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Coronary Artery Bypass Revascularization Using Bilateral Internal Thoracic Arteries in Diabetic Patients: A Systematic Review and Meta-Analysis
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Coronary Artery Bypass Revascularization Using Bilateral Internal Thoracic Arteries in Diabetic Patients: A Systematic Review and Meta-Analysis Kan Kajimoto, MD, PhD, Taira Yamamoto, MD, and Atsushi Amano, MD Department of Cardiovascular Surgery, Juntendo University School of Medicine, Tokyo, Japan
This study examined the effect of coronary artery bypass graft surgery with bilateral internal thoracic artery grafting in diabetic patients. Coronary artery bypass graft surgery using skeletonized bilateral internal thoracic artery grafts was not associated with an increased risk of deep sternal wound infection or early death. Moreover, patients who underwent coronary artery bypass graft surgery using bilateral internal
thoracic artery grafting had lower remote mortality and cardiac mortality. We conclude that coronary artery bypass surgery using bilateral internal thoracic artery grafts is an excellent strategy, even for diabetic patients.
C
with BITA grafts after skeletonized ITA harvesting in diabetic patients.
Address correspondence to Dr Yamamoto, Department of Cardiovascular Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyoku, Tokyo 113-8421, Japan; e-mail: [email protected].
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
Material and Methods Search Strategy Database searches were performed in the first week of February 2014. The following sources were searched for studies comparing single internal thoracic artery (SITA) and BITA grafts for diabetic patients: MEDLINE through PubMed (from 1995 to August 2013), EMBASE, and the Cochrane Library database (Cochrane Central Register of Controlled Trials). The following MeSH subject headings were used: “coronary artery bypass,” “diabetes,” “single internal thoracic artery,” “bilateral internal thoracic artery,” “double internal thoracic artery,” “single internal mammary artery,” “bilateral internal mammary artery,” and “double internal mammary artery.” The clinicaltrials. gov website was also searched for trials comparing SITA and BITA grafts for diabetic patients. The references cited within all available articles were also reviewed to identify candidate studies. All titles and abstracts were downloaded to Zotero version 2.1 (Center for History and New Media of George Mason University, Fairfax, VA).
Inclusion and Exclusion Criteria Studies satisfying the following criteria were included in this systematic review: (1) studies comparing SITA and BITA grafts for diabetic patients; (2) studies evaluating The Appendix Figure 1 can be viewed in the online version of this article [http://dx.doi.org/10.1016/j. athoracsur.2014.09.045] on http://www.annalsthor acicsurgery.org.
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.09.045
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oronary artery bypass graft surgery (CABG) is the coronary revascularization strategy of choice for patients with multivessel coronary artery disease [1]. Nevertheless, diabetes mellitus remains a strong risk factor for mortality and morbidity after CABG [2–4]. In the acute postoperative phase, diabetes is associated with an increased risk of infection due to hyperglycemia, relative immunodeficiency, and microcirculatory insufficiency [5]. Over the long term after CABG, diabetes is associated with an increased risk of death, cardiac death, and other adverse events as a result of a propensity toward severe atherosclerosis due to prothrombotic and proinflammatory states [4]. Meanwhile, CABG with internal thoracic artery (ITA) grafts can produce excellent outcomes, and the use of a left internal thoracic artery (LITA) to left anterior descending coronary artery graft, in particular, is associated with excellent long-term survival and a reduction in cardiac events due to graft patency; as a result, this strategy is the gold standard for CABG [6]. Coronary artery bypass graft surgery with bilateral internal thoracic artery (BITA) grafts is also sometimes used and is associated with good outcomes in nondiabetic patients [7–9]. In contrast, CABG with BITA in diabetic patients has historically been associated with a higher risk of deep sternal wound infection (DSWI) [10–22] and is therefore avoided. However, several recent studies have suggested that CABG with BITA grafts after skeletonized ITA harvesting is not associated with an increased risk of wound infection among diabetic patients [12, 14, 15, 20]. Thus, the goal of this study was to reexamine the safety and efficacy of CABG
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Abbreviations and Acronyms BITA CABG CI DSWI ITA LITA RR SITA
= = = = = = = =
bilateral internal thoracic artery coronary artery bypass graft surgery confidence interval deep sternal wound infection internal thoracic artery left internal thoracic artery relative risk single internal thoracic artery
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was used to assess the between-study heterogeneity in different groups. Publication bias was assessed by Horbold-Egger statistics, with a p value of less than 0.05 indicating significant publication bias among the studies. The meta-analysis was conducted using StatsDirect software version 2.7.2 (StatsDirect, Greater Manchester, UK).
Results Selection and Description of Studies
postoperative DSWI, early mortality, or remote outcomes; and (3) studies published in peer-reviewed journals with full available text in English. Studies in which it was not possible to extract data from the published results, as well as studies that did not report appropriate outcomes, were excluded.
Endpoints and Their Definitions The endpoints of this study were as follows: (1) DSWI; (2) early death; (3) long-term mortality; and (4) long-term cardiac mortality. Deep sternal wound infection was defined as DSWI or mediastinitis. Early death consisted of in-hospital or 30-day mortality. Long-term mortality and cardiac mortality were defined as the cumulative incidence of all-cause and cardiac death.
A total of 104 relevant studies were captured in the initial search (Fig 1). After screening the abstracts of these studies, the full-length articles of 13 studies fulfilled the inclusion criteria (Table 1). All 13 studies evaluated DSWI, had sample sizes ranging from 81 to 2,445, and were retrospective studies [10–22]. Of these, nine studies evaluated early death [11, 14–18, 20–22], eight studies evaluated long-term mortality [11, 12, 14–16, 18, 20, 21], and five studies evaluated long-term cardiac mortality [11, 12, 14, 15, 20]. Propensityscore matched analysis was reported in four studies [15, 18, 20, 21]. Ten studies mentioned a pedicle or skeletonized ITA [10–12, 14–17, 19, 20, 22]. Ten studies indicated the number of grafts or distal anastomoses [11, 12, 14–20, 22]. Seven studies indicated patients’ risk scoring, including EuroSCORE, The Society of Thoracic Surgeon Predicted Risk of Postoperative Mortality (STS-PROM) score, or
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Data Extraction Two reviewers (K.K. and T.Y.) independently assessed studies for inclusion criteria. The following information was extracted from each study: first author, year of publication, study design, loss to follow-up, age, sex, number of participants in each group (SITA and BITA), proportion of ITA skeletonization, proportion of off-pump CABG, number of grafts or distal anastomoses, and European System for Cardiac Operation Risk Evaluation (EuroSCORE). Reviewers extracted the following outcomes: DSWI, early mortality, long-term all-cause mortality, and long-term cardiac mortality. Outcome data are presented as count data.
Statistical Analysis The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement [23]. The endpoints of each study were analyzed using risk ratio (RR) with 95% confidence interval (CI). We conducted these meta-analyses only for studies that reported outcomes as count data; studies that reported outcomes as risk estimates (eg, hazard ratio and RR) were excluded from these analyses. Summary estimates were calculated by DerSimonian-Laird weights for the random effects model. Forest plots were then created for graphic presentation of clinical outcomes. The I2 statistic was calculated as a measure of the proportion of the overall variation attributable to between-study heterogeneity rather than chance. The I2 values of 25%, 50%, and 75% correspond to low, intermediate, and high levels of heterogeneity, respectively. The Cochran c2 (Cochran Q) test
Fig 1. Flow diagram from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines demonstrates the method for selection of the included articles.
