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Usefulness of Postoperative Atrial Fibrillation as an IndependentPredictor for Worse Early and Late Outcomes After Isolated

Coronary Artery Bypass Grafting (Multicenter AustralianStudy of 19,497 Patients)

Akshat Saxena, BMedSca,*, Diem T. Dinh, BSc, PhDb, Julian A. Smith, MBBS, MSc,Gilbert C. Shardey, MBBSd, Christopher M. Reid, BA, MSc, PhDb, and

Andrew E. Newcomb, MBBSa,e

Several studies have shown that postoperative atrial fibrillation (POAF) is associated withpoorer short- and long-term outcomes after isolated coronary artery bypass graftingsurgery. Nevertheless, there is considerable debate as to whether this reflects an indepen-dent association of POAF with poorer outcomes or confounding by other factors. Wesought to investigate this issue. Data obtained from June 2001 through December 2009 bythe Australasian Society of Cardiac and Thoracic Surgeons National Cardiac SurgeryDatabase Program were retrospectively analyzed. Demographic and operative data werecompared between patients who developed POAF and those who did not using chi-squareand t tests. The independent impact of POAF on 14 short-term complications and long-term mortality was determined using binary logistic and Cox regression, respectively.Excluding patients with preoperative arrhythmia, isolated coronary artery bypass graftingsurgery was performed in 19,497 patients. Of these, 5,547 (28.5%) developed POAF. Patientswith POAF were generally older (mean age 69 vs 65 years, p <0.001) and presented more oftenwith co-morbidities including congestive heart failure (p <0.001), hypertension (p <0.001),cerebrovascular disease (p <0.001), and renal failure (p � 0.046). Patients with POAF dem-onstrated a greater 30-day mortality on univariate analysis but not on multivariate analysis(p � 0.376). Patients with POAF were, however, at an independently increased risk of peri-operative complications including permanent stroke (p <0.001), new renal failure (p <0.001),infective complications (p <0.001), gastrointestinal complications (p <0.001), and return to thetheater (p <0.001). POAF was also independently associated with shorter long-term survival(p � 0.002). In conclusion, POAF is a risk factor for short-term morbidity and decreasedlong-term survival. Rigorous evaluation of various therapies that prevent or decrease theimpact of POAF is imperative. Moreover, patients who develop POAF should undergo strictsurveillance and be routinely screened for complications after discharge. © 2012 Elsevier Inc.

All rights reserved. (Am J Cardiol 2012;109:219–225)

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Postoperative atrial fibrillation (POAF) is a commoncomplication in cardiac surgery affecting 11% to 40% ofpatients undergoing isolated coronary artery bypass grafting(CABG) surgery.1,2 As the demographic profile of patients

aDepartment of Cardiothoracic Surgery, St. Vincent’s Hospital Mel-bourne, Fitzroy, Victoria, Australia; bSchool of Public Health and Preven-tive Medicine, Monash University, Prahran, Victoria, Australia; cDepart-

ent of Surgery (MMC), Monash University and Department ofardiothoracic Surgery, Monash Medical Centre, Clayton, Victoria, Aus-

ralia; dCabrini Medical Center, Malvern, Victoria, Australia; eUniversityof Melbourne and Department of Surgery, St. Vincent’s Hospital Mel-bourne, Fitzroy, Victoria, Australia. Manuscript received May 14, 2011;revised manuscript received and accepted August 30, 2011.

The Australasian Society of Cardiac and Thoracic Surgeons NationalCardiac Surgery Database Program is funded by the Department of HumanServices, Melbourne, Victoria, Australia and the Health AdministrationCorporation and Clinical Excellence Commission, Sydney, New SouthWales, Australia.

*Corresponding author: Tel: 61-3-9419-2477; fax: 61-3-9417-1694.

hE-mail address: a.saxena@student.unimelb.edu.au (A. Saxena).

