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Ann Thorac Surg 2006;81:599-607
© 2006 The Society of Thoracic Surgeons
a Department of Cardiac Surgery, College of Physicians and Surgeons of Columbia University, St. Luke's–Roosevelt Hospital Center, New York, New York
b Department of Cardiac Surgery, University of Athens School of Medicine, Attikon Hospital Center, Athens, Greece
Accepted for publication July 26, 2005.
* Address correspondence to Dr Anagnostopoulos, St. Luke's–Roosevelt Hospital Center at Columbia University, 1000 Tenth Ave, Suite 2B-05, New York, NY 10019 (Email: cea8{at}columbia.edu).
Presented at the Forty-first Annual Meeting of The Society of Thoracic Surgeons, Tampa, FL, Jan 24–26, 2005.
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Abstract |
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 Top Abstract IntroductionPatients and MethodsResultsCommentDiscussionReferences |
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METHODS: The propensity for BITA was determined using logistic regression analysis and each BITA patient was matched with one SITA patient. Between January 1992 and March 2002, 980 matched diabetic patients (490 BITA versus 490 SITA) underwent coronary artery bypass surgery. Long-term survival data were obtained from the National Death Index (mean follow-up, 4.7 ± 3.0 years). Groups were compared by Cox proportional hazard models and Kaplan-Meier survival plots.
RESULTS: Multivariate Cox regression analysis determined that BITA grafting had no significant effect on long-term survival (hazard ratio 0.89, 95% confidence interval: 0.69 to 1.14, p = 0.343). There were no differences in 30-day mortality (3.9% for BITA versus 3.7%, p = 0.999) and major postoperative complications except for length of stay (11.4 days for BITA versus 12.7 days, p < 0.001). Five-year survival rate was 79.9% in the BITA group and 75.7% in the SITA group (p = 0.252). There was no difference in 5-year survival rate between matched patients younger than 60 or from 70 to 79 years old. However, BITA patients aged 60 to 69 years had better 5-year survival rates (84.1% versus 71.0%, p = 0.0196), whereas the opposite was observed in patients aged more than 79 years (5-year survival for BITA 43.1% versus 70.0%, p = 0.016).
CONCLUSIONS: Bilateral internal thoracic artery grafting had no significant effect on long-term survival for diabetic patients, but it may increase long-term survival in patients aged 60 to 69 years, whereas SITA grafting may be beneficial for patients more than 79 years old.
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Introduction |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionReferences |
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The purpose of the present study was to compare our data from 1992 to 2002 and determine the long-term survival outcome after BITA and SITA in patients with treated diabetes mellitus. We analyzed propensity-matched groups, and we also focused on different age groups.
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionReferences |
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Data were prospectively collected during admission as part of routine clinical practice and entered into the New York State adult cardiac surgery report for the variables shown in Table 1. Diabetics were considered these patients who were treated with either oral hypoglycemic agents or insulin.
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Ethical Issues
The need for informed consent was waived, because the data used in this study had already been collected for clinical and reporting purposes. Furthermore, the database was organized in a way that makes the identification of an individual patient impossible.
Statistical Methods
Numerical variables were presented as the mean ± SD, and discrete variables were summarized by percentages. Continuous variables were compared using a t test or Mann-Whitney U test as appropriate. Categorical variables were compared using Fisher's exact test or the 
2 test as appropriate. Kaplan-Meier survival curves were compared with the log-rank test [13].
The propensity for BITA was determined using logistic regression analysis [14]. All available preoperative variables were entered into the model. Variables were evaluated first univariately, then multivariately. The model selection was done with backward stepwise method starting from all variables with a p value less than 0.05 in univariate analyses. This model was then used to calculate a propensity score. This propensity score represented the probability that a patient underwent BITA coronary bypass. Each patient with BITA was then matched to one SITA patient using propensity scores identical to within 1%. The two groups were compared for early outcome as well as for long-term survival with the Kaplan-Meier method. Multivariate logistic regression analysis was also used to determine the independent predictors for 30-day death in the entire database as well as in the BITA group.
Finally, the impact of BITA on long-term mortality after CABG in diabetic patients was analyzed by Cox regression analysis (matched database, n = 980 patients) including all available preoperative, intraoperative, and postoperative variables [15]. The model selection was done with backward stepwise method starting from all variables with a p value of less than 0.05 in univariate analyses. The model was then confirmed using forward stepwise selection. The BITA parameter was forced to remain in the multivariate model, and hazard ratios (HR) and 95% confidence intervals (CI) were calculated. All analyses were performed in SPSS 11.0 (SPSS, Chicago, Illinois), and all p values are two-tailed.
