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Ann Thorac Surg 2005;79:532-536
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

Perioperative Stroke and Long-Term Survival After Coronary Bypass Graft Surgery

Lawrence J. Dacey, MDa,*, Donald S. Likosky, PhDa, Bruce J. Leavitt, MDb, Stephen J. Lahey, MDc, Reed D. Quinn, MDd, Felix Hernandez, Jr, MDe, Hebe B. Quinton, MSa, Joseph P. Desimone, MDa, Cathy S. Ross, MSa, Gerald T. O'Connor, DSc, PhDa for the Northern New England Cardiovascular Disease Study Group

a Departments of Surgery, Medicine, and Community and Family Medicine, Dartmouth College, Hanover, New Hampshire
b Department of Surgery, Fletcher Allen Health Care, Burlington, Vermont
c Department of Surgery, University of Massachusetts, Worcester, Massachusetts
d Department of Surgery, Maine Medical Center, Portland, Maine
e Department of Surgery, Eastern Maine Medical Center, Bangor, Maine

Accepted for publication July 12, 2004.

* Address reprint requests to Dr Likosky, Department of Surgery and Community and Family Medicine, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH03756;


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Stroke is a devastating complication of coronary artery bypass graft (CABG) surgery. In-hospital outcomes have been described, yet the long-term effect of stroke on mortality following CABG surgery has not been well studied.

METHODS: We examined the survival of 35,733 consecutive patients undergoing isolated CABG surgery in northern New England from 1992 through 2001. Stroke was defined as a new fixed neurologic defect that persisted at least 24 hours after surgery. Patient records were linked to the National Death Index to assess mortality. There were 147,931 person years of follow-up and 5,705 deaths. Cox proportional hazard regression was used to calculate the adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). We identified the 5-year survival stratified by primary stroke mechanism, the patient's functional impact, and discharge location among a subset of patients who had strokes between 1992 and 2000.

RESULTS: Perioperative stroke occurred in 575 patients (1.61%). Patients who had strokes had more comorbidities. After adjustments for differences in baseline patient and clinical characteristics, patients who had perioperative stroke were at a significantly increased risk for death (HR, 3.20; 95% CI, 2.80 to 3.66; p < 0.0001). Survival for patients with stroke at 1, 5, and 10 years was 83.0%, 58.7%, and 26.9%, respectively. Five-year survival decreased among patients who had major functional limitations before discharge, among those who had hypoperfusion strokes, and among patients who were discharged to locations other than home or rehabilitation facilities.

CONCLUSIONS: Perioperative stroke is associated with a very substantial increased risk of postoperative death among CABG surgery patients. The greatest risk of death was noted within the first year after surgery. Survival after 1 year approximates that of patients who did not suffer a stroke.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Stroke is a devastating complication of coronary artery bypass graft (CABG) surgery. The extent of this complication has been typically described in terms of in-hospital outcomes [1]. These outcomes range from an increased risk of a longer hospital stay to in-hospital mortality [2]. Long-term mortality of stroke has not been similarly studied.

By only focusing on the traditional in-hospital outcomes of patients who have a stroke secondary to CABG surgery, researchers may not be assessing the total impact of this clinical outcome. In a recent report on long-term mortality from mediastinitis secondary to CABG surgery, Braxton found a marked increase in short-term mortality within the first year after the index admission and a threefold increase in mortality at 4 years [3]. Similar information for patients who have strokes may be important for identifying (1) whether the negative impact of this outcome extends beyond the index admission, and (2) other sequelae that may occur and be prevented that could otherwise cause further risk for mortality.

The Northern New England Cardiovascular Disease Study Group is a voluntary research consortium composed of clinicians, research scientists, and hospital administrators. The goal of the group is to foster continuous improvement in the quality of care for patients undergoing cardiovascular interventions through the analysis of process and outcomes data and the timely feedback of this data to the clinicians involved in providing these services.

