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Eur J Cardiothorac Surg 2007;32:711-717. doi:10.1016/j.ejcts.2007.07.025
Copyright © 2007, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
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Hiroyuki Nakajima
Junjiro Kobayashi
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Soichiro Kitamura
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Right arrow Coronary disease

Predictive factors for the intermediate-term patency of arterial grafts in aorta no-touch off-pump coronary revascularization

Hiroyuki Nakajimaa,*, Junjiro Kobayashia, Toshihiro Funatsua, Yusuke Shimaharaa, Masashi Kawamuraa, Atsushi Kawamurab, Toshikatsu Yagiharaa, Soichiro Kitamuraa

a Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan
b Department of Cardiology, National Cardiovascular Center, Osaka, Japan

Received 19 February 2007; received in revised form 6 July 2007; accepted 13 July 2007.

* Corresponding author. Address: Department of Cardiovascular Surgery, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. Tel.: +81 6 6833 5012; fax: +81 6 6872 7486. (Email: hnakajim{at}hsp.ncvc.go.jp).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Objective: Graft flow is one of the important determinants of the arterial graft patency. To establish the optimal graft design, we examined detailed characteristics of the arterial composite and sequential grafts, and sought to delineate the risk factors of graft occlusion due to insufficient bypass flow. Methods: Angiograms of 2547 bypass grafts in 677 consecutive patients who underwent total arterial off-pump CABG without aortic manipulation followed by early postoperative angiography since December 2000 were reviewed. The angiographic flow was graded as A (antegrade), B (competitive), C (reversal), and O (occlusion). Results: The overall early graft patency rate was 98.2% (2502/2547). The rate of grade A was 91.3% (2325/2547), while the rates of grades B and C were 2.9% (73/2547) and 4.1% (104/2547), respectively. For the main trunk of the anterior descending branch (LAD), the graft patency rate was 99.3% (674/679). The grade A rate of the internal thoracic artery (ITA) grafts to LAD in an individual fashion was 99.5% (203/204), being comparable with that in the sequential or composite grafting which had two distal anastomoses (98.1%, 159/162; p = 0.33). The actuarial patency rates at 3 years were 84.7% for the bypass grafts with grade A flow and 33.9% for those with grade B/C flow, respectively (p < 0.0001). The multivariate Cox-regression analysis demonstrated that grade B/C (p < 0.0001, HR = 4.19) and 51–75% stenosis of the native coronary artery (p = 0.02, HR = 2.86) were significant predictors of graft occlusion. Conclusions: For the LAD, the results of graft flow in sequential ITA grafting or composite grafting with two distal anastomoses were comparable with that in individual ITA grafting. Prediction and prevention of competitive and reverse flow are mandatory for achieving the advantages of the arterial materials.

Key Words: Coronary disease • Surgery • Angiography • Off-pump CABG • Arterial graft


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
The arterial grafts have beneficial characteristics in terms of expectancy of long-term patency and improved late outcome after coronary artery bypass grafting (CABG) [1–3]. For the arterial grafts, the circumstance of the blood flow in the graft lumen is considered an important determinant of the patency. It has been reported that occlusion or string sign in the arterial grafts can typically occur when the stenosis in the native coronary artery is moderate, and that these physiologic changes in the luminal diameter occurred within 2 years [4–7]. We previously reported that reverse flow in the sequential or composite graft was commonly associated with the moderately stenotic right coronary artery (RCA) and composite or sequential grafting to more than four target branches [8]. In addition, the management of a coronary branch with critical stenosis played definitive roles [9].

