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Innovations: Technology & Techniques in Cardiothoracic & Vascular Surgery:
doi: 10.1097/IMI.0b013e3182166793
Review Article

Bilateral Internal Thoracic Artery Grafting: Current State of the Art

Kinoshita, Takeshi MD; Asai, Tohru MD, PhD

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From the Division of Cardiovascular Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Japan.

Accepted for publication November 11, 2010.

Address correspondence and reprint requests to Takeshi Kinoshita, MD, Shiga University of Medical Science, Setatsukinowa, Otsu 520-2192, Japan. E-mail: kinotake@belle.shiga-med.ac.jp.

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Abstract

The purpose of this article is to review the key literature and assess the current status of bilateral internal thoracic artery grafting. Numerous retrospective studies have demonstrated a benefit of bilateral internal thoracic artery grafting over single internal thoracic artery grafting in terms of the long-term risk of all-cause death, cardiac-related death, and cardiac events. The survival benefit of bilateral internal thoracic artery grafting manifests relatively early after operation for high-risk patients. The skeletonization technique reduces the risk of sternal wound complications in all patients and particularly in those with diabetes. Both the left and right internal thoracic arteries have better patency when grated to the left coronary territory than saphenous vein. However, the right internal thoracic artery does not always have good patency when grafted to the right coronary artery. Bilateral internal thoracic artery grafting using the skeletonization technique is recommended for revascularization of the left coronary territory.

It was clearly shown that the use of the internal thoracic artery (ITA) as a coronary artery conduit improved survival, reduced the incidence of recurrent angina, and provides excellent graft patency compared with the saphenous vein.1–3 This finding led many surgeons to adopt bilateral ITA (BITA) grafting as a good option for further improving long-term outcomes. On the other hand, some concerns, in particularly sternal wound problems, have prevented widespread use of BITA especially in diabetic patients. In clinical practice, BITA was only used in ∼30% of coronary artery bypass grafting (CABG) patients in Japan,4 10% in Europe,5 and 4% in the United States.6 The purpose of this article is to review the key literature and assess the current status of BITA grafting.

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LONG-TERM CLINICAL OUTCOMES

Numerous retrospective studies have demonstrated a benefit of BITA grafting over single ITA (SITA) grafting in terms of the long-term risk of all-cause death,7–13 cardiac-related death,8,14 and cardiac events.7–9,11,14–17 However, no randomized data exist comparing BITA and SITA grafting.

Lytle and coworkers9 retrospectively compared survival of patients receiving BITA grafting (n = 2001) and SITA grafting (n = 8123) with a mean follow-up of 10 years. Survival for the BITA group was 94%, 84%, and 67% and for the SITA group was 92%, 79%, and 64% at 5, 10, and 15 years postoperatively, respectively (P < 0.01). Death, reoperation, and percutaneous transluminal coronary angioplasty were more frequent for patients undergoing SITA grafting than BITA grafting. The same authors later demonstrated the incremental survival benefit of BITA grafting in 1152 propensity score-matched groups with a mean follow-up of 16.5 years.10 The survival rate of the BITA and SITA groups at 7, 10, 15, and 20 years was 89% versus 87%, 81% versus 78%, 67% versus 58%, and 50% versus 37%, respectively (P < 0.0001). The divergence of BITA and SITA hazard function curves continued to widen through 20 postoperative years. The authors also showed that advanced age, abnormal left ventricular function, and noncardiac risk factors reduced overall survival but that the incremental benefit of BITA grafting persisted.

Buxton et al12 reported on 2826 patients undergoing coronary surgery (1269 receiving BITA grafting and 1557 SITA grafting) who were followed up for a mean postoperative interval of 52 months. A multivariate Cox proportional hazard model identified SITA grafting as a significant predictor of all-cause death [hazard ratio (HR) 1.4; 95% confidence interval (CI) 1.1–1.8]. Actuarial survival rates at 10 years were 86% ± 3% for the BITA group and 71% ± 5% for the SITA group. SITA grafting was also a significant predictor of late myocardial infarction and late reoperation. It was concluded that BITA grafting may improve long-term survival and freedom from late myocardial infarction or reoperation after coronary artery surgery.

In a meta-analysis of 15,962 patients (11,269 SITA grafting and 4,693 BITA grafting), Taggart et al18 demonstrated that the BITA groups had significantly better survival than the SITA group (HR for death 0.81; 95% CI 0.70–0.94).