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Table 1. Characteristics of Included Studies of Single Internal Thoracic Artery Grafts Versus Bilateral Internal Thoracic Artery Grafts
Konstanty-Kalandyk [22], 2012 Puskas [21], 2012 Kinoshita [20], 2010
Agrifoglio [19], 2008 Toumpoulis [18], 2006
Momin [17], 2005 Stevens [16], 2005
Calafiore [15], 2005
Lev-Ran [14], 2004
Hirotani [11], 2003
Gansera [10], 2001 a
DSWI, 30-day mortality DSWI, in-hospital death, long-term all-cause death DSWI, 30-day mortality, long-term all-cause death, long-term cardiac death Sternal wound infection DSWI, 30-day mortality, in-hospital mortality, long-term all-cause death DSWI, 30-day mortality, 30-day in-hospital mortality DSWI, 30-day mortality, in-hospital mortality, long-term all-cause death DSWI, in-hospital mortality, long-term all-cause death, long-term cardiac death DSWI, 30-day mortality, long-term all-cause death, long-term cardiac death DSWI DSWI, long-term all-cause death, long-term cardiac death DSWI, in-hospital mortality, long-term all-cause death, long-term cardiac death DSWI
109/38
Age SITA/BITA (years)
Female SITA/BITA (%)
Skeletonized SITA/BITA (%)
No. Grafts SITA/BITA
EuroSCORE SITA/BITA
Described Postop Glucose Control
66/62
40/34
0/0
2.6/2.6
NA
Yes
Retrospective Propensity score matched Propensity score matched
Study Design
1,213/232
8
64/58
33/16
NA
NA
3.1/2.0a
No
170/170
7
70/70
25/24
100/100
2.4/2.7
7/7
No
10
67/62 64/65
15/15 45/44
0/0 NA
3.3/3.2b 3.3/3.7b
4.2/2.3 6.9/6.8
Yes No
Retrospective Propensity score matched
63/62
38/40
0/0
2.8/3.2
11.4/8.6
No
Retrospective
41/40 490/490
524/396 419/214
15
64/58
35/14
0/0
3.3/3.4
NA
No
Retrospective
200/200
8
67/67
59/70
84/85
2.8/2.9b
7.3/6.6
Yes
Propensity score matched
57/228
7.5
66/66
40/31
100/100
3.1/3.2
3.6/3.8
Yes
Retrospective
177/79 277/190
10
69/60 62/61
3.5/3.6 23/14
NA 100/100
NA 2.7/2.8b
NA NA
No No
Retrospective Retrospective
124/179
6.7
64/65
25/23
0/0
2.8/3.5
NA
No
Retrospective
65/64
24/19
0/0
NA
NA
No
Retrospective
589/418
The Society of Thoracic Surgeons predicted risk of postoperative mortality score.
b
BITA ¼ bilateral internal thoracic artery; DSWI ¼ deep sternal wound infection; assessed; Postop ¼ postoperative; SITA ¼ single internal thoracic artery.
Number of distal anastomoses. EuroSCORE ¼ European System for Cardiac Operation Risk Evaluation;
FU ¼ follow-up;
NA ¼ not
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Tavolacci [13], 2003 Endo [12], 2003
Outcomes
Lost to FU (years)
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First Author [Ref], Year
Patients SITA/BITA (n)
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Parsonnet score [14, 15, 17–21]. Four studies described postoperative glucose control [14, 15, 19, 22].
Deep Sternal Wound Infection Deep sternal wound infection was reported as a variable in 13 studies that included 7,264 patients [10–22]. The Forest plots of DSWI are shown in Figure 2A. One study by Agrifoglio and colleagues [19] was excluded from analysis because of the lack of incidence of DSWI. A DSWI occurred in 2.0% of patients in the SITA group and in 3.2% of patients in the BITA group. Low heterogeneity was seen with this analysis (Cochran c2: p ¼ 0.46,
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Fig 2. Forest plots of deep sternal wound infection. (A) Results of all 13 studies. (B) Results of four studies that included internal thoracic arteries harvested in a skeletonized fashion. Results are shown as risk ratio (RR) with 95% confidence interval (CI). (BITA ¼ bilateral internal thoracic artery; SITA ¼ single internal thoracic artery.)
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I2 ¼ 0%), and no publication bias was indicated (HorboldEgger statistics: p ¼ 0.37). The summary estimate showed that BITA grafting in diabetic patients was associated with an increased risk of DSWI (RR 1.54; 95% CI: 1.13 to 2.11; p ¼ 0.0069). Studies in which skeletonized harvesting of the ITA graft was performed were further analyzed; this analysis included three studies with 1,092 patients [12, 14, 20]. The Forest plots of DSWI are shown in Figure 2B. A DSWI occurred in 1.5% of patients in the SITA group and in 1.4% of patients in the BITA group. Low heterogeneity was seen with this analysis (Cochran c2: p ¼ 0.98, I2 ¼ 0%), and no publication bias was
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indicated (Horbold-Egger statistics: p ¼ 0.53). The summary estimate showed no significant difference in DSWI between the skeletonized SITA group and the skeletonized BITA group (RR 1.01; 95% CI: 0.35 to 2.97; p ¼ 0.98).
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Early Death Nine studies with 5,453 patients that evaluated early death were identified [11, 14–18, 20–22]. The Forest plots of early death are shown in Figure 3A. Early death Fig 3. Forest plots of mortality. (A) Results for early death. (B) Results for long-term mortality. (C) Results for long-term cardiac mortality. Results are shown as risk ratio (RR) with 95% confidence interval (CI). (BITA ¼ bilateral internal thoracic artery; SITA ¼ single internal thoracic artery.)
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occurred in 2.6% of patients in the SITA group and 3.0% of patients in the BITA group. Low heterogeneity was seen with this analysis (Cochran c2: p ¼ 0.86, I2 ¼ 0%), and no publication bias was indicated (Horbold-Egger statistics: p ¼ 0.09). The summary estimate showed no significant difference in early death when comparing the skeletonized SITA group and the BITA group (RR 0.94; 95% CI: 0.67 to 1.32; p ¼ 0.73).
Long-Term Mortality A total of eight studies evaluated long-term mortality [11, 12, 14–16, 18, 20, 21]. Of these, four studies were excluded from meta-analysis because count data could not be obtained [11, 16, 18, 21]. Therefore, four studies with 3,408 patients were enrolled in the meta-analysis [12, 14, 15, 20]. The Forest plots of long-term mortality are shown in Figure 3B. There was significant heterogeneity, driven mainly by one study (Cochran c2: p < 0.0001, I2 ¼ 87%). Publication bias was not indicated (HorboldEgger statistics: p ¼ 0.35). The summary estimate showed that BITA grafting in diabetic patients was associated with a significantly decreased risk of long-term mortality (RR 0.65; 95% CI: 0.46 to 0.92; p ¼ 0.018; Appendix Fig 1).
