During the last years, many reports have clearly

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1 Single Versus Bilateral Internal Mammary Artery for Isolated First Myocardial Revascularization in Multivessel Disease: Long-Term Clinical Results in Medically Treated Diabetic Patients Antonio Maria Calafiore, MD, Michele Di Mauro, MD, Gabriele Di Giammarco, MD, Giovanni Teodori, MD, Angela Lorena Iacò, MD, Valerio Mazzei, MD, Giuseppe Vitolla, MD, and Marco Contini, MD Division of Cardiac Surgery, University Hospital, Torino, Division of Cardiac Surgery, G D Annunzio University, Chieti, and Division of Cardiac Surgery, Papardo Hospital, Messina, Italy Background. We evaluated our experience to investigate if the use of bilateral internal mammary artery (BIMA) grafting, with or without complementary saphenous vein grafts (SVG), increases the quality of the results of coronary bypass grafting in medically treated diabetic patients who undergo first myocardial revascularization, when compared with the use of a single left internal mammary artery (LIMA) and SVG. Methods. From October 1991 to December 2001, 558 diabetic patients with multivessel coronary disease had first isolated myocardial revascularization using LIMA and SVG (group LIMA) in 217 cases and BIMA SVG (group BIMA) in 341. Propensity score analysis identified 400 patients, 200 for each group, with similar preoperative characteristics. Thirty-day outcome and 8-year freedom from death from any cause, cardiac death, acute myocardial infarction (AMI), AMI in a grafted area, redo/percutaneous transluminal coronary angioplasty (PTCA), redo/ptca in a grafted area, target cardiac events, and any event were evaluated. Follow-up ranged from 2.0 to 12.2 years (mean ). Results. There was no difference between groups except the cardiac deaths, which were significantly higher in the LIMA group (7 versus 0, p 0.015). The BIMA group showed better 8-year freedom from death any cause ( versus , p ), cardiac death ( versus , p ), acute myocardial infarction ( versus , p ), and acute myocardial infarction in a grafted area ( versus , p ). Cox analysis confirmed that the use of LIMA and SVG was an independent predictor for lower freedom from death (hazard ratio [HR] 1.8, p ), cardiac death (HR 1.9, p ), AMI (HR 9.7, p ) and AMI in a grafted area (HR 8.2, p ). Conclusions. In diabetic patients with multivessel disease who undergo first myocardial revascularization, BIMA SVG provides higher freedom from death, any cause, and cardiac-related death, if compared with LIMA SVG. It plays a protective role in reducing the incidence of late AMI. (Ann Thorac Surg 2005;80:888 95) 2005 by The Society of Thoracic Surgeons During the last years, many reports have clearly demonstrated the superiority of bilateral internal mammary artery (BIMA) over the single one, regarding freedom from death [1, 2], from cardiac death [3, 4], and from cardiac-related events [3 5]. Nevertheless, the increase of deep sternal wound problems, especially in diabetic patients, represented, for several years, the main limitation for the widespread use of BIMA grafting [6,7]. However, recent reports demonstrated that, if an IMA is harvested in a skeletonized fashion, the sternal vascularization is preserved and the incidence of sternal wound problems is reduced [8 11]. This aspect is relevant especially for diabetic patients. Accepted for publication March 18, Address reprint requests to Dr Calafiore, Division of Cardiac Surgery, S Giovanni Battista Hospital, c.so Bramante 86, Torino, Italy; calafiore@unich.it. Despite the potential benefit of BIMA grafting, cardiac surgeons were reluctant to use this strategy in diabetic patients, since chronic complications of this disease reduce the quality of long-term results. We evaluated our experience in order to investigate if the use of BIMA grafting, with or without complementary saphenous vein graft (SVG), can improve early and late results of coronary bypass grafting in medically treated diabetic patients who undergo first myocardial revascularization, when compared with the use of left internal mammary artery (LIMA) and SVG. Material and Methods From October 1991 to December 2001, 558 medically treated diabetic patients affected by multivessel coronary disease underwent coronary artery bypass grafting 2005 by The Society of Thoracic Surgeons /05/$30.