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BITA FOR PATIENTS WITH DIABETES

The use of BITA in patients with diabetes has been a matter of debate because of the risk of sternal infection. However, the skeletonization technique has encouraged cardiac surgeons to use BITA for diabetic patients.11,19,20 Calafiore et al21 investigated 8-year outcomes of 400 propensity score-matched diabetic patients receiving skeletonized BITA grafting (n = 200) and SITA grafting (n = 200). The BITA group showed better 8-year freedom from all-cause death (86.7 ± 3.2 vs 79.5 ± 4.1; P = 0.0274), cardiac death (96.3 ± 1.4 vs 88.4 ± 4.0; P = 0.0406) and acute myocardial infarction in all area (99.5 ± 0.5 vs 92.0 ± 3.9; P = 0.0092) and in the grafted area (99.5 ± 0.5 vs 93.4 ± 3.7; P = 0.0204). Cox analysis identified SITA grafting as an independent predictor for lower freedom from death (HR 1.8), cardiac death (HR 1.9), and acute myocardial infarction in any area (HR 9.7) and in a grafted area (HR 8.2). Recently, the authors compared 5-year outcomes in 340 propensity score-matched diabetic patients undergoing off-pump CABG using skeletonized BITA (n = 170) or SITA (n = 170).22 The 5-year rate of survival free from overall death in the BITA group versus the SITA group was 87.5% versus 70.8% (log-rank test, P = 0.01). For freedom from cardiac death, the respective rate was 92.1% versus 78.7% (P = 0.01). For freedom from cardiac event, the respective rate was 91.0% versus 72.6% (P = 0.01). In multivariate Cox models, BITA grafting was significantly associated with a lower risk of overall death (HR 0.45; 95% CI 0.22–0.89; P = 0.02), cardiac death (HR 0.43; 95% CI 0.21–0.87; P = 0.02), and cardiac event (HR 0.42; 95% CI 0.20–0.85; P = 0.02). On the other hand, Toumpoulis et al23 found no effect of BITA grafting compared with SITA grafting on long-term survival in 980 propensity score-matched diabetic patients at a mean follow-up of 4.7 years (5-year survival rate 79.9% in BITA group, 75.7% in SITA group; P = 0.252).

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BITA FOR ELDERLY PATIENTS

The impact of BITA grafting on survival in elderly patients has not been well investigated. In a large observational study including >10,000 patients at the Cleveland Clinic, the majority of patients (90.6%) were younger than 70 years.9 Galbut et al24 analyzed the outcomes in 1467 patients older than 65 years who underwent BITA grafting (n = 731) or SITA grafting (n = 736). The 8-year survival was significantly better in the BITA group (67.9% vs 60.7%, P = 0.028).

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PATENCY

The selection of the target vessel is important for better graft patency. The graft patency of the left ITA (LITA) and right ITA (RITA) in on-pump coronary bypass is summarized in Table 1. RITA grafting to the right coronary system has been shown to fail more frequently than grafting to the left coronary territories.

Table 1
Table 1
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Sabik et al25 analyzed the 15-year angiographic results of 2121 ITA and 8733 saphenous vein grafts and demonstrated that ITA grafts are more likely to be patent than saphenous vein grafts when used to bypass all left-sided coronary arteries and the posterior descending artery at all times after surgery and at all degrees of proximal coronary artery stenosis; early (<5 years) after operation, saphenous vein grafts have equivalent or better patency than ITA grafts when bypassing the main right coronary artery; however, at 10 years postoperatively, ITA grafts are more likely to be patent in right coronary arteries with 70% stenosis or greater. Sabik et al recommended that both ITAs should be grafted to the left anterior descending artery and the next most important left-sided coronary artery; if there is no other left-sided coronary artery requiring bypass and the right coronary artery needs to be grafted, the second ITA should be grafted to the posterior descending artery instead of the main right coronary artery.

Shah et al26 evaluated the angiograms of 1482 LITA and 636 RITA with a mean follow-up of 80 months. The LITA was grafted to the left anterior descending coronary artery in 82% of cases, and the RITA to the right coronary artery in 40% and to the circumflex artery in 35% of cases. Both the LITA and RITA had good patency when grafted to the left anterior descending artery (97.2% and 96.0%), the diagonal branch (96.4% and 93.0%), and the circumflex artery (91.0% and 90.0%). The RITA had the worst patency when anastomosed to the right coronary system as an in situ graft (79.2%). The free RITA had significantly better patency than in situ grafting of the RITA to the right coronary system (90.0% vs 79.2%).