0002-9149/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved.doi:10.1016/j.amjcard.2011.08.033

undergoing CABG shifts toward the elderly, the incidenceof POAF will increase because the frequency of this com-plication sharply increases with age.3 Although previoustudies were equivocal about the impact of POAF on earlynd late outcomes,4,5 more recent studies have demonstrated

that POAF is associated with intensive care readmission,6

stroke,6–9 renal failure,9–12 perioperative myocardial infarc-ion,6 gastrointestinal complications,13 infective complica-

tions (e.g., septicemia, mediastinitis and pneumonia),9,11,14

cognitive changes,3,11 and increased resource use.3,14 More-ver, studies examining the impact of POAF on survival afterABG have demonstrated an association with early6,7,15 and

ate7,15 mortality, although a consensus on this issue has byno means been achieved. To this end, several institutionshave invested significant resources to identify predisposingfactors and implement preventative strategies.16 The presenttudy sought to comprehensively evaluate the impact ofOAF on early and late outcomes after isolated CABGurgery using a multi-institutional Australian database. It is

oped that these data will help to better delineate the impact

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220 The American Journal of Cardiology (www.ajconline.org)

of POAF on the immediate and future clinical course ofpatients after CABG.

Methods

The inclusion criterion for the study was patients under-going isolated CABG from June 1, 2001 through Decem-ber 31, 2009 at hospitals in Australia participating in theAustralasian Society of Cardiac and Thoracic Surgeons(ASCTS) Cardiac Surgery Database. Patients having con-

Table 1Preoperative characteristics and patient demographics stratified bypostoperative atrial fibrillation

Preoperative Variables POAF p Value

No Yes(n � 13,950) (n � 5,547)

Age (years), mean � SD 64.02 � 10.72 69.04 � 9.03 �0.001Chronic obstructive

pulmonary disease1,477 (10.6%) 773 (13.9%) �0.001

Diabetes mellitus 4,580 (32.8%) 1,786 (32.2%) 0.387Hypercholesterolemia* 11,277 (80.3%) 4,500 (81.1%) 0.700Hypertension† 10,561 (75.7%) 4,425 (79.8%) �0.001

erebrovascular disease 1,388 (9.9%) 699 (12.6%) �0.001eripheral vascular disease 1,551 (11.1%) 775 (14.0%) �0.001enal failure 424 (3.0%) 200 (3.6%) 0.046revious cardiac surgery 467 (3.3%) 202 (3.6%) 0.316ecent myocardial

infarction3,512 (25.1%) 1,225 (22.1%) �0.001

istory of congestive heartfailure

1,874 (13.4%) 967 (17.4%) �0.001

nstable angina 1,138 (8.2%) 439 (7.9%) 0.580eft main stenosis �50% 3,460 (24.8%) 1,482 (26.7%) 0.007eft ventricular ejection

fraction— — 0.002

�0.60 6,785 (48.6%) 2,574 (46.4%) —0.45–0.60 4,284 (30.7%) 1,750 (31.5%) —0.30–0.45 2,002 (14.4%) 883 (15.9%) —�0.30 523 (3.7%) 239 (4.3%) —

Obesity‡ 4,524 (32.4%) 1,880 (33.9%) 0.050New York Heart

Associationclassification

— — �0.001

I 5,448 (39.1%) 1,911 (34.4%) —II 4,550 (32.6%) 1,983 (35.7%) —III 2,076 (14.9%) 1,053 (19.0%) —IV 660 (4.7%) 313 (5.6%) —

3-Vessel disease 9,791 (70.2%) 4,213 (76.0%) �0.001Critical preoperative state 664 (4.8%) 307 (5.5%) 0.025

Status — — �0.001Elective 8,100 (58.1%) 3,369 (60.7%) —Emergency/salvage 5,360 (38.4%) 1,930 (34.8%) —Urgent 489 (3.5%) 248 (4.5%) —

* Defined as a history of hypercholesterolemia diagnosed and/or treatedby a physician and/or a cholesterol level �5 mmol/L, high-density lipo-protein level �1 mmol/L, or triglyceride level �2 mmol/L.

† Defined as a diagnosis of hypertension documented by any of thefollowing: (1) documented history of hypertension diagnosed and treatedwith medication, diet, and/or exercise; (2) systolic blood pressure �140mm Hg or diastolic blood pressure �90 mm Hg diastolic on �2 occasions;and/or (3) currently on antihypertensive medication.

