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Ann Thorac Surg 2005;79:552-557
© 2005 The Society of Thoracic Surgeons


Original article: Cardiovascular

Coronary Revascularization Without Cardiopulmonary Bypass Versus the Conventional Approach in High-Risk Patients

Sotiris C. Stamou, MD, PhDa,*, Kathleen A. Jablonski, PhDb, Peter C. Hill, MDa,b, Ammar S. Bafi, MDa,b, Steven W. Boyce, MDb, Paul J. Corso, MDa,b,*

a Section of Cardiac Surgery, Washington Hospital Center, Washington, DC
b The Biostatistics Center, The George Washington University, Rockville, Maryland

Accepted for publication July 29, 2004.

* Address reprint requests to Dr Corso, Section of Cardiac Surgery, Washington Hospital Center, Suite 316, South Tower, 106 Irving St NW, Washington, DC, 20010 (E-mail: paul.j.corso{at}medstar.net).


    Abstract
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
BACKGROUND: The premise of coronary revascularization without cardiopulmonary bypass (off-pump coronary artery bypass graft [CABG]) proposes that patient morbidity and, potentially, mortality can be reduced without compromising the excellent results of conventional revascularization techniques (on-pump CABG). High-risk patients may benefit the most from off-pump CABG. The aim of this study was to compare early and mid-term clinical outcomes after off-pump CABG with on-pump CABG in a subset of high-risk patients.

METHODS: Between January 1, 2000 and December 31, 2000, 513 high-risk patients with a Parsonnet's risk scores of 20 or higher underwent CABG; 38.6% (n = 198) underwent on-pump CABG, and 61.4% (n = 315) had off-pump CABG. Logistic regression was used to calculate the probability of being selected for on-pump CABG given a set of preoperative risk factors. Propensity scores or the probability of being selected for on-pump CABG were computed. Relative risks, heterogeneity among strata, and interactions between surgery type and the propensity score were assessed by a multivariate Cox proportional-hazards regression for the outcomes mortality and major adverse cardiac events (death, acute myocardial infarction, stroke, reoperative CABG, percutaneous coronary intervention).

RESULTS: Operative mortality was lower after off-pump versus on-pump CABG between the two groups after controlling for preoperative risk factors using the propensity score (odds ratio = 2.10; 95% confidence intervals = 1.02 to 4.36, p = 0.04). In the Cox-regression analysis, off-pump CABG was associated with an improved survival rate compared with on-pump CABG (p = 0.03). Off-pump CABG was associated with a comparable event-free survival (p = 0.14) compared with on-pump CABG.

CONCLUSIONS: Off-pump CABG can be performed with a reasonably low morbidity and lower early and late mortality in high-risk patients. Off-pump CABG may be a better operative strategy in this subset of patients.


    Introduction
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
Coronary artery bypass graft (CABG) without cardiopulmonary bypass (off-pump CABG) has been associated with lower morbidity and mortality compared with the conventional cardiopulmonary bypass approach (on-pump CABG) [1]. Specifically, previous studies have reported a lower rate of stroke [2], transfusion requirements [3, 4], and renal dysfunction [5] after off-pump compared with on-pump CABG. Avoidance of cardiopulmonary bypass also eliminates the derangements caused by the cardioplegic arrest as demonstrated by the reduced troponine T levels release after off-pump compared with on-pump CABG [6, 7].

The improved outcome after off-pump CABG is primarily related to the avoidance of cardiopulmonary bypass and the inflammatory response it elicits [8, 9]. High-risk patients might particularly benefit from off-pump CABG because avoidance of cardiopulmonary bypass would decrease the systemic inflammatory response and thus reduce organ-specific complications [10, 11].

The present study was designed to evaluate and compare the early and late clinical outcomes of off-pump CABG with conventional on-pump CABG in a risk-adjusted subset of high-risk patients.