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Long-Term Cardiac Mortality A total of five studies evaluated long-term cardiac mortality [11, 12, 14, 15, 20]. Of these, one study was excluded from the meta-analysis because count data could not be obtained [6]. Therefore, four studies with 3,408 patients were enrolled in the meta-analysis [12, 14, 15, 20]. The Forest plots of long-term cardiac mortality are shown in Figure 3C. There was also significant heterogeneity, driven mainly by a study by Hirotani and associates [11] (Cochran c2: p ¼ 0.018, I2 ¼ 67%). Publication bias was not indicated (Horbold-Egger statistics: p ¼ 0.81). The summary estimate showed that BITA grafting in diabetic patients was associated with a significantly decreased risk of long-term cardiac mortality (RR 0.54; 95% CI: 0.30 to 0.97; p ¼ 0.042; Appendix Fig 1).
Comment This study is the first systematic review comparing the use of SITA and BITA grafts in diabetic patients, and it demonstrated that skeletonized BITA grafting is safe in terms of the risk of DSWI and early death. Furthermore, long-term all-cause and cardiac mortality was lower for diabetic patients undergoing CABG with BITA grafting than for diabetic patients undergoing CABG with SITA grafting. However, the benefits of BITA in nondiabetic patients for long-term outcomes were shown by several studies [7–9]. Although CABG using BITA grafting is not common worldwide, the effect of BITA grafting has begun to attract attention. Indeed, the Arterial Revascularization Trial (ART) is an ongoing randomized control study that evaluated the effect of BITA in the general population [24]. The ART demonstrated that 1-year survival after BITA grafting was not associated with better survival beyond that term when compared with SITA grafting.
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However, further research is needed to evaluate the longterm benefit of BITA grafting. Historically, the greatest concern in relation to BITA grafting for diabetic patients has been the potential risk of DSWI; and the guidelines on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) identified the increased risk of postoperative sternal dehiscence and DSWI in diabetic patients [25]. If the increased risk of BITA for DSWI could be resolved in diabetic patients, the demand for BITA could increase in patients with diabetes who have an increased risk of poor long-term outcomes after CABG. This meta-analysis of 13 studies showed that there was an increased risk of DSWI in the entire population of diabetic patients undergoing any type of BITA grafting. Of these studies, five evaluated only pedicle-harvested BITA grafting [10, 11, 16, 17, 19, 22]. When compared with skeletonized harvest of the ITA graft, pedicle ITA grafting reduces blood flow to the sternum. Hence, pedicle harvest of the ITA is prone to skeletonized harvested ITA in terms of the risk of DSWI [26]. In addition, the ART suggested that BITA grafting is associated with an increased risk of DSWI in the general population [24]. However, the ITA harvest approach (skeletonized or pedicled) was not documented in the ART. Hence, a significant number of patients undergoing pedicled harvest of the ITA may be included in the ART. To evaluate risk of skeletonized harvested BITA grafting among diabetic patients, additional analysis of the three studies [12, 14, 20] that included only skeletonized ITA was performed in this study. In the result, skeletonized BITA grafting was not associated with an increased risk of DSWI among diabetic patients (RR 1.01; 95% CI: 0.35 to 2.97; p ¼ 0.98). Furthermore, BITA grafting was not associated with an increased risk for early mortality among diabetic patients when compared with SITA grafting. Thus, skeletonized BITA grafting appears to be a safe and effective strategy, even among diabetic patients, and should be used in preference to pedicle BITA grafting. In addition to reducing the DSWI rate among diabetic patients, skeletonization of the ITA also yields the advantage of extension of graft length, which is particularly helpful when the right ITA is grafted to the left side coronary system. Diabetic patients are more likely to have complex coronary disease and require two or more revascularizations in a single graft (sequential anastomosis). In that case, graft length is very important, and skeletonized harvest is invaluable, regardless of whether the right ITA is used as an in situ graft or as a composite graft. Although skeletonization of the ITA requires a longer preparation time when compared to pedicle harvested ITA, skeletonization of ITA is worth performing among diabetic patients owing to these merits. Skeletonization of ITA and glucose control in the early postoperative period has an impact on the risk of DSWI. Several past studies demonstrated that intensive serum glucose control is associated with reduced early postoperative mortality and a reduced incidence of complications. In this meta-analysis, four studies described a
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inflow of the ITA can be connected to the left coronary system (in situ graft). Second, its histologic and vasophysiologic properties, including a thin smooth muscle layer and abundant elastic fibers, are relatively protective against progression of atherosclerosis, and thereby results in excellent graft patency [31, 32]. One of the important mechanisms underlying diabetesrelated cardiovascular diseases is endothelial dysfunction. Kitamura [33] hypothesized that preservation of the endothelium from ITAs to native coronary arteries results in restoration of otherwise compromised coronary endothelial function, especially in patients with diabetes, advanced age, or multivessel disease. These mechanisms may account for why BITA is better than SITA for diabetic patients. Despite the survival benefits of the BITA graft, this strategy has not been commonly used [7]. Grafting with BITA has several drawbacks other than the increased risk of DSWI. The use of BITA grafts requires a longer preparation time and operation time. The ART showed that operative duration of CABG using BITA grafting was 20 minutes longer than that of SITA grafting [24]. Spasm and atrophic change due to competitive blood flow from native coronary arteries are also problems associated with ITA grafting [25]. Gansera and colleagues [10] showed some advantages of the BITA after CABG. However, there was an increased risk of early complications, including DSWI, after CABG among patients with diabetes, obesity, impaired left ventricular ejection fraction, and chronic obstructive pulmonary disease. Therefore, BITA grafting for patients with these risk factors remains controversial. However, the present analysis demonstrated that BITA grafting is safe and has significant benefit for diabetic patients. Thus, we believe that BITA grafting should be used for diabetic patients to improve their outcomes after CABG. This study has several limitations. All studies included in this systematic review were retrospective analyses rather than randomized, prospective studies, reflecting outcomes after clinical decision making by treating surgeons. Several studies were not even propensity matched, and the opportunity for confounding by bias (eg, using BITA in younger or healthier patients) is a strong possibility. Furthermore, only four of the 13 studies investigated long-term survival analysis; hence, the statistical power of the present analysis was relatively weak. In conclusion, this is the first meta-analysis, to the best our knowledge, of the long-term effects of BITA grafting in diabetic patients. This study also showed that CABG with BITA grafting increased the risk of DSWI in diabetic patients. However, BITA grafting with skeletonized harvest was not associated with an increased risk of DSWI even in diabetic patients. Furthermore, BITA grafting provided significant benefits in long-term all-cause mortality and cardiac mortality for diabetic patients after CABG when compared with SITA grafting. We conclude that BITA grafts with skeletonized harvest should be used for CABG in diabetic patients.
