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(Chest. 2005;128:9S-16S.)
© 2005 American College of Chest Physicians

Epidemiology, Mechanisms, and Risks*

American College of Chest Physicians Guidelines for the Prevention and Management of Postoperative Atrial Fibrillation After Cardiac Surgery

Charles W. Hogue, Jr., MD; Lawrence L. Creswell, MD; David D. Gutterman, MD, FCCP and Lee A. Fleisher, MD

* From the Division of Cardiothoracic Anesthesia (Dr. Hogue), Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO; the Division of Cardiothoracic Surgery (Dr. Creswell), University of Mississippi Medical Center, Jackson. MS; the Department of Internal Medicine (Dr. Gutterman), Medical College of Wisconsin, Milwaukee, WI; and the Department of Anesthesia (Dr. Fleischer), University of Pennsylvania Health System, Philadelphia, PA.

Correspondence to: Charles W. Hogue, Jr., MD, Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Ave, Box 8054, St. Louis, MO 63110; e-mail: hoguec{at}notes.wustl.edu


   Abstract
TOP
 Abstract
Introduction
 Mechanisms
 Associated Patient Outcomes
 Risk Factors
 Conclusion
 References
 
Atrial fibrillation (AF) is one of the most frequent complications of cardiac surgery, affecting more than one third of patients. The mechanism of this arrhythmia is believed to be reentry. The electrophysiologic substrate may be preexisting or may develop due to heterogeneity of refractoriness after surgery. Multiple perioperative factors have been proposed to contribute to the latter, including operative trauma, inflammation, elevations in atrial pressure (including that due to left ventricular diastolic dysfunction), autonomic nervous system imbalance, metabolic and electrolyte imbalances, or myocardial ischemic damage incurred during the operation. Whether ectopic beats originating in the pulmonary veins explain at least some episodes of postoperative AF, as has been shown for nonsurgical patients with the arrhythmia, is of current interest as such sites could easily be isolated at the time of surgery. The development of postoperative AF is associated with a higher risk of operative morbidity, prolonged hospitalization, and increased hospital cost compared with that in patients remaining in sinus rhythm. Many factors have been identified as being associated with postoperative AF, but the most consistent variable across studies is increasing patient age. It is speculated that age-related pathologic changes in the atrium contribute to arrhythmia susceptibility. An important modifiable risk factor for postoperative AF is the failure to resume therapy with ß-adrenergic receptor blockers after surgery. The stratification of patients who are at higher risk for AF would focus preventative strategies on patients who are most likely to benefit from such therapy. Nonetheless, since postoperative AF often develops in patients with comorbidities who are predisposed to other complications and prolonged hospitalization, it is presently unclear whether the prevention of postoperative AF will result in improved patient outcomes, particularly shorter hospitalizations.

Key Words: atrial fibrillation • epidemiology • pathophysiology


   Introduction
TOP
 Abstract
 Introduction
Mechanisms
 Associated Patient Outcomes
 Risk Factors
 Conclusion
 References
 
Nearly 800,000 cardiac surgical procedures are performed annually in the United States.1 Despite the continued trends for patients undergoing these procedures to be of higher-risk and older than in the past, operative mortality remains low and has declined in some series on a risk-adjusted basis.2 In this setting, there is increasing attention being paid to perioperative complications as an important source of patient morbidity and health-care resource utilization. Postoperative atrial fibrillation (AF) is one of the most frequent complications of cardiac surgery, and an important predictor of patient morbidity, prolonged hospitalization, and increased hospital cost.3456789 Importantly, the frequency of this arrhythmia appears to be increasing, most likely due to increasing proportions of elderly cardiac surgical patients.35 As a result, this arrhythmia is the focus of intense investigative efforts as a means for improving patient outcomes.