‡ Body mass index �30 kg/m2.

comitant valve surgery or other concurrent cardiac surgical

procedures were excluded from this study. Moreover, onlypatients with documented preoperative sinus rhythm with-out a history of AF were included. All 6 Victorian publichospitals that perform adult cardiac surgery—Royal Mel-bourne Hospital, Alfred Hospital, Monash Medical Centre,Geelong Hospital, Austin Hospital, and St. Vincent’s Hos-pital, Melbourne—were involved in the prospective datacollection during the entire period. In addition, 14 cardiacsurgical units from South Australia, New South Wales, andQueensland entered the database project in the last 30months of the study period and contributed 41.4% of thetotal patient numbers.

The ASCTS database contained detailed information onpatient demographics, preoperative risk factors, operativedetails, postoperative hospital course, and morbidity andmortality outcomes. These data were collected prospec-tively using a standardized dataset and definitions. Datacollection and audit methods have been previously de-scribed.17 In the State of Victoria, the collection and report-ing of public hospital cardiac surgery data are compulsoryand mandated by the state government; hence, it is all-inclusive. Data validation has been a major focus since theestablishment of the ASCTS database. Data are subjected tolocal validation and an external data quality audit program,which is performed on site to evaluate the completeness(defined as �1% missing data for any variable) and accu-racy (97.4%) of the data held in the combined database.Audit outcomes are used to assist in further development ofappropriate standards. The ethics committee of each partic-ipating hospital had previously approved the use of de-identified patient data contained within the database forresearch and waived the need for individual patient consent.

POAF was defined as evidence of new AF that requiredtreatment by electrocardiography or continuous monitoringduring the postoperative period. Although treatment of AFmay vary slightly between hospitals, it is general practice inthe participating institutions to restore sinus rhythm in most

able 2ntraoperative characteristics stratified by postoperative atrial fibrillation

Variable POAF pValue

No(n � 13,950)

Yes(n � 5,547)

Off-pump procedures 1,234 (8.8%) 318 (5.7%) �0.001Number of distal

anastomoses,mean � SD

3.19 � 1.06 3.33 � 1.02 �0.001

Cardiopulmonary bypasstime (min), mean � SD

87.51 � 42.07 95.26 � 39.37 �0.001

Aortic cross-clamp time(min), mean � SD

63.41 � 34.47 69.70 � 32.60 �0.001

Internal mammary arterygraft used

13,224 (94.8%) 5,246 (94.6%) 0.469

Radial artery graft used 8,099 (58.1%) 3,504 (63.2%) �0.001Intravenous nitrates at time

of surgery1,138 (8.2%) 439 (7.9%) 0.572

Anticoagulants at time ofsurgery

2,944 (21.1%) 1,157 (20.9%) 0.699

Steroids at time of surgery 192 (1.4%) 94 (1.7%) 0.096

patients within 24 hours after the onset of POAF using

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221Coronary Artery Disease/Atrial Fibrillation After CABG Surgery

electrolyte replacement, antiarrhythmic drugs (AADs), orby electrical cardioversion. Patients in AF who are dis-charged home are maintained on warfarin (in the absence ofany contraindication) and usually referred for cardioversionafter 3 to 6 weeks. Patients discharged home on AADs arefollowed up in clinics in 6 weeks. In the absence of evidenceof AF recurrence, their AADs are stopped. The decision tostop warfarin in this instance was left to the discretion of thetreating physician.

For this study patients were separated into 2 groupsbased on the development of POAF (POAF group) or not(no-POAF group). Preoperative characteristics, early out-comes, and long-term survival were compared between the2 groups. Late mortality was defined as death from anycause that occurred at any time after hospital discharge.