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Results |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionReferences |
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Four hundred and ninety BITA patients were appropriately matched with 490 SITA patients for all available preoperative variables, as shown in Table 1. The matched groups had similar mean EuroSCORE (European System for Cardiac Operative Risk Evaluation [p = 0.531]), and no difference in early death and major postoperative complications. However, patients with SITA had still significant prolonged length of stay (12.7 versus 11.4 days, p < 0.001), and this finding may reflect that diabetic patients can tolerate BITA grafting and have an uneventful recovery which in some cases occurs faster when compared with SITA patients. Kaplan-Meier curves of matched groups are shown in Figure 1. Freedom from all-cause mortality in BITA patients at 1, 5, and 10 years after the operation was 90.6% ± 1.4%, 79.9% ± 2.0%, and 51.7% ± 6.0%, respectively, compared with 91.6% ± 1.3%, 75.7% ± 2.1%, and 54.2% ± 3.6% in SITA patients (p = 0.252).
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respectively. There were eight independent predictors for 30-day mortality in the entire database, whereas only three of them were independent predictors in the BITA group. Bilateral internal thoracic artery grafting was not an independent predictor for 30-day mortality (adjusted OR 1.16, 95% CI: 0.57 to 2.39, p = 0.684). There were 12 independent predictors for long-term mortality in the entire database and nine independent predictors in the BITA group. The crude HR of long-term mortality for BITA patients was 0.87 (95% CI: 0.67 to 1.11, p = 0.253); and after adjustment for all available risk factors, the adjusted HR was 0.89 (95% CI: 0.69 to 1.14, p = 0.343). Off-pump coronary artery bypass grafting was an independent predictor both for 30-day and long-term mortality in the entire database, but not in the BITA group. However, we have shown that the detrimental effect of off-pump coronary artery bypass grafting on midterm survival has changed during the last 5 years in our institution after innovative techniques became available [16].
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Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionReferences |
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Previous studies have shown that BITA grafting in diabetic patients does not carry an increased risk for early death [10], especially in selected patients excluding those older than 75 years of age, with chronic obstructive pulmonary disease, obesity, and emergent operation [19]. This observation was confirmed in our study, where in propensity-matched pairs, BITA patients had 3.9% 30-day mortality compared with 3.7% for SITA patients (p = 0.999). In both groups, observed mortality was significantly lower than the predicted mortality as estimated by the additive EuroSCORE algorithm (6.8 and 6.9 for the BITA and SITA groups, respectively). In addition, in our study there were 15.5% BITA patients with chronic obstructive pulmonary disease, 3.7% with body mass index greater than 29, and 8.8% with an emergent operation, who were appropriately matched with the SITA group (Table 1).
Diabetic patients are susceptible to wound infections because of several physiologic derangements. Deep sternal wound infection is a potentially devastating complication after CABG, and many surgeons are reluctant to use BITA grafting in diabetic patients because of concern over the higher rate of this complication in this subgroup of patients. In the present study, deep sternal wound infection developed in 3.3% of BITA patients compared with 1.2% of SITA patients; however, this difference was not statistically significant, but only a trend between matched groups (p = 0.050). Risk factors for the development of deep sternal wound infection after CABG include chronic obstructive pulmonary disease, obesity, BITA grafting, redo CABG, and postoperative complications such as sepsis and endocarditis [11, 20, 21]. Lev-Ran and colleagues [22], in a series of 515 diabetic patients with BITA grafting, reported 1.9% and 4.3% deep sternal wound infections in oral-treated and insulin-treated diabetic patients, respectively; however, their patients had lower rates of chronic obstructive pulmonary disease, emergent operation, and redo CABG compared with our BITA series. Deep sternal wound complications in diabetic patients may be reduced by using the skeletonized BITA grafting technique [21] or by following tight control of glucose with perioperative continuous intravenous insulin infusion [23]. We also support the use of BITA grafting among patients who do not undergo emergent operation and are 70 years old or younger [24]. However, these conclusions became available recently, and we started following contraindications for BITA grafting after 2001; therefore, in the present study there were almost no contraindications for BITA grafting.