Absolute incidence rates for postoperative AF (and flutter) vary depending on many variables, including types of procedures, patient demographics, criteria for diagnosis, and methods of ECG monitoring. When diagnosed based on intermittently obtained 12-lead ECGs, for example, AF is reported in 11% of patients compared with an incidence of > 40% when Holter monitoring is employed.89 Further, when the arrhythmia is diagnosed based on patient symptoms, the frequency of postoperative AF is between 16% and 30%.1011 The clinical importance of symptomatic vs asymptomatic episodes of AF is not known. In most contemporary series, the reported rates for postoperative AF range from > 30% for patients undergoing CABG surgery to nearly 60% for patients having combined CABG and mitral valve surgery.3 The arrhythmia typically occurs on postoperative days 2 to 3 with 70% of events occurring within the first 4 postoperative days.56 This complication, however, may occur any time after surgery including after hospital discharge. In fact, AF is the leading cause of hospital readmission after early discharge from the hospital following cardiac surgery.12


   Mechanisms
TOP
 Abstract
 Introduction
 Mechanisms
Associated Patient Outcomes
 Risk Factors
 Conclusion
 References
 
The pathophysiology of AF as proposed by Moe13 involves multiple wavelets of reentry, or possibly automatic discharge, which can entrain the entire atrium into a chaotic rhythm if sufficient muscle mass is present. Thus, the maintenance of this arrhythmia requires a substantial atrial size and occurs primarily in larger species. Accordingly, any condition that promotes either focal areas of automaticity or multiple short periods of local reentry might be expected to increase the chances for atrial arrhythmias including fibrillation. Even a single premature atrial beat that is blocked in refractory regions of the atrium can cause macro reentrant activation degenerating into multiple wavefronts with subsequent fibrillation.14 Regional refractoriness is the primary determinant of AF in this case.

In the postoperative heart, multiple factors may potentially predispose the patient to AF through alterations in refractoriness and/or local reentry. These include operative trauma from surgical dissection and manipulation, local inflammation with or without pericarditis, elevations in atrial pressure from postoperative ventricular stunning, chemical stimulation during perioperative support with catecholamines and other inotropic agents, reflex sympathetic activation from volume loss, anemia or pain, parasympathetic activation, fever from atelectasis or infection, and hypoglycemia or ischemic damage incurred during the operation.151617 It has been hypothesized that less effective cardioprotection of the atria compared to the ventricles during cardiopulmonary bypass could be an etiology of postoperative AF. The rapid return of atrial temperature after cardioplegic arrest is associated with atrial electrical activity and susceptibility to atrial arrhythmias.1819 In this situation, myocardial oxygen imbalance would result from atrial myocyte electrical activity in the setting of aortic cross-clamping. Nonetheless, augmented topical atrial cooling during cardioplegic arrest did not influence the inducibility of AF after experimental cardiac surgery compared with standard cardioplegia alone.20

The metabolic and chemical milieu may also contribute to the induction and maintenance of AF. Heightened sympathetic or vagal tone may lower the threshold for AF.21 Similarly, the use of adrenergic drugs in the perioperative period can provoke atrial arrhythmias. This has been indirectly detected as an increase in the Gs/Gi {alpha} ratio in lymphocytes from subjects with postoperative AF.22 Metabolic derangements may also provide a substrate for AF. In the presence of hypoglycemia, the susceptibility for the induction of AF and the duration of the arrhythmia was greater than in animals with euglycemia or hyperglycemia.17 Hypothyroidism is a known consequence of cardiac surgery.2324 While hyperthyroidism is a well-recognized cause of AF, hypothyroidism is also associated with an increased incidence of AF in animals and humans, primarily in the elderly.25262728 Correcting this metabolic defect following surgery may prevent the onset of AF.2426