Fourteen early postoperative outcomes were analyzed:(1) 30-day mortality, defined as death within 30 days ofoperation; (2) permanent stroke, defined as a new centralneurologic deficit persisting for �72 hours; (3) transientstroke, defined as a transient neurologic deficit (transientischemic attack or reversible ischemic neurologic deficit);(4) postoperative acute myocardial infarction, defined as �2of the following: enzyme level elevation, new cardiac wallmotion abnormalities, or new Q waves on serial electrocar-diograms; (5) new renal failure, defined as �2 of the fol-lowing: serum creatinine increased to �200 �mol/L, �2imes increase in creatinine compared to the preoperativealue, or new requirement for dialysis or hemofiltration; (6)rolonged ventilation (�24 hours); (7) multisystem failure;efined as concurrent failure of �2 of the cardiac, respira-ory, or renal systems for �48 hours; (8) septicemia, defineds positive blood cultures supported by �2 of the followingndexes of clinical infection: postoperative fever, increasedranulocyte cell counts, increased C-reactive protein, andncreased erythrocyte sedimentation rate; (9) gastrointesti-al complications, defined as postoperative occurrence ofny gastrointestinal complication; (10) deep sternal infec-ion involving muscle and bone as demonstrated by surgicalxploration and 1 of the following: positive cultures or

Table 3Early outcomes stratified by postoperative atrial fibrillation

Outcome POA

No

30-Day mortality 170 (1.2)Permanent stroke 94 (0.7%)Transient stroke 51 (0.4%)Postoperative myocardial infarction 105 (0.8%)New renal failure 376 (2.7%)Deep sternal wound infection 86 (0.6%)Septicemia 96 (0.7%)Pneumonia 560 (4.0%)Red blood cell transfusion 5,511 (39.5%)Multisystem failure 72 (0.5%)Prolonged ventilation 1,074 (7.7%)Gastrointestinal complications 117 (0.8%)Return to theater 606 (4.3%)Return to theater for bleeding 302 (2.2%)

CI � confidence interval; OR � odds ratio.

reatment with antibiotics; (11) pneumonia diagnosed by 1

f the following: positive cultures of sputum, blood, pleuraluid, empyema fluid, transtracheal fluid, or transthoracicuid consistent with the diagnosis and clinical findings ofneumonia; (12) red blood cell transfusion postoperatively;13) return to the operating theater for any cause; and (14)eturn to the operating theater for bleeding.

To assess the impact of POAF on each outcome, logisticegression analysis was used to adjust for 20 preoperativeatient variables, with the outcome as the dependent vari-ble. Long-term survival status was obtained from the Aus-ralian National Death Index. The closing date was March8, 2010. A Kaplan–Meier estimate of survival was ob-ained. Differences in long-term survival were assessed byog-rank test. The role of POAF in long-term survival wasssessed by constructing a Cox proportional hazards modelsing octogenarian status and other preoperative patientharacteristics as variables. Continuous variables are pre-ented as mean � 1 SD. Mann–Whitney U test was used to

compare 2 groups of continuous variables. Fisher’s exacttest or chi-square test was used to compare groups of cate-goric variables. All calculated p values were 2-sided, and ap value �0.05 was considered statistically significant. Sta-tistical analysis was performed using SPSS 17.0 for Win-dows 0 (SPSS, Inc., Munich, Germany).

Results

CABG surgery was undertaken in 21,534 patients at 18Australian institutions. Of these 1,991 patients present pre-operatively with arrhythmia and were excluded from theanalysis; the remaining 19,497 are the principal subjects ofthe present study. Of the remaining patients, 5,547 (28.5%)developed POAF. Preoperative and demographic character-istics of the POAF and no-POAF groups are presented inTable 1. There were some differences in intraoperativevariables between the 2 groups. These are presented inTable 2.

Overall 30-day mortality and operative mortality were1.4% and 1.5%, respectively. The unadjusted 30-day mor-

p Value Adjusted OR (95% CI)

Yes

95 (1.7) 0.376 1.14 (0.86–1.50)73 (1.3%) 0.001 1.80 (1.29–2.51)33 (0.6%) 0.088 1.52 (0.94–2.44)52 (0.9%) 0.116 1.34 (0.93–1.93)

391 (7.0%) �0.001 2.32 (1.98–2.72)68 (1.2%) �0.001 1.90 (1.33–2.71)

111 (2.0%) �0.001 2.68 (1.98–3.63)384 (6.9%) �0.001 1.73 (1.50–2.00),638 (47.6%) �0.001 1.20 (1.12–1.28)

