Quality and Outcomes Management of Postoperative Atrial Fibrillation and Subsequent Outcomes in Contemporary Patients Undergoing Cardiac Surgery: Insights From the Society of Thoracic Surgeons CAPS-Care Atrial Fibrillation Registry
Address for correspondence: Benjamin A. Steinberg, MD Electrophysiology Section, Duke Clinical Research Institute Duke University Medical Center PO Box 17969 Durham, NC 27715 [email protected]
Benjamin A. Steinberg, MD; Yue Zhao, PhD; Xia He, MS; Adrian F. Hernandez, MD; David A. Fullerton, MD; Kevin L. Thomas, MD; Roger Mills, MD; Winslow Klaskala, PhD; Eric D. Peterson, MD, MPH; Jonathan P. Piccini, MD, MHS Department of Medicine (Steinberg, Hernandez, Thomas, Peterson, Piccini), Duke University Medical Center, Durham, North Carolina ; Duke Clinical Research Institute (Steinberg, Zhao, He, Hernandez, Thomas, Peterson, Piccini), Durham, North Carolina; Department of Surgery (Fullerton), University of Colorado, Denver, Colorado; Janssen Research & Development LLC (Mills, Klaskala), Raritan, New Jersey
Background: Postoperative atrial fibrillation (POAF) is a well-recognized complication of cardiac surgery; however, its management remains a challenge, and the implementation and outcomes of various strategies in clinical practice remain unclear. Hypothesis: We hypothesize that treatment for POAF is variable, and that it is associated with particular morbidity and mortality following cardiac surgery. Methods: We compared patient characteristics, operative procedures, postoperative management, and outcomes between patients with and without POAF following coronary artery bypass grafting (CABG) in the Society of Thoracic Surgeons multicenter Contemporary Analysis of Perioperative Cardiovascular Surgical Care (CAPS-Care) registry (2004–2005). Results: Of 2390 patients who underwent CABG, 676 (28%) had POAF. Compared with patients without POAF, those with POAF were older (median age 74 vs 71 years, P < 0.0001) and more likely to have hypertension (86% vs 83%, P = 0.04) and impaired renal function (median estimated glomerular filtration rate 56.9 vs 58.6 mL/min/1.73 m2 , P = 0.0001). A majority of patients with POAF were treated with amiodarone (77%) and β-blockers (68%); few (9.9%) underwent cardioversion. Patients with POAF were more likely to experience complications (57% vs 41%, P < 0.0001), including acute limb ischemia (1.0% vs 0.4%, P = 0.03), stroke (4.0% vs 1.9%, P = 0.002), and reoperation (13% vs 7.9%, P < 0.0001). Length of stay (median 8 days vs 6 days, P < 0.0001), in-hospital mortality (6.8% vs 3.7%, P = 0.001), and 30-day mortality (7.8 vs 3.9, P < 0.0001) were all worse for patients with POAF. In adjusted analyses, POAF remained associated with increased length of stay following surgery (adjusted ratio of the mean: 1.27, 95% confidence interval: 1.2-1.34, P < 0.0001). Conclusions: Postoperative AF is common following CABG, and such patients continue to have higher rates of postoperative complications. Postoperative AF is significantly associated with increased length of stay following surgery.
This analysis was funded by a grant from Janssen Scientific Affairs LLC, Raritan NJ. The study design, analysis plan, statistical analysis, and drafting of the manuscript were performed independently of the funding entity. Each author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Dr. Steinberg was funded by National Institutes of Health T-32 training grant No. 5 T32 HL 7101-37. The following relationships exist related to this article: Dr. Steinberg received minor educational support from Medtronic; Dr. Zhao and Mr. He have no disclosures; Dr. Piccini receives research funding from Johnson & Johnson and provides consulting to Forest Laboratories, Janssen Pharmaceuticals, and Medtronic. Dr. Mills and Dr. Klaskala are full-time employees of Janssen Research & Development, LLC; a detailed description of Dr. Piccini’s, Dr. Hernandez’s, and Dr. Peterson’s disclosures can be found at https://dcri.org/about-us/conflict-of-interest. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Additional Supporting Information may be found in the online version of this article. Received: September 11, 2013 Accepted with revision: October 31, 2013
Clin. Cardiol. 37, 1, 7–13 (2014) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
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Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice and frequently complicates cardiac surgery.1 Several studies have attempted to identify predictors of postoperative AF (POAF), with advanced age persisting as the most potent and consistent risk factor, followed by a history of AF, chronic obstructive pulmonary disease, and several operative characteristics.1 – 3 Previous studies have linked POAF to increased mortality following surgery.4 Several trials have studied interventions for prevention of POAF, including atrial pacing, β-blockers, sotalol, and amiodarone.5 However, there are few data regarding the efficacy of rhythm control and thromboembolic prophylaxis strategies once POAF has occurred. It is also not clear whether preventive strategies are widely employed in clinical practice. Lastly, the impact of POAF on clinical outcomes and health care utilization in contemporary cohorts remains unknown, as operative outcomes have improved overall.6 – 8 We undertook the present study to assess clinical management and outcomes of patients with POAF following coronary artery bypass grafting (CABG) surgery in routine clinical practice settings. Methods The present study utilized data from the Contemporary Analysis of Perioperative Cardiovascular Surgical Care (CAPS-Care) registry, a substudy of the Society of Thoracic Surgeons (STS) database. The details of CAPS-Care have been described previously.9,10 Briefly, the CAPS-Care initiative was an observational prospective cohort study designed to examine the utilization of pharmacotherapies and other interventions in patients undergoing cardiac surgery. The STS National Adult Cardiac Surgery Database served as the primary dataset and