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Burden of preoperative atrial fibrillation in patients undergoing coronary artery bypass grafting

Open ArchivePublished:February 08, 2018DOI:https://doi.org/10.1016/j.jtcvs.2018.01.069

      Abstract

      Background

      This study compares early and late outcomes in patients undergoing coronary artery bypass grafting with and without preoperative atrial fibrillation in a contemporary, nationally representative Medicare cohort.

      Methods

      In the Medicare-Linked Society of Thoracic Surgeons database, 361,138 patients underwent isolated coronary artery bypass from 2006 to 2013, of whom 37,220 (10.3%) had preoperative atrial fibrillation; 13,161 (35.4%) were treated with surgical ablation and were excluded. Generalized estimating equations were used to compare 30-day mortality and morbidity. Long-term survival was summarized using Kaplan-Meier curves and Cox regression models. Stroke and systemic embolism incidence was modeled using the Fine-Gray model and the CHA2DS2-VASc score was used to analyze stroke risk. Median follow-up was 4 years.

      Results

      Preoperative atrial fibrillation was associated with a higher adjusted in-hospital mortality (odds ratio [OR], 1.5; P < .0001) and combined major morbidity including stroke, renal failure, prolonged ventilation, reoperation, and deep sternal wound infection (OR, 1.32; P < .0001). Patients with preoperative atrial fibrillation experienced a higher adjusted long-term risk of all-cause mortality and cumulative risk of stroke and systemic embolism compared to those without atrial fibrillation. At 5 years, the survival probability in the preoperative atrial fibrillation versus no atrial fibrillation groups stratified by CHA2DS2-VASc scores was 74.8% versus 86.3% (score 1-3), 56.5% versus 73.2% (score 4-6), and 41.2% versus 57.2% (score 7-9; all P < .001).

      Conclusions

      Preoperative atrial fibrillation is independently associated with worse early and late postoperative outcomes. CHA2DS2-VASc stratifies risk, even in those without preoperative atrial fibrillation.

      Key Words

      Abbreviations and Acronyms:

      ASCERT (American College of Cardiology Foundation–Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies), AF (atrial fibrillation), CABG (coronary artery bypass graft), CAD (coronary artery disease), CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥ 75, Diabetes, Stroke, VAScular disease, Age 65-74, Sex category), CI (confidence interval), CMS (Centers for Medicare and Medicaid), HR (hazard ratio), OR (odds ratio), SSE (stroke or systemic embolism), STS (Society of Thoracic Surgeons)
      Figure thumbnail fx1
      Survival is worse in patients with preoperative AF compared to those with no AF (P < .001).
      AF before CABG is associated with higher early and late perioperative mortality and morbidity. Survival and risk of stroke or systemic embolism are worse after adjusting for comorbidities.
      Preoperative atrial fibrillation is an independent risk factor for worse outcomes after coronary artery bypass surgery. Further analysis of the comparative effectiveness of concomitant atrial fibrillation ablation has important implications for this high-risk cohort.
      See Editorial Commentary page 2368.
      The incidence of atrial fibrillation in patients with coronary artery disease (CAD) requiring coronary artery bypass grafting (CABG) is approximately 6% according to a historical Society of Thoracic Surgeons (STS) report.
      • Gammie J.S.
      • Haddad M.
      • Milford-Beland S.
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      • Ferguson Jr., T.B.
      • O'Brien S.M.
      • et al.
      Atrial fibrillation correction surgery: lessons from the Society of Thoracic Surgeons National Cardiac Database.
      Published reports on the association between preoperative atrial fibrillation (AF) and post-CABG outcomes have shown worse perioperative mortality and long-term survival.
      • Quader M.A.
      • McCarthy P.M.
      • Gillinov A.M.
      • Alster J.M.
      • Cosgrove D.M .I.I.I.
      • Lytle B.W.
      • et al.
      Does preoperative atrial fibrillation reduce survival after coronary artery bypass grafting?.
      • Rogers C.A.
      • Angelini G.D.
      • Culliford L.A.
      • Capoun R.
      • Ascione R.
      Coronary surgery in patients with preexisting chronic atrial fibrillation: early and midterm clinical outcome.
      • Ngaage D.L.
      • Schaff H.V.
      • Mullany C.J.
      • Sundt III, T.M.
      • Dearani J.A.
      • Barnes S.
      • et al.
      Does preoperative atrial fibrillation influence early and late outcomes of coronary artery bypass grafting?.
      • Ad N.
      • Barnett S.D.
      • Haan C.K.
      • O'Brien S.M.
      • Milford-Beland S.
      • Speir A.M.
      Does preoperative atrial fibrillation increase the risk for mortality and morbidity after coronary artery bypass grafting?.
      • Bramer S.
      • van Straten A.H.
      • Soliman Hamad M.A.
      • Berreklouw E.
      • Martens E.J.
      • Maessen J.G.
      The impact of preoperative atrial fibrillation on early and late mortality after coronary artery bypass grafting.
      • Al-Sarraf N.
      • Thalib L.
      • Hughes A.
      • Tolan M.
      • Young V.
      • McGovern E.
      Effect of preoperative atrial fibrillation on postoperative outcome following cardiac surgery.
      • Saxena A.
      • Kapoor J.
      • Dinh D.T.
      • Smith J.A.
      • Shardey G.C.
      • Newcomb A.E.
      Preoperative atrial fibrillation is an independent predictor of worse early and late outcomes after isolated coronary artery bypass graft surgery.
      Previous STS database studies have shown increased perioperative mortality and stroke in patients with preoperative AF, but long-term outcomes were not studied.
      • Badhwar V.
      • Rankin J.S.
      • Ad N.
      • Grau-Sepulveda M.
      • Damiano R.J.
      • Gillinov A.M.
      • et al.
      Surgical ablation of atrial fibrillation in the United States: trends and propensity matched outcomes.
      The STS database recent linkage to the Centers for Medicare and Medicaid Services (CMS) database allows for study of important long-term endpoints beyond perioperative outcomes provided in the STS National Cardiac Database. Using CMS-linked STS data, this study sought to examine early and late outcomes in 2 groups of first cardiac surgery CABG patients: (1) those with preoperative AF but no surgical AF treatment, and (2) those without preoperative AF.