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg CALAFIORE ET AL ;80: FIRST REVASCULARIZATION IN MULTIVESSEL DISEASE Table 1. Preoperative Characteristics BIMA Group LIMA Group Characteristic n 200 n 200 p Value Age Female 59 (29.5%) 70 (35.0%) Diabetes mellitus, on oral treatment 151 (75.5%) 143 (71.5%) Diabetes mellitus, on insulin treatment 49 (25.5%) 57 (28.5%) Urgent 57 (29.5%) 73 (36.5%) Extracardiac vasculopathy 69 (34.5%) 69 (34.5%) 1.00 Preoperative acute myocardial infarction 102 (51.0) 104 (52.0) Unstable angina 95 (47.5) 106 (53.0) Chronic heart failure 8 (4.0) 12 (6.0) Chronic renal failure (cr 2) 6 (3.0) 9 (4.5) Chronic obstructive pulmonary disease 17 (8.5%) 16 (8.0%) Election fraction % 21 (10.5%) 23 (11.5%) Left main steam 28 (14.0%) 24 (12.0%) Two-vessel disease 58 (29.0%) 57 (28.5%) Three-vessel disease 142 (71.0%) 143 (71.5%) EuroSCORE BIMA bilateral internal mammary artery; LIMA left internal mammary artery. (CABG) using LIMA to the left anterior descending artery (LAD) and SVG (n 217), or BIMA (one IMA always to the LAD) with or without SVG (n 341). Propensity score analysis was used to select 400 patients (71.6%), matching each LIMA SVG with a BIMA SVG with the nearest propensity score. Two groups of patients (LIMA group and BIMA group), 200 each, were obtained (goodness of fit 2 5.5, df 8, p 0.84). Table 1 shows the preoperative characteristics of the patients included in the study. Patient Selection All the patients included in the study were on insulin treatment (n 106) or on oral treatment (n 294), equally divided in the two groups (Table 1). Patients on diet because of mild fasting hyperglycemia were excluded. All the patients were suitable for single LIMA or BIMA grafting. Single or bilateral IMA grafting was mainly decided according to the surgeon s practice or experience. Allocation to off-pump surgery was dependent on the basis of the expertise of the surgeon responsible for the operation. Surgical Technique Cardiopulmonary bypass was used in 254 patients (63.5%), whereas 146 (36.5%) were operated on without cardiopulmonary bypass. For on-pump surgery, in every case a median sternotomy was used. Cardiopulmonary bypass was instituted by cannulation of ascending aorta and right atrium. Intermittent antegrade warm blood cardioplegia has been used in every case. Proximal SVG anastomoses were performed using a side clamp in 105 cases and during a single cross-clamping time in the remaining 183. For off-pump surgery, the method of exposure of the target coronary vessel and of stabilization has already been reported [12]. In most recent years, apical suction was used to expose particularly the lateral and the inferior wall (Xpose; Guidant Corporation, Cupertino, California). When the coronary artery was exposed, stabilization was achieved with a pressure (Acces Ultima System; Guidant Corporation), or suction (Axius Vacuum 2 System; Guidant Corporation) stabilizer. The target vessel was occluded with 4-0 polypropylene, Table 2. Operative Details BIMA Group LIMA Group n 200 n 200 p Value Anastomoses per patient Carotid endarterectomy 7 (3.5) 7 (3.5) 1.00 Cardiopulmonary bypass 129 (64.5) 125 (62.5) Sequential grafts 64 (32.0) 83 (41.5) BIMA bilateral internal mammary artery; LIMA left internal mammary artery.

