Ann Thorac Surg 2003;76:2017-2022
© 2003 The Society of Thoracic Surgeons
Original article: cardiovascular
Risks and benefits of bilateral internal thoracic artery grafting in diabetic patients
Takashi Hirotani, MD*a,
Tsukasa Nakamichi, MDa,
Mamoru Munakata, MDa,
Shigeyuki Takeuchi, MDa
a Department of Cardiovascular Surgery, Tokyo Saiseikai Central Hospital, Minato-Ku, Tokyo, Japan
Accepted for publication June 13, 2003.
* Address reprint requests to Dr Hirotani, Department of Cardiovascular Surgery, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo 108-0073, Japan
e-mail: hero.takashi{at}nifty.ne.jp
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Abstract
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BACKGROUND: There is a tendency to avoid the bilateral internal thoracic artery (ITA) grafting in diabetics. However, we no longer consider diabetes a reason for excluding the bilateral use of ITAs. We compare the early and long-term results in diabetic cases treated by coronary artery bypass grafting (CABG) using unilateral and bilateral ITA grafts.
METHODS: A total of 303 consecutive diabetic cases of CABG using ITA grafts between April 1991 and January 2003 were reviewed. Of these, 149 (49%) were being treated with insulin. The cases were divided into two groups: 179 cases in which bilateral ITA grafts had been used and 124 in which a unilateral ITA graft had been used.
RESULTS: The mortality for the bilateral ITA group and unilateral ITA group were 1.7% and 1.6%, respectively. The fact that patients were receiving insulin had no effect on the mortality of CABG. A review of morbidity revealed that no differences were found between the two groups. The survival curves, cardiac-death-free curves, and cardiac-event-free curves showed that there was no difference between the use of one or two ITA grafts in diabetics, while bilateral use of ITA grafts was significantly better than unilateral use in a comparable group of nondiabetics operated during the same time period.
CONCLUSIONS: There was no significant difference in operative mortality related to single or double ITA grafting in diabetics. There was also no difference between the use of one or two ITA grafts in diabetics in regard to long-term follow-up.
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Introduction
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Diabetes mellitus is an independent risk factor for atherosclerotic lesion progression and coronary bypass graft occlusion [1], and the adverse effects of diabetes on the early and long-term results after coronary artery bypass grafting (CABG) have been reported [2, 3]. Since one of the causes of such adverse effects is thought to be that diffuse coronary artery disease involving the distal vessels is more common in diabetic patients [4], conduits having superior patency are preferred for CABG in diabetic patients, and the importance of using internal thoracic artery (ITA) grafts in diabetic patients has been the focus of several recent studies [5, 6]. Logic seems to dictate that bilateral use of ITAs would further improve the long-term results of CABG in diabetic patients [7]. However, the influence of diabetes on the long-term results of CABG surgery using single or double ITA grafts has been controversial. And, reports documenting the difference of benefits of CABG surgery noted in a study of insulin-treated diabetics versus noninsulin-treated diabetics have been scarce.
This is a report of a retrospective comparative study of our recent cases of CABG surgery in patients with diabetes mellitus. The purpose of this study is to compare the early and long-term benefits after CABG using unilateral ITA graft and bilateral ITA grafts. Another purpose is to analyze whether the fact that patients were receiving insulin had any effect on the benefits of CABG surgery with single or double ITA grafts.
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Patients and methods
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We retrospectively reviewed the charts of 303 consecutive diabetic patients who underwent CABG with at least one ITA graft between April 1991 and January 2003. Patients with valvular heart disease requiring either valve repair or replacement, postinfarction ventricular septal defect, or congenital heart disease were excluded. The diabetes mellitus in all 303 patients had been diagnosed by endocrinologists at our Tokyo Saiseikai Diabetes center. The patients were defined as diabetic based upon the standard published criteria, i.e., a fasting serum glucose level of 140 mg/dl or more. Of these 303 patients, 149 (49%) were being treated with insulin.
Use of ITA
Unilateral ITA had usually been used for CABG since our cardiovascular center was organized in 1991, except when emergency or urgent CABG was performed. Since 1992, bilateral ITAs have been used for CABG, mainly for younger patients not requiring an emergency operation. In 1997 the indications for use of bilateral ITAs were extended to all multivessel patients whenever they had recipient vessels for bilateral ITAs, regardless of the urgency of the operation. Since 1992 diabetes mellitus has not been considered a valid reason for ruling out the bilateral use of ITAs. The annual distribution of diabetic patients who have undergone CABG with bilateral ITA grafts or a unilateral ITA graft is shown in Figure 1.
