-0.87). In addition, other between-trial differences (heterogeneity), such as https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 7/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate control group event rates which ranged between 5 and 54 percent, lead us to be unsure of the true magnitude of the benefit from beta blockers in patients who have not previously received them. The issue of whether some beta blockers lower the risk of postoperative AF more successfully than others has not been well studied. In a meta-analysis of randomized trials with 601 patients that compared carvedilol to metoprolol (succinate and tartrate), carvedilol reduced the incidence of AF (odds ratio 0.50, 95% CI 0.32-0.80) [73]. The benefit is seen when beta blockers are begun prior to or immediately after surgery. We feel the evidence is not strong enough for us to recommend one beta blocker over another. When possible, we start beta blockers at least 48 hours before surgery, due to concerns about the induction of excessive bradycardia. In addition, some experts are concerned about the increased risk of stroke seen in patients undergoing noncardiac surgery who receive beta blockers soon before surgery. (See "Management of cardiac risk for noncardiac surgery", section on 'Patients who may require preoperative initiation of therapy'.) If a patient is a candidate for initiation of a beta blocker but presents within the 48-hour window, our reviewers have differing approaches. Some will start low dose beta blocker at any time before surgery, while others will wait until after the patient has returned to the intensive care unit and is deemed "stable." The optimal duration of therapy for prevention of postoperative atrial arrhythmias is uncertain, but we often continue the beta blocker until the first postoperative visit. However, many patients who undergo CABG have a clear indication for the long-term use of beta blocker therapy (eg, previous myocardial infarction, left ventricular systolic dysfunction with heart failure, or hypertension). Sotalol Sotalol is a class III antiarrhythmic agent that has beta blocking activity. A 2011 meta-analysis of 15 randomized studies of patients undergoing cardiac surgery found that sotalol lowered the risk of AF compared to placebo (relative risk [RR] 0.55, 95% CI 0.45-0.66) [74]. Compared to beta blocker, sotalol was more effective (14 versus 23 percent; RR=0.64 [CI, 0.50- 0.84]). There was no significant difference in the rates between sotalol and amiodarone. Risks of sotalol include torsade de pointes and bradycardia. (See "Clinical uses of sotalol".) Sotalol is effective when begun 24 to 48 hours before surgery or four hours after surgery [75,76]. Amiodarone Most of our contributors prefer beta blockers to amiodarone for the preoperative prevention of AF. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 8/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Amiodarone lowers the incidence of postoperative AF by about 40 to 50 percent [64,71,77-82]. A 2006 meta-analysis of 18 trials that included nearly 3000 patients found that amiodarone lowered the risk of AF or atrial flutter compared to placebo (odds ratio [OR] 0.48, 95% CI 0.40- 0.57) [72]. However, amiodarone is associated with more adverse cardiac events compared to placebo, including bradycardia requiring temporary pacing (5.7 versus 2 percent), and QT prolongation (1.3 versus 0 percent) [82]. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) Metoprolol was directly compared to amiodarone in an equivalence trial of 316 hemodynamically stable patients who underwent CABG or valve surgery [83]. The rates of the development of AF were similar (23.9 and 24.8 percent, respectively). A number of different preoperative regimens of amiodarone have been evaluated. It has been given orally one to seven days before surgery [78,79], intravenously immediately after surgery [80], or intravenously for 24 hours followed by oral therapy for four days [81]. The efficacy of these different regimens is illustrated by the following observations: One study randomly assigned 124 patients to oral amiodarone or placebo for a minimum of seven days prior to elective cardiac surgery, continuing the drug until discharge [78]. The mean total dose of amiodarone administered was 4.8 grams over 13 days (600 mg/day for seven days followed by 200 mg/day until discharge). The amiodarone group had a significant reduction in the incidence of postoperative atrial fibrillation (25 versus 53 percent) without any increase in fatal or nonfatal postoperative complications. Other oral regimens that have been effective include those that begin five days before surgery or one day before surgery [79]. The efficacy of postoperative intravenous therapy was documented in the ARCH trial in which 300 patients were randomly assigned to 1 gram of intravenous amiodarone per day for two days or placebo; therapy was begun immediately after CABG [80]. Amiodarone significantly reduced the incidence of atrial fibrillation (35 versus 47 percent for placebo), but did not lower the length of hospitalization (7.6 versus 8.2 days). In another report, intravenous amiodarone begun on call to the operating room and continued for 48 hours, followed by oral amiodarone for three days, also significantly reduced postoperative atrial fibrillation (6 versus 26 percent) [84]. Although some have suggested that amiodarone might be more effective than a beta blocker for the prevention of atrial fibrillation after cardiac surgery [85], this was not confirmed in