      Patients and Methods

      Data for all patients were obtained from the STS Adult Cardiac Surgery Database (versions 2.52, 2.61, and 2.73) for patients discharged between January 1, 2006, and December 31, 2013, and who could be linked to CMS data using a validated deterministic matching algorithm.
      • Jacobs J.P.
      • Edwards F.H.
      • Shahian D.M.
      • Haan C.K.
      • Puskas J.D.
      • Morales D.L.
      • et al.
      Successful linking of the Society of Thoracic Surgeons adult cardiac surgery database to Centers for Medicare and Medicaid Services Medicare data.

       Study Population

      Medicare recipients age 65 years or older and undergoing CABG as a first cardiac surgery who had complete information on preoperative history of atrial arrhythmias were included. Between January 2006 and December 2013, there were 688,466 isolated CABG surgery procedures reported in the STS database in patients age 65 years or older. Of those, 119,597 patients were excluded because of prior cardiac surgery (n = 44,671), emergent/salvage status–cardiogenic shock/resuscitation (n = 25,542), preoperative intra-aortic balloon pump/inotropes (n = 44,977), history of endocarditis (n = 637), and missing or inconsistent data on arrhythmia, number of diseased vessels, gender, or any of the previous fields considered for exclusion (n = 3770). Of the resulting population, additional exclusions were made for 207,553 with unlinked CMS data, 178 had more than 1 admission on the same day, and 13,161 had surgical ablation. The resulting 347,977 patients with linked CMS data (61%) were categorized according to their preoperative AF status: (1) 89.7% (n = 323,918) no preoperative AF (No AF) or (2) 6.7% (n = 24,059) preoperative AF (AF group) and analyzed (Figure E1).

       Study Outcomes

      The primary outcome was all-cause mortality after CABG. This was defined using STS registry data for in-hospital deaths and the linked Medicare Denominator File for postdischarge deaths.

      Mann E, Asper F, Durham S. Death information in the research identifiable Medicare data. Available at: https://www.resdac.org/resconnect/articles/117. Accessed September 8, 2017.

