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J Thorac Cardiovasc Surg 2004;127:1408-1415
© 2004 The American Association for Thoracic Surgery
Surgery for acquired cardiovascular disease |
a Research Center, Montreal Heart Institute, Montreal, Quebec, Canada
b Department of Surgery, Montreal Heart Institute, Montreal, Quebec, Canada
Received for publication August 4, 2003; revisions received September 30, 2003; accepted for publication October 6, 2003.
* Address for reprints: M. Carrier, MD, Department of Surgery, Montreal Heart Institute, 5000 Belanger St East, Montreal, Quebec H1T 1C8, Canada
michel.carrier{at}icm-mhi.org
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Abstract |
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 Top Abstract Materials and methodsResultsAppendix 1References |
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METHODS: Between March 1985 and April 1995, 6650 patients underwent primary isolated coronary artery bypass grafting with internal thoracic artery grafts, including 4382 patients with multivessel bypass grafting requiring at least 3 grafts. Outcomes of patients undergoing single internal thoracic artery plus saphenous vein grafting (n = 2547) and bilateral internal thoracic artery plus saphenous vein grafting (n = 1835) were obtained at a mean follow-up of 11 ± 3 years.
RESULTS: Patients with bilateral internal thoracic artery grafting were younger, were mostly male, and had less diabetes, hypertension, unstable angina, and recent myocardial infarction than patients undergoing single internal thoracic artery grafting. Thirty-day mortality was 2.3% for the group undergoing single internal thoracic artery grafting versus 1.2% for those undergoing bilateral internal thoracic artery grafting (P = .007). Survival probability at 10 years was 88% for the single-graft group compared with 93% for the bilateral-graft group (P < .001). Multivariate analysis with propensity scoring showed that bilateral internal thoracic artery grafting decreased the risk of death (hazard ratio, 0.74; 95% confidence interval, 0.60-0.90), myocardial infarction (hazard ratio, 0.79; 95% confidence interval, 0.67-0.93), and coronary reoperation (hazard ratio, 0.41; 95% confidence interval, 0.21-0.80) throughout the follow-up period. Other significant predictors of death were diabetes, prior myocardial infarction, need for intra-aortic balloon pump, chronic heart failure, and peripheral vascular disease.
CONCLUSION: Patients undergoing bilateral internal thoracic plus saphenous vein grafting appear to have a significantly better long-term clinical outcome than patients undergoing single internal thoracic artery plus saphenous vein grafting for multivessel coronary artery bypass grafting.
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Single internal thoracic artery (SITA) grafting to the left anterior descending coronary artery has consistently shown benefits over saphenous vein grafting (SVG) in terms of long-term patency, survival, and freedom from cardiac events.1-3 However, controversies still persist concerning the clinical advantages of bilateral internal thoracic artery (BITA) grafting. Farinas and colleagues,4 from our institution, have compared the late clinical outcomes of 600 consecutive patients who underwent coronary artery bypass grafting (CABG) with SVG only (n = 200), SITA grafting (n = 200), and BITA grafting (n = 200) at 10 years of mean follow-up. Ten-year survival after CABG was similar in patients with SITA or BITA grafts, although patients with BITA grafts had a greater number of poor prognostic factors and a higher recurrence rate of angina and need for percutaneous coronary interventions (PCIs) during follow-up. Lytle and coworkers5 reported that patients who received 2 internal thoracic artery (ITA) grafts had a decreased risk of death, reoperation, and angioplasty. Furthermore, 2 recent meta-analyses6,7 of up to 7 published studies of at least 100 patients and 4 years' follow-up have shown a better survival in the BITA group versus that in the SITA group. Although some authors have suggested improved outcomes with BITA grafting, SITA grafting remains the choice of most surgeons because of the controversy regarding short- and long-term results.