We examined the 1-, 5- and 10-year survival of consecutive patients undergoing isolated CABG surgery from 1992 through 2001.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Acknowledgments
 References
 
Patient Population
These analyses were of 35,733 consecutive patients undergoing isolated CABG surgery in northern New England from January 1, 1992, to December 31, 2001.

Data Collection
Data were recorded prospectively for all patients. The collection of patient data included patient age, gender, comorbidities (obesity, vascular disease, diabetes mellitus, chronic obstructive pulmonary disease, dialysis-dependent renal failure), current cardiac condition (recent [< 7 days] myocardial infarction, current congestive heart failure), and previous cardiac surgery. Procedural data included cardiac catheterization data (left ventricular ejection fraction, number of diseased coronary arteries) and priority of surgery. The priority of a patient's surgery was defined as emergent, urgent, or elective:

• Emergent indicated that medical factors relating to the patient's cardiac disease dictated that the procedure be performed within hours to prevent morbidity or death.
• Urgent indicated that medical factors require the patient to stay in the hospital for the procedure before discharge.
• Elective was defined by medical factors that indicated the need for the procedure, but allowed the patient to be discharged from the hospital with readmission at a later date.
Complete definitions of these variables have been previously published [4].

We defined a stroke as a new neurologic deficit that appeared and was still at least partially evident more than 24 hours after its onset, that occurred during or after the CABG procedure, and was established before discharge.

Institutional review board approval was obtained at each participating medical center.

Patient Follow-Up
The outcome measure for this study was all-cause mortality over a 10-year interval. Mortality through December 31, 2001, was determined by a probabilistic match of the regional registry to the National Death Index (NDI) (US Department of Health and Human Services) using a combination of patient name, Social Security number, date of birth, gender, date last known alive, and last known state of residence. The sensitivity of the NDI to identify deaths is between 92% and 99%, depending on which identifiers are available [5, 6].

The primary mechanism of the stroke, functional impact, and discharge location was available for a subset (383, 277, and 285, respectively) of the 583 patients who had strokes between 1992 and 2000. As discussed previously, we used clinical endpoints committees staffed with cardiothoracic surgeons, cardiovascular anesthesiologists, stroke neurologists, and neuroradiologists; and extensive medical record review to divide strokes into two principal mechanisms: hemorrhagic or ischemic [7]. We further divided ischemic strokes into two subcategories: thromboembolism (embolic or some type of in situ clot) and hypoperfusion. We previously reported that 62.1% of strokes that occurred after isolated CABG surgery were secondary to embolism and an additional 8.8%, to hypoperfusion. Because of the dominance of these embolic and hypoperfusion mechanisms, we collapsed the classification system into three groups: embolic, hypoperfusion, and other (hemorrhage, lacunar, thrombotic, other, multiple, and unclassified). Functional impact was classified as resolved, minor, or major. Discharge location was classified as rehabilitation facility, home, or other (skilled nursing facility, nursing home, unknown or other). The methodology used for identifying stroke mechanism as well as definitions for functional impact have been previously reported [7].

Statistical Analysis
Baseline characteristics were summarized by means for the continuous variables and by percentages for the discrete variables. Comparisons of discrete and continuous variables of patients with and without strokes were assessed using {chi}2 and t tests.

Survival analyses were completed with Kaplan-Meier techniques to determine the annual death rate and actual 10-year survival and were compared with the log-rank statistic [8]. Adjusted Kaplan-Meier curves were created by the method described by Ghali and colleagues [9]. We adjusted for variables previously identified as significant factors in our preoperative risk prediction equation [10]. A Cox proportional hazard regression model was used to compare patients with or without strokes while adjusting for baseline characteristics. The outcome measure in these survival analyses was all-cause mortality. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated. Analyses were performed using Stata release 8.0 software (Stata Corp, College Station, TX) [11].