3 890 CALAFIORE ET AL Ann Thorac Surg FIRST REVASCULARIZATION IN MULTIVESSEL DISEASE 2005;80: Table 3. Postoperative Results BIMA Group LIMA Group n 200 n 200 p Value Deaths 6 (3.0) 10 (5.0) Cardiac deaths 0 7 (3.5) Acute myocardial infarction 1 (0.5) 5 (2.5) Cerebrovascular accident 4 (2.0) 2 (1.0) Early negative primary endpoints 8 (4.0) 12 (6.0) Early major events 14 (7.0) 24 (12.0) Sternal wound problems 6 (3.0) 3 (1.5) BIMA bilateral internal mammary artery; LIMA left interval mammary artery. passed on a small piece of silicone tubing and then gently snared. Harvesting Technique Globally, internal mammary arteries were harvested as a pedicle in 62 patients (30 in the BIMA group and 32 in the LIMA group, p 0.890) and 338 in a skeletonized fashion in the remaining (170 versus 168, p 0.890). Postoperative Course After the operation, all the patients were admitted to the intensive care unit (ICU) and, after a mean of hours, were moved to the cardiac surgery ward. Tight perioperative blood glucose control was performed in all patients, by mean of insulin, regardless their own preoperative therapy. They were discharged from the ward after a mean of days. Follow-Up All the patients were followed up in our outpatients clinic 3, 6 and 12 months after surgery and thereafter at yearly intervals. The more recent information was obtained by calling the patient or the referring cardiologist. Follow-up was 100% complete; the deadline was fixed on December 31, Patients at risk after 1, 5, and 8 years were, respectively, 189, 105, 44 in BIMA group patients and 182, 56, 18 in LIMA group patients. Clinical Data Collection, Monitoring, and Definitions A set of perioperative data are collected prospectively for all patients undergoing CABG at our institution. The following were recorded and defined: Mortality included death from any cause. Cardiac mortality included any death from cardiac causes and sudden deaths. Cerebrovascular accident was defined as global or focal neurologic deficit, diagnosed by a neurologist and confirmed by a brain computed tomography (CT) scan. Acute myocardial infarction (AMI) was defined as enzymatic elevation, electrocardiographic sign of necrosis, new akinetic segments at echocardiography, ventricular arrythmias non-k related. During the follow-up, the possibility that AMI occurred in the grafted area was considered. Early major events were defined as the sum of death any cause, cerebrovascular accident, AMI, low output syndrome (need of intra-aortic balloon pump or inotropic drugs, or both, for more than 12 hours), need of mechanical ventilation for more than 24 hours, acute renal failure (postoperative blood creatinine 2.0 mg/100 ml, if the preoperative value was normal ( 1.5), or 1 mg higher if pathologic), and gastrointestinal complications. Early negative primary endpoints were defined as the sum of death any cause, AMI, and cerebrovascular accident; redo/ptca was defined as any intervention in any territory or in the grafted area; target cardiac events were defined as cardiac deaths, AMI in a grafted area, and Table 4. Eight-Year Actuarial Results BIMA Group LIMA Group n 200 n 200 p Value Freedom from death, any cause Cardiac death Acute myocardial infarction Acute myocardial infarction in the grafted area Redo PTCA Redo PTCA in the grafted areas Target cardiac events Any event BIMA bilateral internal mammary artery; LIMA left internal mammary artery; PTCA percutaneous transluminal coronary angioplasty.

4 Ann Thorac Surg CALAFIORE ET AL 2005;80: FIRST REVASCULARIZATION IN MULTIVESSEL DISEASE 891 Fig 1. (A) Eight-year freedom from death any cause; (B) 8-year freedom from cardiac death; (C) 8-year freedom from acute myocardial infarction; and (D) 8-year freedom from acute myocardial infarction in a grafted area. Solid lines bilateral internal mammary artery group; broken lines left internal mammary artery group. redo/ptca in a grafted area; any event was defined as death any cause, AMI any territory, redo/ptca any territory. Statistical Analysis Results are expressed as mean value SD. Statistical analysis comparing two groups was performed with unpaired two-tailed t testing for the means or the 2 test for categorical variables. Stepwise logistic regression analysis was used to realize a model to calculate saturated propensity score (the probability to be selected for LIMA SVG given a set of preoperative risk factors already reported [12]). The goodness of model was evaluated using the Hosmer and Lemeshow goodness-of-fit statistic and residual analysis. Each LIMA SVG patient was matched with the BIMA SVG patient with the closest propensity score. Variables at the basis of the model are shown in Appendix 1. Stepwise logistic regression analysis was used to select the independent variables that could