94 (1.7%) �0.001 2.94 (2.09–4.13)764 (13.8%) �0.001 1.78 (1.59–1.99)119 (2.1%) �0.001 2.04 (1.55–2.69)442 (8.0%) �0.001 1.72 (1.50–1.97)203 (3.7%) �0.001 1.61 (1.31–1.96)

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tality rate was 1.2% in patients without POAF and 1.7% in

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222 The American Journal of Cardiology (www.ajconline.org)

patients who developed POAF. This difference was signif-icant on univariate analysis (p � 0.007). The independentassociation of POAF with other postoperative outcomes ispresented in Table 3. The logistic regression model predict-ing 30-day mortality is presented in Table 4. This model hasa Hosmer–Lemeshow chi-square statistic of 5.46 (p � 0.71)and demonstrates that POAF was not an independent pre-dictor for 30-day mortality (p � 0.376). On univariate

Figure 1. Overall survival in patients undergoing isolated coronary

Table 4Univariate and multivariate predictors of 30-day mortality

Preoperative Variables

OR (9

ena age 1.06 (1.0trial fibrillation 1.41 (1.1

Female gender 1.63 (1.2Chronic obstructive pulmonary disease 1.58 (1.1Diabetes mellitus 1.42 (1.1Hypercholesterolemia 0.72 (0.5Hypertension 1.52 (1.1Cerebrovascular disease 1.49 (1.0Peripheral vascular disease 2.34 (1.7Renal failure 3.84 (2.5Obesity 0.92 (0.7Recent myocardial infarction (�21 days) 2.88 (2.2History of congestive heart failure (%) 3.64 (2.8Unstable angina (%) 4.21 (3.1Left main stenosis �50% 1.98 (1.5Left ventricular ejection fraction �0.45 3.98 (3.1New York Heart Association classification III or IV 3.23 (2.53-Vessel disease 1.84 (1.3Nonelective procedure 2.91 (2.2Critical preoperative state 7.60 (5.7

Abbreviations as in Table 3.

analysis, patients with POAF had a significantly longer

mean postoperative length of stay (10.23 � 9.60 vs 7.63 �7.61 days, p �0.001) and intensive care unit stay (53.77 �98.29 vs 36.81 � 91.80 hours, p �0.001) compared topatients who did not develop POAF.

Mean follow-up period for this study was 44 months(range 0 to 106). Long-term survival at 1 year and 3, 5, and7 years postoperatively was significantly lower in patientswho developed POAF compared to those who did not

ypass grafting surgery stratified by postoperative atrial fibrillation.

nivariate Multivariate

p Value OR (95% CI) p Value

) �0.001 1.04 (1.03–1.06) �0.001) 0.007 1.14 (0.86–1.50) 0.376) �0.001 1.28 (0.95–1.72) 0.101) 0.006 0.93 (0.64–1.34) 0.693) 0.005 1.03 (0.77–1.36) 0.858) 0.020 0.76 (0.55–1.04) 0.084) 0.012 1.42 (0.98–2.08) 0.067) 0.021 0.90 (0.61–1.33) 0.592) �0.001 1.53 (1.10–2.13) 0.012) �0.001 1.95 (1.22–3.12) 0.005) 0.507 1.02 (0.76–1.39) 0.878) �0.001 1.57 (1.15–2.16) 0.005) �0.001 1.83 (1.34–2.50) �0.001) �0.001 1.78 (1.26–2.53) 0.001) �0.001 1.29 (0.97–1.710 0.086) �0.001 1.94 (1.43–2.62) �0.001) �0.001 1.59 (1.18–2.14) 0.002) �0.001 1.10 (0.78–1.56) 0.591) �0.001 1.37 (0.98–1.91) 0.0694) �0.001 2.63 (1.82–3.82) �0.001

U

5% CI)

5–1.070–1.826–2.124–2.181–1.824–0.950–2.106–2.105–3.119–5.690–1.196–3.673–4.689–5.564–2.540–5.101–4.164–2.545–3.785–10.0

(96.4% vs 97.7%, 92.4% vs 95.4%, 86.6% vs 91.4%, and

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223Coronary Artery Disease/Atrial Fibrillation After CABG Surgery

80.6% vs 87.0%, p �0.001; Figure 1). After adjusting fordifferences in patient variables, POAF was independentlyassociated with decreased long-term survival (p � 0.002). ACox regression model predicting late mortality is presentedin Table 5.