      Secondary outcomes included (1) stroke or systemic embolism (SSE; ischemic stroke, hemorrhagic stroke, transient ischemic attack, or systemic arterial embolism), (2) in-hospital mortality, and (3) a composite of in-hospital major morbidity.
      • D'Agostino R.S.
      • Jacobs J.P.
      • Badhwar V.
      • Paone G.
      • Rankin J.S.
      • Han J.M.
      • et al.
      The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2017 Update on Outcomes and Quality.
      Incident SSE was defined by using STS registry data to account for in-hospital strokes and Medicare Part A data to identify subsequent rehospitalizations with SSE as a primary diagnosis (International Classification of Diseases, 9th revision, codes: 433.1, 434.x1, 430, 431, 432.0, 432.1, 432.9, 444,x, 435.x). The STS database does not include the exact date of in-hospital strokes; for the purpose of time-to-event analyses, we assigned the date of in-hospital stroke to be the date of the index operation.
      In-hospital major morbidity, a previously defined composite,
      • Shahian D.M.
      • Edwards F.H.
      • Ferraris V.A.
      • Haan C.K.
      • Rich J.B.
      • Normand S.L.
      • et al.
      Quality measurement in adult cardiac surgery: part 1–Conceptual framework and measure selection.
      • O'Brien S.M.
      • Shahian D.M.
      • DeLong E.R.
      • Normand S.L.
      • Edwards F.H.
      • Ferraris V.A.
      • et al.
      Quality measurement in adult cardiac surgery: part 2–Statistical considerations in composite measure scoring and provider rating.
      referred to any of the following postprocedure complications: permanent stroke, new cases of renal failure, prolonged ventilation (ventilation longer than 24 hours after surgery), reoperation for cardiac reasons (graft dysfunction, bleeding, valve dysfunction or other), and deep sternal wound infection.

       Statistical Methods

      The overall study population and the subgroups of interest (No AF vs AF) were summarized using medians and interquartile ranges (25th and 75th percentiles) for continuous variables and frequency counts and percentages for categorical variables. Differences in distributions among patients with No AF versus AF were evaluated with Wilcoxon and Pearson chi-square tests, respectively.
      Logistic regression models were developed to estimate the association between in-hospital outcomes and AF versus No AF. The generalized estimated equations method with an exchangeable correlation structure was used to compute confidence limits that account for hospital clustering of patients. Adjusted models included predictors of long-term survival after CABG identified with the validated American College of Cardiology Foundation–Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies (ASCERT) model
      • Shahian D.M.
      • O'Brien S.M.
      • Sheng S.
      • Grover F.L.
      • Mayer J.E.
      • Jacobs J.P.
      • et al.
      Predictors of long-term survival after coronary artery bypass grafting surgery: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (the ASCERT study).
      : age, ejection fraction, year of surgery, renal failure (glomerular filtration rate <30 or dialysis), glomerular filtration rate, body mass index, height, sex, race, current smoking, chronic heart failure/New York Heart Association Class IV, urgent operative status, number of diseased vessels, diabetes, previous carotid surgery, carotid stenosis > 75%, transient ischemic attack, chronic lung disease moderate/severe, left main disease, unstable angina, peripheral vascular disease, immunosuppressant medication, hypertension, valve insufficiency (tricuspid, aortic, mitral) moderate/severe, aortic stenosis gradient, preoperative myocardial infarction (less than 6 hours before, between 6 and 24 hours, between 1 and 21 days). These variables were also used for all adjusted time-to-event analyses.
      Time-to-event analysis was used to compare long-term survival and SSE occurrence by group. For survival, patient follow-up was censored at the end of study period (January 1, 2014). Product-limit Kaplan Meier survival estimates were computed for each group and comparisons were made with log-rank tests. Cox regression models were used to compute hazard ratios for the AF versus No AF, both unadjusted and adjusted by other survival predictors. A robust sandwich covariance estimation to compute 95% confidence intervals was used to account for correlation of patients' failure times within the same hospital. The proportional hazard assumption was tested using log-log survival plots (log-log survival vs log-time) for each group and the results indicated no violation of this assumption. Consistent with the validated STS risk models,
      • Shahian D.M.
      • O'Brien S.M.
      • Sheng S.
      • Grover F.L.
      • Mayer J.E.
      • Jacobs J.P.
      • et al.
      Predictors of long-term survival after coronary artery bypass grafting surgery: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (the ASCERT study).
      missing values (<3%) were imputed with relevant groups-specific medians for continuous variables and most common category for categorical ones. The adjusted survival estimates were computed using all possible combinations of covariates in our dataset, estimating survival curves for each patient in the data set and then averaging over patients in each group of interest to obtain the adjusted curves (with point-wise 95% confidence intervals). Lastly, a possible interaction between AF groups and preoperative Congestive heart failure, Hypertension, Age ≥ 75, Diabetes, Stroke, Vascular disease, Age 65-74, Sex category (CHA2DS2-VASc) scores
      • Lip G.Y.
      • Nieuwlaat R.
      • Pisters R.
      • Lane D.A.
      • Crijns H.J.
      Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation.
      was evaluated including a multiplicative interaction term in the model and computing hazard ratios for the AF group in each risk group. A possible effect modification by CHA2DS2-VASc scores, categorized in 3 groups: low risk (1-3), moderate risk (4-7) and high risk (7-9) was also evaluated.
      For the SSE time-to-event analysis, death was considered as a competing risk. Follow-up was censored at death date, end of fee-for-service date or end of study period, whichever came first. Date for in-hospital strokes after a procedure was not available, and surgery date was assigned as the event date (23% of all strokes). Cumulative incidence functions for stroke, overall and by AF groups were computed and comparisons among groups were made using Gray tests. For the regression analysis, the Fine and Gray method was used to calculate the subdistribution hazard ratio. The proportional hazards assumption (accounting for the competing risk of death) was tested by plotting Schoenfeld residuals
      • Fine J.P.
      • Gray R.J.
      A proportional hazards model for the subdistribution of a competing risk.
      • Gray R.J.
      A Class of K-sample tests for comparing the cumulative incidence of a competing risk.
      for each AF group versus log-time and observed no violation. A not-significant interaction term between AF groups and log-time in the regression model was consistent with this finding. Unadjusted and adjusted subdistribution hazard ratios were then computed for AF versus No AF. The interaction with CHA2DS2-VASc scores groups was evaluated with a multiplicative interaction term.
      A P value less than 0.05 was considered statistically significant for all tests. All tests were 2-sided. Analyses were performed using SAS (version 9.4, SAS Institute, Cary, NC).