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specific approach for postoperative glucose control [14, 15, 19, 22]. The protocol in these four studies included intensive glucose control by continuous insulin infusion, and they reported similar DSWI when comparing SITA and BITA grafts. The strategies of glucose control were not equal among these studies, and the whether control of serum glucose levels was established was not mentioned in these four studies. Therefore, we did not perform additional analysis of these four studies. However, the results of these studies might support the notion that intensive glucose control is associated with a reduction in mortality and DSWI after CABG, as was previously reported by Furnary and associates [5]. CABG surgery is the treatment strategy of choice for diabetic patients with multivessel coronary artery disease, because many trials comparing CABG and percutaneous coronary intervention have shown the advantages of CABG on long-term outcomes among diabetic patients [1, 3, 27–30]. However, diabetes remains a strong risk factor for mortality and morbidity after CABG [2–4]. A stratified analysis of 3,889 patients who underwent CABG in the collaborative analysis showed that diabetic patients still had worse outcomes than patients without diabetes over a mean follow-up period of 5.8 years (23% versus 14%, respectively, for long-term mortality) [30]. Thus, the reduction of the negative impact of diabetes on outcomes after CABG remains an unsolved problem. The present meta-analysis demonstrated that BITA grafting significantly reduced all-cause mortality and cardiac mortality. Further, Puskus and coworkers [21] indicated that BITA grafting was associated with a reduction in the hazard of long-term mortality in diabetic patients (hazard ratio 0.65; 95% CI: 0.48 to 0.88; p ¼ 0.006). Stevens and associates [16] reported that the 5-, 10-, and 15-year survival after BITA grafting was significantly higher when compared with that after SITA grafting in a series of 633 consecutive diabetic patients (95%, 88%, 79% versus 93%, 85%, 73%, respectively). Hirotani and colleagues [11] reported that there was no significant difference in long-term mortality when comparing SITA and BITA grafting for diabetic patients, but they concluded that, among patients with normal ejection fraction, BITA grafting was associated with increased 10-year survival when compared with SITA grafting. These three studies were excluded from the present meta-analysis, which evaluated long-term outcomes, because count data were not available; nevertheless, findings of these studies suggest that BITA grafting is a better option than SITA grafting in diabetic patients. The long-term benefit of CABG is maximized with the use of arterial grafts, specifically with the use of the ITA [6–9]. The 10-year patency rate of the LITA is expected to be more than 90% [6–9, 25, 31, 32]. Therefore, LITA grafting to the left anterior descending artery is recommended as the gold standard strategy for graft selection [6, 25]. CABG with BITA grafts is also sometimes used and is associated with good outcomes for nondiabetic patients [7–9]. The ITA has several excellent properties as a coronary artery graft. First, the anatomic
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References 1. Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet 2013;23:629–38. 2. Kajimoto K, Kasai T, Miyauchi K, et al. Metabolic syndrome predicts 10-year mortality in non-diabetic patients following coronary artery bypass surgery. Circ J 2008;72:1481–6. 3. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367:2375–84. 4. Alserius T, Hammar N, Nordqvist T, et al. Improved survival after coronary artery bypass grafting has not influenced the mortality disadvantage in patients with diabetes mellitus. J Thorac Cardiovasc Surg 2009;138:115–22. 5. Furnary AP, Zerr KJ, Grunkemeier GL, et al. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999;67:352–60. 6. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2011;58:e123–210. 7. Tabata M, Grab JD, Khalpey Z, et al. Prevalence and variability of internal mammary artery graft use in contemporary multivessel coronary artery bypass graft surgery: analysis of The Society of Thoracic Surgeons national cardiac database. Circulation 2009;15:935–40. 8. Taggart DP, D’Amico R, Altman DG. Effect of arterial revascularisation on survival: a systematic review of studies comparing bilateral and single internal mammary arteries. Lancet 2001;358:870–5. 9. 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;26:542–8. 10. Gansera B, Schmidtler F, Gillrath G, et al. Does bilateral ITA grafting increase perioperative complications? Outcome of 4462 patients with bilateral versus 4204 patients with single ITA bypass. Eur J Cardiothorac Surg 2006;30:318–23. 11. Hirotani T, Nakamichi T, Munakata M, et al. Risks and benefits of bilateral internal thoracic artery grafting in diabetic patients. Ann Thorac Surg 2003;76:2017–22. 12. Endo M, Tomizawa Y, Nishida H. Bilateral versus unilateral internal mammary revascularization in patients with diabetes. Circulation 2003;16:1343–9. 13. Tavolacci MP, Merle V, Josset V, et al. Mediastinitis after coronary artery bypass graft surgery: influence of the mammary grafting for diabetic patients. J Hosp Infect 2003;55:21–5. 14. Lev-Ran O, Braunstein R, Nesher N, et al. Bilateral versus single internal thoracic artery grafting in oral-treated diabetic subsets: comparative seven-year outcome analysis. Ann Thorac Surg 2004;77:2039–45. 15. Calafiore AM, Di Mauro M, Di Giammarco G, et al. Single versus bilateral internal mammary artery for isolated first myocardial revascularization in multivessel disease: longterm clinical results in medically treated diabetic patients. Ann Thorac Surg 2005;80:888–95. 16. Stevens LM, Carrier M, Perrault LP, et al. Influence of diabetes and bilateral internal thoracic artery grafts on
17. 18.
19. 20. 21.
22.
23.
24.
25.
26. 27. 28. 29.
30.
31. 32.
33.
long-term outcome for multivessel coronary artery bypass grafting. Eur J Cardiothorac Surg 2005;27:281–8. Momin AU, Deshpande R, Potts J, et al. Incidence of sternal infection in diabetic patients undergoing bilateral internal thoracic artery grafting. Ann Thorac Surg 2005;80:1765–72. Toumpoulis IK, Anagnostopoulos CE, Balaram S, et al. Does bilateral internal thoracic artery grafting increase long-term survival of diabetic patients? Ann Thorac Surg 2006;81: 599–606. Agrifoglio M, Trezzi M, Barili F, et al. Double vs single internal thoracic artery harvesting in diabetic patients: role in perioperative infection rate. J Cardiothorac Surg 2008;3:35. Kinoshita T, Asai T, Nishimura O, et al. Off-pump bilateral versus single skeletonized internal thoracic artery grafting in patients with diabetes. Ann Thorac Surg 2010;90:1173–9. Puskas JD, Sadiq A, Vassiliades TA, et al. Bilateral internal thoracic artery grafting is associated with significantly improved long-term survival, even among diabetic patients. Ann Thorac Surg 2012;94:710–6. Konstanty-Kalandyk J, Piatek J, Rudzinski P, et al. Clinical outcome of arterial myocardial revascularization using bilateral internal thoracic arteries in diabetic patients: a single centre experience. Interact Cardiovasc Thorac Surg 2012;15:979–83. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009;18:W65–94. Taggart DP, Altman DG, Gray AM, et al. Randomized trial to compare bilateral vs. single internal mammary coronary artery bypass grafting: 1-year results of the Arterial Revascularisation Trial (ART). Eur Heart J 2010;31:2470–81. S a MP, Ferraz PE, Escobar RR, et al. Skeletonized versus pedicled internal thoracic artery and risk of sternal wound infection after coronary bypass surgery: meta-analysis and meta-regression of 4817 patients. Interact Cardiovasc Thorac Surg 2013;16:849–57. Wijns W, Kolh P, Danchin N, et al. Guidelines on myocardial revascularization. Eur Heart J 2010;31:2501–55. BARI Investigators. The final 10-year follow-up results from the BARI randomized trial. J Am Coll Cardiol 2007;49:1600–6. Frye RL, August P, Brooks MM, et al; for the BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med 2009;360:2503–15. Kapur A, Hall RJ, Malik IS, et al. Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial. J Am Coll Cardiol 2010;55:432–40. Hlatky MA, Boothroyd DB, Bravata DM, et al. Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials. Lancet 2009;4:1190–7. Sabik JFI, Lytle BW, Blackstone EH, et al. Comparison of saphenous vein and internal thoracic artery graft patency by coronary system. Ann Thorac Surg 2005;79:544–51. FitzGibbon GM, Kafka HP, Leach AJ, et al. Coronary bypass graft fate and patient outcome: angiographic followup of 5,065 grafts related to survival and reoperation in 1, 388 patients during 25 years. J Am Coll Cardiol 1996;28: 616–26. Kitamura S. Physiological and metabolic effects of grafts in coronary artery bypass surgery. Circ J 2011;75:766–72.