The objectives of this study were (1) to delineate the effects of detailed characteristics of the target coronary branches and the bypass grafts on the occurrence of competitive flow, (2) to delineate the risk of graft occlusion, and (3) to establish a theoretical basis for optimizing the strategy for graft arrangement to the left anterior descending artery (LAD) and to non-LAD branches, which include the diagonal branch, left circumflex artery (LCX), and RCA.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
The pre- and postoperative coronary angiograms of 2547 bypass grafts in 677 consecutive patients, who underwent off-pump complete revascularization for coronary artery disease using only the internal thoracic artery (ITA) with or without the radial artery between December 2000 and May 2006, were reviewed. The patients who had a bypass of the gastroepiploic artery, the inferior epigastric artery or the saphenous vein, those with individual grafts only, and those who did not undergo early postoperative coronary angiography were excluded. All patients provided written informed consent after explanation of the potential risks. All procedures were performed under social insurance coverage, and institutional approval was obtained. There were 563 men and 114 women, and their mean age was 66.1 ± 9.1 years. The number of distal anastomoses was 3.76 ± 1.01 per patient (Table 1 ).


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  		Table 1 Baseline characteristics
 
Early postoperative coronary angiography was performed within a month after surgery. Cardiologists independently evaluated the native coronary artery stenosis and the graft patency. The maximal severity of stenosis was recorded for all target branches. The definitions of terms used in the present study are as follows. A patent graft meant that the graft had a complete continuity of the graft lumen throughout its entire length from the origin of the ITA to the target coronary branch, irrespective of the flow direction. Whenever the continuity of the graft lumen from an in-situ ITA graft to the anastomosis with the target coronary branch was interrupted at any level, or when repeated angioplasty was performed, they were defined as Grade O (occlusion). Grade A was defined as a situation in which antegrade graft flow was found in most of the multi-plane ITA angiographs. Grade B (competitive) was defined as a situation in which the target vessel was slightly opacified from the ITA graft injection, and the bypass graft did fill by retrograde flow from the native coronary injection. Grade C (reverse flow) was defined as a situation in which the distal anastomotic site was not opacified from the ITA graft injection at all, but it did fill clearly by retrograde flow from the native coronary injection. Flow grade was recorded for each target coronary branch, and these data were collected prospectively.

An individual bypass is defined as a bypass conduit having one in-situ ITA and one distal anastomosis. A non-individual bypass graft means a bypass conduit having two or more distal anastomoses, such as sequential or composite grafting. The in-situ ITA is ITA divided only at its distal portion.

2.1 Graft design strategy
The arrangement of the bypass conduits was primarily determined by the operative risk and positional relationship of the target sites. Our current standard technique since March 2003 was based on our previous angiographic studies and introduced for minimizing competitive and reverse flow. One in-situ ITA, usually the left, supplies the LAD territory, while an I-graft of the contralateral ITA, usually the right, and the radial artery supply the LCX and RCA territories in a clockwise orientation, via a side-to-side anastomosis with LCX and an end-to-side anastomosis with RCA. The counterclockwise orientation was occasionally chosen to avoid grafting to RCA branch with 75% stenosis at the end of the conduit, because reverse flow was commonly found at the distal end of the conduit with the end-to-side anastomosis [8,9]. Before introduction of this strategy, the I-graft was used only in a counterclockwise orientation for the safety of redo operation in the future. For patients aged more than 75 years or with considerable operative risks, such as chronic obstructive pulmonary disease or diabetes mellitus treated by insulin therapy, we harvested only a single ITA. In the present series, all ITA grafts were greater than 1.5 mm in diameter at the distal end.

2.2 Late angiographic results
Follow-up angiography was performed between 3 and 66 months after the operation for 325 bypass grafts in 91 patients with recurrent angina, or ischemic findings on electrocardiography or scintigraphy. The mean follow-up period was 29 ± 19 months.

