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".)
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 .
●Low-intensity physical activity in the year prior to surgery .
●Being a White person .
●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.)
●Higher preoperative plasma concentration of brain natriuretic peptide (BNP) . (See "Natriuretic peptide measurement in heart failure".)
●Severe right coronary artery stenosis .
●Preoperative increase in P wave duration on surface (>116 msec)  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.
●Long bypass and aortic cross-clamp times.
●Hyperadrenergic state (eg, use of postoperative inotropic medications).
●Pulmonary complications, hypoxemia.
●Hypokalemia and hypomagnesemia [26-29].
●Pericardial effusion and pericarditis.
●Oxidative stress .
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 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 , studies. (See "Off-pump and minimally invasive direct coronary artery bypass graft surgery: Clinical use".)
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 . 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.)
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 .
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  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 .
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) . 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) .
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 . (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) . 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) .
●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 . 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).
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 . (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 . 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 . (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 . 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 . 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 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) .
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 with indications for long-term 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) . 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".)
Amiodarone — Most of our contributors prefer beta blockers to amiodarone for the preoperative prevention of AF.
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) .
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) . (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 . 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 , or intravenously for 24 hours followed by oral therapy for four days . 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 . 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 .
●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 . 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) .
Although some have suggested that amiodarone might be more effective than a beta blocker for the prevention of atrial fibrillation after cardiac surgery , this was not confirmed in two 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) . 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 . 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) . 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 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 . 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:
●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) . 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.
In a 2012 meta-analysis of seven randomized trials (n = 1028), which were felt to have no heterogeneity (I2 = 0), intravenous magnesium reduced the incidence of postoperative AF (relative risk 0.64, 95% CI 0.50-0.83) .
●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 . 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 .
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) . 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 . 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 (20 mg daily) or placebo up to eight days before surgery . 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 . 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 . 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 . 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 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 . 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 .
●Naproxen – The potential benefit from naproxen was evaluated in the NAFARM trial, which randomly assigned 161 patients to either naproxen or placebo . 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 . 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'.)
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 :
●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 titrated postoperative based on the heart rate and blood pressure. We continue this therapy until the first postoperative visit, unless there is a contraindication.
The evidence to support the use of antioxidant vitamins is less robust than that for traditional antiarrhythmic drugs. While awaiting larger randomized trials, we believe it is reasonable to use antioxidant therapy as given in the small randomized trial .
MANAGEMENT — While prevention with beta blockers, amiodarone, sotalol, or pacing lowers the risk of postoperative atrial fibrillation (AF), many patients still develop AF (see 'Prevention of atrial fibrillation' above). We are uncertain as to the optimal management of these patients, in part because it is not known whether postoperative AF represents the same arrhythmia as AF occurring without cardiac surgery or if it possesses a similar natural history in terms of portending adverse events.
We think the initial management should include correction of predisposing factors such as hypoxemia, electrolyte abnormalities, and hemodynamic instability as well as pain management and withdrawal of stimulating factors such as inotropic agents. Subsequent management relates to the issues of rate control versus rhythm control cardioversion and anticoagulation .
Options for management of AF include rate or rhythm control strategies. For patients with atrial flutter, we cardiovert to sinus rhythm prior to discharge in most cases, as this rhythm is more difficult than AF to control medically.
Rate control — Given the transient nature of the arrhythmia (see 'Incidence and time course' above), initial control of the ventricular response rate is an effective and relatively safe strategy in many patients who develop postoperative AF [44,131].
Rate control is most commonly achieved with beta blockers. The benefit is partly due to blockade of the augmented postoperative sympathetic state and to prevention of beta blocker withdrawal in patients on beta blockers preoperatively. Intravenous esmolol, a beta blocker with a short half-life, can be given for acute rate control if there is a concern for bradyarrhythmias, hypotension, or bronchospasm. Slowing of the ventricular rate in many AF patients receiving inotropic agents postoperatively can be achieved by lowering the dose or discontinuation of these agents.
The optimal rate goal for patients with AF after cardiac surgery has not been determined. As these patients vary widely in many clinical features (co-morbidities, need for rapid ventricular rate, etc), we suggest that the optimal ventricular rate be determined on a case by case basis. In many patients, a ventricular rate of less than 110 beats per minute will prevent symptoms such as palpitations and allow for optimal cardiac performance. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy", section on 'Evaluation and goal ventricular rate'.).
Calcium channel blockers and digoxin are other atrioventricular (AV) nodal blockers that can control the ventricular rate in AF, but they are not more effective than beta blockers. In patients in whom alternate agents have not been successful in controlling the rate in atrial fibrillation, intravenous amiodarone can be used to slow the ventricular response. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".)
Rhythm control — Restoration of sinus rhythm from well-tolerated postoperative AF is usually not necessary but occasionally can be beneficial. (See 'Incidence and time course' above.)