two https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 9/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate meta-analyses [64,71]. Antioxidant vitamins Oxidative stress plays a role in ischemia-reperfusion injury, which occurs in open heart surgery. It is also involved in the pathogenesis of AF. Based on limited supportive evidence, as well as the absence of side effects in the short term or significant cost, we believe it is reasonable to give antioxidant vitamins to lower the rate of postoperative AF. (See "Reperfusion injury of the heart", section on 'Arrhythmias' and "Reperfusion injury of the heart", section on 'Antioxidant therapy' and 'Pathogenesis' above.) A 2011 meta-analysis evaluating five randomized trials comprising 567 patients found that the prophylactic use of the antioxidant vitamins C and E lowered the rate of postoperative AF (odds ratio 0.43, 95% CI 0.21-0.89) [86]. The conclusion of the meta-analysis is limited by the inclusion of small, low-quality studies. Subsequent to the meta-analysis, a small trial randomly assigned 203 patients scheduled to undergo on-pump cardiac surgery to supplementation with n-3 PUFA (1 gram twice daily), vitamin C (1 g/day), and vitamin E (400 international units/day) or placebo [87]. n-3 PUFA was started approximately seven days and the vitamins two days before surgery; treatment was continued until hospital discharge. The primary outcome of the occurrence of electrocardiographically confirmed postoperative AF occurred significantly less often in the antioxidant therapy group (9.7 versus 32 percent; relative risk 0.28, 95% CI 0.14-0.56). Due to the small number of events (postoperative AF), as well as the unusually low relative risk found, we believe this trial provides weak evidence in favor of antioxidant vitamins. In addition, we do not believe that the trial, which combined n-3 PUFA with vitamins, changes our view that n-3 PUFA are of no benefit in this setting. If antioxidant vitamins are given to prevent postoperative AF, we suggest using them with the timing and dosing used in the above trial and adding them to another preventative therapy. Atrial pacing Atrial pacing to prevent postoperative AF has been examined in a number of studies. Most [88-92], but not all [81,93,94], showed benefit. In a 2006 meta-analysis, pacing was associated with a significant reduction in AF (OR 0.60, 95% CI 0.47-0.77) [72]. With regard to the optimal pacing strategy (eg, left compared to right atrium or pacing from one or both atria), studies are not definitive [89-94]. Atrial pacing is not considered an invasive procedure in these patients because placement of temporary pacing wires is routinely done at the time of surgery. Reducing risk of pericardial effusion There are several methods to reduce the incidence of pericarditis and residual pericardial effusion. One approach we use is placement of a large drain (eg, Blake drain), left in postoperatively until they no longer drain. Colchicine can be added in this setting to prevent pericarditis when a drain is in place. However, outside of this particular https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 10/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate setting, the evidence supporting colchicine's efficacy in reducing postoperative AF is mixed. (See 'Ineffective or possibly effective therapies' below.) Posterior left pericardiotomy can reduce the incidence of pericardial effusions, which are common triggers for postoperative AF. In patients without a known diagnosis of AF, posterior left pericardiotomy was shown to reduce the incidence of postoperative AF after surgery on the coronary arteries, aortic valve, and/or ascending aorta, without additional risk of postoperative complications [95]. Patients undergoing mitral or tricuspid valve surgeries were not studied. In an adaptive randomized trial of 420 patients, patients assigned posterior left pericardiotomy had a lower incidence of postoperative AF compared with controls (17 versus 32 percent). Patients assigned posterior left pericardiotomy also had a lower incidence of pericardial effusion (12 versus 21 percent). Postoperative major events were similar in the intervention and control groups (3 versus 2 percent), and no pericardiotomy-related complications occurred. Factors that limited generalizability of this study were that it was done in a single center, and there were relatively high rates of postoperative AF, even in a study population at lower risk for AF. We await further studies before recommending this approach for all patients undergoing cardiac surgery. Ineffective or possibly effective therapies We do not recommend any of the following preventative strategies to prevent the development of atrial arrhythmias: Digoxin Digoxin, given preoperatively or postoperatively, does not appear to prevent AF [14,68,69,96]. Antiarrhythmic drugs Data about the prophylactic use of class I antiarrhythmic drugs to prevent postoperative AF are limited. Procainamide appears to reduce the number of episodes and duration of AF compared to placebo, but not the incidence of AF [97,98]. Calcium channel blockers Calcium channel blockers have uncertain utility in preventing AF after cardiac surgery [68,99-102]. Intravenous magnesium Based on the fact that hypomagnesia is a risk factor for AF (see 'Risk factors' above), magnesium supplementation has been evaluated as a possible therapy to reduce postoperative atrial arrhythmias [103-108]. In a 2006 meta-analysis of 22 trials including 2896 patients, supraventricular arrhythmias occurred significantly less often in patients treated with magnesium compared to controls (odds ratio 0.57, 95% CI 0.42-0.77) [72]. However, there was no effect on hospital stay, perioperative myocardial infarction, or mortality. There was also significant heterogeneity in the size of the effect among trials, and the possibility of publication bias was suggested. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 11/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate In a 2012 meta-analysis of seven randomized trials (n = 1028), which were felt to have no 2 heterogeneity (I = 0), intravenous magnesium reduced the incidence of postoperative AF (relative risk 0.64, 95% CI 0.50-0.83) [109]. Angiotensin inhibition Although angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have not previously been considered a specific therapy in patients with AF, a number of observations suggest benefit in nonsurgical settings. (See "ACE inhibitors, angiotensin receptor blockers, and atrial fibrillation".) A significant reduction in the incidence of postoperative AF (20 versus 34 percent) with ACE inhibitors was seen in an observational study of 4657 patients undergoing CABG [6]. However, in a study of 445 patients randomly assigned to placebo, ramipril, or spironolactone one week to four days prior to cardiac surgery, there was no significant difference in the rate of AF after surgery [110]. In a prospective study of 4657 patients undergoing CABG, postoperative AF occurred significantly less often in patients who were treated preoperatively and postoperatively with ACE inhibitors compared to those who were not (20 versus 34 percent, odds ratio 0.62) [6]. In addition, patients who had previously been taking ACE inhibitors and were withdrawn from therapy had a significant increase in risk (46 percent, odds ratio 1.69). The utility of these agents in preventing AF after cardiac surgery remains controversial, however, as other studies have not found a significant benefit [111-113]. A retrospective analysis of 8889 patients undergoing CABG described an increase in major adverse events, including postoperative renal dysfunction as well as AF, in patients receiving preoperative ACE inhibitors [114]. Given the inconsistency in the results among these studies, we do not recommend preoperative ACE inhibitors specifically for prevention of AF in patients undergoing CABG. Statins Some, but not all, studies have shown that statins lower the rate of postoperative AF [115,116]. A 2015 meta-analysis of 17 randomized trials that compared statin therapy with either placebo or no therapy prior to cardiac surgery (predominantly coronary artery bypass graft surgery) found that such treatment reduced the incidence of postoperative AF (odds ratio 0.54, 95% CI 0.43-0.67), but failed to influence short-term mortality or postoperative stroke [117,118]. However, the meta-analysis pointed out significant limitations of the evidence. The largest randomized trial of preoperative statin therapy was published after the meta- analysis. In the STICS trial, 1922 patients in sinus rhythm scheduled for elective cardiac surgery (87 percent CABG) were randomly assigned to receive perioperative rosuvastatin https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 12/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate (20 mg daily) or placebo up to eight days before surgery [116]. Any previously prescribed statin was stopped. The rate of the primary outcome of postoperative AF within five days of surgery was similar in both groups (21.1 and 20.5 percent, respectively; odds ratio 1.04, 95% CI 0.84-1.30). Of note, there was no difference in the rate of myocardial injury within 120 hours after surgery. In addition, rosuvastatin was associated with a significant absolute excess in the rate of postoperative acute kidney injury (24.7 versus 19.3 percent; p = 0.005). Based upon established benefits of statin therapy in patients with coronary heart disease, all patients should be on long-term statin. However, for patients who have not started statin therapy prior to CABG, we suggest waiting until after surgery, as there is no clear evidence of benefit from preoperative initiation and possible harm. (See "Coronary artery bypass surgery: Perioperative medical management", section on 'Statins'.) N-acetylcysteine N-acetylcysteine (NAC) has the potential to protect against the development of perioperative AF due to its antioxidant and anti-inflammatory properties. (See 'Pathogenesis' above.) This hypothesis was tested in a trial of 115 patients undergoing either CABG or valve surgery who were randomly assigned to either NAC or placebo given one hour before and continued for 48 hours after surgery [119]. The primary end point of an AF episode lasting longer than five minutes during hospitalization was seen in 15 patients and was significantly less common in those who received NAC (5.2 versus 21.2 percent). In a small study designed to evaluate the potential benefit of anti-inflammatory therapy (with NAC or carvedilol), 311 patients undergoing cardiac surgery who had no history of AF were randomly assigned to metoprolol, carvedilol, or carvedilol plus NAC [120]. The incidence of postoperative AF was significantly lower in the carvedilol plus NAC group compared to either of the other two interventions (35.9, 24.0, and 8.7 percent, respectively). Colchicine Colchicine reduces the incidence of the postpericardiotomy syndrome. (See "Post-cardiac injury syndromes", section on 'Prevention'.) The issue of whether