2.3 Statistical analysis
The continuous variables are expressed as the mean values ± standard deviation (SD). The data of two independent groups were compared by Fisher's exact probability test. Longitudinal data were estimated by the Kaplan–Meier method and the difference of two groups was compared by log-rank method. Cox regression analysis was used to examine the significance of the variables in predicting graft occlusion. Statistical analyses were performed using SPSS software (SPSS 8.0 Inc., Chicago, IL). The differences in the outcomes were considered statistically significant when the p-value was less than 0.05.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
The overall graft patency rate was 98.2% (2502/2547), and the grade A rate was 91.3% (2325/2547). The actuarial graft patency rates at 3 years were 84.7% for the bypass grafts graded A and 33.9% for the bypass grafts graded B/C (p < 0.0001). The early patency rate of the bypass grafts to 51–75% stenotic coronary branches was 98.1% (1140/1162), and their grade A rate was 85.1% (989/1162), being significantly lower than that of the bypass grafts to 76–100% stenotic branches (96.5%, 1336/1385; p < 0.0001). For 75% stenotic branches, the actuarial graft patency rates at 3 years were 77.1% for the bypass grafts graded A and 34.5% for the bypass grafts graded B/C (p < 0.0001) (Fig. 1 ).


Figure 1
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  		Fig. 1. The actuarial graft patency rate of the bypass grafts to 51–75% stenotic branches. Grade A vs grade B/C.

 
Regarding the main trunk of LAD, the grade A rate of the in-situ ITA in individual fashion was 99.5% (203/204), and was significantly higher than that of non-individual conduit grafting (93.1%, 442/475; p = 0.0001), whereas the patency rates were similar (p = 0.99). The grade A rate of the conduit with two distal anastomoses was comparable with that of the individual grafting (p = 0.33) (Table 2 ). For the bypass grafts to LAD, the actuarial graft patency rates at 1 year were 95.7% for the bypass grafts graded A and 83.3% for the bypass grafts graded B/C (p = 0.001) (Fig. 2 ). The actuarial graft patency rates of the bypass graft to the LAD with 51–75% stenosis and those with 76–100% stenosis at 2 years were 79.9% and 96.7%, respectively (p = 0.16).


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  		Table 2 Early angiographic results: flow grading of bypass grafts to main trunk of left anterior descending artery
 

Figure 2
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  		Fig. 2. The actuarial graft patency rate of the bypass grafts to the main trunk of LAD. Grade A vs grade B/C.

 
For the non-LAD branches, including the diagonal, LCX, and RCA branches, the grade A rate of the in-situ ITA was comparable to that of the Y- or K-graft or I-graft (90.8% vs 89.9%; p = 0.87), and the grade A rate of the individual grafts was comparable to that of the sequential and composite grafts (91.9% vs 89.9%; p = 0.99) (Table 3 ). The patency rate of the bypass grafts to 51–75% stenotic branches was similar to that of the bypass grafts to 76–100% stenotic branches (97.8% vs 97.9%; p = 0.87), while the grade A rate of the bypass grafts to 51–75% stenotic branches was significantly lower than that of the bypass grafts to 76–100% stenotic branches (82.6% vs 96.1%; p < 0.0001). The actuarial graft patency rates at 2 years were 94.5% for the bypass grafts graded A and 57.6% for the bypass grafts graded B/C (p < 0.0001). The actuarial graft patency rate of the bypass grafts to branches with 76–100% stenosis at 2 years was 89.8%, being significantly higher than that of the bypass grafts to branches with 51–75% stenosis (82.2%; p = 0.009). The actuarial graft patency rate of the bypass grafts in the end-to-side fashion at 2 years was 80.5%, being significantly lower than that of the bypass grafts in the side-to-side fashion (91.4%; p = 0.01) (Fig. 3A). The actuarial graft patency rates at 2 years were 85.6% for the I-grafts graded A and 88.8% for the bypass grafts graded B/C (p = 0.31) (Fig. 3B).


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  		Table 3 Early angiographic results: flow grading of bypass grafts to diagonal branch, LCX, and RCA
 

Figure 3
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  		Fig. 3. (A) The actuarial graft patency rate of the bypass grafts to the non-LAD branches. End-to-side anastomoses (graft end) vs side-to-side anastomoses. (B) The actuarial graft patency rate of the bypass grafts to the non-LAD branches. I-graft vs Y- or K-graft.