      Results

       Baseline Characteristics

      Characteristics for patients are summarized in Table 1. Compared to the patients with No AF, patients in the AF group were older and had prior hypertension, renal failure, chronic lung disease, lower ejection fraction and New York Heart Association class III/IV heart failure, but a lower incidence of dyslipidemia.
      Table 1Baseline characteristics of patients in No AF or AF groups
      Variable
      Summaries reported for continuous variables are median (first quartile, third quartile); for variables with discrete distributions, we report counts and (%).
      No AF (N = 323,918)AF (N = 24,059)Standardized differenceP value
      Age, y72 (68, 77)75 (71, 80)39.94<.0001
      Female sex99,345 (31)6920 (29)−4.17<.0001
      Body mass index, kg/m228.09 (25, 32)28.10 (25, 32)1.93.954
      Height, cm172.7 (163, 178)173 (165, 180)12.06<.0001
      Race<.0001
       Other6725 (2.08)428 (1.78)−2.16
       Asian5138 (1.59)283 (1.18)−3.51
       Hispanic11,218 (3.46)548 (2.28)−7.10
       Black16,326 (5.04)751 (3.12)−9.71
       Caucasian283,245 (87.44)21,952 (91.24)12.33
       Missing1266 (0.39)97 (0.40)0.20
      Current smoking46,294 (14.29)3111 (12.93)−4.00<.0001
      Diabetes129,348 (40)9903 (41)2.50<.0001
      Hypertension283,689 (88)21,615 (90)7.15<.0001
      Dyslipidemia272,651 (84)19,776 (82)−5.40<.0001
      Peripheral vascular disease56,113 (17.3)5355 (22.3)12.42<.0001
      Renal failure (GFR< 30 or dialysis)16,379 (5.06)1761 (7.32)9.40<.0001
      Glomerular filtration rate66 (54, 81)61 (49, 74)−15.30<.0001
      Chronic lung disease<.0001
       Severe13,365 (4.1)1644 (6.8)11.92
       Moderate20,380 (6.3)2179 (9)10.40
      Cerebrovascular disease57,406 (18)5735 (24)15.11<.0001
      Transient ischemic attack15,283 (4.72)1620 (6.73)8.68<.0001
      Previous carotid surgery17,425 (5.38)1739 (7.23)7.61<.0001
      Carotid stenosis >75%10,742 (3.32)964 (4.01)3.68<.0001
      Immunosuppressive treatment8167 (2.5)993 (4.1)8.97<.0001
      Preoperative myocardial infarction<.0001
       ≤6 h652 (0.20)47 (0.20)−0.13
       >6 h but <24 h3291 (1.02)212 (0.88)−1.39
       1-21 d68,921 (21.3)7476 (31.1)22.42
      Coronary artery disease
       Left main ≥ 50%108,365 (33)8713 (36)5.81<.0001
       3 vessels249,559 (77)18,524 (77)−0.12.77
       2 vessels63,154 (20)4720 (20)0.31
       1 vessel11,205 (3.5)815 (3.4)−0.39
      Left ventricular ejection fraction ≥ 55%182,144 (58)10,761 (46)−24.45<.0001
      NYHA class IV9567 (21)1796 (25)8.63<.0001
      Valve insufficiency, severe<.0001
       Tricuspid595 (0.18)141 (0.59)6.50
       Aortic216 (0.07)25 (0.10)1.28
       Mitral1050 (0.32)189 (0.79)6.21
      Aortic stenosis (moderate or severe)9627 (2.97)1124 (4.67)8.87<.0001
      Urgent procedure163,417 (50)14,303 (59)18.16<.0001
      Surgery years<.0001
       201332,815 (10.13)2332 (9.69)−1.47
       201233,588 (10.37)2376 (9.88)−1.64
       201136,708 (11.33)2864 (11.90)1.78
       201040,521 (12.51)3336 (13.87)4.01
       200942,879 (13.24)3399 (14.13)2.59
       200844,666 (13.79)3351 (13.93)0.40
       200745,181 (13.95)3259 (13.55)−1.17
       200646,382 (14.46)3071 (12.76)−4.94
       2005728 (0.22)71 (0.30)1.38
      AF, Atrial fibrillation; GFR, glomerular filtration rate; NYHA, New York Heart Association.
      Summaries reported for continuous variables are median (first quartile, third quartile); for variables with discrete distributions, we report counts and (%).