The objective of this study was to compare the long-term outcome of patients who underwent either SITA plus SVG or BITA plus SVG for multivessel CABG. We retrospectively studied the late clinical outcomes of 4382 consecutive patients who underwent isolated CABG at the Montreal Heart Institute between 1985 and 1995. The primary outcome of the study was death from any cause. Secondary outcomes were occurrence of acute myocardial infarction, need for PCI, need for coronary reoperation, event-free survival, and the composite end point consisting of death, myocardial infarction, PCI, and coronary reoperation.
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Materials and methods |
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TopAbstractMaterials and methodsResultsAppendix 1References |
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The indication for myocardial revascularization was based on standard angiographic and clinical criteria. The left ITA was harvested as a pedicle and usually grafted on the left anterior descending artery or a diagonal branch; when used, the right ITA was mostly harvested pedicled, aiming at the circumflex or the right coronary territory or used as a free graft.4 Patients underwent SITA or BITA grafting depending on the preference of the attending surgeon. Selection criteria favoring SITA grafting over BITA grafting were insulin-dependent diabetes, chronic obstructive pulmonary disease, older age, and serious comorbidities affecting long-term survival (diffuse disease, severe peripheral vascular disease, and dialysis-dependent renal insufficiency). Demographic variables (sex and age) and risk factors for coronary artery disease and major comorbidities were obtained by means of retrospective review of the institutional discharge summary.
Patient survival during follow-up and the occurrence of acute myocardial infarction, coronary reoperation, and PCI were recorded. Follow-up data were obtained by matching the patients' health insurance numbers in the institutional database with the corresponding files in a governmental centralized health care database (Régie de l'assurance-maladie du Québec) in which all deaths and episodes of health care use (in and out of the hospital) are recorded. Permission to use the denominated database was obtained from the Information Access Board of the Quebec government. Follow-up was complete except for 76 patients (62 in the SITA group and 14 in the BITA group) for whom the health insurance numbers were unavailable; these were mostly foreign patients. Thus complete data were available for 4306 (98%) of the 4382 patients. The mean duration of follow-up was higher in the SITA group (12 ± 3 years) than in the BITA group (8 ± 2 years, P < .001) for an overall mean follow-up of 11 ± 3 years.
Data are expressed as means ± SD or medians (ranges) for continuous variables and frequency for categoric variables. Univariate analysis was performed with the Student t test and the Wilcoxon test depending on the distribution of the continuous variable and the 
2 test for categoric variables. Stepwise logistic regression models were used to determine the influence of demographic and operative covariates on early survival. Survival analysis was performed with the Kaplan-Meier method, and the log-rank test was used to compare curves. Cox proportional hazard regression models were used to determine the influence of demographic and operative covariates on late survival, freedom from myocardial infarction, PCI and coronary reoperation, and event-free survival. Hazard ratios (HRs), 95% confidence intervals (CIs) and levels of statistical significance (P value) were calculated. The statistical analyses were performed with SAS release 8.2 (SAS Institute, Cary, NC).
The influence of BITA grafting on outcome was analyzed by using a stepwise multivariate approach with use of the propensity score to better account for selection bias in both groups. First, we calculated a propensity score for each patient. Variables included in the propensity score are listed in Appendix 1. Demographic data were then compared for the SITA and BITA groups in each quintile. There were few intergroup differences in each quintile, as shown in Appendix 2:patients with SITA grafting were younger in quintile 4 and older in quintile 5, presented more hypertension in quintile 1, and presented more recent myocardial infarction in quintile 5 than patients with BITA grafting. As pointed out by Blackstone,8 it is common that 2% to 3% of variables included in the propensity score remain slightly different. As shown, the number of patients from both groups in each quintile was sufficient to keep all patients in the final model. The propensity score was used as a categoric variable, as recommended by D'Agostino.9 Second, multivariate analysis was performed by forcing sequentially the group variable (SITA vs BITA) and the propensity score in the model before including the covariables identified in the univariate analysis. For an illustrative purpose, we also obtained survival curves corrected for the propensity score and the significant covariables.