The distribution differed from year to year for the reasons described above.
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Fig 1. Annual distribution of the diabetic patients in the two groups. Black bars = CABG with bilateral internal thoracic surgery (ITA); white bars = CABG with unilateral ITA. (CABG = coronary artery bypass grafting.)
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The left ITA was usually used for revascularization of the left anterior descending (LAD) artery. However, when the right ITA was used for the LAD artery, the left ITA was used for either the left circumflex (LCX) or diagonal (D) artery. The right ITA was usually bypassed to the proximal right coronary artery (RCA) or LCX artery through the transverse sinus. The right ITA was further used for the LAD or D artery anterior to the hearts in some patients according to the combination of bilateral ITAs. In principle, the ITA was used as an in situ pedicled (nonskeletonized) graft, but in 12 patients either the entire ITA or a part of it was used as a free graft between the ascending aorta and the coronary artery or between the two segments of the same coronary artery beyond the stenotic lesion, as previously reported [8]. ITA grafts were sometimes used as a sequential bypass graft, but Y arterial grafting using free ITA or radial artery was not performed.
Table 1
shows the division of the cases into two groups: 179 cases treated by bilateral ITA bypass grafting with or without additional saphenous vein (SV) and/or gastroepiploic artery (GEA) grafts and 124 cases treated by unilateral ITA bypass grafting with or without additional SV and/or GEA grafts. Statistically significant differences between the two groups were seen regarding the extent of the coronary lesions and frequency of urgent operations.
Table 2
shows the coronary arteries revascularized with the left ITA, right ITA, SV, and GEA grafts. In almost all diabetic patients (99%), the LAD artery was revascularized with at least one arterial graft.
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Table 2. Coronary Arteries Revascularized with Internal Thoracic Artery, Saphenous Vein, and Gastroepiploic Artery Grafts
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Operative technique
After a median sternotomy, single or bilateral ITAs were mobilized from their origin to the distal end close to the bifurcation. Cardiopulmonary bypass was performed under moderate hypothermia, and myocardial protection was provided with antegrade crystalloid cardioplegia and topical cooling. Both proximal and distal anastomoses were performed during a single period of aortic occlusion. Grafting was attempted on all vessels measuring 1.5 mm or greater in diameter with a 75% or greater obstruction regardless of the degree of distal runoff.
The operative variables are shown in Table 3,
and no statistically significant differences were detected.
Morbidity
Among the operative complications, myocardial infarction was diagnosed on the basis of persistent CK-MB enzyme elevations, new Q waves, or ST elevation on electrocardiograms. Arrhythmias were defined as complications, if they were considered life-threatening or required medication. Strokes were diagnosed based on the physical findings and were documented by brain computerized tomography. Respiratory failure due to any causes was diagnosed when mechanical ventilation support was required for more than 48 hours. Both chest and leg wounds were defined as infected if any discharge from the wound except blood was observed, regardless of the results of cultures. Minor chest wound infections included infections limited to the subcutaneous tissue. Major chest wound infections included all cases in which tissues were infected down to the sternal wire or beyond and required reexploration of the wound and refixation of the sternum. Leg wound infections were not stratified based on depth of involvement by infection.
Follow-up data were obtained from each patient's hospital record. The data were completely reviewed in 95% of the patients.
Data analysis
Data are reported as means &cct; standard deviation. The differences in all discrete data between groups were tested for statistical significance by either 
2 test or Fischer's exact test as appropriate and all continuous data were tested by the unpaired t-test. Survival curves were estimated by the Kaplan–Meier method, and the differences in survival curves between groups were compared by using log-rank tests. The incidences of operative complications were compared between groups by univariate analysis using either 2 test or Fischer's exact test, as appropriate. Statistical significance was considered to exist whenever the p value was < 0.05.