In subset analyses, log-rank tests were performed to test for equality of survivorship by stroke mechanism, functional impact, and discharge location. Long-term survival for these subset analyses was calculated to 5 years.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Acknowledgments
 References
 
In these data, 575 strokes occurred among 35,733 patients (1.61%) undergoing isolated CABG surgery. The characteristics of patients with and without strokes are summarized in Table 1. Patients with strokes were approximately 5 years older (70.7 vs 65.4 years), more likely to be women (35.1% vs 28.3%), slightly smaller (1.90 m2 vs 2.0 m2), and had a lower ejection fraction (49.7% vs 52.9%). Patients who had strokes also had more comorbidities in the form of vascular disease (33.9% vs 18.9%), three-vessel disease (59.5% vs 48.0%), left main disease (30.8% vs 24.5%), diabetes mellitus (42.4% vs 30.5%), and renal failure or creatinine of 2.0 mg/dL or more (8.4% vs 3.2%). Patients with strokes were also more likely to have urgent (66.4% vs 62.0%) or emergent surgery (11.8% vs 6.5%).


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  		Table 1. Patient and Disease Characteristics
 
During 147,931 patient-years of follow-up, 5,705 deaths occurred. The annual incidence of death was 3.86/100 person-years in the entire cohort. The crude annual incidence of death was 18.1/100 person-years among patients with strokes and 3.7/100 person-years among patients without strokes (log-rank test {chi}2[1 d.f.] = 763.7, p < 0.001) (Table 2). After adjusting for baseline patient and disease characteristics, the hazard ratio was 3.20 (95% CI, 2.80 to 3.66, p < 0.001). The adjusted survival rates at 1, 5, and 10 years were 94.1%, 83.3%, and 61.9% among patients free from stroke and 83.0%, 58.7% and 26.9% among patients who had strokes, respectively. The adjusted Kaplan-Meier survival curves are shown in Fig 1.


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  		Table 2. Multivariate 1-, 5-, and 10-Year Survival Following Isolated CABG Surgery
 


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  		Fig 1. Ten-year adjusted survival among isolated patients undergoing coronary artery bypass graft surgery.

 
Table 3 displays the short-term and long-term survival for patients who had strokes, stratified by the impact of the deficit, the type of stroke, and discharge location. In terms of functional limitations at discharge, survival at 1, 5, and 10 years was lowest among patients with major limitations (p = 0.001). Survivorship was worse among patients who had minor or major strokes than in patients who did not have a stroke (Fig 2). Survival at each time point was lowest among patients who had hypoperfusion strokes (Fig 3), and was lowest among patients discharged to locations other than home or rehabilitation facilities (Fig 4).


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  		Table 3. Postoperative Survival After Isolated CABG Surgery by Stroke Impact, Mechanism, and Discharge Location
 


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  		Fig 2. Five-year survival by functional impact among patients undergoing isolated coronary artery bypass graft surgery.

 


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  		Fig 3. Five-year survival by stroke mechanism among patients undergoing isolated coronary artery bypass graft surgery.

 


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  		Fig 4. Five-year survival by discharge location among patients undergoing isolated coronary artery bypass graft surgery.

 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Acknowledgments
 References
 
In this prospective, regional cohort study of 35,733 patients undergoing isolated CABG surgery, median survival among patients who had strokes was 5.2 years (adjusted 6.3 years). After multivariate adjustments for baseline differences in patient and disease characteristics, those diagnosed with stroke had a threefold increased risk of death during the 10-year follow-up period (HR, 3.20; 95% CI, 2.80 to 3.66; p < 0.0001). At 10 years post-CABG the adjusted survival was 26.9% for patients with strokes and 61.9% without. Among those who had strokes, decreased functionality at discharge, hypoperfusion strokes, and discharge to locations other than home or rehabilitation facilities were associated with an increased risk of long-term mortality.

The primary limitation to this study is that we did not have information on the quality of life for patients who had strokes. We believe, however, that the information presented on the patient's functional impairment at discharge is likely a proxy for the patient's quality of life.