Mechanical and electrical factors may play an important role in the initiation of atrial arrhythmias. In dogs, acute atrial dilation increases the dispersion of refractoriness throughout the atrium in a heterogeneous manner, lowering the threshold for the development of AF.29 Easier induction of AF was observed by Sideris et al16 in dogs with elevated left atrial pressures. Although acute atrial stretch may be effective in initiating AF, chronic distention elicits an ultrastructural and electrical remodeling with fibrotic infiltrates that may serve to isolate micro-reentrant pathways and may perpetuate the arrhythmia for long periods of time.3031323334 Some studies have implicated specific anatomic regions of atrial tissue as being critical in the initiation of AF. Segments of atrialized pulmonary vein tissue appear to be the earliest sites of electrical activation in some animal models of AF.3536 Ectopic beats emanating from the pulmonary veins have been demonstrated in nonsurgical patients with paroxysmal AF; the ablation of these sites restores sinus rhythm.3637 Whether this intriguing and potentially treatable mechanism is also critical in patients with postoperative AF remains to be determined.

A common underlying factor in the induction of AF by mechanical, metabolic, or pharmacologic stimuli in the postoperative state may be the redox changes associated with the tachyarrhythmia. Evidence38 has shown an association between human AF and oxidative stress in the form of elevated atrial levels of peroxynitrite, which is a highly reactive nitrogen species that is formed by the interaction of superoxide and nitric oxide. In this study, the oral treatment of dogs with ascorbic acid, which is a free-radical scavenger that can reduce the amount of endogenously formed peroxynitrite, attenuated the pacing-induced atrial effective refractory period shortening, which is a change that would be expected to reduce the propensity for AF. The authors further tested this redox hypothesis in humans. Treatment with vitamin C for 5 days from the time of cardiac surgery reduced the incidence of postoperative AF by 50%, supporting the concept that oxidative stress contributes to the mechanism of postoperative AF.39

Thus, the mechanisms of AF in the postoperative patient are likely to be fundamentally similar to those in patients with AF who have not undergone surgery, although there have been few detailed investigations examining the electrophysiologic basis for the postoperative arrhythmia. The conditions surrounding the surgical procedure that elevate the risk of AF include the propensity for ischemic myocardial damage during the procedure due to hypotension or inadequate cardioprotection, traumatic pericarditis and myocarditis, postoperative and postanesthetic decreases in left ventricular function associated with elevated atrial pressures, and the chemical and metabolic milieu, including administered adrenergic and cholinergic medications, hypoglycemia or hypothyroidism, and reflex autonomic activation. The usually transient nature of postoperative AF correlates with the recovery of these mechanical or metabolic imbalances.


   Associated Patient Outcomes
TOP
 Abstract
 Introduction
 Mechanisms
 Associated Patient Outcomes
Risk Factors
 Conclusion
 References
 
Historically, postoperative AF has often been considered to be a "benign," self-limiting complication of cardiac surgery. The accumulated evidence suggests otherwise, since AF (1) is often associated with other serious complications, (2) results in an increased utilization of hospital resources and a lengthened postoperative length of hospital stay, and (3) may be a persistent or recurrent problem for affected patients even after hospital discharge.

Common symptoms of postoperative AF include palpitations, chest pain, fatigue, shortness of breath, or generalized anxiety. Although the data regarding the hemodynamic consequences are few and conflicting, there may be a modest decrease in the systemic BP and urine output, and some patients may develop congestive heart failure (CHF).3 These difficulties may limit the patient’s recovery by limiting their mobility at a time when increased activity is usually encouraged.

Patients who develop postoperative AF often experience other postoperative complications as well. Associations have been documented between postoperative AF and perioperative myocardial infarction, CHF, ventricular arrhythmias, the need for permanent pacemaker, renal insufficiency, infection, pneumonia, increased need for inotropic medications, increased use of the intraaortic balloon pump, increased need for reexploration of the chest for bleeding or cardiac tamponade, prolonged ventilation, reintubation of the trachea, readmission to the ICU, and increased need for tracheostomy.357 Importantly, patients with postoperative AF have a nearly threefold higher risk for perioperative stroke.35 It is important to keep in mind, however, that these associations do not necessarily indicate a causal relationship between this arrhythmia and the other complications. That is, postoperative AF may actually be an epiphenomenon and not necessarily the cause of these complications. This is an important point insofar as the prevention of postoperative AF, then, might not necessarily reduce the frequency of these associated complications.