       Perioperative Outcomes

      In-hospital outcomes for the 2 groups are shown in Table 2. Patients in the AF group were more likely to have reoperation, permanent stroke, prolonged ventilation, new renal failure, deep sternal wound infection, and in-hospital mortality. Results of regression analysis are shown in Table 3. Compared to those with No AF, the AF group was associated with higher (4.00% vs 1.81%) adjusted in-hospital mortality (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.39-1.62; P < .0001) and combined major in-hospital morbidity including stroke, renal failure, prolonged ventilation, reoperation for any cause and deep sternal wound infection (OR, 1.32; 95% CI, 1.27-1.37; P < .0001). The AF group had higher adjusted major morbidity in every category except deep sternal wound infection (OR, 1.15; 95% CI, 0.94-1.32; P = .17).
      Table 2Perioperative morbidity and mortality frequency (unadjusted in-hospital outcomes by study group)
      Variable
      Summaries reported for continuous variables are median (first quartile, third quartile); for variables with discrete distributions, values are n and (%).
      No AFAFP value
      (N = 323,918)(N = 24,059)
      In-hospital mortality4730 (1.46)799 (3.32)<.0001
      Operative mortality5862 (1.81)962 (4.00)<.0001
      In-hospital complications
       Reoperation9259 (2.86)936 (3.89)<.0001
       Neurologic-permanent stroke4358 (1.35)474 (1.97)<.0001
       Prolonged ventilation25,798 (7.96)3326 (13.82)<.0001
       New renal failure10,390 (3.28)1438 (6.19)<.0001
       Deep sternal wound infection966 (0.30)103 (0.43).0004
       Major morbidity composite40,092 (12.38)4781 (19.87)<.0001
      AF, Atrial fibrillation.
      Summaries reported for continuous variables are median (first quartile, third quartile); for variables with discrete distributions, values are n and (%).
      Table 3Summary of unadjusted and adjusted logistic regression models for in-hospital outcomes of AF group (No AF as reference)
      In-hospital outcomesUnadjusted modelsAdjusted models
      Odds ratio95% Confidence intervalP-valueOdds ratio95% Confidence intervalP value
      In-hospital mortality2.322.15-2.50<.00011.501.39-1.62<.0001
      Operative mortality2.262.11-2.43<.00011.471.37-1.59<.0001
      Major morbidity1.761.69-1.82<.00011.321.27-1.37<.0001
      Prolonged ventilation1.851.77-1.94<.00011.361.30-1.42<.0001
      Reoperation: bleeding, graft, valve, other1.381.28-1.48<.00011.181.09-1.26<.0001
      Deep sternal wound infection1.441.18-1.76.00041.150.94-1.42.175
      Permanent stroke1.471.34-1.62<.00011.201.09-1.32.0003
      Renal failure1.951.84-2.06<.00011.351.27-1.44<.0001