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Results |
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TopAbstractMaterials and methodsResultsAppendix 1References |
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The difference in patient survival between the 2 groups persisted after correction for the propensity score and significant covariables, with adjusted survivals averaging 97%, 93%, and 88% in the BITA group compared with 96%, 91%, and 84% in the SITA group 5, 10 and 15 years after the operation, respectively (Figure 4).
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Controversy still persists about the clinical benefit of BITA grafting over the already good results of SITA grafting. Unfortunately, there is no conclusive prospective randomized clinical trial published or ongoing comparing SITA and BITA grafting. As pointed out by Taggart and associates6 and others,4,5 a prospective randomized trial would be arduous, with demonstration of a 5% reduction in mortality at 10 years with 90% power and a 1% significance level requiring randomization of about 4200 patients and follow-up of at least 10 years. BITA grafting has not met wide acceptance among surgeons because of the perception of an increased perioperative risk reported in earlier trials and because BITA grafting is technically more demanding.6,10
Usually, surgeons tend to offer BITA grafting to patients with low surgical risk and the greatest chance of survival and long-term benefit from CABG.5 With the benefit of coronary artery bypass surgery over percutaneous techniques demonstrated in sicker patient subgroups (ie, left-main disease, 3-vessel disease, diabetes, and heart failure)11 and the recent advancement in coronary artery stenting, the population referred for surgical intervention has changed markedly. Faced with higher-risk patients, surgeons should question whether the choice of surgical technique can improve the long-term benefits of patients undergoing CABG. Challenged by this question, we retrospectively reviewed the results of patients undergoing multivessel CABG who underwent SITA plus SVG compared with those of patients who underwent BITA plus SVG.
Although Lytle and colleagues5 have shown that "2 internal thoracic artery grafts are better than one," complex methods of statistical analysis were used to address the variation in confounding factors between the 2 groups, and patients who underwent SITA grafting were not consecutive. Also, the authors included all patients undergoing primary isolated revascularization with both ITAs, including patients with complete arterial grafting (both ITAs and no SVG). To address some of these biases, we included all patients undergoing primary isolated revascularization with SITA plus SVG or BITA plus SVG and excluded single and double CABG.
Predictors of 30-day mortality
In the most recent series, early mortality is similar for patients who underwent SITA or BITA grafting.2,5,12-15 In the present series 30-day and hospital mortalities was significantly lower for the BITA group. Nevertheless, SITA grafting versus BITA grafting was not identified as a significant predictor of 30-day mortality in multivariate analyses.
Postoperative complications
Several studies have reported BITA grafting as an independent risk factor for sternal wound infection,5,15-18 along with obesity,15,16,18 diabetes, older age,12,18 reoperation, and prolonged use of inotropic agents18 or prolonged mechanical ventilation. We have previously shown that ITA dissection as a pedicle causes a significant, although partial and temporary, sternal ischemia that is more severe after BITA than SITA mobilization.19 Skeletonization of the ITA seems to have decreased the risk of sternal wound complications, but obese diabetic patients still make up a group that is at an increased risk and thus a relative contraindication to the use of BITA grafting.20 In the present report both groups had similar rates of sternal wound infection and reoperation for bleeding, possibly because of better selection of patients for BITA grafting. Hospital stay was significantly longer in the SITA group than in the BITA group, reflecting the difference in patient populations and the increased early mortality in the SITA group.
Survival
Earlier series reported no survival benefit with BITA grafting.3,21-23 However, in a large study with 2001 patients undergoing BITA grafting and 8123 patients undergoing SITA grafting and longer follow-up, Lytle and colleagues5 reported a significantly better overall survival after BITA grafting (94%, 84%, and 67%) than after SITA grafting (91%, 79%, and 64%) at 5, 10, and 15 years postoperatively, respectively. Also, 2 recent meta-analyses have shown a significant reduction in mortality after omission of methodologically weak investigations (HR, 0.76; 95% CI, 0.67-0.866 and HR, 0.79; 95% CI, 0.66-0.917). We report a survival benefit for BITA grafting (97%, 93%, and 89%) over SITA grafting (95%, 88%, and 79%) at 5, 10, and 15 years postoperatively, respectively. The benefit persisted after adjustment for propensity score and multivariate analysis and is consistent with the results of recent published series.