predict the endpoints of this study and included all the univariate variable with a p value of 0.2 or less. In the final regression model independent variables were expressed as odds ratio (OR) and related p value. Stepwise logistic regression was used to identify the independent predictors of early events. Actuarial curves were obtained with the Kaplan-Meier method. The statistical significance was calculated with the log-rank test. Cox analysis was used to evaluate the independent risk factors for reduced late events. In the Cox analysis model, independent variables were expressed as hazard ratio (HR) and the related p value. The variables included in either stepwise logistic regression or Cox analysis are listed in Appendix 2. The SPSS software (SPSS, Chicago, Illinois) was used. All p values of 0.05 or less were considered significant. Results The operative details are reported in Table 2. In the LIMA group, the internal mammary artery was anastomosed always to the LAD, in 39 cases sequentially with the diagonal. In the BIMA group, an IMA (the left in 115 cases [57.5%], and the right in 85 cases [42.5%]) was always anastomosed to the LAD, whereas the diagonal was sequentially grafted with an IMA in 28 cases (14.0%). The remaining IMA was grafted to the circumflex artery system in 173 patients (86.5%) and to the right coronary artery system in the remaining 27 (13.5%). The right coronary artery was chosen when it was the main artery after the LAD. It was directly grafted in 19 cases (only when its wall was not sclerocalcific); in the remaining 8, the distal anastomosis was performed to the posterior descending artery, being the right internal mammary artery (RIMA) proximally anastomosed to the LIMA. The BIMAs were in situ in 110 cases (55.0%) and as a Y graft

5 892 CALAFIORE ET AL Ann Thorac Surg FIRST REVASCULARIZATION IN MULTIVESSEL DISEASE 2005;80: in 90 cases (45.0%); in 112 cases (56.0%), no veins were used. Globally, the LAD system received 491 distal anastomoses (244 in the BIMA group and 247 in the LIMA group, p 0.410), the circumflex artery system, 381 (209 versus 172, p 0.054), and the right coronary artery system, 260 (120 versus 140, p 0.116). Table 3 shows the postoperative results. There was no difference between the two groups except for the cardiac deaths, which were significantly higher in the LIMA group. The stepwise logistic regression analysis showed that the surgical strategy (choice of grafts, off-pump or on-pump) was not a risk factor for death any cause, cardiac death, AMI, cerebrovascular accident, early negative primary endpoints, or early major events. Sternal wound problems had an overall incidence of 2.25%, without a difference between groups (Table 3). Obesity (OR 2.8, p 0.032) and chronic obstructive pulmonary disease (OR 4.0, p 0.036) were risk factors for a higher incidence of sternal wound problems. As a whole, patients with pedicled IMA had a higher incidence of sternal wound problem (6.4% versus 1.5%, p 0.045). Within the groups, pedicled IMA harvesting was related to a higher incidence of sternal complications, both in the LIMA group (6.6% versus 1.8%, p 0.335) and in the BIMA group (6.7% versus 1.2%, p 0.204), even if not statistically different because of the small size of both pedicled IMA subsets. Mean follow-up of the survivors was years (range, 2.0 to 12.2), for the LIMA group and for the BIMA group (p 0.294). After a mean of years, 36 had patients died, 22 in the LIMA group versus 14 in the BIMA group, 15 from cardiac causes (8 versus 7). Three patients of the LIMA group had an AMI, 2 in the grafted area; none of the BIMA group experienced any late AMI; 8 patients had a redo or PTCA (3 versus 5), 7 in the grafted area (3 versus 4); 14 patients had a TCE (7 versus 7), and 42 had any event (24 versus 18). Table 4 shows the 8-year actuarial results of the investigated events. The use of LIMA and SVG was an independent predictor for lower freedom from death (HR 1.8, p ), cardiac death (HR 1.9, p ), AMI (HR 9.7, p ), and AMI in a grafted area (HR 8.2, p ). Figure 1 shows the curves related to these events. Off-pump surgery had no independent effect on late outcomes in this subgroup of patients. Patients with insulin-dependent diabetes showed similar results as patients on oral treatment. Interestingly, there was a trend toward better results, even if not statistically significant. Comment The prevalence of diabetic patients referred to surgical or percutaneous coronary revascularization has remarkably increased, reaching 25% in the United States [13]. Diabetes mellitus represents one of the most important limitations for PTCA. Indeed, most of the previous studies comparing PTCA and CABG have fully demonstrated that diabetic patients, treated with PTCA, have lower survival [14 