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Results
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Mortality
Of the 303 diabetic patients who underwent CABG using at least one ITA graft, 5 died before being discharged or within 30 days of the operation, and the mortality of all patients was 1.7%. The causes of hospital death were low output syndrome in 2 patients, stroke in 1, myocardial infarction in 1, and mediastinitis in 1. According to group, mortality was 1.7% in the bilateral ITA group and 1.6% in the unilateral ITA group, and the difference in mortality was not statistically significant. The fact that patients were receiving insulin at surgery had no effect on the mortality of CABG surgery. The mortality of the bilateral ITA group was 1.2% in the insulin-treated diabetics, 2.2% in the noninsulin-treated diabetics. And, the mortality of the unilateral ITA group was 1.6% in the insulin-treated diabetics, 1.6% in the noninsulin-treated diabetics.
Morbidity
The operative complications and their rates are shown in Table 4. The results of univariate analyses showed that the incidences of any complications did not differ significantly according to whether ITAs were used bilaterally or unilaterally.
The incidence of both minor and major chest wound infection did not differ significantly according to whether ITAs were used bilaterally or unilaterally (p = 0.533). However, the incidence of chest wound infection differed significantly according to whether patients were treated with insulin (11%) or not (3.9%) (p = 0.014). The incidence of chest wound infection of the bilateral ITA group was 10% in the insulin-treated diabetics, 6.5% in the noninsulin-treated diabetics (p = 0.357). And, that of the unilateral ITA group was 13% in the insulin-treated diabetics, 0% in the noninsulin-treated diabetics (p = 0.0040).
Minor chest wound infections were managed conservatively with antibiotics and major chest wound infections required drainage of the wound and refixation of the sternum. One patient of the bilateral ITA group died of mediastinitis secondary to wound infection.
Early graft patency
The angiographic studies conducted approximately 2 to 3 weeks after surgery in 294 patients (97% of the subjects) revealed a whole graft patency rate of 97.1%. The patency rate for all ITA grafts was 98.5%, and statistically superior (p = 0.0090) to the rate for all SV grafts (95.4%). The patency rate of left ITA grafts (99.6%) was statistically higher than that of right ITA grafts (97.0%) (p = 0.047). Table 4 shows the FitzGibbon scores (grade A: excellent, grade B: fair, grade O: occluded) for each type of conduit placed.
Long-term results
The overall survival curves and cardiac-death-free curves of the patients who underwent CABG with bilateral ITA grafts and a unilateral ITA graft were compared between the 2 groups (Fig 2). Cardiac death, acute myocardial infarction, coronary intervention, congestive heart failure requiring hospitalization, and reoperation for coronary ischemia were included as cardiac events, and the cardiac-event-free curves were also compared between the 2 groups (Fig 2). In every comparison, the bilateral use of ITA grafts for CABG showed no benefit over unilateral use of ITA grafts.
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Fig 2. Overall survival curves (top), cardiac-death-free curves (bottom left), and cardiac-event-free curves (bottom right) (Kaplan–Meier method) of diabetic patients who received bilateral ITA grafts (thick line) and a unilateral ITA graft (thin line). The numbers of patients at risk are also shown. (ITA = internal thoracic artery.)
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We also analyzed whether the fact that patients were treated with insulin had any effect on the benefits of CABG surgery in the long-term follow-up of the diabetic patients (Fig 3).
As a result, there was no difference in either survival, cardiac death, or cardiac-related event-free survival noted in the long-term follow-up of the diabetic patients being treated with insulin versus without insulin. And, in either insulin-treated or noninsulin-treated diabetic patients, there was no beneficial effect noted in the long-term follow-up of the diabetic patients having two versus one ITA graft. However, in the unilateral ITA group, noninsulin-treated patients showed better survival than insulin-treated patients (p = 0.0122).
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Fig 3. Overall survival curves (top), cardiac-death-free curves (bottom left), and cardiac-event-free curves (bottom right) (Kaplan–Meier method) of diabetic patients who were treated with insulin (thick line) and without insulin (thin line). The numbers of patients at risk are also shown. (pts = patients.)
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Comment
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Diabetes usually has an adverse influence on the outcome of CABG [2, 3]. The results of our previous study showed that when ITA grafts were aggressively used for CABG there was no significant difference in operative mortality between the nondiabetic and the diabetic patients, and no adverse effects of diabetes were apparent from either the overall survival curve, the cardiac-death-free curve, or the cardiac-event-free curve [6]. Moreover, a recent bypass angioplasty revascularization investigation (BARI) study in diabetic patients demonstrated that the survival benefit of CABG was limited to the use of ITA grafts [5]. The observed superior performance of ITA grafts as conduits for CABG was thus expected to lead to an increase in the bilateral use of ITA grafts, but in most institutions, the use of bilateral ITA grafts is still avoided because of fear of increased operative morbidity [7, 9]. However, diabetes has not been a reason for avoiding the use of bilateral ITAs for CABG in our institution, because ITA grafts have been considered preferred grafts for coronary arteries containing diffuse lesions and of small caliber in diabetic patients.