Freedom from myocardial infarction, PCI, and coronary reoperation
The benefits of BITA grafting on the freedom from myocardial infarction have been reported by some authors,13,14,24 whereas others could not show a significant difference.3,22 In our experience BITA grafting significantly improved the freedom from myocardial infarction at long-term follow-up. The benefit is more recognizable after 8 years, which could be related to late occlusion of SVG and the better patency of ITA grafts. This could be explained also by native disease progression in the higher-risk patients undergoing SITA grafting; nonetheless, the overall benefit of BITA grafting over SITA grafting remained after correction with propensity score. Younger age was identified as a significant risk factor for myocardial infarction, as well as need for PCI or coronary reoperation. Blackstone and Lytle25 and Lytle and colleagues5 recently reported that young and old patients have quite similar event-free survival estimates, which is more influenced by coronary reintervention in the young and by death in the elderly. In others words, the expected improvement in survival in younger patients with BITA grafting is small because young patients undergoing both BITA and SITA grafting have favorable survivals compared with the larger benefit of decreased rate of coronary reintervention.5
A common indication for reintervention, either coronary reoperation or PCI, is the progression of disease in the native circulation or failure of saphenous vein or arterial grafts. After 5 to 15 years' follow-up, some authors did not find significant differences in freedom from coronary reoperation or PCI,13,14,22 whereas others reported a significantly lower occurrence of PCI,23 coronary reoperation, or both.5 In this report BITA grafting was associated with improved freedom from coronary reoperation but not PCI. During the follow-up period, the number of events reported for PCI (182) and coronary reoperation (52) were far less than death (500) and myocardial infarction (714), which limits the conclusions about these 2 outcomes.
Limitations
This study reported the retrospective experience of a single tertiary center with SITA plus SVG versus BITA plus SVG. Statistical methods, such as propensity score and multivariate analysis, were used to improve the comparability of the groups and reduce the influence of selection bias. However, a retrospective study does not have the strength of a prospective randomized trial, and other patient-related or operation-related factors could influence the results of the analysis. The population characteristics depended on the information reported by the attending surgeon on the discharge summary, with the possibility of underreporting. Some significant risk factors for coronary artery disease were not available, such as smoking, angina functional class, and left ventricular ejection fraction. This might have affected propensity scores and multivariate analyses.
Follow-up data were obtained by review of the government database. In the Province of Quebec, the Régie de l'assurance-maladie du Québec (RAMQ) serves the entire population. All residents of Quebec, within the meaning of the Health Insurance Act, are insured under the Quebec Health Insurance Plan and have access to medical services, including cardiac surgery. There is no private clinic for cardiac surgery in Quebec. A report is sent to the RAMQ each time a patient is seen in consultation, treated, or hospitalized or dies. This represents a model of a closed population and allows precise evaluation and follow-up of the population studied. Death and occurrence of coronary reoperation or PCI are consistently reported in the database. Acute myocardial infarction is specifically defined in the RAMQ diagnosis manual and reliably reported in the database, although we could only corroborate the results with our registry when patients were rehospitalized at our institution. Also, silent myocardial infarctions in patients with left bundle-branch block could have been missed.
Conclusion
We demonstrated in this large retrospective study that patients undergoing BITA plus SVG for multivessel CABG have a significantly better long-term clinical outcome than patients undergoing SITA plus SVG. Selected patients undergoing BITA grafting are likely to experience superior survival, less myocardial infarction and coronary reoperation, and better overall event-free survival. This study adds to the wealth of clinical data supporting the benefit of BITA grafting at long-term follow-up. Other studies are needed to better define the subgroup of patients that most benefits from BITA grafting.
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Appendix 1 |
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TopAbstractMaterials and methodsResultsAppendix 1References |
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References |
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TopAbstractMaterials and methodsResultsAppendix 1References |
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