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|Year : 2010
: 13 | Issue : 3 | Page
|Atrial fibrillation after cardiac surgery
Suresh G Nair
Department of Anaesthesia and Critical Care, Amrita Institute of Medical Sciences, Cochin-682 041, Kerala, India
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|Date of Submission||09-Jun-2010|
|Date of Acceptance||22-Jul-2010|
|Date of Web Publication||6-Sep-2010|
| Abstract|| |
Once considered as nothing more than a nuisance after cardiac surgery, the importance of postoperative atrial fibrillation (POAF) has been realized in the last decade, primarily because of the morbidity associated with the condition. Numerous causative factors have been described without any single factor being singled out as the cause of this complication. POAF has been associated with stroke, renal failure and congestive heart failure, although it is difficult to state whether POAF is directly responsible for these complications. Guidelines have been formulated for prevention of POAF. However, very few cardiothoracic centers follow any form of protocol to prevent POAF. Routine use of prophylaxis would subject all patients to the side effects of anti-arrhythmic drugs, while only a minority of the patients do actually develop this problem postoperatively. Withdrawal of beta blockers in the postoperative period has been implicated as one of the major causes of POAF. Amiodarone, calcium channel blockers and a variety of other pharmacological agents have been used for the prevention of POAF. Atrial pacing is a non-pharmacological measure which has gained popularity in the prevention of POAF. There is considerable controversy regarding whether rate control is superior to rhythm control in the treatment of established atrial fibrillation (AF). Amiodarone plays a central role in both rate control and rhythm control in postoperative AF. Newer drugs like dronedarone and ranazoline are likely to come into the market in the coming years.
Keywords: Amiodarone, atrial fibrillation, atrial pacing, beta blockers, cardiac surgery
|How to cite this article:|
Nair SG. Atrial fibrillation after cardiac surgery. Ann Card Anaesth 2010;13:196-205
Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery. The potential for POAF to prolong postoperative hospital length of stay (LOS-hospital) and induce neurological and renal complications has renewed interest in the management of this condition. The prevalence of POAF varies from 30% after isolated coronary artery bypass surgery (CABG) to 40% after valve surgery and 50% after combined CABG and valve surgery.  POAF normally develops between days 2 and 4 after surgery, with the maximum incidence on postoperative day 2. Ninety percent of the patients who develop POAF do so by day 4 after surgery; and 94%, by the end of day 6.  A recent single-center evaluation of 16,169 patients undergoing isolated coronary artery bypass surgery, showed that new-onset atrial fibrillation (AF) independently predicted mortality (hazard ratio, 1.2) during a mean follow-up period of 6 years.  Patients who were on anticoagulants for AF had a lower mortality rate.
| Electrophysiological Basis of POAF|| |
Although our understanding of the pathophysiological mechanisms responsible for atrial fibrillation (AF) in the general population is improving, it is still not clear whether the same mechanisms are responsible for the onset of AF in the postoperative period. Non-uniform or heterogeneous atrial refractoriness provides the substrate for development of POAF.  This non-uniform refractoriness of the atrial tissue facilitates multiple wavelet re-entry and incessant stimulation of various regions of the atria through multiple re-entry pathways, resulting in sustained AF. "After depolarizations" are oscillations in membrane potential that occur before (early) or after (delayed) after repolarization.  When the changes in membrane potential reach depolarization threshold, an action potential or depolarization can be triggered. Such fluctuation in membrane potential can trigger latent atrial pacemakers and promote an AF. Ectopic focal depolarization originating in the pulmonary veins and the inferior vena cava is increasingly being recognized as a source of persistent AF.  Redistribution of interstitial fluid into the vascular compartment can cause atrial stretch and predispose to POAF. As these changes occur usually around the second postoperative day, it could also explain the high incidence of POAF during this time. Inadequate atrial protection during aortic cross-clamping due to various causes can lead to POAF. A significant correlation between the systemic inflammatory response syndrome initiated by cardiopulmonary bypass (CPB) and the incidence of POAF is well established. Kaireviciute and colleagues demonstrated that elevated levels of inflammatory mediators from samples obtained from within intracardiac chambers correlated well with POAF.  Excessive sympathetic nervous system activity or heightened parasympathetic nervous system activity can lead to POAF.  The clinical implications of these findings are that measures aimed at suppressing sympathetic activity alone may not be sufficient to prevent POAF. Other probable causes include inter-individual susceptibility and physical alterations of cardiac structure resulting from incisions on the atria.