Mortality
Recent reports have shown no increase in operative mortality in association with bilateral ITA grafting [10–12]. Also in our own study, bilateral use of ITAs did not affect the operative mortality at all. Moreover, mortality in the bilateral ITA group in our study was 1.7%, and comparable to the mortality of diabetic patients after CABG in recently published reports, in which it has ranged from 1.2% to 4.1% [3, 5, 7, 13].
Morbidity
Diabetic patients are more prone to wound infection whatever the type of operation, and the mobilization of bilateral ITAs may lead to devascularization of the sternum, leading to an even higher risk of wound infection and dehiscence [14,15]. The incidences of major and minor chest wound infection in the patients who underwent bilateral ITA grafting in the present study were 2.2% and 6.1%, respectively, as opposed to 1.6% and 4.8%, respectively, in the patients who underwent unilateral ITA grafting, and they are comparable to previously reported incidences of chest wound infection after CABG in diabetic patients, which have ranged from 7.5% to 19% [11,16]. However, our study was too small to demonstrate the absence of any effect on sternal infection of bilateral ITA grafting with an acceptable test power, and one of the bilateral ITA graft patients in our series died of mediastinitis secondary to wound infection.
Early graft patency
The results of the postoperative angiography performed in 97% of the subjects demonstrated the superior patency of ITA grafts over SV grafts. One of the angiographic characteristics of the coronary disease in diabetic patients is diffuse disease involving distal vessels. This angiographical characteristic of diabetic patients affected the relative benefit attributable to ITA grafting. However, the right ITA graft patency rate was statistically lower than the left ITA graft and similar to the SV graft patency rate (p = 0.47). Therefore, it appeared that the difference of the target coronary arteries had beneficial effects on the superior patency rate of ITA grafts.
Long-term benefits
The goals of CABG are to prolong survival, improve quality of life, and reduce the need for subsequent procedures. The long-term results of bilateral ITA grafting have recently been reported to be superior to those of unilateral ITA grafting [10–12, 17]. However, contrary to our expectation that with the more ITA grafts patients received, the more benefit they would obtain long-term, no benefit of bilateral use of ITA grafts was demonstrated. To understand the meaning of this finding, we analyzed 324 consecutive patients without diabetes mellitus who underwent CABG during the same time period as subjects of this study and compared the long-term results in bilateral ITA graft patients with unilateral ITA graft. The results clearly demonstrated the benefits of bilateral use of ITA grafts in nondiabetic patients (Fig 4).
The influence of diabetes alone in contributing to long-term morbidity and/or mortality independent of a unilateral or bilateral ITA grafting may explain the discrepancy in the diabetic and nondiabetic population.
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Fig 4. Overall survival curves (top), cardiac-death-free curves (bottom left), and cardiac-event-free curves (bottom right) (Kaplan–Meier method) of nondiabetic patients who received bilateral ITA grafts (thick line) and a unilateral ITA graft (thin line). The numbers of patients at risk are also shown. (ITA = internal thoracic artery.)
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Conclusion
Bilateral ITA grafts in the diabetics were not associated with any increased morbidity or mortality than the unilateral graft. There was only a small difference in the incidence of sternal wound infection in the diabetics between single and double ITA utilization, and the difference was not nearly significant (p = 0.53). Remarkably, there was no beneficial effect in either survival, cardiac death, or cardiac-event-free survival noted in the long-term follow-up of the diabetic patients having one versus two ITA grafts, while there was a significant benefit noted in a comparable group of nondiabetics operated during the same time period. Table 5
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References
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- Faglia E., Brivio M., Pizzi G.L., et al. Coronary angiography and aorto-coronary bypass surgery in type 2 diabetic patients. Diabetes & Metabolisme 1995;21:420-427.
- The BARI investigators. Influence 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;96:1761-1769.[Abstract/Free Full Text]
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Abstract
Introduction