Discussion

In our study of 19,497 patients, 5,547 (28.5%) developedPOAF. This incidence is consistent with the reported liter-ature. Early mortality rate was significantly higher in pa-tients with POAF on univariate analysis (1.7% vs 1.2%, p �0.007) but not multivariate analysis (p � 0.376). To thisend, our data suggest that confounding factors more prev-alent in the POAF study population largely account for thehigher incidence of early mortality observed in that group.Indeed, patients with POAF were 5 years older at the timeof cardiac surgery and presented more often with co-mor-bidities independently associated with early mortality in-cluding hypertension, renal failure, and peripheral vasculardisease. Our findings are similar to those reported byBramer et al18 who also showed an association of POAF

ith early mortality on univariate analysis (3.1% vs 1.6%,� 0.002) but not multivariate analysis (p � 0.169). The

nvestigators also showed that a worse preoperative riskrofile in patients with POAF accounted for the higher ob-erved early mortality. Kalavrouziotis et al9 used propensity-

score analysis to demonstrate that POAF was not associatedwith an increase in 30-day mortality in matched patients. Sim-ilar findings have been reported elsewhere.6,14,19 In contrast,Villareal et al7 showed that POAF was independently asso-ciated with early mortality (7.4% vs 3.4%, p � 0.0007). Ithas been argued by some investigators that this may haveresulted from adjusting for age as a dichotomous variable

Table 5Univariate and multivariate predictors of late mortality

Preoperative Variables

OR (9

ge (mean) 1.07 (1.Atrial fibrillation 1.57 (1.Female gender 1.15 (1.Chronic obstructive pulmonary disease 1.74 (1.Diabetes mellitus 1.42 (1.Hypercholesterolemia 0.73 (0.Hypertension 1.49 (1.Cerebrovascular disease 1.49 (1.Peripheral vascular disease 2.58 (2.Renal failure 4.13 (3.Obesity 0.88 (0.Recent myocardial infarction (�21 days) 1.17 (1.History of congestive heart failure (%) 2.37 (2.Unstable angina (%) 1.23 (1.Left main stenosis �50% 1.45 (1.Left ventricular ejection fraction �0.45 2.39 (2.New York Heart Association classification III or IV 1.85 (1.3-Vessel disease 1.75 (1.Nonelective procedure 1.40 (1.Critical preoperative state 1.41 (1.

Abbreviations as in Table 3.

rather than a continuous variable, which may have been i

inadequate because age is such a powerful predictor of earlydeath and POAF.18,20 Regardless, these conflicting datanderscore the need for further investigation into the influ-nce of POAF on early mortality.

Of the 13 other early complications evaluated, POAFas associated with an increased incidence of 11. Postop-

rative renal dysfunction/failure was significantly higher onultivariate analysis in patients with POAF (7.0% vs 2.7%,�0.001). Albahrani et al12 demonstrated a link between

POAF and acute postoperative renal dysfunction afterCABG. In that study, POAF occurred almost synchronouslywith deterioration in renal function; as such, the researcherspostulated a common etiologic process for the 2. Kalavrou-ziotis et al9 showed that POAF significantly increased therisk of renal failure even after matching patients usingpropensity analysis (7.6% vs 4.3%, p �0.001). Other inves-tigators have shown likewise.3,10 Interestingly, our datashowed on multivariate analysis that POAF independentlydoubled the risk of developing gastrointestinal complica-tions (2.1% vs 0.8%, p �0.001). These findings closelycorrelate with those of Andersson et al13 who also showedthat POAF more than doubled the likelihood of gastrointes-tinal complications (odds ratio 2.4, p � 0.006). In accor-ance with other studies, the incidence of infective compli-ations in our cohort was higher in patients with POAF onultivariate analysis.9,11,14 Perhaps encouragingly, how-

ever, our study did not show that POAF increases theincidence of perioperative myocardial infarction, which isconsistent with some studies7,21 but contrary to the findingsof others.3,11