Risk factors and predictors of POAF
Identifying patients at risk of POAF would be useful in initiating prophylactic measures. Risk variables associated with POAF include valvular heart disease, right coronary artery stenosis, preoperative digoxin use, male gender, history of rheumatic heart disease, left ventricular hypertrophy, chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), type of surgery, duration of surgery and prolonged aortic cross-clamp time. , The early return of atrial activity after cardioplegia while still on aortic cross-clamp may reflect an imbalance between oxygen delivery and oxygen supply in the atrial tissue and may be a cause of POAF. Postoperative withdrawal of beta blockers (BBs) and / or angiotensin-converting enzyme inhibitors is also a significant predictor of POAF.  Ramakrishna and colleagues have shown that in the Indian scenario, patients with mild renal dysfunction undergoing CABG surgery have a higher incidence of POAF and prolonged duration of ICU stay.  POAF has also been shown to lead to greater decline in cognitive dysfunction, which persisted at 6 weeks after surgery. , Bi-caval venous cannulation (versus single atrial cannula), right superior pulmonary vein cannulation (for left ventricular decompression) and cardioplegia can contribute to POAF. Pericardial effusions can be another cause of POAF. The exact mechanism involved in the initiation of POAF by pericardial effusions is not known, although one can assume that a certain amount of fluid or hematoma in the pericardial cavity may present a stimulus to the atria, whose function can be affected by external compression. A common underlying factor associated with POAF induced by mechanical, metabolic or pharmacologic stimuli is the redox changes in atrial tissue associated with tachyarrhythmias.  A close association has been found between the atrial tissue levels of peroxynitrite, a highly reactive nitrogen species, and POAF. Thus, oxidative stress may be an important contributor to POAF.
The "P" wave, signal-averaged (SA) electrocardiogram (ECG) is an important and accurate predictor of POAF. An SA-ECG "P" wave duration of more than 140 ms predicted POAF with a sensitivity of 77%, specificity of 55%, a positive predictive value of 37% and a negative predictive value of 87%.  Shore-Lesserson and colleagues using transesophageal echocardiography showed that the probability of developing POAF for the combination of age (>75 years), left atrial (LA) appendage area (>4.0 cm 2 ) and post-CPB left superior pulmonary vein systolic/ diastolic velocity ratio (<0.5) was 0.83. 
Karthikeyan and colleagues in a systematic review and meta-analysis showed statistically significant correlation between elevated preoperative BNP/ NT-BNP (N-terminal pro-B-type natriuretic peptide) levels and adverse cardiovascular outcome, including cardiac death, non-fatal myocardial infarction and AF, with an odds ratio of 19.3.  These authors concluded that BNP / NT-BNP is a powerful indicator of adverse cardiovascular events, including POAF, within the first 30 days after non-cardiac surgery.
There is considerable controversy surrounding the beneficial effects of warm cardioplegia versus cold cardioplegia, normothermic cardiopulmonary bypass (CPB) versus hypothermic CPB and "off-pump" CABG versus "on-pump" CABG on the incidence of POAF.
A recent study also showed that perioperative use of milrinone was associated with a two-to-four fold increase in the incidence of POAF (58% versus 26.1%, P= ≤0.0001).  An elevated cyclic-AMP level induced by milrinone may be the mechanism leading to the increased incidence of POAF.
Outcome after POAF
Patients who develop POAF often experience other postoperative complications. Associations have been documented between AF and ventricular arrhythmias, perioperative myocardial infarction, congestive heart failure, need for permanent pacemaker implantation, renal insufficiency, infection, pneumonia, prolonged mechanical ventilation, increased need for tracheostomy, need for intra-aortic balloon pump, increased postoperative bleeding and cardiac tamponade. The incidence of stroke in association with POAF is threefold higher.  However, it is important to remember that postoperative AF is not necessarily the cause of these complications. Thus, treatment or prevention of POAF need not necessarily result in reduction of these complications.