included demographics, medical history, operative characteristics, and additional data on hospital course, including procedures, in-hospital outcomes, and discharge disposition, as well as discharge medications, 30-day rehospitalization, and mortality.11 Further details on STS data collected are available at http://www. sts.org/sts-national-database/database-managers/adult-car diac-surgery-database/data-collection. These data were augmented by chart review using the CAPS-Care casereport form, emphasizing perioperative pharmacotherapies (including vasoactive drugs). The CAPS-Care data were ascertained from 55 STS sites from May 11, 2006, to December 31, 2006. The study cohort was limited to those undergoing CABG (with or without concomitant valve or AF surgery) between 2004 and 2005. The patients were stratified by incidence of POAF, captured on the case-report form and defined as any sustained AF that occurred in the postoperative period while hospitalized. Atrial fibrillation occurring after hospital discharge was not captured. In-hospital, postoperative medication use, complications, and clinical outcomes were compared between groups with and without POAF. Statistical Analysis Continuous variables are displayed as medians (interquartile ranges), with categorical variables displayed as percentages. For categorical variables, P values were calculated
8
Clin. Cardiol. 37, 1, 7–13 (2014) B. Steinberg et al: Treatment and outcomes of postoperative AF Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
using Pearson χ2 tests, whereas Wilcoxon rank-based group means were used for all continuous or ordinal variables. All P values were calculated by comparing nonmissing data. P values < 0.05 were considered significant. Readmission within 30 days was defined from the date of surgery. Patients who died or who had length of stay >10 days (or whose length of stay was missing) were excluded from analyses of readmission rates within 30 days of surgery to minimize the impact of outliers and survival bias. Multivariate analyses for the outcome of length of stay (a continuous variable) were modeled using a negative binomial regression model. Robust sandwich variance estimates were used to obtain 95% confidence intervals (CI) to account for statistical dependence of patients within sites. Subsequently, a parsimonious model was selected from the full list of candidate variables using a backward algorithm with a significance criterion of P = 0.05. All statistical analyses of the aggregate, de-identified data were performed by the Duke Clinical Research Institute using SAS software version 9.2 (SAS Institute Inc., Cary, NC). All of the authors had full access to the data and take responsibility for the validity herein.
Results Among 2390 patients enrolled in CAPS-Care during the study period, 676 (28%) experienced POAF following CABG, whereas 1714 were free of POAF in the postoperative period. Those with POAF were older (median age 74 vs 71 years, P < 0.0001) and more likely to have hypertension (86% vs 83%, P = 0.04) and impaired renal function (median estimated glomerular filtration rate 56.9 vs 58.6 mL/min/1.73 m2 , P = 0.0001) but had lower rates of hypercholesterolemia (72% vs 77%, P = 0.02) and tobacco use (12% vs 20%, P < 0.0001; Table 1). Patients in the POAF group had higher average left ventricular ejection fraction (median 48% vs 40%, P = 0.002) and were at greater risk for thromboembolic events as assessed by CHADS2 scores (81% with CHADS2 ≥2 vs 75% for no POAF, P = 0.001). Patients with POAF were less likely to have undergone an isolated CABG procedure (72% vs 76%, P = 0.001) and more likely to have concomitant valve or AF intervention. Significantly more patients in the POAF group underwent aortic-valve replacement (16% vs 9.9%, P < 0.0001), and median perfusion and cross-clamp times (for both onpump and off-pump procedures) were all longer in the POAF group (Table 2). More than three-quarters of patients with POAF received amiodarone postoperatively, and more than two-thirds received β-blockers (Figure 1). Less than one-third of patients received calcium channel blockers or other antiarrhythmic agents. Slightly 10 days (n = 381), or missing length of stay (n = 10). Of the remaining 1890, 445 (24%) had POAF. Patients with and without POAF in this population mirrored those of the overall study—those with POAF were older with a similar distribution of comorbidities (see Supporting Information, Appendix Tables 1–5, in the online version of this article). Patients with POAF in this subset were readmitted at numerically greater rate, although the difference was not statistically significant (12% vs 9.9%, P = 0.2). The reasons for readmission were similar in those with and without POAF (Table 4). A sensitivity analysis was conducted excluding patients with preoperative AF (n = 184/2390, 7.7%). The results were consistent with the overall analysis (see Supporting Information, Appendix Tables 1–5, in the online version of Clin. Cardiol. 37, 1, 7–13 (2014) B. Steinberg et al: Treatment and outcomes of postoperative AF Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
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Table 2. Operative Characteristics No POAF, n = 1714
POAF, n = 676
Status of surgery
0.7
Elective
51
52
Urgent
49
48
Procedure groups
0.001
Isolated CABG
76
72
CABG and valve intervention (no AF correction)
16
22
CABG and AF correction
3.0
1.8
CABG and other
5.4
4.3
Cardiopulmonary bypass
0.7
None
11
10
Combination
0.6
0.9
Full
47
49
Off-pump
9.9
9.9
Perfusion time, min (all) Perfusion time, min (if on pump) Cross-clamp time, min (all) Cross-clamp time, min (if on pump)
P Value
1.0
108 (83–143) 115 (88–148)
0.002
107 (85–141) 116 (89–148)
0.01
74 (54–105)
81 (59–112)
0.004
71 (53–100)
80 (58–111)
0.003
Abbreviations: AF, atrial fibrillation; CABG, coronary artery bypass grafting; IQR, interquartile range; POAF, postoperative atrial fibrillation. Operative characteristics of all included patients, stratified by occurrence of POAF. Values are presented as % or median (IQR).