The rate of clinically apparent stroke associated with CABG surgery has not changed appreciably over time [10]. Traditional efforts with regard to this outcome have focused on the identification of preoperative risk factors associated with stroke [1, 10, 12–14]. These efforts have been incorporated in national guidelines for CABG [15]. More recent efforts have focused on identifying the intraoperative and postoperative factors that are associated with the development of a stroke [16, 17].

In the present study, the perioperative mortality rate was 24.4% among patients with strokes (highest among patients with hypoperfusion strokes) and 2.6% among patients who did not have a stroke. These findings are similar to other published reports. Puskas and colleagues. in a series of 10,860 patients undergoing primary coronary operations, found 22.5% of patients with strokes and 2.0% of patients without strokes died before discharge [18]. Roach and colleagues described findings from 2108 patients undergoing elective, isolated CABG surgery at 24 institutions in the United States. They classified neurologic outcomes as either type I (death because of stroke or hypoxic encephalopathy, nonfatal stroke, transient ischemic attack, stupor, or coma) or type II deficits (nonfocal neurologic deficits). In-hospital mortality was 21.2% for patients who had type I or type II deficits and 1.9% for those who did not have either [1].

Although much of the work surrounding survival after stroke has focused on the predictors and procedural mortality, less work has been devoted to long-term outcomes. Puskas and colleagues reported detailed long-term outcomes of 10,860 patients with or without stroke secondary to primary CABG at a single medical center from 1988 to 1996 [18]. These investigators found that that 63.7% of patients with strokes and 94.3% of patients without strokes survived 1 year after CABG surgery. We report more favorable results (83.0% and 94.1%, respectively). In the current study, survivorship in this "middle phase" (survival within 1 year after surgery) appears to be related to the mechanism of injury, functional impact at discharge, and discharge location. Discharge location is likely a proxy for a patient's functional impact, as patients discharged home are likely at a higher functional level than those transferred to rehabilitation facilities.

The difference in survivorship between patients with or without strokes was evident during the "late phase" (beyond 1 year after surgery). While an 11.1% risk difference was noted at 1 year after surgery for patients with and without strokes (83.0% vs 94.1%), this widened to 24.6% (58.7% vs 83.3%) at 5 years and 35.0% (26.9% vs 61.9%) at 10 years. Our findings are similar to the 5-year (44.3% vs 81.1%) and 10-year (36.2% vs 60.9%) survivorship among patients with and without strokes, respectively, reported by Puskas and colleagues. In the current study, survivorship in this late phase appears to be proportional in each of the subgroups that we studied (Figs 1 to 4), with much of the differences among these groups occurring during the first year after surgery.

The poor survivorship among patients with strokes underscores the importance of preventing this adverse outcome. Our findings suggest a need for early identification of opportunities to reduce the impact of stroke during the patient's index admission. Work continues to be conducted by our group to reduce the incidence of stroke after CABG surgery through the prediction and identification of the primary mechanism of these deficits [7, 10, 17]. A portion of these injuries are likely iatrogenic and may be prevented through the identification of modifiable processes of clinical care associated with their creation [19]. The present findings suggest that a reduction in the functional impact of strokes may result in improvements in short-term and long-term survivorship. Reduction in this impact may be realized through the assessment of patient needs and the resulting coordination of care services.

This study demonstrates the negative effect of stroke on patient survival, extending beyond the perioperative and acute care setting. Long-term survivorship appears to depend in part on the mechanism and functional impact of the stroke as well as survival past the acute hospital setting. Early diagnosis and rehabilitation may offer benefits to patients having strokes after CABG surgery.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
References
 
This work was supported by an Individual National Research Service Award Post-Doctoral Fellowship Award (F32 HL68357) (DSL).