17] and significantly higher restenosis and reintervention rate [16 18]. Therefore, most diabetic patients are indicated exclusively for CABG. Abramov and colleagues [19] reported that the incidence of diabetic patients undergoing CABG was 18.6% at the beginning of the 1990s, but rose significantly up to 26.7% at the end of the same decade. Over the last years, several reports have clearly demonstrated that the use of BIMA grafting allows greater freedom from death any cause [1, 2], cardiac death [3, 4], and cardiac-related events [3 5] when compared with single IMA grafting. Nevertheless, many surgeons have been reluctant for long time to use BIMA grafting in diabetic patients because of a greater risk of deep sternal problems [6, 7]. Recently, IMA harvesting as a skeletonized conduit [8 11], together with better-controlled glucose management in the postoperative period [20], was shown to reduce the incidence of this complication. Diabetes mellitus is a widely recognized risk factor for lower early and late outcome [3, 14, 17, 18, 21, 22] after myocardial revascularization in patients with multivessel disease. This has forced many surgeons to reconsider BIMA grafting to improve early and late outcome of diabetic patients [9, 21, 23, 24]. In our series, no difference was found between the two groups regarding early mortality and morbidity, as reported by others [23]. Overall mortality was 4.0%, higher than in other reports [23, 24]. Endo and associates [23] reported an overall mortality of 1.1% in 467 diabetic patients who underwent elective CABG, but 63.2% of them were on diet therapy. These patients were excluded from our study. Moreover, 368 of 467 patients (78.8%) had an ejection fraction higher than 40%, against 71.5% in our study (p 0.016). In another recent report [24], the overall mortality was 2.7%, but 90.1% of patients were on oral treatment, reporting a mortality of 2.4%, compared with 6.7% of patients on insulin treatment. In our series, just 73.6% of patients were on oral treatment, with a 30-day mortality of 2.9% compared with 6.9% of patients treated by insulin. The BIMA group showed an higher incidence of sternal wound problems, even if not statistically significant. Obesity and chronic obstructive pulmoonary disease were risk factors for the higher incidence of sternal wound problems, as previously reported by Matsa and associates [9]. The main endpoint of our study is to evaluate whether BIMA grafting can provide better late clinical results than the single IMA in diabetic patients as well. There are not many studies in the literature that have clearly demonstrated the superiority of BIMA versus LIMA grafting in diabetic patients. Hirotani and colleagues [21] did not find any benefit. Endo and associates [23] found no significant difference for 10-year survival between BIMA patients (80.2%) and single IMA patients (75.4%; p 0.46). In 368 of 467, with ejection fraction greater than

6 Ann Thorac Surg CALAFIORE ET AL 2005;80: FIRST REVASCULARIZATION IN MULTIVESSEL DISEASE 40%, they reported 10-year freedom from all deaths (87.4% versus 75.2%, p 0.04; HR 0.61) and freedom from all deaths, re-cabg and AMI (86.6% versus 69.0%, p ; HR 0.53), significantly higher in the BIMA group. But the patients in the group with a single IMA were significantly older, and this group had a higher prevalence of women and diabetic patients on oral insulin treatment rather than on diet. In a retrospective nonmatched study published very recently by Lev-Rahn and colleagues [26], 228 oraltreated patients who received left-sided BIMA have been compared with 57 patients who received a single IMA. They demonstrated that the use of BIMA grafting improved long-term survival and freedom from cardiac-related mortality and from major adverse cardiac events in this particular subset of CABG patients. In our series, patients were fully comparable regarding preoperative and operative data, being selected by mean of propensity score. Kaplan-Meier analysis showed that BIMA grafting provides higher freedom from death any cause, cardiac death and AMI, in any area and in the grafted area. These findings were confirmed by Cox analysis. The BIMA grafting group reached, in this study, a higher freedom from death any cause and cardiac death, compared either with other diabetic series [14, 16, 18] or with results obtained using BIMA grafting in diabetic patients [23, 24]. Patients in the BIMA group did not experience any late AMI. The BIMA grafting did not provide any benefit for freedom from redo/ptca, in any area or in the grafted area. The preoperative treatment did not influence neither the early nor the late outcome. On the contrary, there was a trend toward better results in insulin-dependent diabetic patients. This finding was consistent with