this article). Rates of complications were significantly higher in patients with POAF, and POAF remained a significant, multivariate predictor of increased length of stay (adjusted ratio of the mean: 1.29, 95% CI: 1.22-1.36, P < 0.0001).
Discussion Postoperative AF complicated 28% of surgeries in a contemporary cohort of 2390 patients undergoing high-risk CABG. Patients with POAF were older and more likely to have renal dysfunction, yet they had higher median ejection fractions and were less likely to have hypercholesterolemia. The majority of patients with POAF were treated with amiodarone and β-blockers. Only 1 in 10 patients with POAF underwent cardioversion. Patients with POAF experienced a 50% higher complication rate postoperatively, and the occurrence of POAF was highly associated with increased length of stay in both unadjusted and adjusted analyses. Increased age has been associated with POAF in several prior studies,2,12,13 yet hypercholesterolemia, as a negative association, represented a paradox in our data. Previous research demonstrated a potential protective effect of preoperative use of HMG-CoA reductase inhibitors (statins)14,15 ;
10
Clin. Cardiol. 37, 1, 7–13 (2014) B. Steinberg et al: Treatment and outcomes of postoperative AF Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
Figure 1. Management of patients with POAF following coronary artery bypass grafting surgery. Abbreviations: AF, atrial fibrillation; POAF, postoperative atrial fibrillation.
however, we observed similar use of statins immediately prior to surgery. Thus, although we cannot exclude a difference in long-term prior statin exposure between the groups, we did not observe a protective effect. Nevertheless, statin use as prophylaxis for POAF continues to be a subject of interest, with a recent meta-analysis demonstrating a reduction in POAF as high as 60%.16 The same study also observed a concomitant reduction in intensive care unit and overall hospital length of stay, suggesting POAF may be a major contributor to such outcomes. Previous studies have described higher mortality associated with POAF,4,17 yet few have described the details of postoperative complications in a contemporary cohort. Patients with POAF in our cohort were more likely to have myriad other postoperative problems, including reoperation, neurological events, infections, and multisystem organ failure. Despite potential confounders, POAF persisted in multivariate analysis as a significant predictor of increased length of stay, which likely drives the increased cost of care associated with POAF.18 Additional predictors of length of stay in this study may represent events causally associated with POAF (eg, the development of heart failure, neurologic events, and peripheral vascular complications), and preliminary data suggest that more aggressive rhythm control may improve length of stay.19 With intensive care unit costs rising to several thousand dollars per day, reducing length of stay could save millions of dollars annually. Management strategies for POAF in this study were consistent with general clinical practice, where physicians commonly opt to treat POAF medically in the near term with high rates of reversion to sinus rhythm.19 Amiodarone and β-blockers were the most common pharmacologic interventions in our POAF cohort, consistent with prior trials demonstrating their utility in both preventing and treating POAF.5,20,21 In the current study, roughly 1 in 10 patients with POAF underwent cardioversion in the hospital prior to discharge; however, the benefit of predischarge conversion is unclear. Overall data in the general AF population are equivocal on the value of rhythm control,22 and similar data on cardioversion for POAF are limited.19
Table 3. Unadjusted Outcomes, Stratified by POAF No POAF, n = 1714
POAF, n = 676
Any complication
41
57
< 0.0001
All-cause reoperation
7.9
13
< 0.0001
Any neurological event
2.9
6.7
< 0.0001
Stroke >24 hours
1.9
4.0
0.002
TIA
0.8
2.1
0.005
TIA or stroke >24 hours
2.5
6.1
< 0.0001
Radiographic evidence of HF
30
41
< 0.0001
Vascular and other events (excluding AF)
11
21
< 0.0001
Anticoagulant complication
0.9
1.8
0.09
Renal failure
5.6
13
< 0.0001
Dialysis
1.9
5.6
< 0.0001
Acute limb ischemia
0.4
1.0
0.03
Heart block
2.5
3.0
0.5
VT/VF requiring intervention
3.4
7.0
0.0001
Cardiac arrest
2.7
4.1
0.07
GI complication
2.8
6.7
< 0.0001
Any infection
2.2
5.3
< 0.0001
Prolonged ventilation
12
20
< 0.0001
Multisystem failure
1.0
3.1
0.0002
Other complications
3.5
7.8
< 0.0001
6 (5–8)
8 (6–12)
< 0.0001
6.8
18
< 0.0001
Readmission within 30 days of surgerya
9.9
12
0.3
In-hospital mortality (any timeframe)
3.7
6.8
0.001
30-day mortality
3.9
7.8
< 0.0001
Postoperative length of stay, d >14 days
P Value
Abbreviations: AF, atrial fibrillation; GI, gastrointestinal; HF, heart failure; IQR, interquartile range; POAF, postoperative atrial fibrillation; TIA, transient ischemic attack; VT/VF, ventricular tachycardia/ventricular fibrillation. Unadjusted rates of postoperative outcomes, stratified by POAF. Values are presented as % or median (IQR). a Readmission rates exclude patients who died or who had postoperative length of stay >10 days or missing (see Table 4).