Dion et al32 reported the angiographic outcomes of 161 patients at a mean postoperative interval of 7.5 years. The patency of the RITA was similar to that of the saphenous vein when grafted to the right coronary artery (83.4% vs 75.2%, P = 0.50).

Should the RITA be used as an in situ or a free graft? One possible problem is that the RITA is not long enough to reach the anastomotic site even if skeletonized. Calafiore et al33 compared the long-term outcomes of 1818 patients in whom BITA was used as an in situ (n = 1378) or a Y graft (n = 440). The number of BITA anastomoses per patient and the number of RITA anastomoses per patient were significantly higher in patients with Y grafts (2.7 ± 0.9 and 1.4 ± 0.6 vs 2.2 ± 0.6 and 1.0 ± 0.3, both P < 0.001). Y grafts also increased the number of sequential anastomoses per RITA from 4.1% to 34.3% (P < 0.001). The patency rate at a mean of 17.5 ± 18.4 months was 100% in the in situ group and 99.2% in the Y graft group. No Y anastomosis was occluded or stenosed. Calafiore commented that survival, incidence of cardiac events, and angiographic patency in the early and late phases are similar for BITA used either in situ or as a Y graft but that Y grafting with BITA increases the number of anastomoses per bilateral thoracic artery, as well as the flexibility of the RITA.

There is limited data on the long-term patency of BITA grafting. Pick et al8 compared the remote outcomes of 160 patients who received BITA grafting with 161 patients who received a single LITA and saphenous vein grafting and presented the angiographic results of 84 patients undergoing repeat angiography with a mean of 6.9 years follow-up. One ITA was anastomosed to the left anterior descending artery in 94% of patients. In the BITA group, a second ITA was used to revascularize the left coronary system in 93% of patients. The overall ITA patency was 84% (LITA 88%, RITA 75%).

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STERNAL WOUND INFECTION

Sternal wound infection is a rare but life-threatening complication after surgery. Although the use of BITA has been considered as a risk factor for sternal wound infection especially in diabetic patients,34,35 reduction of wound complications in patients with diabetes has been demonstrated in some reports when BITA are harvested using the skeletonization technique,36–41 and serum glucose levels are well controlled in the postoperative period.42

In a recent study by the authors' group including 340 propensity score-matched diabetic patients undergoing off-pump CABG using BITA (n = 170) or SITA (n = 170),22 ITA was harvested using the skeletonization technique in all patients and postoperative serum glucose was well controlled: blood glucose levels (mg/dL) of the BITA versus SITA group on postoperative days 0, 1, and 2 were 150 ± 38 versus 149 ± 34 (P = 0.35), 180 ± 42 versus 177 ± 38 (P = 0.33), and 154 ± 36 versus 149 ± 30 (P = 0.26), respectively. Deep sternal infection occurred in 2.4% in the BITA group and 1.8% in the SITA group (P = 0.72). Meanwhile, Nakano et al43 analyzed the data of 1500 consecutive patients undergoing off-pump bypass surgery using BITA or SITA. On multivariate analysis with logistic regression, use of BITA grafts (HR 2.5; 95% CI 1.1–6.1) were found to be independent risk factors for wound infection in the diabetic subgroup. They concluded that the use of BITA, even when harvested using the skeletonization technique, was a risk factor for wound infection in diabetic patients.

In a recent meta-analysis by Saso et al,44 skeletonization was associated with beneficial reduction in the odds ratio of sternal wound infection (odds ratio 0.41; 95% CI 0.26–0.64). This effect was more evident when analyzing diabetic patients undergoing BITA grafting (odds ratio, 0.19; 95% CI, 0.10–0.34). They concluded that the risk of all sternal wound infection decreases by 60% when skeletonizing the ITA; this advantage is amplified in diabetic patients in whom an even greater benefit was demonstrated with the incidence of sternal wound infection reduced from 21.3% to 3.57% by skeletonization of the ITA; when harvesting BITA, the advantage of skeletonization is maintained with a reduction of postoperative sternal wound infection rates from 11.7% to 2.96% for all studies and from 14.2% to 2.4% in diabetic patient. Subgroup analyses demonstrate that the reduction in sternal wound infection rates is maintained for the whole spectrum of postoperative sternal wound infection including mediastinitis.