Coronary Artery Bypass Revascularization Using Bilateral Internal Thoracic Arteries in Diabetic Patients: A Systematic Review and Meta-Analysis Kan Kajimoto, MD, PhD, Taira Yamamoto, MD, and Atsushi Amano, MD Department of Cardiovascular Surgery, Juntendo University School of Medicine, Tokyo, Japan
This study examined the effect of coronary artery bypass graft surgery with bilateral internal thoracic artery grafting in diabetic patients. Coronary artery bypass graft surgery using skeletonized bilateral internal thoracic artery grafts was not associated with an increased risk of deep sternal wound infection or early death. Moreover, patients who underwent coronary artery bypass graft surgery using bilateral internal
thoracic artery grafting had lower remote mortality and cardiac mortality. We conclude that coronary artery bypass surgery using bilateral internal thoracic artery grafts is an excellent strategy, even for diabetic patients.
C
with BITA grafts after skeletonized ITA harvesting in diabetic patients.
Address correspondence to Dr Yamamoto, Department of Cardiovascular Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyoku, Tokyo 113-8421, Japan; e-mail: [email protected].
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
Material and Methods Search Strategy Database searches were performed in the first week of February 2014. The following sources were searched for studies comparing single internal thoracic artery (SITA) and BITA grafts for diabetic patients: MEDLINE through PubMed (from 1995 to August 2013), EMBASE, and the Cochrane Library database (Cochrane Central Register of Controlled Trials). The following MeSH subject headings were used: “coronary artery bypass,” “diabetes,” “single internal thoracic artery,” “bilateral internal thoracic artery,” “double internal thoracic artery,” “single internal mammary artery,” “bilateral internal mammary artery,” and “double internal mammary artery.” The clinicaltrials. gov website was also searched for trials comparing SITA and BITA grafts for diabetic patients. The references cited within all available articles were also reviewed to identify candidate studies. All titles and abstracts were downloaded to Zotero version 2.1 (Center for History and New Media of George Mason University, Fairfax, VA).
Inclusion and Exclusion Criteria Studies satisfying the following criteria were included in this systematic review: (1) studies comparing SITA and BITA grafts for diabetic patients; (2) studies evaluating The Appendix Figure 1 can be viewed in the online version of this article [http://dx.doi.org/10.1016/j. athoracsur.2014.09.045] on http://www.annalsthor acicsurgery.org.
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.09.045
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oronary artery bypass graft surgery (CABG) is the coronary revascularization strategy of choice for patients with multivessel coronary artery disease [1]. Nevertheless, diabetes mellitus remains a strong risk factor for mortality and morbidity after CABG [2–4]. In the acute postoperative phase, diabetes is associated with an increased risk of infection due to hyperglycemia, relative immunodeficiency, and microcirculatory insufficiency [5]. Over the long term after CABG, diabetes is associated with an increased risk of death, cardiac death, and other adverse events as a result of a propensity toward severe atherosclerosis due to prothrombotic and proinflammatory states [4]. Meanwhile, CABG with internal thoracic artery (ITA) grafts can produce excellent outcomes, and the use of a left internal thoracic artery (LITA) to left anterior descending coronary artery graft, in particular, is associated with excellent long-term survival and a reduction in cardiac events due to graft patency; as a result, this strategy is the gold standard for CABG [6]. Coronary artery bypass graft surgery with bilateral internal thoracic artery (BITA) grafts is also sometimes used and is associated with good outcomes in nondiabetic patients [7–9]. In contrast, CABG with BITA in diabetic patients has historically been associated with a higher risk of deep sternal wound infection (DSWI) [10–22] and is therefore avoided. However, several recent studies have suggested that CABG with BITA grafts after skeletonized ITA harvesting is not associated with an increased risk of wound infection among diabetic patients [12, 14, 15, 20]. Thus, the goal of this study was to reexamine the safety and efficacy of CABG
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Abbreviations and Acronyms BITA CABG CI DSWI ITA LITA RR SITA
= = = = = = = =
bilateral internal thoracic artery coronary artery bypass graft surgery confidence interval deep sternal wound infection internal thoracic artery left internal thoracic artery relative risk single internal thoracic artery
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was used to assess the between-study heterogeneity in different groups. Publication bias was assessed by Horbold-Egger statistics, with a p value of less than 0.05 indicating significant publication bias among the studies. The meta-analysis was conducted using StatsDirect software version 2.7.2 (StatsDirect, Greater Manchester, UK).
Results Selection and Description of Studies
postoperative DSWI, early mortality, or remote outcomes; and (3) studies published in peer-reviewed journals with full available text in English. Studies in which it was not possible to extract data from the published results, as well as studies that did not report appropriate outcomes, were excluded.
Endpoints and Their Definitions The endpoints of this study were as follows: (1) DSWI; (2) early death; (3) long-term mortality; and (4) long-term cardiac mortality. Deep sternal wound infection was defined as DSWI or mediastinitis. Early death consisted of in-hospital or 30-day mortality. Long-term mortality and cardiac mortality were defined as the cumulative incidence of all-cause and cardiac death.
A total of 104 relevant studies were captured in the initial search (Fig 1). After screening the abstracts of these studies, the full-length articles of 13 studies fulfilled the inclusion criteria (Table 1). All 13 studies evaluated DSWI, had sample sizes ranging from 81 to 2,445, and were retrospective studies [10–22]. Of these, nine studies evaluated early death [11, 14–18, 20–22], eight studies evaluated long-term mortality [11, 12, 14–16, 18, 20, 21], and five studies evaluated long-term cardiac mortality [11, 12, 14, 15, 20]. Propensityscore matched analysis was reported in four studies [15, 18, 20, 21]. Ten studies mentioned a pedicle or skeletonized ITA [10–12, 14–17, 19, 20, 22]. Ten studies indicated the number of grafts or distal anastomoses [11, 12, 14–20, 22]. Seven studies indicated patients’ risk scoring, including EuroSCORE, The Society of Thoracic Surgeon Predicted Risk of Postoperative Mortality (STS-PROM) score, or
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Data Extraction Two reviewers (K.K. and T.Y.) independently assessed studies for inclusion criteria. The following information was extracted from each study: first author, year of publication, study design, loss to follow-up, age, sex, number of participants in each group (SITA and BITA), proportion of ITA skeletonization, proportion of off-pump CABG, number of grafts or distal anastomoses, and European System for Cardiac Operation Risk Evaluation (EuroSCORE). Reviewers extracted the following outcomes: DSWI, early mortality, long-term all-cause mortality, and long-term cardiac mortality. Outcome data are presented as count data.
Statistical Analysis The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement [23]. The endpoints of each study were analyzed using risk ratio (RR) with 95% confidence interval (CI). We conducted these meta-analyses only for studies that reported outcomes as count data; studies that reported outcomes as risk estimates (eg, hazard ratio and RR) were excluded from these analyses. Summary estimates were calculated by DerSimonian-Laird weights for the random effects model. Forest plots were then created for graphic presentation of clinical outcomes. The I2 statistic was calculated as a measure of the proportion of the overall variation attributable to between-study heterogeneity rather than chance. The I2 values of 25%, 50%, and 75% correspond to low, intermediate, and high levels of heterogeneity, respectively. The Cochran c2 (Cochran Q) test
Fig 1. Flow diagram from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines demonstrates the method for selection of the included articles.