For patients with POAF, numerically lower readmission rates were observed in those discharged on warfarin. It is striking that a significant percentage of patients with POAF in this study were not discharged on anticoagulation (173 of 445). Guidelines cite POAF as a ‘‘reversible’’ cause,23 which has led to the common practice of either limited, temporary, or no thromboembolic prophylaxis in these patients, even
Figure 2. Unadjusted outcomes of stroke and 30-day mortality in patients with and without POAF, and stratified by CHADS2 score in those with POAF. Abbreviations: CHADS2 , congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke/transient ischemic attack or thromboembolism; POAF, postoperative atrial fibrillation.
in those who remain in AF at discharge.24 Although data from large randomized trials of thromboembolic prophylaxis in POAF are lacking, patients with POAF in the current study had higher CHADS2 scores and significantly higher rates of stroke or transient ischemic attack early after surgery, when compared with those who did not have POAF. In view of prior observations that POAF portends a significantly higher risk of late AF (>5 years) and stroke,4 our observational data warrant testing of the hypothesis that patients with any occurrence of POAF may benefit from both early and long-term anticoagulation for thromboembolic prophylaxis. Study Limitations The present study represents data from a retrospective, observational cohort and thus carries the limitations inherent to such methods. These may include biases related to the selection, enrollment, and/or reporting of such patients. Other studies have noted a significant incidence of postdischarge AF early after cardiac surgery,25 which was not captured in the present study. Additionally, postoperative medical therapy cannot be specifically attributed to POAF, vs other indications (eg, β-blockers for CAD vs POAF). Lastly, the observed relationship between POAF and outcome is an association, and we cannot, based on these analyses, infer a causal relationship between POAF and outcome.
Conclusions Postoperative AF is a common complication for contemporary patients undergoing CABG, and the majority of patients are medically managed with amiodarone and/or β-blockers. When compared with patients without POAF, those with POAF also have consistently and significantly higher rates of all types of complications. After multivariable adjustment, POAF remains a significant predictor of increased length of stay following CABG. Further investigations of strategies for the prevention and management of POAF are warranted. Clin. Cardiol. 37, 1, 7–13 (2014) B. Steinberg et al: Treatment and outcomes of postoperative AF Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
11
Table 4. Readmission Rates by POAF No POAF POAF Readmission Before Before Rate, Discharge, Discharge, N = 1890 n = 1445 n = 445 P Value Overall readmission rates within 30 d of surgery
10
9.9
12
0.2
n = 196
n = 143
n = 53
0.8
Arrhythmia or heart block
10
9.8
11
CHF
17
17
15
MI and/or recurrent angina
4.6
5.6
1.9
Pericardial effusion and/or tamponade
4.1
3.5
5.7
Pneumonia or other respiratory complication
12
12
13
Any infection
12
11
13
Renal failure
1.0
1.4
0
TIA
1.0
0.7
1.9
Permanent CVA
1.5
2.1
0
Acute vascular complication
3.1
2.8
3.8
Anticoagulation complication
0.5
0.7
0
Other complication
11
13
7.6
Other, related readmission
12
13
9.4
Other, nonrelated readmission
7.7
6.3
11
Reason for readmission
Acknowledgments The authors dedicate this article to the memory of our good friend and colleague, Winslow Klaskala, PhD.
References 1.
2.
3.
4.
5.
6.
Readmission by anticoagulation status
7.
8. 9.
10.
11.
12.
13. 0.08
Discharged on warfarin, n = 207
15
17 (22/128) 11.4 (9/79)
Not discharged on warfarin, n = 876
10
9.7 (68/703) 13 (22/173)
Warfarin data missing, n = 807
9.3
8.6 (53/614) 11 (22/193)
15.
16.
Abbreviations: AF, atrial fibrillation; CHF, congestive heart failure; CVA, cerebrovascular accident; MI, myocardial infarction; POAF, postoperative atrial fibrillation; TIA, transient ischemic attack. Readmission rates by reason, stratified by POAF and use of anticoagulation at discharge. Rates exclude patients who died or who had postoperative length of stay >10 days or missing. Values are presented as column % for overall rates, and as % of subgroups for readmission reason and anticoagulation.