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SKELETONIZATION TECHNIQUE

Sternal ischemia may impair sternal wound healing and lead to an increased risk of infection. In the skeletonization technique which moves only the ITA and preserves the surrounding tissue, the collateral vessels supplying the sternum are protected and sternal ischemia is reduced in comparison with the conventional pedicle technique (Fig. 1).45 The skeletonization technique subsequently lowers the risk of sternal wound complications in all patients and particularly in those with diabetes (Fig. 2).

Figure 1
Figure 1
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Figure 2
Figure 2
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Cohen et al46 compared the effect of skeletonized ITA on sternal vascularity with pedicled ITA using single photon emission computed tomography and concluded that pedicled ITA reduced blood flow to the left side of the sternum during the acute postoperative period; this does not occur when the ITA is skeletonized. Medalion and coworkers47 also demonstrated that acute postoperative sternal ischemia caused by harvesting of a pedicled LITA was temporary and resolved with time. Kamiya et al48 investigated the influence of skeletonized ITA on the sternal microcirculation in the perioperative phase using a laser Doppler flowmetric and remission spectroscopic system and concluded that the damage to the tissue microcirculation in the retrosternal area is significantly less after ITA skeletonization than after pedicled ITA.

This technique also increases the length of the conduit,36 which allows thorough visual inspection to identify spastic or damaged areas that could otherwise be obscured by perivascular fat, facilitating sequential anastomoses and composite arterial grafting and minimizing the risks of kinks or twists in the conduit.

Calafiore et al36 compared the early and late outcomes of 304 patients undergoing pedicled BITA grafting with 842 cases of skeletonized BITA grafting. Skeletonized ITA was longer than pedicled ITA (20.1 vs 16.4 cm, P < 0.001). As a result, the number of BITA anastomoses per patients was significantly higher in patients receiving skeletonized conduits (2.4 ± 0.3 vs 2.1 ± 0.4, P < 0.001), as was the number of sequential grafts (288 vs 42, P < 0.001). The incidence of sternal wound complications in diabetic patients was lower in patients receiving skeletonized conduits (2.2% vs 10.0%, P < 0.05).

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BITA FOR OFF-PUMP BYPASS

There is little information on the remote outcome of off-pump coronary bypass using BITA.22,49 The authors' group recently reported the midterm outcomes in 314 propensity score-matched patients with chronic kidney disease receiving off-pump skeletonized BITA or SITA grafting.49 During a mean observation period of 2.9 years, the rates of overall death and cardiac death (myocardial infarction, heart failure, and sudden death) in the BITA group were significantly lower than those in the SITA group (5.1% vs 15.9%, P = 0.01; 1.3% vs 8.3%, P = 0.01). In multivariate Cox models including BITA grafting and all other potential predictors, BITA grafting was significantly associated with a lower risk for overall death (HR 0.29; 95% CI 0.10–0.89; P = 0.03) and cardiac death (HR 0.14; 95% CI 0.03–0.63; P = 0.02).

Interestingly, the survival benefit of BITA grafting was seen as early as in 2 to 3 years in these studies. This finding is in contrast with the report from the Cleveland Clinic, in which the survival benefit of BITA grafting was seen only after 10 years.9,10 The authors commented that the study patients had higher risk profiles than those from the Cleveland Clinic and that this is the reason why the survival benefit of BITA grafting was evident during the short follow-up period. Lytle also commented that patient-related factors such as age, left ventricular dysfunction, and noncardiac morbidity (hypertension, diabetes, peripheral vascular disease, and smoking) were more important for survival and that the survival benefit of BITA grafting occurred relatively early after operation in such high-risk patients.

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PATENCY

Several investigators have reported on the patency of the LITA and RITA after off-pump coronary bypass (Table 2). However, there is insufficient data on long-term patency of >5 years (Fig. 2).

Table 2
Table 2
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Kim et al50 reported the 5-year angiographic results of 240 patients who underwent off-pump coronary bypass using skeletonized ITA. The RITA was used as a free graft in 43% of patients. Both the LITA and RITA demonstrated >90% patency rate at 5 years postoperatively (early phase: 99.4% and 99.5%; 1-year: 95.5% and 95.9%; 5-years: 91.9% and 93.1%). The 5-year patency of RITA anastomosed to the right coronary territory was 85.3%. Distal anastomoses with the composite RITA connected to the side of the in situ LITA showed good patency (early phase: 100%; 1 year: 95.1%; 5 years: 92.7%).