Prevention of postoperative atrial fibrillation
A number of pharmacological and non-pharmacological methods are available for prevention of POAF. However, the majority of patients undergoing CABG do not develop POAF. Since most of the anti-arrhythmic drugs used for prevention of AF have their own drawbacks and side effects, by institution of prophylactic measures for all patients, we are subjecting the entire population of patients undergoing CABG to the side effects of these drugs. Hence prophylactic measures should be instituted only in patients at higher risk of developing this complication rather than apply these measures as a routine for all patients undergoing cardiac surgery.
Although numerous studies have shown the beneficial effects of beta blockers (BBs) in preventing POAF, there are a number of limitations to these studies. POAF has been evaluated in various studies using methods ranging from continuous Holter monitoring to once-a-day ECG recordings. Thus, the actual incidence of POAF may be grossly underestimated. Extrapolation of the findings from many of these studies into actual clinical practice may be difficult, because many studies have excluded patients with left ventricular (LV) dysfunction, COPD, DM and renal failure. Moreover, many of the patients included in these studies have been on preoperative BBs; and once randomized into the placebo group, the BBs were withdrawn in the postoperative period. BB withdrawal is well known to increase the incidence of POAF.
Two meta-analyses looked at various interventions to prevent POAF. , One meta-analysis looked at 54 studies where BBs, sotalol, amiodarone and atrial pacing were used for prevention of POAF.  All drugs were effective in reducing the incidence of POAF. No study showed any drawbacks associated with the use of BBs. Pacing, including bi-atrial pacing, was also effective in reducing POAF. A second meta-analysis of 94 randomized controlled trials (RCTs) evaluated 5 commonly used interventions, viz., BBs, sotalol, amiodarone, magnesium and pacing, for prevention of POAF.  All drugs were effective in preventing POAF. BBs were effective in reducing the incidence of POAF (OR, 0.36); but after removal of trials in which non-study BBs that were withdrawn were excluded from the analysis, the beneficial effects of BBs were modest (0.69). This trial was also notable for identifying the confounding effect of BB on the use of magnesium as prophylaxis for POAF. Although magnesium showed a significant reduction in the incidence of POAF (OR, 0.57), there was considerable heterogeneity between trials. The largest effect of magnesium was seen in two trials which did not include BBs; and the least effect, in trials that allowed continued use of BBs in both the control and the treatment groups. Only amiodarone and pacing effectively reduced the LOS-hospital (− 0.60 days for amiodarone and − 1.5 days for pacing). Amiodarone was the only intervention that effectively reduced the incidence of stroke (OR, 0.54).
The BLOS (beta-Blocker Length of Stay) study which looked at the effect of prophylactic BBs on the duration of hospital stay, could not demonstrate any beneficial effects of BBs (152 ± 61 hours for placebo versus 155 ± 90 hours for metoprolol group, P= 0.79) on the LOS-hospital or on cost effectiveness. 
A recent single-center, double-blind, randomized control trial in patients undergoing valvular heart surgery showed that intravenous amiodarone administered for 48 hours after surgery resulted in an increased incidence of POAF.  Although there was a statistically significant reduction in the heart rate and incidence of POAF in the first 3 days after surgery in the amiodarone group, this advantage was lost once the drug was stopped. The incidence of POAF showed a reversal from the fourth postoperative day. This change in trend was associated with 50% less patients taking BBs on that day and increased use of temporary pacemakers.
Current guidelines from the American College of Cardiology (ACC), American Heart Association (AHA) and the European Society of Cardiology (ESC) give a Class 1 (level of evidence, A) indication for BBs to prevent POAF.  The 2005 guideline of the American College of Chest Physicians (ACCP) also recommends the use of BBs for the same purpose.  A local survey conducted across 37 cardiothoracic units in UK showed that only 6 units had guidelines for prophylaxis against POAF.  Five of the 6 units used BBs as their chemo-prophylactic agent against POAF. The authors concluded that although international guidelines for prevention of POAF were established, these were under-used in their country.