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Clin. Cardiol. 37, 1, 7–13 (2014) B. Steinberg et al: Treatment and outcomes of postoperative AF Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
13
Address for correspondence: Benjamin A. Steinberg, MD Electrophysiology Section, Duke Clinical Research Institute Duke University Medical Center PO Box 17969 Durham, NC 27715 [email protected]
Benjamin A. Steinberg, MD; Yue Zhao, PhD; Xia He, MS; Adrian F. Hernandez, MD; David A. Fullerton, MD; Kevin L. Thomas, MD; Roger Mills, MD; Winslow Klaskala, PhD; Eric D. Peterson, MD, MPH; Jonathan P. Piccini, MD, MHS Department of Medicine (Steinberg, Hernandez, Thomas, Peterson, Piccini), Duke University Medical Center, Durham, North Carolina ; Duke Clinical Research Institute (Steinberg, Zhao, He, Hernandez, Thomas, Peterson, Piccini), Durham, North Carolina; Department of Surgery (Fullerton), University of Colorado, Denver, Colorado; Janssen Research & Development LLC (Mills, Klaskala), Raritan, New Jersey
Background: Postoperative atrial fibrillation (POAF) is a well-recognized complication of cardiac surgery; however, its management remains a challenge, and the implementation and outcomes of various strategies in clinical practice remain unclear. Hypothesis: We hypothesize that treatment for POAF is variable, and that it is associated with particular morbidity and mortality following cardiac surgery. Methods: We compared patient characteristics, operative procedures, postoperative management, and outcomes between patients with and without POAF following coronary artery bypass grafting (CABG) in the Society of Thoracic Surgeons multicenter Contemporary Analysis of Perioperative Cardiovascular Surgical Care (CAPS-Care) registry (2004–2005). Results: Of 2390 patients who underwent CABG, 676 (28%) had POAF. Compared with patients without POAF, those with POAF were older (median age 74 vs 71 years, P < 0.0001) and more likely to have hypertension (86% vs 83%, P = 0.04) and impaired renal function (median estimated glomerular filtration rate 56.9 vs 58.6 mL/min/1.73 m2 , P = 0.0001). A majority of patients with POAF were treated with amiodarone (77%) and β-blockers (68%); few (9.9%) underwent cardioversion. Patients with POAF were more likely to experience complications (57% vs 41%, P < 0.0001), including acute limb ischemia (1.0% vs 0.4%, P = 0.03), stroke (4.0% vs 1.9%, P = 0.002), and reoperation (13% vs 7.9%, P < 0.0001). Length of stay (median 8 days vs 6 days, P < 0.0001), in-hospital mortality (6.8% vs 3.7%, P = 0.001), and 30-day mortality (7.8 vs 3.9, P < 0.0001) were all worse for patients with POAF. In adjusted analyses, POAF remained associated with increased length of stay following surgery (adjusted ratio of the mean: 1.27, 95% confidence interval: 1.2-1.34, P < 0.0001). Conclusions: Postoperative AF is common following CABG, and such patients continue to have higher rates of postoperative complications. Postoperative AF is significantly associated with increased length of stay following surgery.
This analysis was funded by a grant from Janssen Scientific Affairs LLC, Raritan NJ. The study design, analysis plan, statistical analysis, and drafting of the manuscript were performed independently of the funding entity. Each author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Dr. Steinberg was funded by National Institutes of Health T-32 training grant No. 5 T32 HL 7101-37. The following relationships exist related to this article: Dr. Steinberg received minor educational support from Medtronic; Dr. Zhao and Mr. He have no disclosures; Dr. Piccini receives research funding from Johnson & Johnson and provides consulting to Forest Laboratories, Janssen Pharmaceuticals, and Medtronic. Dr. Mills and Dr. Klaskala are full-time employees of Janssen Research & Development, LLC; a detailed description of Dr. Piccini’s, Dr. Hernandez’s, and Dr. Peterson’s disclosures can be found at https://dcri.org/about-us/conflict-of-interest. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Additional Supporting Information may be found in the online version of this article. Received: September 11, 2013 Accepted with revision: October 31, 2013
Clin. Cardiol. 37, 1, 7–13 (2014) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
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Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice and frequently complicates cardiac surgery.1 Several studies have attempted to identify predictors of postoperative AF (POAF), with advanced age persisting as the most potent and consistent risk factor, followed by a history of AF, chronic obstructive pulmonary disease, and several operative characteristics.1 – 3 Previous studies have linked POAF to increased mortality following surgery.4 Several trials have studied interventions for prevention of POAF, including atrial pacing, β-blockers, sotalol, and amiodarone.5 However, there are few data regarding the efficacy of rhythm control and thromboembolic prophylaxis strategies once POAF has occurred. It is also not clear whether preventive strategies are widely employed in clinical practice. Lastly, the impact of POAF on clinical outcomes and health care utilization in contemporary cohorts remains unknown, as operative outcomes have improved overall.6 – 8 We undertook the present study to assess clinical management and outcomes of patients with POAF following coronary artery bypass grafting (CABG) surgery in routine clinical practice settings. Methods The present study utilized data from the Contemporary Analysis of Perioperative Cardiovascular Surgical Care (CAPS-Care) registry, a substudy of the Society of Thoracic Surgeons (STS) database. The details of CAPS-Care have been described previously.9,10 Briefly, the CAPS-Care initiative was an observational prospective cohort study designed to examine the utilization of pharmacotherapies and other interventions in patients undergoing cardiac surgery. The STS National Adult Cardiac Surgery Database served as the primary dataset and included