Restoration of sinus rhythm is indicated in symptomatic patients or in those when rate control is difficult to achieve. An attempt at the restoration of sinus rhythm can be beneficial in patients with a low ejection fraction. In addition, cardioversion in asymptomatic patients may be reasonable when well-tolerated AF occurs near the time of anticipated hospital discharge or when it does not spontaneously terminate within 24 hours, so that oral anticoagulation can be avoided; this is particularly true in patients at high risk of bleeding. We believe that an attempt at cardioversion with either electrical or pharmacologic therapy is reasonable. The choice between the two should be made on local practice and patient conditions.
Electrical therapy of AF involves direct current external transthoracic cardioversion and it is effective in approximately 95 percent of cases  (see "Cardioversion for specific arrhythmias"). For patients who are refractory to transthoracic cardioversion or when reversion is desirable but the patient's respiratory status makes anesthesia for electrical conversion potentially difficult, pharmacologic therapy with intravenous sotalol or amiodarone is reasonable. (See 'Sotalol' above and 'Amiodarone' above.)
Amiodarone dosing regimens are available in the relevant drug monograph.
Rate versus rhythm control — For patients who do not spontaneously revert to sinus rhythm within a few hours, rate control and rhythm control (with or without electrical cardioversion) appear to be comparable strategies [45,46,142]. The choice between the two strategies should take into account patient and physician preferences. Advantages of a rate control strategy include the absence of side effects from drug therapy; disadvantages include a slower resolution of AF, thereby leading to a potentially greater need for anticoagulation at discharge. In many patients, we chose a rhythm control strategy.
In a study of patients with no history of AF undergoing cardiac surgery, 523 individuals were randomly assigned to either rate or rhythm control . In the rate control group, the heart rate goal was less than 100 beats per minute and in the rhythm control group, amiodarone was given with or without a rate slowing drug. If AF persisted for 24 to 48 hours, electrical cardioversion was recommended. The primary end point was the total number of days of hospitalization within 60 days after randomization. There was no difference between the two groups in the primary outcome (median, 5.1 and 5 days, respectively; p = 0.76). This study had limitations, such as including heterogenous patients and lacking the power to assess effect on death or serious adverse events.
Patients on long-term anticoagulant — For AF patients who are taking warfarin or direct oral anticoagulants, we suggest stopping this therapy at least three days before surgery. We restart oral anticoagulant therapy three to five days after surgery. The role of bridging heparin therapy for patients at high risk of an embolic complication while off oral anticoagulant, such as those with AF and a prior embolic event, is discussed elsewhere. (See "Perioperative management of patients receiving anticoagulants".)
Patients not taking anticoagulant prior to cardiac surgery — Patients with AF or atrial flutter, regardless of the setting, are at risk for thromboembolic events; the magnitude of that risk varies based upon a number of factors. Thromboembolic risk is primarily limited to AF or atrial flutter of more than 48 hours duration and is greater in patients with certain high risk features (eg, rheumatic mitral valve disease, previous thromboembolism, hypertension, or heart failure) (table 2) . The general recommendations for anticoagulation in patients with AF are discussed in detail elsewhere. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation" and "Embolic risk and the role of anticoagulation in atrial flutter".)
Patients who develop AF after cardiac surgery are at risk of thromboembolic events, including in-hospital stroke. However, in the individual post-surgical patient with an embolic event, the cause may be unclear, as underlying comorbidities are often responsible for such strokes, rather than the arrhythmia itself [56,64,143]. (See 'Incidence and time course' above.)
Based on evidence that oral anticoagulant therapy prevents episodes of systemic embolization in the broad population of patients with atrial fibrillation, we believe that such therapy will lead to fewer embolic events in patients with postoperative AF. However, a reduction of events with anticoagulant therapy in this population has never been well studied. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Summary and recommendations'.)
As factors other than AF contribute to in-hospital stroke rates, it is not clear that aggressive early anticoagulation (eg, intravenous heparin as a bridge to warfarin) will reduce the incidence of stroke. In addition, the bleeding risk associated with anticoagulation in the immediate postoperative period (within the first 48 hours in most patients) makes the overall impact of this approach less certain. The potential complications associated with anticoagulation were illustrated in several observational series of patients who were treated with intravenous heparin or oral anticoagulants for a variety of indications [144-146]. When closely monitored, complication rates appear to be low [144,145]. However, one report found a significant increase in large pericardial effusions and tamponade in patients treated with warfarin, particularly when the International normalized ratio (INR) was above the therapeutic target . These large effusions all occurred one week or more after surgery. Thus, when anticoagulation is initiated, the patient must be monitored carefully. (See "Perioperative management of patients receiving anticoagulants".)
Similarly, the optimal duration of anticoagulation after hospital discharge is unknown. Among patients with new-onset AF after cardiac surgery, many will revert to and maintain sinus rhythm [1,45-47].
Due to the inability to reverse their therapeutic effect, we do not start newer oral anticoagulants in the early postoperative period. There are limited data at present, but this is an evolving strategy that may gain support as our understanding evolves . (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".)
Left atrial appendage closure — Evidence is emerging that the left atrial appendage may play a major role in the development of stroke, and surgical closure may reduce this risk. Patients who have AF who are undergoing cardiac surgery for other indications may benefit from closure. Specific recommendations are provided separately. (See "Atrial fibrillation: Left atrial appendage occlusion".)