       Long-Term Survival

      Unadjusted survival at 30 days, 1 year, 3 years, and 5 years was 98% versus 96%, 94% versus 87%, 88% versus 75%, and 80% versus 63% in patients with No AF versus AF (hazard ratio [HR], 2.09; 95% CI, 2.04-2.14; P < .0001). Adjusted survival at 30-days, 1-year, 3-years, and 5 years was 98% versus 97%, 94% versus 91%, 88% versus 83%, and 80% versus 73% in patients with No AF versus AF (HR 1.45, 95% CI, 1.41-1.48; P < .0001; Figure 1). A subgroup analysis for mortality by CHA2DS2-VASc scores is displayed in Figure 2. When stratified by scores, 53% of patients had score 1 to 3, 44% of patients had score 4 to 6, and 3% of the overall study population of patients had score 7 to 9. In unadjusted analysis, patients with AF had consistently worse long-term survival compared with No AF patients, within each CHA2DS2-VASc score category. At 5 years, the survival probability in the AF group by CHA2DS2-VASc scores was 74.8% (score 1-3), 56.5% (score 4-6), and 41.2% (score 7-9); in comparison, survival in patients with No AF was 86.3%, 73.2%, and 57.2% respectively (log-rank test P value < .001 in all 3 CHA2DS2-VASc score groups).
      Figure thumbnail gr1
      Figure 1Survival curves in patients with and without preoperative atrial fibrillation (AF) undergoing coronary artery bypass grafting, Cox regression, unadjusted (hazard ratio, 2.09; 95% confidence interval (CI); P < .0001) and adjusted (hazard ratio, 1.45; 95% CI, 1.41-1.48; P < .0001).
      Figure thumbnail gr2
      Figure 2Kaplan-Meier survival curves in patients with preoperative atrial fibrillation (AF) stratified by CHA2DS2-VASc score. CHA2DS2-VASc, Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke, VAScular disease, Age 65-74, Sex category.

       Long-Term Risk of Stroke and Systemic Embolism

      Unadjusted risk of SSE at 30-days, 1-year, 3-years, and 5 years was 1.7% versus 2.4%, 3.0 versus 4.4%, 5.3% versus 7.8%, and 7.5% versus 10.7%, respectively, in patients with No AF versus AF (HR, 1.43; 95% CI, 1.36-1.49; P < .0001; Figure 3). Adjusted HR for SSE was 1.24 (95% CI, 1.19-1.30; P < .001). When stratified by CHA2DS2-VASc scores, the 5-year risk of SSE in patients with preoperative AF was 7.9% (score 1-3), 12.2% (score 4-6), and 15.4% (score 7-9; P < .001; Figure 4). In comparison, the 5-year risk of SSE in patients with No AF by CHA2DS2-VASc scores also increased and was 5.3% (score 1-3), 9.7% (score 4-6), and 16.9% (score 7-9; P < .001).
      Figure thumbnail gr3
      Figure 3Cumulative incidence curves of stroke or systemic embolic incidence (in-hospital and stroke readmissions) in patients with and without atrial fibrillation (AF) undergoing coronary artery bypass grafting (P < .0001). Accounting for death as competing risk.
      Figure thumbnail gr4
      Figure 4Cumulative incidence curves of stroke or systemic embolic incidence in patients with preoperative atrial fibrillation (AF) stratified by CHA2DS2-VASc scores. Adjusted for death as competing risk. CHA2DS2-VASc, Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke, VAScular disease, Age 65-74, Sex category.