demographics, medical history, operative characteristics, and additional data on hospital course, including procedures, in-hospital outcomes, and discharge disposition, as well as discharge medications, 30-day rehospitalization, and mortality.11 Further details on STS data collected are available at http://www. sts.org/sts-national-database/database-managers/adult-car diac-surgery-database/data-collection. These data were augmented by chart review using the CAPS-Care casereport form, emphasizing perioperative pharmacotherapies (including vasoactive drugs). The CAPS-Care data were ascertained from 55 STS sites from May 11, 2006, to December 31, 2006. The study cohort was limited to those undergoing CABG (with or without concomitant valve or AF surgery) between 2004 and 2005. The patients were stratified by incidence of POAF, captured on the case-report form and defined as any sustained AF that occurred in the postoperative period while hospitalized. Atrial fibrillation occurring after hospital discharge was not captured. In-hospital, postoperative medication use, complications, and clinical outcomes were compared between groups with and without POAF. Statistical Analysis Continuous variables are displayed as medians (interquartile ranges), with categorical variables displayed as percentages. For categorical variables, P values were calculated
8
Clin. Cardiol. 37, 1, 7–13 (2014) B. Steinberg et al: Treatment and outcomes of postoperative AF Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
using Pearson χ2 tests, whereas Wilcoxon rank-based group means were used for all continuous or ordinal variables. All P values were calculated by comparing nonmissing data. P values < 0.05 were considered significant. Readmission within 30 days was defined from the date of surgery. Patients who died or who had length of stay >10 days (or whose length of stay was missing) were excluded from analyses of readmission rates within 30 days of surgery to minimize the impact of outliers and survival bias. Multivariate analyses for the outcome of length of stay (a continuous variable) were modeled using a negative binomial regression model. Robust sandwich variance estimates were used to obtain 95% confidence intervals (CI) to account for statistical dependence of patients within sites. Subsequently, a parsimonious model was selected from the full list of candidate variables using a backward algorithm with a significance criterion of P = 0.05. All statistical analyses of the aggregate, de-identified data were performed by the Duke Clinical Research Institute using SAS software version 9.2 (SAS Institute Inc., Cary, NC). All of the authors had full access to the data and take responsibility for the validity herein.
Results Among 2390 patients enrolled in CAPS-Care during the study period, 676 (28%) experienced POAF following CABG, whereas 1714 were free of POAF in the postoperative period. Those with POAF were older (median age 74 vs 71 years, P < 0.0001) and more likely to have hypertension (86% vs 83%, P = 0.04) and impaired renal function (median estimated glomerular filtration rate 56.9 vs 58.6 mL/min/1.73 m2 , P = 0.0001) but had lower rates of hypercholesterolemia (72% vs 77%, P = 0.02) and tobacco use (12% vs 20%, P < 0.0001; Table 1). Patients in the POAF group had higher average left ventricular ejection fraction (median 48% vs 40%, P = 0.002) and were at greater risk for thromboembolic events as assessed by CHADS2 scores (81% with CHADS2 ≥2 vs 75% for no POAF, P = 0.001). Patients with POAF were less likely to have undergone an isolated CABG procedure (72% vs 76%, P = 0.001) and more likely to have concomitant valve or AF intervention. Significantly more patients in the POAF group underwent aortic-valve replacement (16% vs 9.9%, P < 0.0001), and median perfusion and cross-clamp times (for both onpump and off-pump procedures) were all longer in the POAF group (Table 2). More than three-quarters of patients with POAF received amiodarone postoperatively, and more than two-thirds received β-blockers (Figure 1). Less than one-third of patients received calcium channel blockers or other antiarrhythmic agents. Slightly 10 days (n = 381), or missing length of stay (n = 10). Of the remaining 1890, 445 (24%) had POAF. Patients with and without POAF in this population mirrored those of the overall study—those with POAF were older with a similar distribution of comorbidities (see Supporting Information, Appendix Tables 1–5, in the online version of this article). Patients with POAF in this subset were readmitted at numerically greater rate, although the difference was not statistically significant (12% vs 9.9%, P = 0.2). The reasons for readmission were similar in those with and without POAF (Table 4). A sensitivity analysis was conducted excluding patients with preoperative AF (n = 184/2390, 7.7%). The results were consistent with the overall analysis (see Supporting Information, Appendix Tables 1–5, in the online version of Clin. Cardiol. 37, 1, 7–13 (2014) B. Steinberg et al: Treatment and outcomes of postoperative AF Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
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Table 2. Operative Characteristics No POAF, n = 1714
POAF, n = 676
Status of surgery
0.7
Elective
51
52
Urgent
49
48
Procedure groups
0.001
Isolated CABG
76
72
CABG and valve intervention (no AF correction)
16
22
CABG and AF correction
3.0
1.8
CABG and other
5.4
4.3
Cardiopulmonary bypass
0.7
None
11
10
Combination
0.6
0.9
Full
47
49
Off-pump
9.9
9.9
Perfusion time, min (all) Perfusion time, min (if on pump) Cross-clamp time, min (all) Cross-clamp time, min (if on pump)
P Value
1.0
108 (83–143) 115 (88–148)
0.002
107 (85–141) 116 (89–148)
0.01
74 (54–105)
81 (59–112)
0.004
71 (53–100)
80 (58–111)
0.003
Abbreviations: AF, atrial fibrillation; CABG, coronary artery bypass grafting; IQR, interquartile range; POAF, postoperative atrial fibrillation. Operative characteristics of all included patients, stratified by occurrence of POAF. Values are presented as % or median (IQR).