The evaluation and treatment of postoperative AF is expensive and may not be immediately successful. The evaluation of patients who develop this complication necessitates not only time on the part of the physician, but often includes ordering laboratory and other diagnostic studies. The available treatments (ie, cardioversion, antiarrhythmic medications, or pacing) all carry specific costs. Historically, the restoration of sinus rhythm before discharge from the hospital is preferred. As a result, the hospital length of stay for patients who develop this complication is prolonged. There has been increased interest in discharging from the hospital patients before the restoration of sinus rhythm. Loubani et al40 noted that, among patients who developed postoperative supraventricular arrhythmias, 50% had persistent arrhythmias at the time of hospital discharge and 39% still had AF 6 months after undergoing surgery despite the use of antiarrhythmic medications.

Because postoperative AF is a relatively frequent complication, there have been many reports on the costs (both economic and resource) associated with it. Mathew et al5 reported on 2,417 patients who underwent CABG, with or without other concomitant procedures, and noted a longer ICU stay (by 13 h) and longer step-down unit stay (2.0 days). Affected patients were also more likely to require readmission to the ICU. Aranki et al6 reported the most detailed analysis of resource utilization related to postoperative AF. These investigators reported on 570 patients who underwent CABG and noted that the excess length of stay that was independently attributable to postoperative AF was 4.9 days. They also note that although postoperative AF may not be the single most expensive complication for an individual patient, the cumulative costs associated with this complication are very high due to its frequent occurrence. They estimated that at their institution, the complication was associated with $10,055 to $11,500 in additional hospital charges per affected patient. Kowey et al41 documented total charges of $74,561 for patients with postoperative AF vs $53,057 for those without this complication. Similarly, Taylor et al42 reported the additional attributable costs associated with postoperative AF to be approximately $5,000 per patient, and Mauldin et al43 reported an extra cost of approximately $6,000 per patient among those who developed major postoperative arrhythmias. Given the large number of patients undergoing cardiac surgery each year, the aggregate economic costs associated with this complication are enormous. Any decrease in the frequency of this complication that can result from prevention efforts could potentially result in a large decrease in the total costs associated with cardiac surgery.

Many cardiothoracic surgery programs have initiated care pathways for patients undergoing cardiac surgery in an effort to promote efficiency and early discharge from the hospital.6 Many of these pathways include strategies for pharmacologic prophylaxis for postoperative atrial arrhythmias.44 With any such prevention strategy, however, all (or perhaps, most) patients receive prophylactic antiarrhythmic medications, yet only the minority will actually develop the complication. As would be expected, there are necessarily risks and costs associated with treating many individuals who will never develop the complication. Since the effectiveness of many prevention strategies is not yet clear, the argument has been made that this approach may contribute unnecessarily to the overall hospital cost.74546 Moreover, Reddy47 reviewed seven recent clinical trials that reported the effect of prophylaxis against postoperative AF (six using amiodarone and one using sotalol). These investigators concluded that although postoperative AF was reduced in five of the seven trials, there was little evidence that the application of prevention strategies actually reduced hospital costs or hospital length of stay. Among five trials4849505152 that reported cost data, only one demonstrated a reduction in costs associated with a prophylaxis regimen. As a result, it has been suggested53 that prevention strategies should be aimed only at high-risk patient subgroups.