    Patients and Methods
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
Patients
The computerized database of the Section of Cardiac Surgery of the Washington Hospital Center was queried to identify all patients who underwent CABG between January 1, 2000 and December 31, 2000 (n = 1800). Of those patients, 513 had Parsonnet's risk scores of 20 or higher [12]. Parsonnet scores are derived from 14 risk factors for mortality during open heart operation, with 0 being low risk and higher than 20 being extremely high risk. Patients who did not reside in the United States, and did not give informed consent for follow-up were excluded from the study. Of the 513 patients, 38.6% (n = 198) underwent on-pump CABG and 61.4% (n = 315) had off-pump CABG. Baseline demographics, procedural data, and perioperative outcomes were recorded and entered prospectively into a database by a dedicated data-coordinating center.

Definitions
High-risk patients were considered those whose Parsonnet's score was higher than the 75th percentile of the Parsonnets' scores of all patients who underwent isolated CABG during the same period of time. In our database this number equals to a Parsonnet's score higher than 20. Diabetes was defined as a history of diabetes mellitus, regardless of disease duration or control by diet, and oral agents or insulin medications. Chronic renal insufficiency was defined as a serum creatinine value of equal to or greater than 2.0 mg/dL. Low output syndrome was defined as the use of postoperative inotropic support for more than 24 hours. Prolonged ventilatory support was defined as pulmonary insufficiency requiring ventilatory support for more than 24 hours. Postoperative stroke was defined as any new major (type II) neurologic deficit beginning in the hospital and persisting for more than 72 hours [13]. Prolonged length of stay was considered length of stay greater than 7 days (50th percentile of the hospital stay). Operative mortality was defined as any death occurring within 30 days from the date of surgery. Major adverse cardiac events included stroke or acute myocardial infarction that required hospital admission, repeat CABG or percutaneous therapeutic intervention, and death.

Operative Technique and Selection Criteria
Standard anesthesia and surgical techniques, extracorporeal circulation, and myocardial protection methods were used with on-pump CABG. Indications for off-pump CABG included patients who were considered high risk for on-pump CABG because of medical comorbidities such as renal failure, diffuse cerebrovascular and peripheral vascular disease, aortic arteriosclerosis, chronic obstructive pulmonary disease, and religious convictions that precluded blood transfusions [14]. Contraindications for off-pump CABG included extremely small, heavily calcified, or intramyocardial vessels and inadequate exposure.

Follow-Up
Baseline demographics, procedural data, and perioperative outcomes were recorded at the time of the procedure and entered in a computerized database by a dedicated data-coordinating center. All adverse events occurring in the hospital were source documented and entered with standardized criteria in a computerized database by research nurses (exclusive of the nurses who performed the data collection). A separate team of research assistants prospectively collected follow-up clinical data by telephone questionnaire after the patient was discharged from the hospital, and events were similarly reconciled after reviewing the original source documents (medical records, electrocardiograms, laboratory reports, and catheterization sheets). Event-free survival was defined as the period of freedom from hospitalized myocardial infarction, stroke requiring hospitalization, death, or reinterventions (percutaneous transcatheter interventions or reoperative CABG), whichever occurred first.

Data Analysis
Univariate comparisons of categorical preoperative, operative, and postoperative variables were performed between off-pump and on-pump CABG groups. Dichotomous variables were compared using a X2 test of general association or a Fisher's exact test for expected cell counts less than 5. Comparisons between continuous variables were performed using the Student's t test for normally distributed data or the Wilcoxon rank-sum test for nonparametric data. Ordinal data were compared using the Cochran-Armitage trend test. All tests were two-sided, and p values equal to or less than 0.05 were considered significant.

Logistic regression was used to calculate the probability of being selected for on-pump CABG given a set of preoperative risk factors. Any preoperative risk factor that was significantly related to on-pump versus off-pump selection (p value < 0.5 for univariate comparisons and with a frequency ≥ 5%) was included in the multivariate model. Model fit was evaluated using the Hosmer and Lemeshow goodness-of-fit statistic and residual analysis. The c-statistic is reported as a measure of predictive power. The presence of linear dependencies or correlation among the independent variables (multicollinearity) was checked using diagnostics from ordinary logistic regression (tolerance and the variance inflation factor) [15]. Models, which include variables that are highly correlated, produce poor estimates of their effects on the dependent variable. Propensity scores [16, 17] or the probability of being selected for on-pump CABG were computed from these models.