| Sotalol|| |
Sotalol is a BB with additional Vaughan-Williams Class 111 antiarrhythmic effect. Numerous studies have evaluated the efficacy of sotalol in preventing POAF. In the meta-analysis by Burgess and colleagues, there were 14 trials (2,583 patients) that compared sotalol with placebo or other BBs.  Overall, sotalol reduced POAF from 33.7% to 16.9% (OR, 0.37). In the meta-analysis by Crystal et al., 4 trials compared sotalol directly with other BBs.  The incidence of AF decreased from 22% in the BB group to 12% in the sotalol group. In the second meta-analysis, trials that compared sotalol with other BBs showed that sotalol reduced the incidence of POAF from 25.7% to 13.7% (OR, 0.42), showing that sotalol offers additional significant protection when compared with other BBs.  However, significantly more patients were withdrawn from the groups that received sotalol than those that received placebo because of side effects, predominantly bradycardia and hypotension. This difference was however not significant when sotalol was compared with other BBs. Use of sotalol is however associated with a significant incidence (1%-5%) of torsades de pointes. 
Current ACC/ AHA/ ESC guidelines give a Class 11b (level of evidence, B) indication for sotalol to prevent POAF.  The ACCP indicates that sotalol may be used for prevention of POAF. 
| Amiodarone|| |
Amiodarone has been used both as an oral and intravenous agent for prevention of POAF. A recent meta-analysis of 19 studies comparing amiodarone with placebo showed that amiodarone significantly reduced the incidence of atrial fibrillation (OR, 0.53), ventricular tachycardia (OR, 0.39) and stroke (OR, 0.6 days) but did not show statistically significant reduction in postoperative mortality (OR, 0.9). 
The prophylactic oral Amiodarone for Prevention of Arrhythmias that Begin Early After Revascularization (PAPABEAR) trial randomized 601 patients according to their age, preoperative BB status and type of surgery performed.  As compared to patients on placebo, prophylactic oral amiodarone use resulted in fewer atrial arrhythmias, lower incidence of POAF in patients younger than 65 years, in patients older than 65 years, in patients who had CABG surgery only, in patients who had valve replacement surgery with or without CABG, in patients who were on BBs preoperatively and in patients who did not receive preoperative BBs. Sustained ventricular tachycardia occurred less frequently in amiodarone-treated patients. There was no significant difference in serious postoperative complications or in-hospital mortality.
Another meta-analysis evaluating the safety of amiodarone for prophylaxis against POAF showed amiodarone increased the odds of developing bradycardia (OR, 1.7) and hypotension (OR, 1.62).  Intravenous amiodarone in an average daily dose of 1 gm/day or intravenous amiodarone given postoperatively was associated with a greater likelihood of bradycardia and hypotension when given as prophylaxis against POAF.
Current guidelines from ACC/ AHA/ ESC give a Class 11a (level of evidence, A) indication for amiodarone as a prophylaxis against POAF after cardiac surgery.  Current recommendations from ACCP suggest that prophylactic amiodarone should be considered for patients with a contraindication for BB therapy.  The Canadian Cardiovascular Society (CCS) Consensus Conference gives a Class 11a recommendation for the use of amiodarone as prophylaxis in patients undergoing cardiac surgery who have not been on BBs.  The OR in their own meta-analysis of amiodarone for prevention of POAF was 0.59 (P= 0.≤ 0001).
| Calcium-Channel Blockers|| |
Numerous studies have evaluated the usefulness of calcium-channel blockers (CCBs) in prevention of POAF. A recent meta-analysis including 41 studies and 3,327 patients showed that CCBs were effective in reducing the incidence of myocardial infarctions (OR, 0.58), myocardial ischemia (OR, 0.53) and revealed a trend towards reduced mortality (OR, 0.66).  Non-dihydropyridines showed a significant reduction in the incidence of supraventricular tachycardia (OR, 0.62). The OR in the weighted meta-analysis by Mitchell and colleagues of the use of verapamil for prophylaxis against POAF was 0.94 (P= NS).  However, perioperative use of CCBs may be associated with an increased incidence of atrioventricular block and low-output syndrome, which may be related to the negative chronotropic and ionotropic effects of the drug.
| Other Drugs Used for Prevention of POAF|| |
Various other modalities have been tried for the prevention of POAF. Magnesium therapy has been shown to reduce the incidence of POAF. Magnesium deficiency may persist up to 4 days after cardiac surgery. Limiting magnesium therapy to the immediate postoperative period may not be adequate to prevent occurrence of POAF, which has a maximum incidence on the second postoperative day. Current guidelines from ACC/ AHA/ ESC do not recognize an indication for intravenous magnesium to prevent POAF.  The ACCP recommends against magnesium therapy.  The CCS has given a Class 11a recommendation for the use of magnesium as prophylaxis against POAF in patients who were not on BBs prior to cardiac surgery. 