this article). Rates of complications were significantly higher in patients with POAF, and POAF remained a significant, multivariate predictor of increased length of stay (adjusted ratio of the mean: 1.29, 95% CI: 1.22-1.36, P < 0.0001).
Discussion Postoperative AF complicated 28% of surgeries in a contemporary cohort of 2390 patients undergoing high-risk CABG. Patients with POAF were older and more likely to have renal dysfunction, yet they had higher median ejection fractions and were less likely to have hypercholesterolemia. The majority of patients with POAF were treated with amiodarone and β-blockers. Only 1 in 10 patients with POAF underwent cardioversion. Patients with POAF experienced a 50% higher complication rate postoperatively, and the occurrence of POAF was highly associated with increased length of stay in both unadjusted and adjusted analyses. Increased age has been associated with POAF in several prior studies,2,12,13 yet hypercholesterolemia, as a negative association, represented a paradox in our data. Previous research demonstrated a potential protective effect of preoperative use of HMG-CoA reductase inhibitors (statins)14,15 ;
10
Clin. Cardiol. 37, 1, 7–13 (2014) B. Steinberg et al: Treatment and outcomes of postoperative AF Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
Figure 1. Management of patients with POAF following coronary artery bypass grafting surgery. Abbreviations: AF, atrial fibrillation; POAF, postoperative atrial fibrillation.
however, we observed similar use of statins immediately prior to surgery. Thus, although we cannot exclude a difference in long-term prior statin exposure between the groups, we did not observe a protective effect. Nevertheless, statin use as prophylaxis for POAF continues to be a subject of interest, with a recent meta-analysis demonstrating a reduction in POAF as high as 60%.16 The same study also observed a concomitant reduction in intensive care unit and overall hospital length of stay, suggesting POAF may be a major contributor to such outcomes. Previous studies have described higher mortality associated with POAF,4,17 yet few have described the details of postoperative complications in a contemporary cohort. Patients with POAF in our cohort were more likely to have myriad other postoperative problems, including reoperation, neurological events, infections, and multisystem organ failure. Despite potential confounders, POAF persisted in multivariate analysis as a significant predictor of increased length of stay, which likely drives the increased cost of care associated with POAF.18 Additional predictors of length of stay in this study may represent events causally associated with POAF (eg, the development of heart failure, neurologic events, and peripheral vascular complications), and preliminary data suggest that more aggressive rhythm control may improve length of stay.19 With intensive care unit costs rising to several thousand dollars per day, reducing length of stay could save millions of dollars annually. Management strategies for POAF in this study were consistent with general clinical practice, where physicians commonly opt to treat POAF medically in the near term with high rates of reversion to sinus rhythm.19 Amiodarone and β-blockers were the most common pharmacologic interventions in our POAF cohort, consistent with prior trials demonstrating their utility in both preventing and treating POAF.5,20,21 In the current study, roughly 1 in 10 patients with POAF underwent cardioversion in the hospital prior to discharge; however, the benefit of predischarge conversion is unclear. Overall data in the general AF population are equivocal on the value of rhythm control,22 and similar data on cardioversion for POAF are limited.19
Table 3. Unadjusted Outcomes, Stratified by POAF No POAF, n = 1714
POAF, n = 676
Any complication
41
57
< 0.0001
All-cause reoperation
7.9
13
< 0.0001
Any neurological event
2.9
6.7
< 0.0001
Stroke >24 hours
1.9
4.0
0.002
TIA
0.8
2.1
0.005
TIA or stroke >24 hours
2.5
6.1
< 0.0001
Radiographic evidence of HF
30
41
< 0.0001
Vascular and other events (excluding AF)
11
21
< 0.0001
Anticoagulant complication
0.9
1.8
0.09
Renal failure
5.6
13
< 0.0001
Dialysis
1.9
5.6
< 0.0001
Acute limb ischemia
0.4
1.0
0.03
Heart block
2.5
3.0
0.5
VT/VF requiring intervention
3.4
7.0
0.0001
Cardiac arrest
2.7
4.1
0.07
GI complication
2.8
6.7
< 0.0001
Any infection
2.2
5.3
< 0.0001
Prolonged ventilation
12
20
< 0.0001
Multisystem failure
1.0
3.1
0.0002
Other complications
3.5
7.8
< 0.0001
6 (5–8)
8 (6–12)
< 0.0001
6.8
18
< 0.0001
Readmission within 30 days of surgerya
9.9
12
0.3
In-hospital mortality (any timeframe)
3.7
6.8
0.001
30-day mortality
3.9
7.8
< 0.0001
Postoperative length of stay, d >14 days
P Value
Abbreviations: AF, atrial fibrillation; GI, gastrointestinal; HF, heart failure; IQR, interquartile range; POAF, postoperative atrial fibrillation; TIA, transient ischemic attack; VT/VF, ventricular tachycardia/ventricular fibrillation. Unadjusted rates of postoperative outcomes, stratified by POAF. Values are presented as % or median (IQR). a Readmission rates exclude patients who died or who had postoperative length of stay >10 days or missing (see Table 4).