It is widely thought that the risk of recurrence of postoperative AF drops considerably in the first few days after surgery and continues to fall after discharge from the hospital. As a result, patients who develop postoperative AF traditionally have been treated with antiarrhythmic medications for a period of several weeks after undergoing surgery. Unfortunately, there have been few reports that describe the post-hospital discharge course for patients who have developed AF after undergoing cardiac surgery. Landymore and Howel54 reported that, among a small group of CABG patients (n = 58) who had developed postoperative AF and who were followed up after discharge from the hospital, Holter monitoring rarely demonstrated the occurrence of recurrent AF. Moreover, patients who developed recurrent arrhythmias were often asymptomatic. Similarly, Yilmaz et al55 reported that < 10% of 120 patients discharged from the hospital in sinus rhythm experienced recurrent AF during the 6 weeks after hospital discharge. Since many contemporary cardiac surgical patients are discharged from the hospital on the third through fifth days after undergoing surgery, we could expect that some patients might experience a first episode of postoperative AF at home. Unfortunately, there are no detailed reports on the frequency of this problem. We do know, however, that persistent, recurrent, or new-onset AF may cause sufficient disability for at least some patients after hospital discharge and that readmission to the hospital or evaluation in the emergency department may be necessary. Lahey et al12 have reported that AF was the most common reason for readmission to the hospital after cardiac surgery, accounting for approximately 23% of hospital readmissions.


   Risk Factors
TOP
 Abstract
 Introduction
 Mechanisms
 Associated Patient Outcomes
 Risk Factors
Conclusion
 References
 
Multiple investigations have attempted to identify mostly demographic risk factors for postoperative AF. These analyses have the potential to provide insight into the potential pathophysiologic mechanism of the disorder, but they also could foster the development of preventive strategies that properly target patients who are the most likely to benefit from such therapy. Nonetheless, there are inconsistencies in many of the results that, in part, are explained by differences in the characteristics of the patients examined, the inconsistent method of patient monitoring, the varied criteria used for the diagnosis of arrhythmia, the small sample size, and the variability in the risk factors evaluated. Patient variables that have been identified to be associated with postoperative AF by some but not all studies have included prior AF, valvular heart disease, male gender, chronic obstructive lung disease, hypertension, left ventricular hypertrophy based on ECG diagnosis, preoperative digoxin use, history of CHF, elevated left ventricular diastolic pressures, right coronary artery stenosis, hypokalemia, hypomagnesemia, and hypothyroidism.345682324565758

The variable that has most consistently been independently associated with the risk for postoperative AF across studies is increasing patient age.3457 In the series by Aranki et al,6 for example, the frequency of AF was 18% for patients who were < 60 years old undergoing cardiac surgery, but 52% for those > 80 years of age. Mathew et al5 reported an increase of 24% in the odds of developing postoperative AF for every 5-year increase in age. Although the number of nonagenarians in many series remains low, the effect of age on the incidence of AF appears to plateau after the age of 80 years.3 The most common explanation for the relationship between patient age and postoperative AF is age-associated structural changes in the atrium that provide the substrate for the arrhythmia.5960

Intraoperative practices and postoperative variables have been examined for their relationship with postoperative AF. The duration of aortic cross-clamping and, as mentioned, the early return of atrial electrical activity after cardioplegia have been shown by some studies31819 to be independently related to the risk for postoperative AF, suggesting a role of atrial ischemia in the pathogenesis of the disorder. The use of bicaval venous cannulation for cardiopulmonary bypass and left ventricular venting via the pulmonary vein have also been identified as being associated with the risk for postoperative AF.5 Systemic and pericardial inflammation and pericardial effusions have been found by some investigators61 to be associated with the risk for postoperative AF. The postoperative withdrawal of therapy with ß-adrenergic receptor blockers has been reported62 to increase the risk for postoperative AF. In a series of patients who were receiving therapy with ß-blockers before undergoing surgery, Ali et al62 found that the frequency of AF was 38% vs 17%, respectively, depending on whether therapy with ß-blockers was randomly withheld or continued. The use of atrial pacing has been suggested63 to predispose a patient to AF by some studies, while others have suggested that pacing actually can lower the risk of AF after surgery.6465666768697071 Tachycardia and atrial ectopy are associated with higher rates of postoperative AF.770 The former might represent higher postoperative sympathetic tone, which has been suggested to predispose the patient to postoperative AF, while the latter is of interest in light of data showing that AF in nonsurgical patients was often initiated and/or maintained by ectopic beats often arising in the cuffs of the myocardium located in the pulmonary veins.3771