the results of a previous study of ours [22], in which insulin-treated patients showed a long-term survival higher than that of diabetic patients on oral treatment. Perhaps long-term treatment with insulin, because antidiabetic centers are widely diffused, can better control hyperglycemia, lowering the complication rate in the long term. Our study shows some limits. It is not randomized, but retrospective. However, applying the propensity score, we were able to select two groups of patients with similar preoperative characteristics. This statistical mechanism led to two similar but small-size groups, and this was another limitation. Nevertheless, we can say in conclusion that, among medically treated diabetic patients with multivessel disease who undergo first myocardial revascularization, BIMA grafting reduces significantly the incidence of early cardiac mortality, without any significant negative impact on incidence of sternal wound problems, especially if the conduits are harvested skeletonized. Bilateral IMA SVG provides higher freedom from death, any cause and cardiac related, if compared with LIMA SVG. It plays a protective role in reducing the incidence of late AMI. In our opinion, the use of both IMAs is not to be denied to diabetic patients. References Lytle BW, Blackstone EH, Loop FD, et al. Two internal thoracic artery grafts are better than one. J Thorac Cardiovasc Surg 1999;117: Schmidt SE, Jones JW, Thornby JI, Miller CC, Beall ACJ. Improved survival with multiple left-sided bilateral internal thoracic artery grafts. Ann Thorac Surg 1997;64: Pick AW, Orszulak TA, Anderson BJ, Schaff HV. Single versus bilateral internal mammary artery grafts: 10-year outcome analysis. Ann Thorac Surg. 1997;64: Calafiore AM, Di Giammarco G, Teodori G, et al. Late results of first myocardial revascularization in multiple vessel disease: single versus bilateral internal mammary artery with or without saphenous vein grafts. Eur J Cardiothorac Surg 2004;26: Berreklouw E, Rademakers PP, Koster JM, van Leur L, van der Wielen BJW, Wsters P. Better ischemic event-free survival after two internal thoracic artery grafts: 13 years of follow up. Ann Thorac Surg 2001;72: Cosgrove DM, Lytle BW, Loop FD, et al. Does bilateral internal mammary artery grafting increase surgical risk? J Thorac Cardiovasc Surg 1988;95: Grossi EA, Esposito R, Harris LJ, et al. Sternal wound infections and use of internal mammary artery grafts. J Thorac Cardiovasc Surg 1991;102: Calafiore AM, Vitolla G, Iaco AL, et al. Bilateral internal mammary artery grafting: midterm results of pedicled versus skeletonized conduits. Ann Thorac Surg 1999;67: Matsa M, Paz Y, Gurevitch J, et al. Bilateral skeletonized internal thoracic artery grafts in patients with diabetes mellitus. J Thorac Cardiovasc Surg 2001;121: Uva MS, Braunberger E, Fisher M, et al. Does bilateral internal thoracic artery grafting increase surgical risk in diabetic patients? Ann Thorac Surg 1998;66: Peterson MD, Borger MA, Rao V, Peniston CM, Feindel CM. Skeletonization of bilateral internal thoracic artery grafts lowers the risk of sternal infection in patients with diabetes. J Thorac Cardiovasc Surg 2003;126: Calafiore AM, Di Mauro M, Canosa C, Di Giammarco G, Iaco AL, Contini M. Myocardial revascularization with and without cardiopulmonary bypass: advantages, disadvantages and similarities. Eur J Cardiothorac Surg 2003;24: Smith SC Jr, Faxon D, Cascio W, et al. Prevention conference VI: diabetes and cardiovascular disease. Writing group VI: revascularization in diabetic patients. Circulation 2002;105: e The BARI Investigators. Influences of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease. The Bypass Angioplasty Revascularization Investigation (BARI). Circulation 1997;96: Kurbaan AS, Bowker TJ, Ilsley CD, Sigwart U, Rickards AF. Difference in mortality of the CABRI diabetic and nondiabetic population and its relation to coronary artery disease and revascularization mode. Am J Cardiol. 2001;87: King SB, Kosinski AS, Guyton RA, Lembo NJ, Weintraub WS. Eight-year mortality in the Emory Angioplasty versus Surgery Trial (EAST). J Am Coll Cardiol 2000;35: Abizaid A, Costa MA, Centemero M, and the Arterial Revascularization Therapy Study Group. Clinical and economic impact of diabetes mellitus on percutaneous and surgical treatment of multivessel coronary artery disease. Insights from the Arterial Revascularization Therapy Study (ARTS) trial. Circulation 2001;104: Weintraub WS, Stein B, Kosinski A, et al. Outcome of coronary bypass surgery versus coronary angioplasty in diabetic patients with multivessel coronary artery disease. J Am Coll Cardiol 1998;31: Abramov D, Tamariz MG, Fremes SE, et al. Trends in coronary artery bypass surgery results: a recent 9-year study. Ann Thorac Surg 2000;70:84 90.