Digoxin has very limited role in prevention of POAF. In their weighted meta-analysis, Mitchell and colleagues showed that the OR for digoxin in prevention of POAF was 0.91 (P= NS). 
It is well established that statins have significant anti-inflammatory effects, which has resulted in a reduction of morbidity and mortality in patients undergoing cardiac surgery under CPB. Preoperative statin use has been associated with a significant reduction in the incidence of POAF. 
Procanamide has also been used in prophylaxis against POAF. However, the well-known side effects of Class 1 antiarrhythmic agents in patients with structural heart disease have precluded the acceptance of these agents as prophylaxis against atrial tachyarrhythmias.
Pericardial effusions in the postoperative period have been considered as an important stimulus for the development of POAF. Posterior pericardiotomy has been shown to be useful in the prevention of POAF as it allows blood and effusions to drain away into the left pleural space. A meta-analysis of 6 RCTs (763 patients) showed that the use of posterior pericardiotomy was associated with a cumulative incidence of AF of 10.8% as compared to 28.1% in the control group.  Posterior pericardiotomy was associated with significant reduction in supraventricular arrhythmias and early and late pericardial effusions.
Use of methylprednisolone has been shown to reduce the incidence of POAF but was associated with significant complications.  Even nonsteroidal anti-inflammatory agents have been shown to have beneficial effects on POAF, although the potential for these drugs to aggravate renal problems is yet to be evaluated. 
| Atrial Pacing|| |
Prophylactic atrial pacing may be useful in preventing POAF by virtue of its favorable effects on intra-atrial conduction and atrial refractoriness. There are a number of mechanisms by which atrial pacing may influence POAF: i) reduction of bradycardia-induced dispersion of atrial repolarization, which contributes to the electrophysiological substrate for AF; ii) atrial overdrive pacing may suppress premature atrial ectopics and supraventricular tachycardia, thus avoiding the trigger for AF; and iii) simultaneous pacing of right and left atria can overcome conduction delays and reduce dispersion of refractoriness that contribute to the development of AF. 
In a small study of 24 postoperative CABG patients, prophylactic right atrial pacing continued for 96 hours postoperatively reduced the incidence of POAF from 31.1% to 5.2% (P=0.03).  Two meta-analyses showed that prophylactic atrial pacing was as efficient as pharmacological methods in reducing the incidence of POAF. , In another randomized trial, bi-atrial pacing resulted in more significant reduction in the incidence of POAF as compared to left atrial or right atrial pacing or no pacing.  Bi-atrial pacing resulted in more significant reduction in "P" wave dispersion and also resulted in a nonsignificant reduction in the LOS-hospital.
| Comparison of Therapies|| |
Comparison among various BBs shows that most BBs are equivalent in their efficacy. A recent retrospective evaluation of 115 patients showed that carvedilol was more effective than metoprolol or atenolol in preventing POAF (8% versus 32%, P=≤0.05).  Acikel et al. compared metoprolol with carvedilol started 3 days prior to surgery in 110 patients.  Thirty-six percent of the patients in the metoprolol group developed POAF as compared to 16% in the carvedilol group (P=0.02). In their meta-analysis, Burgess et al. showed that when sotalol was compared to other BBs, sotalol offered additional protection against POAF as compared to other BBs. 
A comparative study of oral amiodarone versus bisoprolol started 6 hours after surgery showed no significant difference in the incidence of POAF (15.3% in amiodarone group versus 12.7% in the bisoprolol group).  Patients given bisoprolol tended to have lower ventricular rates (125 versus 144 beats/min, P=0.06). There was no significant difference between groups regarding onset time of AF, total AF duration, AF recurrence or postoperative LOS-hospital.