Adverse cardiac-related event rates (death, acute myocardial infarction, stroke, reoperative CABG, percutaneous coronary intervention) were estimated by the method of Kaplan and Meier. Treatment groups were compared on the endpoints by a two-sided log-rank test, at the p = 0.05 significance level.

Relative risks, heterogeneity among strata, and interactions between surgery type and the propensity score were assessed by a multivariate Cox proportional-hazards regression for the outcomes mortality and major adverse cardiac events. The Cox-regression model was performed using propensity score as a covariate. Residual anlaysis, such as the likelihood displacement statistic and df beta statistics were used to assess the model fit.


    Results
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
Eight patients could not be contacted: 7 patients (3.5%) in the on-pump group and 1 (0.3%) in the off-pump group. The median follow-up period for the on-pump CABG patients was 12.2 months (0 to 28.6 months), and for the off-pump patients follow-up was 12.6 months (0 to 26.4 months).

Preoperative patient characteristics are presented in Table 1. Patients who had off-pump CABG were more likely to be older and have a higher rate of preoperative impaired renal function, lower rate of placement of intraaortic balloon pump, better ejection fraction, higher rates of urgent and emergent cases, fewer number of grafts, and a lower rate of reoperative CABG compared with patients who had on-pump CABG. Despite the lower number of grafts in the off-pump CABG group complete revascularization was obtained in all patients.


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Table 1. Preoperative Patient Characteristics
 
The fit of the logistic regression model used to produce propensity scores was good (Hosmer and Lemeshow p = 0.86, c-statistic = 0.74). Variables included in the final model were age, hypertension, chronic renal failure, ejection fraction, case priority, number of grafts (≤3 vs >3), reoperative CABG and body mass index (BMI).

Early Clinical Outcomes
Postoperative patient characteristics are shown in Table 2. Off-pump CABG was associated with lower rates of prolonged ventilation, low cardiac output, pulmonary edema, and lower mortality compared with on-pump CABG. Off-pump CABG was associated with a lower amount of postoperative blood transfusions and a shorter length of hospital stay than on-pump CABG.


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Table 2. Postoperative Patient Characteristics (Univariate Analysis)
 
Operative Mortality
After adjusting for baseline differences using the propensity score, the risk of 30-day mortality was 2.10 times greater in the on-pump group (95% confidence interval [CI], 1.02–4.36; p = 0.04) than in the off-pump group.

Survival Analysis
Unadjusted clinical outcomes in 30 days, 1 year, and 2 years are depicted in Table 3. Off-pump CABG was associated with better overall survival and event-free survival compared with on-pump CABG.


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Table 3. Overall and Event-Free Survival Probabilities by On-Pump or Off-Pump Status in 513 Patients (Univariate Analysis)
 
Time to Event Analysis
Table 4 summarizes the time to event analysis of the outcomes death, acute myocardial infarction, stroke, reoperative CABG, and percutaneous coronary intervention adjusted by risk. The large width of the confidence intervals are indicative of a small sample size. Only mortality was significant (p = 0.03). The hazard of death for the on-pump surgery patients is 1.83 times the hazard of patients operated off-pump.


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Table 4. Risk of On-Pump Versus Off-Pump Surgery for Outcomes Following CABG Surgery Adjusted by the Propensity Score
 

    Comment
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
One of the most challenging aspects of coronary artery revascularization is optimal management of high-risk patients to achieve acceptable morbidity, mortality, and quality of life [1]. The use of cardiopulmonary bypass has been associated with a systemic inflammatory response that may involve multiple organ systems, such as the brain, heart, lungs, kidney, and the gastrointestinal tract [8]. Elimination of cardiopulmonary bypass would lead to a more physiologic milieu that would optimize organ function and reduce organ-specific complications, especially in high-risk patients [10]. Compared with on-pump CABG, off-pump CABG has been associated with decreased foreign surface-blood interaction and shear stresses [18], lower rates of atrial fibrillation [18] and stroke [19], and improved survival [20]. Previous studies have indicated an improved outcome of off-pump compared with on-pump CABG in high-risk patients [21]. The late clinical outcome of off-pump CABG in this subset of patients, however, is largely unknown.