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Table 1. Characteristics of Included Studies of Single Internal Thoracic Artery Grafts Versus Bilateral Internal Thoracic Artery Grafts
Konstanty-Kalandyk [22], 2012 Puskas [21], 2012 Kinoshita [20], 2010
Agrifoglio [19], 2008 Toumpoulis [18], 2006
Momin [17], 2005 Stevens [16], 2005
Calafiore [15], 2005
Lev-Ran [14], 2004
Hirotani [11], 2003
Gansera [10], 2001 a
DSWI, 30-day mortality DSWI, in-hospital death, long-term all-cause death DSWI, 30-day mortality, long-term all-cause death, long-term cardiac death Sternal wound infection DSWI, 30-day mortality, in-hospital mortality, long-term all-cause death DSWI, 30-day mortality, 30-day in-hospital mortality DSWI, 30-day mortality, in-hospital mortality, long-term all-cause death DSWI, in-hospital mortality, long-term all-cause death, long-term cardiac death DSWI, 30-day mortality, long-term all-cause death, long-term cardiac death DSWI DSWI, long-term all-cause death, long-term cardiac death DSWI, in-hospital mortality, long-term all-cause death, long-term cardiac death DSWI
109/38
Age SITA/BITA (years)
Female SITA/BITA (%)
Skeletonized SITA/BITA (%)
No. Grafts SITA/BITA
EuroSCORE SITA/BITA
Described Postop Glucose Control
66/62
40/34
0/0
2.6/2.6
NA
Yes
Retrospective Propensity score matched Propensity score matched
Study Design
1,213/232
8
64/58
33/16
NA
NA
3.1/2.0a
No
170/170
7
70/70
25/24
100/100
2.4/2.7
7/7
No
10
67/62 64/65
15/15 45/44
0/0 NA
3.3/3.2b 3.3/3.7b
4.2/2.3 6.9/6.8
Yes No
Retrospective Propensity score matched
63/62
38/40
0/0
2.8/3.2
11.4/8.6
No
Retrospective
41/40 490/490
524/396 419/214
15
64/58
35/14
0/0
3.3/3.4
NA
No
Retrospective
200/200
8
67/67
59/70
84/85
2.8/2.9b
7.3/6.6
Yes
Propensity score matched
57/228
7.5
66/66
40/31
100/100
3.1/3.2
3.6/3.8
Yes
Retrospective
177/79 277/190
10
69/60 62/61
3.5/3.6 23/14
NA 100/100
NA 2.7/2.8b
NA NA
No No
Retrospective Retrospective
124/179
6.7
64/65
25/23
0/0
2.8/3.5
NA
No
Retrospective
65/64
24/19
0/0
NA
NA
No
Retrospective
589/418
The Society of Thoracic Surgeons predicted risk of postoperative mortality score.
b
BITA ¼ bilateral internal thoracic artery; DSWI ¼ deep sternal wound infection; assessed; Postop ¼ postoperative; SITA ¼ single internal thoracic artery.
Number of distal anastomoses. EuroSCORE ¼ European System for Cardiac Operation Risk Evaluation;
FU ¼ follow-up;
NA ¼ not
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Tavolacci [13], 2003 Endo [12], 2003
Outcomes
Lost to FU (years)
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First Author [Ref], Year
Patients SITA/BITA (n)
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Parsonnet score [14, 15, 17–21]. Four studies described postoperative glucose control [14, 15, 19, 22].
Deep Sternal Wound Infection Deep sternal wound infection was reported as a variable in 13 studies that included 7,264 patients [10–22]. The Forest plots of DSWI are shown in Figure 2A. One study by Agrifoglio and colleagues [19] was excluded from analysis because of the lack of incidence of DSWI. A DSWI occurred in 2.0% of patients in the SITA group and in 3.2% of patients in the BITA group. Low heterogeneity was seen with this analysis (Cochran c2: p ¼ 0.46,
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Fig 2. Forest plots of deep sternal wound infection. (A) Results of all 13 studies. (B) Results of four studies that included internal thoracic arteries harvested in a skeletonized fashion. Results are shown as risk ratio (RR) with 95% confidence interval (CI). (BITA ¼ bilateral internal thoracic artery; SITA ¼ single internal thoracic artery.)
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I2 ¼ 0%), and no publication bias was indicated (HorboldEgger statistics: p ¼ 0.37). The summary estimate showed that BITA grafting in diabetic patients was associated with an increased risk of DSWI (RR 1.54; 95% CI: 1.13 to 2.11; p ¼ 0.0069). Studies in which skeletonized harvesting of the ITA graft was performed were further analyzed; this analysis included three studies with 1,092 patients [12, 14, 20]. The Forest plots of DSWI are shown in Figure 2B. A DSWI occurred in 1.5% of patients in the SITA group and in 1.4% of patients in the BITA group. Low heterogeneity was seen with this analysis (Cochran c2: p ¼ 0.98, I2 ¼ 0%), and no publication bias was
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indicated (Horbold-Egger statistics: p ¼ 0.53). The summary estimate showed no significant difference in DSWI between the skeletonized SITA group and the skeletonized BITA group (RR 1.01; 95% CI: 0.35 to 2.97; p ¼ 0.98).
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Early Death Nine studies with 5,453 patients that evaluated early death were identified [11, 14–18, 20–22]. The Forest plots of early death are shown in Figure 3A. Early death Fig 3. Forest plots of mortality. (A) Results for early death. (B) Results for long-term mortality. (C) Results for long-term cardiac mortality. Results are shown as risk ratio (RR) with 95% confidence interval (CI). (BITA ¼ bilateral internal thoracic artery; SITA ¼ single internal thoracic artery.)
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occurred in 2.6% of patients in the SITA group and 3.0% of patients in the BITA group. Low heterogeneity was seen with this analysis (Cochran c2: p ¼ 0.86, I2 ¼ 0%), and no publication bias was indicated (Horbold-Egger statistics: p ¼ 0.09). The summary estimate showed no significant difference in early death when comparing the skeletonized SITA group and the BITA group (RR 0.94; 95% CI: 0.67 to 1.32; p ¼ 0.73).
Long-Term Mortality A total of eight studies evaluated long-term mortality [11, 12, 14–16, 18, 20, 21]. Of these, four studies were excluded from meta-analysis because count data could not be obtained [11, 16, 18, 21]. Therefore, four studies with 3,408 patients were enrolled in the meta-analysis [12, 14, 15, 20]. The Forest plots of long-term mortality are shown in Figure 3B. There was significant heterogeneity, driven mainly by one study (Cochran c2: p < 0.0001, I2 ¼ 87%). Publication bias was not indicated (HorboldEgger statistics: p ¼ 0.35). The summary estimate showed that BITA grafting in diabetic patients was associated with a significantly decreased risk of long-term mortality (RR 0.65; 95% CI: 0.46 to 0.92; p ¼ 0.018; Appendix Fig 1).
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Long-Term Cardiac Mortality A total of five studies evaluated long-term cardiac mortality [11, 12, 14, 15, 20]. Of these, one study was excluded from the meta-analysis because count data could not be obtained [6]. Therefore, four studies with 3,408 patients were enrolled in the meta-analysis [12, 14, 15, 20]. The Forest plots of long-term cardiac mortality are shown in Figure 3C. There was also significant heterogeneity, driven mainly by a study by Hirotani and associates [11] (Cochran c2: p ¼ 0.018, I2 ¼ 67%). Publication bias was not indicated (Horbold-Egger statistics: p ¼ 0.81). The summary estimate showed that BITA grafting in diabetic patients was associated with a significantly decreased risk of long-term cardiac mortality (RR 0.54; 95% CI: 0.30 to 0.97; p ¼ 0.042; Appendix Fig 1).