The Atrial Fibrillation Suppression Trial (AFIST)-11 trial compared intravenous amiodarone to atrial septal pacing alone or a combination of amiodarone and atrial pacing or neither intervention.  Amiodarone reduced the risk of AF by 43% (P= 0.037) and the risk of symptomatic AF by 68% (P= 0.019). Atrial septal pacing did not reduce the incidence of AF or symptomatic AF versus no pacing. The risk of POAF was lower in the atrial pacing and amiodarone group when compared with placebo with no pacing group or placebo with pacing group.
Treatment of atrial fibrillation occurring after cardiac surgery
The therapeutic goals in the treatment of POAF include prevention of thromboembolism, control of ventricular rate, and conversion and maintenance of sinus rhythm. Two important aspects to be remembered during the management are i) POAF is a self-terminating but frequently recurrent tachyarrhythmia that usually subsides in 6 to 8 weeks after surgery, and ii) the adrenergic response in the postoperative period weakens the effectiveness of any therapy that does not include BBs.
Rhythm or rate control: The controversy
The aim of conversion of AF into sinus rhythm is to relieve symptoms, improve hemodynamics, reduce the risk of thromboembolism and in the long term, prevent tachycardia-associated cardiomyopathy. However, it is still not clear whether maintenance of sinus rhythm is effective in achieving these aims or for reducing the risk of death associated with therapy directed at rate control only. Suggestions that have been put forward are based on large trials on patients with AF in the nonsurgical settings.
Both the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] and the Rate Control versus Electrical cardioversion [RACE] studies have shown that rhythm control was in no way superior to rate control in terms of mortality, morbidity and quality of life. , It was also shown in these studies that rhythm control does not prevent stroke. Moreover, a subhoc analysis of the RACE study showed that there were no substantial differences in terms of cardiovascular mortality, morbidity and quality of life with regard to the different heart rates achieved. 
The ACC/ AHA/ ESC guidelines state that the initial management of patients with AF includes anticoagulation, as well as rate control.  For patients with long-term AF, rhythm control is required when rate control alone is not sufficient to control symptoms. In elderly patients, rate control alone may be sufficient. Since POAF is a self-limiting process, no long-term therapy is required in patients with normal left ventricular function and restored sinus rhythm. In such patients, amiodarone on maintenance dose may be given up to 1 month after surgery or a maximum of 3 months. However, in patients with impaired left ventricular function and only rate control achieved, longer therapy may be required.
Based on the above evidence, the only situations where rhythm control is required are i) patients remaining persistently symptomatic despite adequate rate control, ii) situations in which adequate rate control cannot be achieved and iii) patient preference.
Rate control of AF
Heart rate control is the primary focus in the treatment of POAF. Control of ventricular rate can be achieved with a variety of drugs, including BBs and CCBs and amiodarone. Routine BB re-institution is mandatory after surgery and should be done as early as possible in the postoperative period. Diltiazem may be better tolerated than verapamil where there are concerns about the negative ionotropic effect of the drug. Digoxin has limited efficacy in the postoperative period owing to enhanced sympathetic drive resulting from the surgical stress.  Digoxin has been given a Class 1 recommendation for control of ventricular rate in patients without pre-excitation syndromes and in patients with AF and congestive heart failure; although in the post-cardiac surgery setting, digoxin has very limited utility.  Digoxin may be considered when both BBs and CCBs are contraindicated. Amiodarone has also been extensively used for control of heart rate in the postoperative period and is probably the single most popular drug used for rate control after BBs. Amiodarone has been given a Class 1 recommendation by CCS for rate control in POAF. 
The primary aim is to achieve a heart rate of 80-90 beats/min. However, in the post-cardiac surgery setting, the heart rate has to be titrated keeping the hemodynamic and myocardial oxygen balance stable.
| Rhythm Control|| |
As recurrence of atrial arrhythmia is the rule rather than an exception, pharmacological cardioversion or direct cardioversion after initiation of pharmacotherapy is generally recommended, provided hemodynamic stability is present. This will help prevent recurrence of atrial arrhythmias. Antiarrhythmic therapy is indicated for conversion of AF into sinus rhythm and for sustaining sinus rhythm after cardioversion. It is also indicated in recurrent and refractory AF.