colchicine can reduce the incidence of postoperative AF was addressed in a post hoc substudy. In COPPS, 360 patients undergoing cardiac surgery were randomly assigned to either colchicine 1.0 mg given twice daily on day one followed by 0.5 mg twice daily for one month (the dose was halved in patients <70 kg) or placebo [121]. The first dose was given on postoperative day three. The COPPS Prevention of Atrial Fibrillation (POAF) substudy evaluated outcomes in the 336 patients in sinus rhythm on day three. Colchicine significantly reduced the incidence of postoperative AF (12 versus 22 https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 13/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate percent; relative risk reduction 45.5 percent, 95% CI 34.0-94.0 percent) at 30 days. In addition, patients taking colchicine had a significantly shorter in-hospital stay (9.4 versus 10.3 days). There was a trend toward a higher rate of side effects (9.5 versus 4.8 percent) and drug withdrawal (11.8 versus 6.6 percent) with colchicine, but no severe side effects were recorded. In the COPPS-2 trial, 360 patients scheduled for cardiac surgery were randomly assigned to oral colchicine or placebo before surgery [122]. The drug was continued for one month after surgery. At three months, there was no significant difference between the two groups in the secondary end point of postoperative AF (34 versus 41 percent, respectively). (See "Post-cardiac injury syndromes", section on 'Prevention'.) We believe there is insufficient evidence to recommend the routine use of colchicine, in part out of a concern that it may negatively impact wound healing and that it leads to gastrointestinal side effects. The 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society AF guideline states that colchicine may be considered [123,124]. This was not changed in the 2019 focused update [125]. Naproxen The potential benefit from naproxen was evaluated in the NAFARM trial, which randomly assigned 161 patients to either naproxen or placebo [126]. There was no significant difference in the rate of postoperative AF (7 versus 15 percent, respectively). The study was stopped early because of an increase in renal failure in the naproxen group. Glucocorticoid Based upon the hypothesis that perioperative inflammation may contribute to the development of AF, glucocorticoids have been suggested as prophylactic therapy. (See "Glucocorticoid effects on the immune system".) Two meta-analyses of small trials in which glucocorticoid treatment was compared to placebo or no treatment in adult cardiac surgery found 26 and 40 percent reductions in the incidence of AF, irrespective of the dose given [127,128]. However, the large, randomized SIRS trial, published after the meta-analyses, found no difference in the rate of new AF [129]. Due to their potential adverse effects on glucose metabolism, wound healing, infection, and the absence of a lowering of the risk of death, we do not recommend the routine use of glucocorticoid therapy to prevent AF. The potential role for glucocorticoid therapy for other outcomes is discussed separately. (See "Coronary artery bypass surgery: Perioperative medical management", section on 'Glucocorticoid therapy'.) https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 14/43 7/5/23, 9:03 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Prevention of complications of atrial fibrillation While beta blockers, sotalol, amiodarone, and pacing decrease the risk of postoperative AF, the evidence is less robust that the risk of complications such as stroke, death, or length of stay can be prevented. It may be difficult to demonstrate a lowering of the risk of in-hospital stroke with these therapies, as AF is only one risk factor for stroke and as the incidence of stroke is low. (See 'Adverse outcomes following atrial fibrillation' above.) The best available evidence of the impact of these interventions on the complications of AF comes from a 2006 meta-analysis of heterogenous trials, which noted the following [72]: In 29 trials that evaluated length of stay, only amiodarone and pacing shortened the average length of stay (-0.60 days, 95% CI -0.92 to -0.29 and -1.3 days 95% CI -2.55 to -0.08, respectively). In 25 trials that reported on the incidence of postoperative stroke, the risk of stroke was decreased from 1.9 to 1.1 percent with treatment (odds ratio 0.63, 95% CI 0.41-0.98). Amiodarone was the only single intervention that significantly lowered the risk of stroke compared to placebo. Our approach to prevention We recommend preventative therapy to reduce the incidence of postoperative AF, especially in patients at high risk of its development. While the evidence is not robust, prevention of AF may lead to a lowering of the risk of in-hospital stroke and a shortened length of stay. In addition, successful prevention of AF will prevent the need for anticoagulation in some patients. Beta blockers, sotalol, amiodarone, and atrial pacing are significantly more effective than placebo in lowering the rate of postoperative AF [64,71,72]. There is some evidence to support the use of antioxidant vitamins for this purpose. We prefer beta blockers to amiodarone or sotalol due to lower cost and lower risk of potential side effects and to pacing because of its relative complexity and cost. Amiodarone or sotalol is a reasonable alternative in patients who cannot tolerate beta blockade. If possible, we prefer to start beta blockers prior to CABG. We suggest metoprolol 25 mg twice daily; the dose can be