Comment This study is the first systematic review comparing the use of SITA and BITA grafts in diabetic patients, and it demonstrated that skeletonized BITA grafting is safe in terms of the risk of DSWI and early death. Furthermore, long-term all-cause and cardiac mortality was lower for diabetic patients undergoing CABG with BITA grafting than for diabetic patients undergoing CABG with SITA grafting. However, the benefits of BITA in nondiabetic patients for long-term outcomes were shown by several studies [7–9]. Although CABG using BITA grafting is not common worldwide, the effect of BITA grafting has begun to attract attention. Indeed, the Arterial Revascularization Trial (ART) is an ongoing randomized control study that evaluated the effect of BITA in the general population [24]. The ART demonstrated that 1-year survival after BITA grafting was not associated with better survival beyond that term when compared with SITA grafting.
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However, further research is needed to evaluate the longterm benefit of BITA grafting. Historically, the greatest concern in relation to BITA grafting for diabetic patients has been the potential risk of DSWI; and the guidelines on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) identified the increased risk of postoperative sternal dehiscence and DSWI in diabetic patients [25]. If the increased risk of BITA for DSWI could be resolved in diabetic patients, the demand for BITA could increase in patients with diabetes who have an increased risk of poor long-term outcomes after CABG. This meta-analysis of 13 studies showed that there was an increased risk of DSWI in the entire population of diabetic patients undergoing any type of BITA grafting. Of these studies, five evaluated only pedicle-harvested BITA grafting [10, 11, 16, 17, 19, 22]. When compared with skeletonized harvest of the ITA graft, pedicle ITA grafting reduces blood flow to the sternum. Hence, pedicle harvest of the ITA is prone to skeletonized harvested ITA in terms of the risk of DSWI [26]. In addition, the ART suggested that BITA grafting is associated with an increased risk of DSWI in the general population [24]. However, the ITA harvest approach (skeletonized or pedicled) was not documented in the ART. Hence, a significant number of patients undergoing pedicled harvest of the ITA may be included in the ART. To evaluate risk of skeletonized harvested BITA grafting among diabetic patients, additional analysis of the three studies [12, 14, 20] that included only skeletonized ITA was performed in this study. In the result, skeletonized BITA grafting was not associated with an increased risk of DSWI among diabetic patients (RR 1.01; 95% CI: 0.35 to 2.97; p ¼ 0.98). Furthermore, BITA grafting was not associated with an increased risk for early mortality among diabetic patients when compared with SITA grafting. Thus, skeletonized BITA grafting appears to be a safe and effective strategy, even among diabetic patients, and should be used in preference to pedicle BITA grafting. In addition to reducing the DSWI rate among diabetic patients, skeletonization of the ITA also yields the advantage of extension of graft length, which is particularly helpful when the right ITA is grafted to the left side coronary system. Diabetic patients are more likely to have complex coronary disease and require two or more revascularizations in a single graft (sequential anastomosis). In that case, graft length is very important, and skeletonized harvest is invaluable, regardless of whether the right ITA is used as an in situ graft or as a composite graft. Although skeletonization of the ITA requires a longer preparation time when compared to pedicle harvested ITA, skeletonization of ITA is worth performing among diabetic patients owing to these merits. Skeletonization of ITA and glucose control in the early postoperative period has an impact on the risk of DSWI. Several past studies demonstrated that intensive serum glucose control is associated with reduced early postoperative mortality and a reduced incidence of complications. In this meta-analysis, four studies described a
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inflow of the ITA can be connected to the left coronary system (in situ graft). Second, its histologic and vasophysiologic properties, including a thin smooth muscle layer and abundant elastic fibers, are relatively protective against progression of atherosclerosis, and thereby results in excellent graft patency [31, 32]. One of the important mechanisms underlying diabetesrelated cardiovascular diseases is endothelial dysfunction. Kitamura [33] hypothesized that preservation of the endothelium from ITAs to native coronary arteries results in restoration of otherwise compromised coronary endothelial function, especially in patients with diabetes, advanced age, or multivessel disease. These mechanisms may account for why BITA is better than SITA for diabetic patients. Despite the survival benefits of the BITA graft, this strategy has not been commonly used [7]. Grafting with BITA has several drawbacks other than the increased risk of DSWI. The use of BITA grafts requires a longer preparation time and operation time. The ART showed that operative duration of CABG using BITA grafting was 20 minutes longer than that of SITA grafting [24]. Spasm and atrophic change due to competitive blood flow from native coronary arteries are also problems associated with ITA grafting [25]. Gansera and colleagues [10] showed some advantages of the BITA after CABG. However, there was an increased risk of early complications, including DSWI, after CABG among patients with diabetes, obesity, impaired left ventricular ejection fraction, and chronic obstructive pulmonary disease. Therefore, BITA grafting for patients with these risk factors remains controversial. However, the present analysis demonstrated that BITA grafting is safe and has significant benefit for diabetic patients. Thus, we believe that BITA grafting should be used for diabetic patients to improve their outcomes after CABG. This study has several limitations. All studies included in this systematic review were retrospective analyses rather than randomized, prospective studies, reflecting outcomes after clinical decision making by treating surgeons. Several studies were not even propensity matched, and the opportunity for confounding by bias (eg, using BITA in younger or healthier patients) is a strong possibility. Furthermore, only four of the 13 studies investigated long-term survival analysis; hence, the statistical power of the present analysis was relatively weak. In conclusion, this is the first meta-analysis, to the best our knowledge, of the long-term effects of BITA grafting in diabetic patients. This study also showed that CABG with BITA grafting increased the risk of DSWI in diabetic patients. However, BITA grafting with skeletonized harvest was not associated with an increased risk of DSWI even in diabetic patients. Furthermore, BITA grafting provided significant benefits in long-term all-cause mortality and cardiac mortality for diabetic patients after CABG when compared with SITA grafting. We conclude that BITA grafts with skeletonized harvest should be used for CABG in diabetic patients.