       Comment

      This study confirms prior studies and adds to important late observations. Preoperative AF is common in patients undergoing CABG (10%) and is independently associated with increased in-hospital mortality (OR, 1.5) and major morbidity (OR, 1.32). In this study, patients with preoperative AF were older and had more comorbidities than those without AF, and they had worse long-term mortality (HR, 1.45), even after adjusting for these risk factors. The long-term risk of SSE was significantly worse in patients with preoperative AF (HR, 1.43). Unsurprisingly, they also had higher CHA2DS2-VASc scores (Video 1).
      Figure thumbnail fx2
      Video 1Dr S. Chris Malaisrie provides an overview of the study aims and outcomes. Video available at: http://www.jtcvsonline.org/article/S0022-5223(18)30312-X/fulltext.
      Previous reports of patients with preoperative AF undergoing CABG have produced conflicting results for the perioperative period. While most studies have shown that preoperative AF is associated with higher perioperative mortality
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      • McCarthy P.M.
      • Gillinov A.M.
      • Alster J.M.
      • Cosgrove D.M .I.I.I.
      • Lytle B.W.
      • et al.
      Does preoperative atrial fibrillation reduce survival after coronary artery bypass grafting?.
      • Ad N.
      • Barnett S.D.
      • Haan C.K.
      • O'Brien S.M.
      • Milford-Beland S.
      • Speir A.M.
      Does preoperative atrial fibrillation increase the risk for mortality and morbidity after coronary artery bypass grafting?.
      • Bramer S.
      • van Straten A.H.
      • Soliman Hamad M.A.
      • Berreklouw E.
      • Martens E.J.
      • Maessen J.G.
      The impact of preoperative atrial fibrillation on early and late mortality after coronary artery bypass grafting.
      • Al-Sarraf N.
      • Thalib L.
      • Hughes A.
      • Tolan M.
      • Young V.
      • McGovern E.
      Effect of preoperative atrial fibrillation on postoperative outcome following cardiac surgery.
      • Saxena A.
      • Kapoor J.
      • Dinh D.T.
      • Smith J.A.
      • Shardey G.C.
      • Newcomb A.E.
      Preoperative atrial fibrillation is an independent predictor of worse early and late outcomes after isolated coronary artery bypass graft surgery.
      • Banach M.
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      • et al.
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      (OR 1.39-2.77), some have shown no difference.
      • Rogers C.A.
      • Angelini G.D.
      • Culliford L.A.
      • Capoun R.
      • Ascione R.
      Coronary surgery in patients with preexisting chronic atrial fibrillation: early and midterm clinical outcome.
      • Ngaage D.L.
      • Schaff H.V.
      • Mullany C.J.
      • Sundt III, T.M.
      • Dearani J.A.
      • Barnes S.
      • et al.
      Does preoperative atrial fibrillation influence early and late outcomes of coronary artery bypass grafting?.
      This study documents that preoperative AF is independently associated not only with worse perioperative mortality, but also significant major morbidity (excluding deep sternal wound infection). Prior single-center studies may have failed to detect this difference because of low event rates and inadequate power. Increased perioperative morbidity for stroke, renal failure, and respiratory failure was seen in the AF patients, likely because of the higher thromboembolic events and postoperative low-cardiac output syndrome, perhaps associated with the loss of atrial transport function in the AF patients. Perioperative anticoagulation in the AF patients may explain the higher incidence of reoperation for bleeding.
      Long-term survival has been shown in many previous reports to be adversely affected in patients with preoperative AF and several have shown AF to be an independent risk factor with HRs ranging from 1.39 to 2.77.
      • Rogers C.A.
      • Angelini G.D.
      • Culliford L.A.
      • Capoun R.
      • Ascione R.
      Coronary surgery in patients with preexisting chronic atrial fibrillation: early and midterm clinical outcome.
      • Ngaage D.L.
      • Schaff H.V.
      • Mullany C.J.
      • Sundt III, T.M.
      • Dearani J.A.
      • Barnes S.
      • et al.
      Does preoperative atrial fibrillation influence early and late outcomes of coronary artery bypass grafting?.
      • Bramer S.
      • van Straten A.H.
      • Soliman Hamad M.A.
      • Berreklouw E.
      • Martens E.J.
      • Maessen J.G.
      The impact of preoperative atrial fibrillation on early and late mortality after coronary artery bypass grafting.
      • Saxena A.
      • Kapoor J.
      • Dinh D.T.
      • Smith J.A.
      • Shardey G.C.
      • Newcomb A.E.
      Preoperative atrial fibrillation is an independent predictor of worse early and late outcomes after isolated coronary artery bypass graft surgery.
      • Banach M.
      • Goch A.
      • Misztal M.
      • Rysz J.
      • Zaslonka J.
      • Goch J.H.
      • et al.
      Relation between postoperative mortality and atrial fibrillation before surgical revascularization–3-year follow-up.
      Similarly, our study showed that preoperative AF increased long-term mortality by almost 50%. Patients with preoperative AF may continue to be at risk for further SSE and thromboembolic events while also remaining at risk for bleeding from anticoagulation therapy. Several additional mechanisms may contribute to the link between AF and long-term mortality, including low cardiac output, tachycardia-mediated cardiomyopathy, and worsening heart failure with loss of atrioventricular synchrony.
      The observation that late SSE risk is increased in patients with preoperative AF has not been reported previously. This observation supports the hypothesis that AF-related SSE contributes to poor survival. Our study shows that post-CABG patients who had AF preoperatively have a continuing increased risk of long-term SSE and mortality risk despite controlling for other risk factors. The analysis of CHA2DS2-VASc is also new to this study. Moreover, the CHA2DS2-VASc score further stratified the risk of SSE concordant with established models, even in patients without preoperative AF.
      • Lip G.Y.
      • Nieuwlaat R.
      • Pisters R.
      • Lane D.A.
      • Crijns H.J.
      Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation.
      A direct link between SSE and mortality has not been previously demonstrated, and further study is justified.