Procainamide has been successfully used for conversion of POAF into sinus rhythm. Hypotension, gastrointestinal and lupus-like side effects are the major drawbacks of procainamide. In addition, procainamide may also lead to rapid ventricular rates in the absence of prior administration of drugs that slow A-V conduction.
Ibutilide is a Class 111 antiarrhythmic agent. In a non-randomized prospective study, the efficacy of ibutilide was evaluated in 45 medical and post-cardiac surgery patients.  Use of ibutilide was associated with a 56.8% conversion rate, and the mean time to conversion after onset was 177 ± 12.5 minutes. Conversion rate was significantly higher in medical patients. Serious ibutilide-induced ventricular arrhythmias occurred in 8.1% of the patients. Evaluation of 312 patients with POAF or atrial flutter showed an overall conversion rate of 48% with ibutilide. Efficacy was dose related, more effective in atrial flutter, and the major drawback with the use of this drug was torsades de pointes ventricular tachyarrhythmias. 
Propafenone is a Class 1c agent which leads to slowed conduction through the A-V node and reduction in the upstroke of the action potential. Amiodarone has been compared to propafenone in two studies. , Although both drugs were equally effective in restoring sinus rhythm, propafenone was found to be more efficient than amiodarone in early restoration of sinus rhythm.
Amiodarone still remains the chemotherapeutic agent of choice for rhythm control in POAF. Dronedarone is a non-iodinated congener of amiodarone developed to maintain sinus rhythm. Studies in medical patients with AF and additional risk factors for death, showed that when compared to placebo, dronedarone reduced the incidence of death and hospitalization from cardiovascular causes from 39.4% to 31.9% (hazard ratio for dronedarone, 0.76).  Death from cardiovascular causes was reduced significantly with dronedarone, primarily because of a reduction in the mortality due to arrhythmias. However, when compared to amiodarone, dronedarone was found to be less efficient. 
| Electrical Cardioversion|| |
Overdrive atrial pacing may be successful in converting POAF to sinus rhythm if the atrial rate is < 300/min. Electrical cardioversion is indicated when POAF is associated with hemodynamic compromise, myocardial ischemia, worsening LV function and rapid ventricular response. Direct cardioversion (DC) using adequate energy levels (360 joules for monophasic waveform and 200 joules for biphasic waveform) can result in immediate cardioversion. The response to DC has important clinical implications.  It is important to differentiate "failure to cardiovert," where even a single beat of sinus rhythm does not result after DC; from early re-initiation of AF (ERAF). In the latter, DC results in immediate return of sinus rhythm only for AF to take over in a few beats. In case of "failure to cardiovert," additional measures, including increasing the delivered energy, greater pressure applied to paddles, internal cardioversion and repeating cardioversion after antiarrhythmic drug therapy, may be tried. In the latter instance, repeating cardioversion would be futile as the same pattern of events is likely to repeat. In such situations, initiation of antiarrhythmic drug therapy and correction of other contributing factors should be undertaken before attempting cardioversion again. As mentioned earlier, use of an antiarrhythmic agent prior to direct cardioversion has the advantage of the potential to prevent recurrence in atrial arrhythmias.
Anticoagulation or risk of bleeding
The risk of electrical cardioversion includes thromboembolic events, bradycardia, sinus arrest and ventricular arrhythmias. Both pharmacological cardioversion and electrical cardioversion are associated with a 1%-7% risk of thromboembolism. Whether guidelines for anticoagulation before cardioversion in nonsurgical patients apply to the postsurgical scenario is not clear. In the general population, anticoagulation for 3 to 4 weeks before cardioversion is recommended for AF that has lasted for more than 48 hours.  An acceptable approach in the postoperative period would be to perform a transesophageal echocardiography to exclude mural thrombus, particularly in the left atrial appendage. The patient should be placed on heparin immediately, and anticoagulation should be continued for at least 3 to 4 weeks after successful cardioversion of POAF to sinus rhythm. 