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgeryMulticenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. [see comments] N Engl J Med 1996;335(25):1857-1863.[Abstract/Free Full Text]
  2. Stamou SC, Hill PC, Dangas G, et al. Stroke after coronary artery bypass: incidence, predictors, and clinical outcome Stroke 2001;32(7):1508-1513.[Abstract/Free Full Text]
  3. Braxton JH, Marrin CA, McGrath PD, et al. Mediastinitis and long-term survival after coronary artery bypass graft surgeryNorthern New England Cardiovascular Disease Study Group. Ann Thorac Surg 2000;70(6):2004-2007.[Abstract/Free Full Text]
  4. O'Connor GT, Plume SK, Olmstead EM, et al. Multivariate prediction of in-hospital mortality associated with coronary artery bypass graft surgeryNorthern New England Cardiovascular Disease Study Group. [see comments] Circulation 1992;85(6):2110-2118.[Abstract/Free Full Text]
  5. Wentworth DN, Neaton JD, Rasmussen WL. An evaluation of the Social Security Administration master beneficiary record file and the National Death Index in the ascertainment of vital status Am J Public Health 1983;73(11):1270-1274.[Abstract/Free Full Text]
  6. Williams BC, Demitrack LB, Fries BE. The accuracy of the National Death Index when personal identifiers other than Social Security number are used Am J Public Health 1992;82(8):1145-1147.[Abstract/Free Full Text]
  7. Likosky DS, Marrin CA, Caplan LR, et al. Determination of etiologic mechanisms of strokes secondary to coronary artery bypass graft surgery Stroke 2003;34(12):2830-2834.[Abstract/Free Full Text]
  8. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations J Am Stat Assoc 1958;53:547-581.
  9. Ghali WA, Quan H, Brant R, et al. Comparison of 2 methods for calculating adjusted survival curves from proportional hazards models JAMA 2001;286(12):1494-1497.[Abstract/Free Full Text]
  10. Charlesworth DC, Likosky DS, Marrin CA, et al. Development and validation of a prediction model for strokes after coronary artery bypass grafting Ann Thorac Surg 2003;76(2):436-443.[Abstract/Free Full Text]
  11. Stata, Stata Statistical Software. Release 8.0. 2003, College Station, TX: Stata Corporation..
  12. Gardner TJ, Horneffer PJ, Manolio TA, et al. Stroke following coronary artery bypass grafting: a ten-year study Ann Thorac Surg 1985;40(6):574-581.[Abstract]
  13. Hartman GS, Yao FS, Bruefach 3rd M, et al. Severity of aortic atheromatous disease diagnosed by transesophageal echocardiography predicts stroke and other outcomes associated with coronary artery surgery: a prospective study Anesth Analg 1996;83(4):701-708.[Abstract]
  14. Redmond JM, Greene PS, Goldsborough MA, et al. Neurologic injury in cardiac surgical patients with a history of stroke Ann Thorac Surg 1996;61(1):42-47.[Abstract/Free Full Text]
  15. Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA guidelines for coronary artery bypass graft surgery: executive summary and recommendationsA report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation 1999;100(13):1464-1480.[Free Full Text]
  16. Charlson M, Krieger KH, Peterson JC, Hayes J, Isom OW. Predictors and outcomes of cardiac complications following elective coronary bypass grafting Proc Assoc Am Physicians 1999;111(6):622-632.[Medline]
  17. Likosky DS, Leavitt BJ, Marrin CA, et al. Intra- and postoperative predictors of stroke after coronary artery bypass grafting Ann Thorac Surg 2003;76(2):428-434.[Abstract/Free Full Text]
  18. Puskas JD, Winston AD, Wright CE, et al. Stroke after coronary artery operation: incidence, correlates, outcome, and cost Ann Thoracic Surgery 2000;69(4):1053-1056.[Abstract/Free Full Text]
  19. Likosky DS, Groom RC, Clark C, et al. A method for identifying mechanisms of neurologic injury from cardiac surgery The Heart Surgery Forum 2004;7:E348-52.



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