It has been widely speculated that patients who are prone to atrial arrhythmias after surgery possess the substrate for the arrhythmia before surgery, suggesting that electrophysiologic measurements might identify susceptibility.46 Supporting this hypothesis are data72 showing that postoperative AF is more likely to occur in patients in whom the arrhythmia can easily be induced prior to aortic cross-clamping. The measurement of prolonged atrial conduction, which predisposes to reentry, using the scalar or processed ECG has been suggested as a means for identifying susceptibility for postoperative AF.5373 Steinberg et al73 reported that a signal-averaged P-wave duration of > 140 ms identified patient risk for postoperative AF with a 37% positive predictive accuracy and an 87% negative predictive accuracy. These results were supported by a study by Zaman et al53 who found that a signal-averaged P-wave duration of > 155 ms identified AF risk with a 49% positive predictive accuracy and an 84% negative predictive accuracy. In the latter study, a P-wave duration of > 155 ms (odds ratio [OR], 5.37; 95% confidence interval [CI], 3.10 to 9.30; p < 0.0005), advanced age (OR, 1.53; 95% CI, 1.26 to 1.86; p < 0.0005), and male gender (OR, 2.88; 95% CI, 1.30 to 6.40; p < 0.01) were independently associated with the risk for AF, but there was no relationship between P-wave duration and age. However, whether these methods can be broadly applied to nonresearch clinical situations is not clear.

Atrial enlargement is related to the risk for AF in individuals in the general population, particularly for those with mitral valvular disease or ventricular systolic dysfunction.7475 Skubas et al76 found that there was no difference in left atrial diameter or transmitral and pulmonary venous pulsed-Doppler measurements obtained with transesophageal echocardiography before CABG surgery or between patients with postoperative AF and those that remained in sinus rhythm. Shore-Lesserson et al77 found that patient age, left atrial appendage area measured before surgery with transesophageal echocardiography, and a ratio of pulmonary venous systolic Doppler blood flow velocity to diastolic Doppler blood flow velocity of < 0.5 measured after surgery were independently related to the risk for postoperative AF. In that study, though, left atrial dimensions were not different between patients with and without AF after surgery. These results together suggest that, while atrial enlargement may predispose the patient to postoperative AF, it is not a prerequisite. That is, the common form of postoperative AF occurs in the absence of atrial dilation, but this does not exclude the notion that transient increases in left atrial pressures precede the onset of the arrhythmia, as can be demonstrated in animals.1629


   Conclusion
TOP
 Abstract
 Introduction
 Mechanisms
 Associated Patient Outcomes
 Risk Factors
 Conclusion
References
 
Postoperative AF is one of the most frequent complications of cardiac surgery. The mechanism of this arrhythmia is likely the reentry that may result from either a preexisting or developing electrophysiologic substrate after surgery. Postoperative AF is usually well-tolerated, but it may result in hemodynamic instability and subjective discomfort. Importantly, compared with patients remaining in sinus rhythm, patients developing postoperative AF are more likely to have other operative morbidity, including stroke, prolonged hospitalization, and increased hospital cost. In the setting of early hospital discharge after cardiac surgery, AF is the most common cause for hospital readmission. The identification of patients who are at higher risk for AF might allow for preventive strategies to be focused on the patients who are most likely to benefit from such therapy. Postoperative AF is more common in elderly patients and often develops in those patients who have comorbidities that also predispose them to other complications and prolonged hospitalization. The prevention of postoperative AF should result in improved patient outcomes and shorter hospital stays, but further studies are required to delineate the full potential benefit and the best strategies for prevention.


   Footnotes
 
Abbreviations: AF = atrial fibrillation; CHF = congestive heart failure; CI = confidence interval; OR = odds ratio


   References
TOP
 Abstract
 Introduction
 Mechanisms
 Associated Patient Outcomes
 Risk Factors
 Conclusion
 References
 

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