For patients with POAF, numerically lower readmission rates were observed in those discharged on warfarin. It is striking that a significant percentage of patients with POAF in this study were not discharged on anticoagulation (173 of 445). Guidelines cite POAF as a ‘‘reversible’’ cause,23 which has led to the common practice of either limited, temporary, or no thromboembolic prophylaxis in these patients, even
Figure 2. Unadjusted outcomes of stroke and 30-day mortality in patients with and without POAF, and stratified by CHADS2 score in those with POAF. Abbreviations: CHADS2 , congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke/transient ischemic attack or thromboembolism; POAF, postoperative atrial fibrillation.
in those who remain in AF at discharge.24 Although data from large randomized trials of thromboembolic prophylaxis in POAF are lacking, patients with POAF in the current study had higher CHADS2 scores and significantly higher rates of stroke or transient ischemic attack early after surgery, when compared with those who did not have POAF. In view of prior observations that POAF portends a significantly higher risk of late AF (>5 years) and stroke,4 our observational data warrant testing of the hypothesis that patients with any occurrence of POAF may benefit from both early and long-term anticoagulation for thromboembolic prophylaxis. Study Limitations The present study represents data from a retrospective, observational cohort and thus carries the limitations inherent to such methods. These may include biases related to the selection, enrollment, and/or reporting of such patients. Other studies have noted a significant incidence of postdischarge AF early after cardiac surgery,25 which was not captured in the present study. Additionally, postoperative medical therapy cannot be specifically attributed to POAF, vs other indications (eg, β-blockers for CAD vs POAF). Lastly, the observed relationship between POAF and outcome is an association, and we cannot, based on these analyses, infer a causal relationship between POAF and outcome.
Conclusions Postoperative AF is a common complication for contemporary patients undergoing CABG, and the majority of patients are medically managed with amiodarone and/or β-blockers. When compared with patients without POAF, those with POAF also have consistently and significantly higher rates of all types of complications. After multivariable adjustment, POAF remains a significant predictor of increased length of stay following CABG. Further investigations of strategies for the prevention and management of POAF are warranted. Clin. Cardiol. 37, 1, 7–13 (2014) B. Steinberg et al: Treatment and outcomes of postoperative AF Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
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Table 4. Readmission Rates by POAF No POAF POAF Readmission Before Before Rate, Discharge, Discharge, N = 1890 n = 1445 n = 445 P Value Overall readmission rates within 30 d of surgery
10
9.9
12
0.2
n = 196
n = 143
n = 53
0.8
Arrhythmia or heart block
10
9.8
11
CHF
17
17
15
MI and/or recurrent angina
4.6
5.6
1.9
Pericardial effusion and/or tamponade
4.1
3.5
5.7
Pneumonia or other respiratory complication
12
12
13
Any infection
12
11
13
Renal failure
1.0
1.4
0
TIA
1.0
0.7
1.9
Permanent CVA
1.5
2.1
0
Acute vascular complication
3.1
2.8
3.8
Anticoagulation complication
0.5
0.7
0
Other complication
11
13
7.6
Other, related readmission
12
13
9.4
Other, nonrelated readmission
7.7
6.3
11
Reason for readmission
Acknowledgments The authors dedicate this article to the memory of our good friend and colleague, Winslow Klaskala, PhD.
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2.
3.
4.
5.
6.
Readmission by anticoagulation status
7.
8. 9.
10.
11.
12.
13. 0.08
Discharged on warfarin, n = 207
15
17 (22/128) 11.4 (9/79)
Not discharged on warfarin, n = 876
10
9.7 (68/703) 13 (22/173)
Warfarin data missing, n = 807
9.3
8.6 (53/614) 11 (22/193)
15.
16.
Abbreviations: AF, atrial fibrillation; CHF, congestive heart failure; CVA, cerebrovascular accident; MI, myocardial infarction; POAF, postoperative atrial fibrillation; TIA, transient ischemic attack. Readmission rates by reason, stratified by POAF and use of anticoagulation at discharge. Rates exclude patients who died or who had postoperative length of stay >10 days or missing. Values are presented as column % for overall rates, and as % of subgroups for readmission reason and anticoagulation.
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Clin. Cardiol. 37, 1, 7–13 (2014) B. Steinberg et al: Treatment and outcomes of postoperative AF Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22230 © 2013 Wiley Periodicals, Inc.
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