Fukui51 assessed the early and 1-year angiographic patency rates of grafts of 930 patients who underwent isolated CABG (95.1% off-pump). Early and 1-year postoperative angiography was performed in 729 (78.4%) and 445 (47.8%) patients, respectively. The 1-year patency rates of the LITA, RITA, radial artery, gastroepiploic artery, and saphenous vein were 96.1%, 92.0%, 69.5%, 81.4%, and 82.6%, respectively. The 1-year patency rates of in situ and free RITA were not significantly different (93.2% and 87.2%, P = 0.13). The 1-year patency rate of the radial artery was significantly worse than that of the free RITA graft (P < 0.01) and saphenous vein graft (P < 0.01).

The Randomized On/Off Bypass trial, in which nearly haft of the off-pump group (55.4%) was performed by surgical trainee, clearly shows that off-pump CABG is a highly demanding procedure with a long learning curve.56 The 1-year patency rate was significantly lower in the off-pump group than in the on-pump group (82.6% vs 87.8%, P < 0.01). The patency rate for LITA grafted to the left anterior descending artery was similar in the off-pump group and the on-pump group (95.3% and 96.2%, respectively; P = 0.48). However, when LITA grafts to the left anterior descending artery were classified according to the FitzGibbon grade, there were fewer grade A grafts in the off-pump group than in the on-pump group (89.0% vs 93.2%, P = 0.01). Intraoperative graft assessment, such as transit time flow measurement, epicaridial echography (Fig. 3), and fluorescence imaging (Fig. 4), may play an important role to confirm graft patency and function, especially in developing surgeons.

Figure 3
Figure 3
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Figure 4
Figure 4
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COMMENT

BITA grafting appears to be a surgical strategy for further improving late outcomes of patients undergoing myocardial revascularization. However, many surgeons hesitate to adopt this strategy. We speculate a few reasons. First, there is no gold standard for how to use the RITA. It is easier to make the RITA as a free graft to make a composite graft; however, reduced early graft patency is increasingly reported in recent publications.57–59 On the other hand, an in situ RITA reaches limited area of major target coronary arterial sites. It only reaches left anterior descending, diagonal, proximal high marginal arteries, distal right coronary arteries, and sometimes posterior descending arteries even with its skeletonization. Some surgeons may not agree to bring the RITA in front of heart for left anterior descending artery in case of increased danger in future resternotomy. In addition, without tedious skeletonization of a whole length of the RITA, it becomes shorter and reaches target sites only with thin and vasoreactive distal bifurcating part of the artery. Is skeletonization of ITA a standard technique? It is certainly ideal; ITA becomes longer, dilated, and easy to use, but it is technically more demanding than a conventional harvesting method. Only with precise understanding of local anatomy of ITA and delicate technique, we can avoid injury of the arterial trunk especially where branches come off. Currently, we have been adopted complete skeletonization technique of ITA and liberally used the RITA to left anterior descending artery targets. We have successfully had resternotomies for aortic valve surgery and total aortic arch replacement with extreme care taken. We however admit that careful planning and experienced hands are required in these operations. Is benefit of BITA use worth while to trade of these demands? There is still controversy remained in the real world of cardiac surgery. To make progress, we may need to change a mind-set to perform coronary artery bypass surgery, which has been the most popular procedure for us.

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SUMMARY

BITA grafting is independently associated with superior results compared with SITA grafting in terms of the long-term risk of all-cause death, cardiac-related death, and cardiac events. The survival benefit of BITA grafting manifests relatively early after operation for high-risk patients. The skeletonization technique reduces the risk of sternal wound complications in all patients and particularly in those with diabetes. Both the LITA and RITA have better patency when grated to the left coronary territory than saphenous vein. However, the RITA does not always have good patency when grafted to the right coronary artery. The role of BITA grafting in off-pump coronary bypass is promising; however, we still need to wait for adequate data on long-term survival and patency.

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Keywords:

Coronary artery bypass grafting; Internal thoracic artery

© 2011 Lippincott Williams & Wilkins, Inc.

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