Stroke is an important complication after CABG andnumerous studies have implicated POAF as a significantrisk factor.6,7,9 Our data showed a significant increase in the

nivariate Multivariate

p Value OR (95% CI) p Value

) �0.001 1.06 (1.05–1.07) �0.001) �0.001 1.19 (1.06–1.32) 0.002) 0.017 0.91 (0.80–1.02) 0.112) �0.001 1.32 (1.15–1.50) �0.001) �0.001 1.20 (1.08–1.34) 0.001) �0.001 0.77 (0.68–0.87) �0.001) �0.001 1.19 (1.03–1.36) 0.015) �0.001 1.35 (1.18–1.54) �0.001) �0.001 1.61 (1.42–1.82) �0.001) �0.001 2.52 (2.08–3.05) �0.001) 0.015 1.05 (0.94–1.18) 0.398) �0.001 1.04 (0.91–1.19) 0.593) �0.001 1.44 (1.28–1.63) �0.001) �0.001 1.06 (0.89–1.25) 0.517) �0.001 1.14 (1.01–1.28) 0.030) �0.001 1.68 (1.49–1.89) �0.001) �0.001 1.21 (1.08–1.36) 0.001) �0.001 1.20 (1.04–1.37) 0.010) �0.001 1.11 (0.98–1.26) 0.092) �0.001 1.42 (1.17–1.71) �0.001

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5% CI)

06–1.0842–1.7403–1.2954–1.9729–1.5765–0.8231–1.6931–1.6930–2.8950–4.8879–0.9811–1.2413–2.6314–1.3231–1.6215–2.6466–2.0554–1.9927–1.5534–1.49

ncidence of permanent stroke in patients with POAF (1.3%

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224 The American Journal of Cardiology (www.ajconline.org)

vs 0.7%, p �0.001). It is comforting to note, however, thatthe total incidence of stroke in patients with POAF in thepresent study (1.9%) was generally lower than has beenreported elsewhere.6 The increased morbidity attributable to

OAF invariably translates into an increased length of in-ensive care unit and hospital stay.3,11,14 This then results in

an increased cost of hospitalization. Although we did notcalculate cost in our study, significant increases in hospitallength of stay and intensive care unit stay were apparent(p �0.001). Aranki et al14 demonstrated that POAF wasindependently associated with increased hospital stay; thistranslated into additional costs exceeding $10,000 in 1996.Although POAF is not the most expensive complication, itis among the most frequent; therefore, the cumulative costof POAF is very high. Several studies have demonstrated anindependent association of POAF with decreased long-termsurvival.2,7,19,21,22 Our data replicated these findings andhowed that POAF was independently associated with a9% increase in late mortality (p � 0.002). Almassi et al6

first observed a higher 6-month mortality in cardiac surgicalpatients affected by POAF (9.4% vs 4.2%, p �0.001).Subsequent studies have confirmed these findings anddemonstrated that POAF, independent of age, increasesthe risk of late mortality by up to 50%.7 El-Chami et al21

specifically analyzed the impact of AF on long-termsurvival and showed that the negative impact of POAFpersisted after excluding patients who died during theinitial hospitalization.

Several plausible mechanisms supporting a direct effectof POAF on late mortality have been proposed, although aconcrete explanation has not been provided. These includeheart failure and potential AF recurrence with subsequentthromboembolic sequelae.23 Animal and human studieshave shown that AF can, by impairing atrial systolic con-traction, predispose to ventricular dilation and decrease car-diac output.23,24 The decreased cardiac output and impairederebral circulation render the patient susceptible to nonem-olic stroke. Moreover, AF promotes impaired hemody-amics from decreased ventricular filling and circulatorytasis in the left atrium, rendering the patient susceptible totroke and embolic events.25 Recent studies have corrobo-ated the association of POAF and late mortality secondaryo stroke and heart failure. El-Chami et al21 demonstrated a2% decrease in late mortality in patients discharged onarfarin, implicating embolic events as a potential cause ofeath. Ahlsson et al22 observed that POAF doubled the riskf death secondary to cerebral ischemia and myocardialnfarction (4.2% vs 0.2% and 6.7% vs 3.0%, respectively).

possible explanation for the poorer outcome of patientsith POAF was also provided by the investigators; POAFas associated with an eightfold increase in the develop-ent of late AF after hospital discharge. Although signifi-

ant advances have been made, our study and others under-core the need to further investigate the mechanismsnderlying the impact of POAF on late survival.

