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Ann Thorac Surg 2005;80:888-895
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

Single Versus Bilateral Internal Mammary Artery for Isolated First Myocardial Revascularization in Multivessel Disease: Long-Term Clinical Results in Medically Treated Diabetic Patients

^a Division of Cardiac Surgery, University Hospital, Torino
^b Division of Cardiac Surgery, "G D’Annunzio" University, Chieti
^c Division of Cardiac Surgery, Papardo Hospital, Messina, Italy

Accepted for publication March 18, 2005.

^_* Address reprint requests to Dr Calafiore, Division of Cardiac Surgery, "S Giovanni Battista" Hospital, c.so Bramante 86, Torino, Italy (Email: calafiore{at}unich.it).

	Abstract

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 References

 
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 6.0 ± 2.0).

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 (86.7 ± 3.2 versus 79.5 ± 4.1, p = 0.0274), cardiac death (96.3 ± 1.4 versus 88.4 ± 4.0, p = 0.0406), acute myocardial infarction (99.5 ± 0.5 versus 92.0 ± 3.9, p = 0.0092), and acute myocardial infarction in a grafted area (99.5 ± 0.5 versus 93.4 ± 3.7, p = 0.0204). 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 = 0.0310), cardiac death (HR = 1.9, p = 0.0426), AMI (HR = 9.7, p = 0.0033) and AMI in a grafted area (HR = 8.2, p = 0.0410).

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.

	Introduction

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 References

 
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.

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

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 References

 
From October 1991 to December 2001, 558 medically treated diabetic patients affected by multivessel coronary disease underwent coronary artery bypass grafting (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.

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, 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 20 ± 25 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 4.8 ± 2.8 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, 2003. 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 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

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 References

 
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 in 90 cases (45.0%); in 112 cases (56.0%), no veins were used.

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.

Mean follow-up of the survivors was 6.0 ± 2.0 years (range, 2.0 to 12.2), 6.1 ± 2.0 for the LIMA group and 5.9 ± 1.8 for the BIMA group (p = 0.294).

After a mean of 2.3 ± 1.9 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 = 0.0310), cardiac death (HR = 1.9, p = 0.0426), AMI (HR = 9.7, p = 0.0033), and AMI in a grafted area (HR = 8.2, p = 0.0410). Figure 1 shows the curves related to these events. Off-pump surgery had no independent effect on late outcomes in this subgroup of patients.

View larger version (18K): [in this window] [in a new window]   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.

	Comment

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 References

 
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 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 = 0.0086; 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 oral-treated 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.

	Appendix 1

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 References

 

	Appendix 2

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 References

	References

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Antonio Maria Calafiore Gabriele Di Giammarco Giovanni Teodori Valerio Mazzei Giuseppe Vitolla Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Calafiore, A. M. Articles by Contini, M. Search for Related Content PubMed PubMed Citation Articles by Calafiore, A. M. Articles by Contini, M.