Our approach to postoperative anticoagulation — Among patients who develop AF following cardiac surgery, we suggest the following approach to anticoagulation:
●For patients with multiple episodes of AF or one episode that lasts more than 24 to 48 hours, we recommend the initiation of oral anticoagulant therapy, but only if bleeding risks are considered acceptable. As the role of direct thrombin and factor Xa inhibitors has not been established for patients with postoperative AF, we suggest that warfarin be chosen for most patients (International normalized ratio 2 to 3).
●We suggest continuation of anticoagulation for at least four weeks after return to sinus rhythm, particularly if the patient has risk factors for thromboembolism. Longer duration of anticoagulation is recommended by some of our experts in patients with high CHA2DS2-VASc scores (table 3), at low risk for bleeding based on the HAS-BLED score (table 4), or at high risk of AF recurrence.
●Long-term anticoagulation should be considered for patients who remain in AF or who have paroxysmal AF at four weeks. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Summary and recommendations'.)
●We suggest maintaining oral anticoagulation in patients in which a concomitant Cox-Maze procedure has been performed for at least three months, regardless of no postoperative atrial arrhythmias. (See "Atrial fibrillation: Surgical ablation", section on 'Maze procedure'.) After three months with no AF recurrence, anticoagulation may be interrupted, considering the patient risk profile for stroke by the CHA2DS2-VASc score (table 3) .
In most cases, we do not use intravenous heparin as a bridge to full oral anticoagulation, as the risk of postoperative bleeding outweighs the small benefit from stroke prevention. For patients with prior systemic or pulmonary embolization or those with a mechanical valve, bridging anticoagulation with heparin may be reasonable.
Both intravenous and oral anticoagulation should be monitored closely, as bleeding complications, including pericardial effusion and tamponade increase with excessive anticoagulation.
RECOMMENDATIONS OF OTHERS — Guidelines from the American College of Cardiology Foundation/American Heart Association and the European Society of Cardiology [130,148,149]. Our recommendations are generally consistent with recommendations from these groups.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Coronary artery bypass graft surgery".)
SUMMARY AND RECOMMENDATIONS
●Presentation – Atrial fibrillation (AF) and atrial flutter occur frequently after cardiac surgery. Most episodes occur by the third postoperative day. (See 'Incidence and time course' above.)
●Adverse outcomes – Potential adverse outcomes of these atrial arrhythmias include a longer length of stay, stroke, or death. (See 'Adverse outcomes following atrial fibrillation' above.)
●Preventive strategies – Beta blockers, sotalol, amiodarone, atrial pacing, reducing the risk of pericardial effusion, and antioxidant vitamins lower the risk of the development of AF and atrial flutter after cardiac surgery and may reduce the length of stay and lower the risk of in-hospital stroke. (See 'Prevention of atrial fibrillation and complications' above.)
•For patients undergoing cardiac surgery, we recommend treatment with beta blockers (Grade 1B). Beta blocker therapy should be started prior to surgery and continued at least until the first postoperative visit unless contraindicated. We prefer oral metoprolol 25 mg twice daily.
For patients who cannot take beta blockers, either amiodarone or sotalol may be used, with the decision based on patient characteristics and physician familiarity. (See 'Our approach to prevention' above.)
•We suggest antioxidant therapy in addition to beta blocker therapy (Grade 2C). We start this therapy two days prior to surgery and continue until discharge. We prefer the regimen of vitamin C (1 gram) and vitamin E (400 international units), each given daily. (See 'Our approach to prevention' above.)
●Management of postoperative atrial fibrillation
•Ventricular rate control – For hemodynamically stable patients who develop postoperative AF, the optimal ventricular rate range should be determined for each patient. In many patients, this rate will be less than 110 beats per minute.
•Cardioversion – For patients who develop well-tolerated postoperative AF and whose rate is well controlled, we suggest not performing cardioversion within the first 24 hours of its development (Grade 2B).
Cardioversion may be required within this time frame for those whose AF is poorly tolerated or whose rate is not well controlled. (See 'Rhythm control' above.)
Cardioversion in asymptomatic patients may be reasonable when well-tolerated AF is present near the time of anticipated hospital discharge, or when it does not spontaneously terminate within 24 to 48 hours, so that oral anticoagulation can be avoided.
•Anticoagulation – For patients with multiple episodes of AF or one episode that lasts more than 24 to 48 hours, and if the perioperative bleeding risks are considered reasonable, we recommend oral anticoagulation (Grade 1B). (See 'Our approach to postoperative anticoagulation' above.)
For patients in whom anticoagulation is started and irrespective of the rhythm status at the time of discharge from the hospital, we suggest continuation of anticoagulation for at least four weeks, rather than stopping at the time of discharge (Grade 2C).
ACKNOWLEDGMENT — The UpToDate editorial staff would like to thank Drs. John M. Stulak, Manuel Castellá, and Arie P. Kappetein for their contributions to previous versions of this topic review.
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