       Limitations

      The increase in relative risk for perioperative morbidity was statistically significant because of the large sample size in this analysis; however, the absolute increase in risk was close to only 1% for 30-day stroke, reoperation, and renal failure. Individually, each complication is of low clinical significance, but the increased absolute risk of combined morbidities was shown to have a greater magnitude of effect size and remains useful for clinical decision making. Likewise, although the absolute increase in risk of 30-day mortality was only about 1%, the absolute increase in risk of death was magnified to 17% at 5 years.
      Recent clinical practice guidelines
      • Badhwar V.
      • Rankin J.S.
      • Damiano Jr., R.J.
      • Gillinov A.M.
      • Bakaeen F.G.
      • Edgerton J.R.
      • et al.
      The Society of Thoracic Surgeons 2017 Clinical Practice Guidelines for the Surgical Treatment of Atrial Fibrillation.
      and expert consensus guidelines
      • Ad N.
      • Damiano Jr., R.J.
      • Badhwar V.
      • Calkins H.
      • La Meir M.
      • Nitta T.
      • et al.
      Expert consensus guidelines: examining surgical ablation for atrial fibrillation.
      recommend surgical ablation for AF in patients undergoing cardiac surgery. Further analysis of the comparative effectiveness of concomitant AF ablation may have important implications for this high-risk cohort.
      This study includes only Medicare-linked patients; therefore, it may be more pertinent to older patients. Because of incomplete linking between the STS and CMS databases, 207,731 patients (37%) were excluded. Limitations to both registries include lack of data for type of preoperative AF, causality of AF, AF status post procedure, and anticoagulation status. Finally, some patients with AF received surgical AF ablation during CABG and were subsequently excluded from the analysis.

      Conclusions

      Preoperative AF is common in patients undergoing CABG and associated with higher perioperative mortality and morbidity. Long-term survival and risk of SSE were worse even after adjusting for comorbidities. Higher CHA2DS2-VASc scores were associated with worse long-term outcomes including death and SSE.

       Conflict of Interest Statement

      Authors have nothing to disclose with regard to commercial support.
      The authors thank Mr. and Mrs. Timothy Thoelecke for their financial support of the Bluhm Cardiovascular Institute, which made this project possible.

      Appendix

      Figure thumbnail fx3
      Figure E1Flow diagram for patients undergoing isolated coronary artery bypass grafting as their first cardiovascular surgery with discharge dates from January 1, 2006, to December 31, 2013. CV, Cardiovascular; CABG, coronary artery bypass graft; IABP, intra-aortic balloon pump; PCI, percutaneous coronary intervention; STS, Society of Thoracic Surgeons; CMS, Centers for Medicare and Medicaid; AF, atrial fibrillation.

      Supplementary Data

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