7 894 CALAFIORE ET AL Ann Thorac Surg FIRST REVASCULARIZATION IN MULTIVESSEL DISEASE 2005;80: Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999;67: Hirotani T, Kameda T, Kumamoto T, Shirota S, Yamano M. Effects of coronary artery bypass grafting using internal mammary arteries for diabetic patients. J Am Coll Cardiol 1999;34: Calafiore AM, Di Mauro M, Di Giammarco G, et al. Effect of diabetes on early and late survival after isolated first coronary bypass surgery in multivessel disease. J Thorac Cardiovasc Surg 2003;125: Endo M, Tomizawa Y, Nishida H. Bilateral versus unilateral internal mammary revascularization in patients with diabetes. Circulation 2003;108: Lev-Ran O, Mohr R, Amir K, et al. Bilateral internal thoracic artery grafting in insulin-treated diabetics: should it be avoided? Ann Thorac Surg 2003;75: Lev-Ran O, Mohr R, Pevini D, et al. Bilateral internal thoracic artery grafting in diabetic patients: short-term and long-term results of 515-patients series. J Thorac Cardiovasc Surg 2003;27: Lev-Rhan, Braunstein R, Nehser N, Ben-gal Y, Bolotin G, Uretzky G. Bilateral versus single internal thoracic artery grafting in oral-treated diabetic subsets: comparative sevenyear outcome analysis. Ann Thorac Surg 2004;77: Appendix 1 Variables Included in the Propensity Score Model Variables B Value p Value Chronic obstructive pulmonary disease Number of anastomoses Extracardiac vasculopathy Age Previous acute myocardial infarction Hypertension Female sex Urgency Hypercholesterolemia Ejection fraction 35% Unstable angina Left main steam Appendix 2 Variables Included in Either Stepwise Logistic Regression or Cox Analysis Variable Age Continuous (years) Age 75 years old Dichotomous Female Sex Dichotomous Obesity Body mass index higher than 30 kg/m 2 History of hypertension Need of medical treatment (Calcium channel blockers, -blockers, angiotensionconverting enzyme inhibitors) History of smoking More than 10 cigarettes a day smoked for at least 10 years Hypercholesterolemia History or at present cholesterol value 200 mg/dl Chronic renal failure Creatinine value.2.0 mg/dl Chronic hepatic failure Bilirubin value 2.0 mg/dl Chronic obstructive pulmonary disease Unstable angina Chronic heart failure Acute myocardial infarction 24 hours Preoperative intraaortic balloon pump (IABP) Previous atrial fibrillation Urgency Forced expiratory volume in 1 second (FEV 1 ), 75% of predicted value, air PO 2 lower than 60 mm Hg, or chronic medical treatment Presence of angina at rest, stable angina with worsening pattern or de novo angina Heart failure in the history or at present admission without angina Acute myocardial infarction 24 hours before surgery Use of IABP for cardiogenic shock or to stabilize an unstable angina Dichotomous Any condition (unstable angina, cardiogenic shock, critical left main stenosis, etc) that prevents the patient s discharge from the hospital Ventricular arrhythmia In the history or requiring medical treatment at this admission Extracoronary vasculopathy Peripheral vasculopathy (symptoms or angiographic or echographic evidence of dilation or reduction of flow) of any artery with the exclusion of carotid arteries) and/or carotid disease (presence of a fibrocalcific plaque with a stenosis 50% or presence of a soft plaque conditioning any degree of stenosis) and/or untouchable ascending aorta (detected before the operation or when the chest is open) Previous cerebrovascular accident History of previous cerebrovascular accident with or without persistent neurologic defect Previous acute myocardial Electrocardiographic sign of previous myocardial infarction or documented non-q infarction infarction Left main disease Stenosis 50%

8 Ann Thorac Surg CALAFIORE ET AL 2005;80: FIRST REVASCULARIZATION IN MULTIVESSEL DISEASE Appendix 2 (cont) Variable Ejection fraction Continuous Ejection fraction 35% Dichotomous Inotropes Need of inotropic support at the admission in the operating room Nitroglycerin intravenously Need of nitroglycerin intravenously at admission in the operating room Perioperative Use of cardiopulmonary bypass Dichotomous Simultaneous carotid surgery Dichotomous Number of anastomoses From 2 to 7 Number of arterial anastomoses From 2 to 6 Surgeon First operator Left internal mammary artery Use of left internal mammary artery and at least one saphenous vein and saphenous vein 895