Operative Mortality
In our study, operative mortality was lower in the off-pump group compared with the on-pump CABG group after controlling for preoperative risk factors (p = 0.04).

Mid-Term Outcomes
In the current study, at 2-year follow-up, off-pump CABG was associated with an improved overall and event-free survival compared with patients who underwent on-pump CABG. The survival advantage associated with off-pump CABG is taking place in the first 6 months after the operation as demonstrated from Figures 1 and 2. Afterwards the survival curves run parallel, suggesting that late survival is not affected by off-pump versus on-pump CABG. The results of this study confirmed the results of Arom and colleagues [21], who demonstrated significantly lower mortality after off-pump than on-pump CABG in high-risk patients.



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Fig 1. On- and off-pump mortality. Kaplan-Meier overall survival analysis curves with 95% confidence intervals (n = 513). · · – · · – = on-pump; —— = off-pump.

 


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Fig 2. All on- and off-pump events. Kaplan-Meier event-free survival analysis curves with 95% confidence intervals (n = 513). · · – · · – = on-pump (198); —— = off-pump (315).

 
Clinical Implications
The typically poor postoperative course of high-risk patients after CABG underlines the need for further improvement of surgical technique. The current study has demonstrated improved clinical outcome, comparable operative and lower mid-term mortality after off-pump versus on-pump CABG. The heightened mortality rate documented after on-pump CABG may be related to the postoperative organ dysfunction triggered by the cardiopulmonary bypass and the systemic inflammatory response it elicits ("post pump syndrome") [22, 23]. Avoidance of cardiopulmonary bypass was associated with an improved 2-year survival rate, emphasizing the deleterious effects of on-pump cardiopulmonary bypass on mid-term patient survival. However, off-pump CABG is technically more challenging than CABG on an arrested heart and is warranted in selected patients. Interestingly, a recent randomized controlled study has demonstrated worse graft patency rates 3 months after off-pump versus on-pump CABG (88% vs 98%, respectively, p = 0.002) [24].

Technical improvements and better stabilization also have facilitated an increase in the rate of revascularization procedures performed on a beating heart. In the current study, off-pump CABG became more common over time (in 1994, only 2% of coronary procedures were done on a beating heart, whereas the respective value for 2001 was 68%).

Limitations
We studied a cohort of 513 CABG patients that allowed the creation of a statistically powerful regression model to compare the outcomes of off-pump versus on-pump CABG in high-risk patients. Limitations of this study include limitations inherent in any retrospective single-institution analysis. All data elements, however, were prospectively entered according to prespecified definitions. Furthermore, secondary to the small sample size, the lower operative mortality and major adverse cardiac-related event rate after off-pump compared with on-pump CABG failed to reach statistical significance. Moreover, adjustment by the propensity score although may limit the selection bias does not provide weighing for unknown determinants of treatment strategy.

Patients with small calcified vessels or with massive cardiomegaly were also assigned to the on-pump CABG group, which may have skewed the analysis.

Conclusion
Coronary revascularization without cardiopulmonary bypass is a safe and advantageous alternative to conventional on-pump CABG in high-risk patients. However, anatomic factors may limit on-pump CABG in some high-risk patients. Prospective randomized studies are warranted to confirm the results of the current study. Thorough scientific analysis in a prospective randomized setting should ideally be performed in all surgical management paradigms.