There are few studies in the literature evaluating the long-term outcome of diabetic patients with BITA grafting. Hirotani and associates [25] showed that there was no significant difference in long-term survival between BITA and SITA grafting in a series of 303 consecutive diabetic patients; this finding was also confirmed by Endo and associates [26] in a series of 367 diabetics, but these authors concluded than in patients with preserved ejection fraction (>40%), BITA grafting had a significantly higher 10-year survival rate compared with SITA grafting. Our results are in concordance with these studies; however, we did not detect any difference between groups when we analyzed subgroups with preserved ejection fraction (data not shown). In a recent study, Lev-Ran and colleagues [27] reported superiority of BITA grafting at 7 years in terms of survival, freedom from cardiac death, and major adverse cardiac events in a series of 285 consecutive diabetics. This study included only orally treated diabetic patient subsets, and the same authors have reported similar 6-year survival among insulin-treated diabetic patients with BITA and SITA grafting [28].
In our study, which is one of the largest in literature and involves 980 propensity-matched pairs of treated diabetic patients, we found that patients with BITA grafting aged between 60 and 69 years had better long-term survival; and careful observation of the Kaplan-Meier curves (Fig 2B) showed that the diversion of the curves occurred during the first 36 months, whereas after this time point there was almost no diversion. The reason for this beneficial effect of BITA grafting in this subgroup cannot be deduced from our data, however, because we do not have postoperative angiographic data. Our hypothesis for this is the earlier saphenous vein graft failure in diabetic patients when compared with nondiabetic patients (first 3 years instead of 5 to 10 years postoperatively). Clearly, considering patients aged more than 79 years, there was no death in the SITA group during the first 36 months, suggesting that a longer and more technically demanding surgical technique such as BITA grafting may be inappropriate for octogenarians. Among patients younger than 60 years or between 70 and 79 years, there was no difference in long-term mortality. Probably the effect of age on coronary bypass grafts is superior to that of diabetes in these subgroups. Therefore, in younger patients, saphenous vein grafts may remain patent during an almost 5-year follow-up, whereas in older diabetic patients, the coronary arteries bypassed with both arterial and saphenous vein grafts experience the same degree of failure, resulting in similar survival rates between the two groups. Overall, when 490 propensity-matched BITA subjects were compared with 490 SITA subjects, there was no difference in long-term mortality, despite the higher number of distal anastomoses in the BITA group, as has been shown in other studies [26].
Several limitations of this study need to be addressed. This is a retrospective study. Nevertheless, the information on preoperative, intraoperative, and postoperative factors has been collected using highly standardized methods for the New York State audited database. Our study refers to a single-center regional database, and it is likely that selection of patients, choice of procedures, and management of the perioperative period may be important determinants of long-term mortality; and these determinants may vary among cardiac surgical units. Furthermore, changes in the hospital may influence the results during our 10-year study. It has been demonstrated by previous published studies that the longer the follow-up, the more effective the BITA strategy appears. The average follow-up in our study is less than 5 years; therefore, a longer follow-up period may provide additional information in terms of the advantage of survival in BITA group. The cause of death in these patients is not documented and is not necessarily cardiac related, and we were not able to study separately patients treated with oral hypoglycemic agents and those treated with insulin or to examine the effect of skeletonized BITA grafting and its anastomosis to the left circumflex coronary artery.
In conclusion, there was no significant effect of BITA grafting compared with SITA grafting on long-term survival among diabetic patients treated with oral hypoglycemic agents or insulin. As this finding is well in concordance with previous studies, a randomized trial seems warranted. It is possible that not all diabetic patients benefit from BITA grafting equally and that the benefit occurs among different subgroups at different times during the follow-up period. The present study showed that this benefit may be related to age.
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Discussion |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionReferences |
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The long-term success of coronary artery bypass surgery is directly related to graft patency. Internal thoracic artery grafts, because of their resistance to atherosclerosis, have stable and better long-term patency than saphenous vein grafts, and this patency of ITA grafts is believed to be responsible for the increased survival and decreased recurrence of angina and need for reoperation when they are used to bypass the LAD.