Given the impact of POAF on early and late outcomes,umerous prevention and treatment strategies have beenxplored. With regard to preventative options, only � block-

ers,16,26 rate-limiting calcium antagonists,27 magnesium,26

and amiodarone28 have been shown to potently decrease AF

ostoperatively. In 1 meta-analysis,29 however, prophylac- W

tic treatment to decrease POAF decreased overall cost andlength of stay but did not significantly affect stroke andmortality. In the prophylaxis and management of POAF,judicious use of thrombotic prophylaxis and correction ofidentifiable precipitants such as electrolyte imbalances arerecommended.16 The role of other drugs including renin–ngiotensin–aldosterone system blockers and statins inodulating the incidence of POAF requires further study.16

Unfortunately, given the retrospective design of this study,we are unable to comment on the effect of the variouspreventative methods proposed. A prospective investigationwould be most helpful in this regard. Moreover, previousstudies have implied that the incidence of POAF may belower after off-pump surgery.30 It has been argued that thiss because of cardiopulmonary bypass–induced systemicnflammatory response syndrome, which is likely to play anmportant role in the occurrence of POAF. Our data alsohowed a lower incidence of POAF in the off-pump popu-ation (8.8% vs 5.7%, p �0.001). This pertinent topic meritsurther research.

The present study has several limitations, the most im-ortant of which is its retrospective nature. Our data also doot allow us to differentiate between early and late occur-ing AF or determine the duration of AF, factors likely to berognostic. Our dataset lacks information on drug medica-ion at discharge and during follow-up. In particular, knowl-dge about the administration of antiarrhythmic medicationnd long-term use of anticoagulation therapy during theostoperative period would have been useful. The associa-ion observed between POAF and late mortality also doesot necessarily imply causation. Although, cerebrovascularccidents and myocardial infarction secondary to AF areell established, our study does not provide autopsy results

nd only all-cause mortality was considered. We acknowl-dge a limitation in our methodology. Although we at-empted to adjust for different variables, it is very likely thatnmeasured factors may have influenced outcomes. Never-heless, our study reaffirms, with sufficient conviction, thatOAF affects short- and long-term outcomes after isolatedABG surgery.

ppendix

The following investigators, data managers, and institu-ions participated in the ASCTS database: Alfred Hospital:. Pick, J. Duncan; Austin Hospital: S. Seevanayagam, M.haw; Cabrini Health: G. Shardey; Geelong Hospital: M.orteza, C. Bright; Flinders Medical Centre: J. Knight,. Baker, J. Helm; Jessie McPherson Private Hospital: J.mith, H. Baxter H; John Hunter Hospital: A. James, S.caybrook; Lake Macquarie Hospital: B. Dennett, M. Ja-obi; Liverpool Hospital: B. French, N. Hewitt; Materealth Service Hospital: A.M. Diqer, J. Archer; Monashedical Centre: J. Smith, H. Baxter; Prince of Wales Hos-

ital: H. Wolfenden, D. Weerasinge; Royal Melbourne Hos-ital: P. Skillington, S. Law; Royal Prince Alfred Hospital:. Wilson, L. Turner; St. George Hospital: G. Fermanis, C.edmond; St. Vincent’s Hospital, Victoria: M. Yii, A. New-omb, J. Mack, K. Duve; St. Vincent’s Hospital, New South

ales: P. Spratt, T. Hunter; Canberra Hospital: P. Bissaker,

225Coronary Artery Disease/Atrial Fibrillation After CABG Surgery

K. Butler; Townsville Hospital: R. Tam, A. Farley; West-mead Hospital: R. Costa, M. Halaka.

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