POAF increases the risk of thromboembolism and perioperative strokes. Conversely, anticoagulation can increase the risk of bleeding and cardiac tamponade. Considering the limited duration of POAF, the clinician must weigh the benefits of anticoagulation against the risk of increased bleeding. This risk of increased bleeding may outweigh the benefits of anticoagulation, particularly in patients with advanced age, uncontrolled hypertension and history of bleeding.
| The Future|| |
Existing antiarrhythmic drugs have limited efficacy and significant side effects. This has spawned the need for new-drug research. Vernakalant is an "atrial selective" drug that is useful for conversion of AF but not for atrial flutter.  Its advantage over ibutilide is that it is less likely to result in torsades de pointes. Ranazoline, initially developed for treatment of chronic angina, has important ion-channel effect and can be useful in treatment of arrhythmias. However, these drugs require further evaluation.
Practical approach to management of POAF
- . Continue BBs up to the day of surgery, including the morning of operation.
- Restart BBs at the earliest in the postoperative period.
- In patients at high risk of POAF (age >65 years, COPD, prior history of AF, congestive cardiac failure, echocardiography (ECHO) findings suggestive of POAF, prolonged CPB, etc.), prophylactic intravenous amiodarone therapy may be started.
- In patients who develop POAF, the management differs depending on the heart rate (HR) and the hemodynamic response.
- In patients with fast ventricular rates and hemodynamic instability, immediate DC is indicated. Once cardioverted, patients may be placed on intravenous amiodarone after correction of any associated factors to ensure non-recurrence of the arrhythmia. If ERAF occurs, intravenous amiodarone or diltiazem therapy should be initiated along with correction of any contributing factors. Cardioversion may be tried at a later stage (24-36 hours later) if patient's ventricular rate does not settle. However, if the patient remains unstable, another attempt at DC may be made after the loading dose of amiodarone is given.
- In patients with POAF who remain hemodynamically stable with high ventricular rates, intravenous amiodarone therapy should be initiated after a loading dose. Sotalol and intravenous diltiazem are the other drugs of choice. Simultaneously, other contributing factors, including pain, electrolyte imbalance, should be corrected and magnesium therapy initiated.
- In patients with POAF and low ventricular rates, continue observation of the patient along with correction of all contributing factors. Amiodarone therapy may result in severe bradycardia. If POAF persists after 24 to 48 hours, DC may be attempted.
- POAF persisting for more than 48 hours is an indication for starting intravenous heparin therapy followed by oral anticoagulants.
- In patients who have been cardioverted with a single DC shock and are on amiodarone, the drug can be discontinued after 7 days. In patients who have recurrent POAF, amiodarone therapy may be continued up to 1 month.
- Rhythm control is not an absolute must, especially in elderly patients.
| Summary|| |
POAF is one of the most common complications occurring after cardiac surgery. POAF predisposes to thromboembolism and stroke in the postoperative period and prolongs postoperative hospital stay. It can also lead to hemodynamic compromise and worsen ventricular function, particularly in patients with impaired LV function.
Beta blockers have been extensively studied in the prevention of POAF. Therefore, unless there is a specific contraindication, these drugs should be restarted at the earliest in the postoperative period. Amiodarone is another drug which has been extensively studied. Although amiodarone started a few days before surgery is acceptable, intravenous amiodarone started as prophylaxis after surgery may be particularly useful in patients susceptible to AF. Amiodarone is also the drug to be used for restoration of sinus rhythm / rate control in cases of established POAF. Bi-atrial pacing although found useful is less well established because of complexities associated with its use. There is limited data on the usefulness of CCBs, digoxin and anti-inflammatory drugs in preventing POAF. At best, they may be considered as adjuvant to the regular drugs.
If POAF occurs, electrical cardioversion is indicated in patients with hemodynamic compromise. In stable patients, a drug which prolongs A-V conduction may be used. However, if sinus rhythm is not established in 24 hours, then a rhythm-control strategy (Class 111 antiarrhythmic agents) may be used, associated with early anticoagulation. Anticoagulation should be continued for 3 to 4 weeks in high-risk patients.
| References|| |
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Suresh G Nair
Department of Anaesthesia and Critical Care, Amrita Institute of Medical Sciences, Cochin-682 041, Kerala
Source of Support: None, Conflict of Interest: None
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