Logic dictates that adding an additional internal thoracic artery graft should further improve the long-term outcomes of coronary artery bypass surgery. We, as well as others, have demonstrated better survival and fewer reoperations and reinterventions in patients after bilateral ITA grafting as compared with patients after single ITA grafting. Despite these observations, bilateral ITA grafting remains very low. In a recent review of this Society's adult cardiac database, bilateral ITA grafts are being used in only 3% to 4% of coronary operations. Doctor Anagnostopoulos and his colleagues should be commended for their high usage of bilateral ITA grafts.
The incremental benefit of a second internal thoracic artery graft takes time to appear. In our studies at the Cleveland Clinic Foundation, we have followed patients for a long period of time after surgery to demonstrate the advantages of bilateral ITA grafting. The mean follow-up in our first study was about 10 years. This requirement for long follow-up may be due to the success of single ITA grafting in achieving good outcomes during the first decade after surgery. I have several questions for Dr Anagnostopoulos.
You did not find in both your multivariate analysis and in the comparison of all the propensity-matched patients that bilateral ITA grafting improved survival. However, your mean follow-up was only 4.5 years. Do you think this follow-up is long enough and might your findings be different if your patients were followed for a longer period of time?
My next question relates to the selection of patients for bilateral versus single ITA grafting. How were diabetic patients selected to undergo bilateral ITA grafting? Did you follow a protocol or was it surgeon preference? In particular, were insulin-treated diabetic patients less likely to undergo bilateral ITA surgery? In your paper you grouped all diabetic patients together as medically treated. You did not stratify or propensity match the patients on whether or not they were insulin-dependent diabetics. One would expect the risk and outcomes of coronary artery bypass surgery to be different in insulin-treated and noninsulin-treated diabetics. Why did you not stratify the patients by insulin dependence?
The patency of internal thoracic artery grafts is better when they are used to bypass left-sided coronary arteries, and therefore when performing bilateral ITA grafting, using the right or second internal thoracic artery grafts to graft the circumflex may result in better long-term outcomes than if it is used to graft the right coronary artery. What coronary artery was the right or second ITA graft preferentially used to bypass in this series? I believe we would all agree that the left internal thoracic artery should be used to bypass the LAD.
Also, how often were other arterial grafts, such as radial grafts, used in these patients? In particular, how often did the single ITA patients receive an additional non-ITA arterial graft and how might their usage have influenced your findings?
Finally, your propensity matching is very thorough, and by including many variables in the analysis, two well-matched groups were formed. However, one has to be careful not to overuse this technique. Similar to the fact that subgroup analysis in randomized studies is unlikely to result in subgroups with similar characteristics, stratifying propensity-matched patients into subgroups will unlikely result in subgroups with similar characteristics. For instance, your subgroup of 60- to 69-year-olds who received single internal thoracic arteries may not have similar characteristics as the subgroup of 60- to 69-year-olds who received bilateral ITAs. Therefore, any improvement in survival observed in the 60- to 69-year-old subgroup that received BITA grafts may not be due to the grafting strategy, but instead due to the different preoperative characteristics of the patients receiving bilateral ITA grafts. Did you compare the characteristics of your age subgroups to make sure you were comparing patients with similar characteristics? I once again would like to congratulate Dr Anagnostopoulos on a fine presentation and to thank the Society for the privilege of discussing this paper.
DR ANAGNOSTOPOULOS: Thank you, Dr Sabik. Yes, we agree that the patency is related to survival. I would like to remind the audience that in some studies one needs survival, angina recurrence, and reoperative endpoints to demonstrate superiority of BITA grafts early on.
In a previous study, when we compared BITA grafting (not as in this paper, but all BITA grafting), superiority was shown at 3 to 5 years in contrast to the Cleveland Clinic study. So we do think, in answer to your question, that it was long enough to do a 0- to 10-year study (average 4.5 years), to demonstrate any potential "early" advantages or lack thereof (we actually call these mid-term results).
Our selection protocol was surgeon-driven, largely. There were three teams. One did 90% BITA, the other 50%, the other 20%, and it was equally applied to insulin- and noninsulin-dependent diabetic patients. However, we were unable to tell by using the database how many were insulin dependent and how many were not insulin dependent.
The right internal thoracic artery was used in the circumflex in 80% of the cases.
In this particular study, we used only single and double internal thoracic arteries; no other arterial grafts such as radials were in this analysis.
In answer to your last question, we actually did look at the characteristics of the 60- to 69-year-old group where BITA showed to be better, and they were similar to those of the whole base.
Thank you, and I thank the Society for the privilege of the floor.
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionReferences |
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