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specific approach for postoperative glucose control [14, 15, 19, 22]. The protocol in these four studies included intensive glucose control by continuous insulin infusion, and they reported similar DSWI when comparing SITA and BITA grafts. The strategies of glucose control were not equal among these studies, and the whether control of serum glucose levels was established was not mentioned in these four studies. Therefore, we did not perform additional analysis of these four studies. However, the results of these studies might support the notion that intensive glucose control is associated with a reduction in mortality and DSWI after CABG, as was previously reported by Furnary and associates [5]. CABG surgery is the treatment strategy of choice for diabetic patients with multivessel coronary artery disease, because many trials comparing CABG and percutaneous coronary intervention have shown the advantages of CABG on long-term outcomes among diabetic patients [1, 3, 27–30]. However, diabetes remains a strong risk factor for mortality and morbidity after CABG [2–4]. A stratified analysis of 3,889 patients who underwent CABG in the collaborative analysis showed that diabetic patients still had worse outcomes than patients without diabetes over a mean follow-up period of 5.8 years (23% versus 14%, respectively, for long-term mortality) [30]. Thus, the reduction of the negative impact of diabetes on outcomes after CABG remains an unsolved problem. The present meta-analysis demonstrated that BITA grafting significantly reduced all-cause mortality and cardiac mortality. Further, Puskus and coworkers [21] indicated that BITA grafting was associated with a reduction in the hazard of long-term mortality in diabetic patients (hazard ratio 0.65; 95% CI: 0.48 to 0.88; p ¼ 0.006). Stevens and associates [16] reported that the 5-, 10-, and 15-year survival after BITA grafting was significantly higher when compared with that after SITA grafting in a series of 633 consecutive diabetic patients (95%, 88%, 79% versus 93%, 85%, 73%, respectively). Hirotani and colleagues [11] reported that there was no significant difference in long-term mortality when comparing SITA and BITA grafting for diabetic patients, but they concluded that, among patients with normal ejection fraction, BITA grafting was associated with increased 10-year survival when compared with SITA grafting. These three studies were excluded from the present meta-analysis, which evaluated long-term outcomes, because count data were not available; nevertheless, findings of these studies suggest that BITA grafting is a better option than SITA grafting in diabetic patients. The long-term benefit of CABG is maximized with the use of arterial grafts, specifically with the use of the ITA [6–9]. The 10-year patency rate of the LITA is expected to be more than 90% [6–9, 25, 31, 32]. Therefore, LITA grafting to the left anterior descending artery is recommended as the gold standard strategy for graft selection [6, 25]. CABG with BITA grafts is also sometimes used and is associated with good outcomes for nondiabetic patients [7–9]. The ITA has several excellent properties as a coronary artery graft. First, the anatomic
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References 1. Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet 2013;23:629–38. 2. Kajimoto K, Kasai T, Miyauchi K, et al. Metabolic syndrome predicts 10-year mortality in non-diabetic patients following coronary artery bypass surgery. Circ J 2008;72:1481–6. 3. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367:2375–84. 4. Alserius T, Hammar N, Nordqvist T, et al. Improved survival after coronary artery bypass grafting has not influenced the mortality disadvantage in patients with diabetes mellitus. J Thorac Cardiovasc Surg 2009;138:115–22. 5. Furnary AP, Zerr KJ, Grunkemeier GL, et al. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999;67:352–60. 6. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2011;58:e123–210. 7. Tabata M, Grab JD, Khalpey Z, et al. Prevalence and variability of internal mammary artery graft use in contemporary multivessel coronary artery bypass graft surgery: analysis of The Society of Thoracic Surgeons national cardiac database. Circulation 2009;15:935–40. 8. Taggart DP, D’Amico R, Altman DG. Effect of arterial revascularisation on survival: a systematic review of studies comparing bilateral and single internal mammary arteries. Lancet 2001;358:870–5. 9. 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;26:542–8. 10. Gansera B, Schmidtler F, Gillrath G, et al. Does bilateral ITA grafting increase perioperative complications? Outcome of 4462 patients with bilateral versus 4204 patients with single ITA bypass. Eur J Cardiothorac Surg 2006;30:318–23. 11. Hirotani T, Nakamichi T, Munakata M, et al. Risks and benefits of bilateral internal thoracic artery grafting in diabetic patients. Ann Thorac Surg 2003;76:2017–22. 12. Endo M, Tomizawa Y, Nishida H. Bilateral versus unilateral internal mammary revascularization in patients with diabetes. Circulation 2003;16:1343–9. 13. Tavolacci MP, Merle V, Josset V, et al. Mediastinitis after coronary artery bypass graft surgery: influence of the mammary grafting for diabetic patients. J Hosp Infect 2003;55:21–5. 14. Lev-Ran O, Braunstein R, Nesher N, et al. Bilateral versus single internal thoracic artery grafting in oral-treated diabetic subsets: comparative seven-year outcome analysis. Ann Thorac Surg 2004;77:2039–45. 15. Calafiore AM, Di Mauro M, Di Giammarco G, et al. Single versus bilateral internal mammary artery for isolated first myocardial revascularization in multivessel disease: longterm clinical results in medically treated diabetic patients. Ann Thorac Surg 2005;80:888–95. 16. Stevens LM, Carrier M, Perrault LP, et al. Influence of diabetes and bilateral internal thoracic artery grafts on
17. 18.
19. 20. 21.
22.
23.
24.
25.
26. 27. 28. 29.
30.
31. 32.
33.
long-term outcome for multivessel coronary artery bypass grafting. Eur J Cardiothorac Surg 2005;27:281–8. Momin AU, Deshpande R, Potts J, et al. Incidence of sternal infection in diabetic patients undergoing bilateral internal thoracic artery grafting. Ann Thorac Surg 2005;80:1765–72. Toumpoulis IK, Anagnostopoulos CE, Balaram S, et al. Does bilateral internal thoracic artery grafting increase long-term survival of diabetic patients? Ann Thorac Surg 2006;81: 599–606. Agrifoglio M, Trezzi M, Barili F, et al. Double vs single internal thoracic artery harvesting in diabetic patients: role in perioperative infection rate. J Cardiothorac Surg 2008;3:35. Kinoshita T, Asai T, Nishimura O, et al. Off-pump bilateral versus single skeletonized internal thoracic artery grafting in patients with diabetes. Ann Thorac Surg 2010;90:1173–9. Puskas JD, Sadiq A, Vassiliades TA, et al. Bilateral internal thoracic artery grafting is associated with significantly improved long-term survival, even among diabetic patients. Ann Thorac Surg 2012;94:710–6. Konstanty-Kalandyk J, Piatek J, Rudzinski P, et al. Clinical outcome of arterial myocardial revascularization using bilateral internal thoracic arteries in diabetic patients: a single centre experience. Interact Cardiovasc Thorac Surg 2012;15:979–83. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009;18:W65–94. Taggart DP, Altman DG, Gray AM, et al. Randomized trial to compare bilateral vs. single internal mammary coronary artery bypass grafting: 1-year results of the Arterial Revascularisation Trial (ART). Eur Heart J 2010;31:2470–81. S a MP, Ferraz PE, Escobar RR, et al. Skeletonized versus pedicled internal thoracic artery and risk of sternal wound infection after coronary bypass surgery: meta-analysis and meta-regression of 4817 patients. Interact Cardiovasc Thorac Surg 2013;16:849–57. Wijns W, Kolh P, Danchin N, et al. Guidelines on myocardial revascularization. Eur Heart J 2010;31:2501–55. BARI Investigators. The final 10-year follow-up results from the BARI randomized trial. J Am Coll Cardiol 2007;49:1600–6. Frye RL, August P, Brooks MM, et al; for the BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med 2009;360:2503–15. Kapur A, Hall RJ, Malik IS, et al. Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial. J Am Coll Cardiol 2010;55:432–40. Hlatky MA, Boothroyd DB, Bravata DM, et al. Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials. Lancet 2009;4:1190–7. Sabik JFI, Lytle BW, Blackstone EH, et al. Comparison of saphenous vein and internal thoracic artery graft patency by coronary system. Ann Thorac Surg 2005;79:544–51. FitzGibbon GM, Kafka HP, Leach AJ, et al. Coronary bypass graft fate and patient outcome: angiographic followup of 5,065 grafts related to survival and reoperation in 1, 388 patients during 25 years. J Am Coll Cardiol 1996;28: 616–26. Kitamura S. Physiological and metabolic effects of grafts in coronary artery bypass surgery. Circ J 2011;75:766–72.