    References
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

  1. Stamou SC, Corso PJ. Coronary revascularization without cardiopulmonary bypass in high-risk patients: a route to the future Ann Thorac Surg 2001;71:1056-1061.[Abstract/Free Full Text]
  2. Trehan N, Mishra M, Sharma OP, Mishra A, Kasliwal RR. Further reduction in stroke after off-pump coronary artery bypass grafting: a 10-year experience Ann Thorac Surg 2001;72:S1026-32.[Abstract/Free Full Text]
  3. Ascione R, Williams S, Lloyd CT, et al. Reduced postoperative blood loss and transfusion requirement after beating-heart coronary operations: a prospective randomized study J Thorac Cardiovasc Surg 2001;121:689-696.[Abstract/Free Full Text]
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  5. Ascione R, Lloyd CT, Underwood MJ, Gomes WJ, Angelini GD. On-pump versus off-pump coronary revascularization: evaluation of renal function Ann Thorac Surg 1999;68:493-498.[Abstract/Free Full Text]
  6. Koh TW, Carr-White GS, Desouza AC, et al. Intraoperative cardiac troponinT release and lactate metabolism during coronary artery surgery: comparison of beating heart with conventional coronary artery surgery with cardiopulmonary bypass Heart 1999;81:495-500.[Abstract/Free Full Text]
  7. Krejca M, Skiba J, Szmagala P, et al. Cardiac troponin T release during coronary surgery using intermittent cross-clamp with fibrillation, on-pump and off-pump beating Eur J cardiothorac Surg 1999;16:337-341.[Abstract/Free Full Text]
  8. Edmunds Jr LH. Why cardiopulmonary bypass makes patients sick: strategies to control the blood-synthetic surface interface Adv Card Surg 1995;6:131-167.[Medline]
  9. Myles PS, Olenikov I, Bujor MA, Davis BB. ACE-inhibitors, calcium antagonists and low systemic vascular resistance following cardiopulmonary bypassA case-control study. Med J Aust 1993;158:675-677.[Medline]
  10. Yokoyama T, Baumgartner FJ, Gheissari A, Capouya ER, Panagiotides GP, Declusin RJ. Off-pump versus on-pump coronary bypass in high-risk subgroups Ann Thorac Surg 2000;70:1546-1550.[Abstract/Free Full Text]
  11. Chamberlain MH, Ascione R, Reeves BC, Angelini GD. Evaluation of the effectiveness of off-pump coronary artery bypass grafting in high-risk patients: an observational study Ann Thorac Surg 2002;73:1866-1873.[Abstract/Free Full Text]
  12. Bernstein AD, Parsonnet V. Bedside estimation of risk as an aid for decision-making in cardiac surgery Ann Thorac Surg 2000;69:823-828.[Abstract/Free Full Text]
  13. Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgeryMulti Center Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996;335:1857-1863.[Abstract/Free Full Text]
  14. Stamou SC, Pfister AJ, Dangas G, et al. Beating heart versus conventional single-vessel reoperative coronary artery bypass Ann Thorac Surg 2000;69:1383-1387.[Abstract/Free Full Text]
  15. Allison P. Logistic regression using the SAS systemCary, NC: SAS Institute Inc; 1999.
  16. Rubin DB, Thomas N. Matching using estimated propensity scores: relating theory to practice Biometrics 1996;52:249-264.[Medline]
  17. Blackstone EH. Comparing apples and oranges J Thorac Cardiovasc Surg 2002;123:8-15.[Free Full Text]
  18. Allen KB, Matheny RG, Robinson RJ, Heimansohn DA, Shaar CJ. Minimally invasive versus conventional reoperative coronary artery bypass Ann Thorac Surg 1997;64:616-622.[Abstract/Free Full Text]
  19. Stamou SC, Jablonski KA, Pfister AJ, et al. Stroke after conventional versus minimally invasive coronary artery bypass Ann Thorac Surg 2002;74:394-399.[Abstract/Free Full Text]
  20. Magee MJ, Jablonski KA, Stamou SC, et al. Elimination of cardiopulmonary bypass improves early survival for multivessel coronary artery bypass patients Ann Thorac Surg 2002;73:1196-1203.[Abstract/Free Full Text]
  21. Arom KV, Flavin TF, Emery RW, Kshettry VR, Janey PA, Petersen RJ. Safety and efficacy of off-pump coronary artery bypass grafting Ann Thorac Surg 2000;69:704-710.[Abstract/Free Full Text]
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