 
As shown in Table 4 , the univariate Cox regression analysis demonstrated that the RCA territory, 51–75% stenosis, small coronary branch (diameter < 1.5 mm), and grade B/C were significant predictors of graft occlusion. The multivariate Cox regression analysis identified 51–75% stenosis (HR = 2.86, p = 0.02) and grade B/C (HR = 4.19, p < 0.0001) as significant predictors.


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  		Table 4 Predictors of graft occlusion in the intermediate-term follow-up period
 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
A composite graft allowed total arterial revascularization with excellent graft patency rate and lower incidence of perioperative cardiac and cerebrovascular events [10,11]. Although various arrangements of the in-situ and free arterial grafts have already been reported [3,12,13], no optimal strategy for graft arrangement has been established yet. We have applied our grading system of angiographic graft flow for 5.5 years. The results of the present study imply some suggestions regarding the strategy for graft arrangement.

For the main trunk of the LAD, the use of the in-situ ITA graft has been generally accepted as a standard strategy, which provides a long-term patency and improves the late survival after CABG. The in-situ ITA in an individual fashion may be ideal for the main trunk of the LAD; however, sequential and composite grafting to the LAD and a diagonal branch is an important option of choice. Dion et al. reported that the long-term patency of sequential grafting with the in-situ ITA to the LAD and a diagonal branch was identical to that of the individual in-situ ITA [14]. We previously reported that early angiographic results of the Y-graft to the LAD and a diagonal branch were similar to that of sequential grafting [9]. As shown in Table 2, our present study demonstrated that, in the LAD region, the sequential graft and the Y-graft to two distal anastomoses were as reliable as individual grafting. We consider that the in-situ ITA, which is anastomosed to the LAD, can be connected with at least one diagonal branch by sequential or composite grafting without disturbance of graft flow to the main trunk of the LAD. Different from bypass grafts to LCX or RCA, the difference between the patency rate of bypass grafts to LAD 51–75% and that of bypass grafts to 76–100% stenosis was not significant. The in-situ ITA grafts could confidently supply the sufficient antegrade flow to the LAD territory, even with moderate stenosis.

For the coronary branches besides LAD, there was no obvious disadvantage of the composite grafts versus the individual graft and the in-situ ITA. In addition, native coronary stenosis had stronger impact on the bypass grafts to the non-LAD branches than on the bypass grafts to the LAD in the follow-up angiographic results. For the bypass grafts to the non-LAD regions, both grade B/C and 51–75% stenosis in the native coronary branch significantly correlated with graft occlusion.

One of the possible explanations for these differences between the grafts to LAD and those to non-LAD branches may be the difference in the graft materials. About 90% of the anastomoses were performed with the composite radial artery. The radial artery may be more sensitive for the blood flow in the lumen than the ITA graft. More severe stenosis will be necessary for the long-term patency of the radial artery, as compared with the ITA graft.

Regarding the conduit type, no significant difference was found between the I-graft and the Y- or K-graft in the non-LAD regions. We consider that the appropriate pressure slope in each segment of the bypass conduit, highest at the proximal and lowest at the end of the conduit, was the most important for antegrade bypass flow to all target vessels. The bypass grafts with the side-to-side anastomoses presented better graft patency than those with the end-to-side anastomoses. Therefore, when the positional relationship of the target sites allows, the I-graft would be favorable, because it has only one end-to-side anastomosis and the target coronary branch at the end of the conduit can be changed by simply determining its orientation. On the other hand, the Y-graft has the advantages of increased flow capacity [15] and availability to the distant target branches.

Dion et al. reported that the patency rate of end-to-end grafting was comparable with side-to-side grafting with excellent long-term patency of sequential grafting using the ITA graft [14]. In their report, the target branches of 78% of bypass graft restudied were the LAD and a diagonal branch, whereas, in the present study, sequential ITA grafting to the LAD and a diagonal branch was only 9%, and sequential grafting to four or more target branches was performed in about 11% of patients. We consider that the difference is owing to differences in target site, graft material, and probably the number of target coronaries in sequential anastomoses.

Selection of patients suitable for this procedure would be a next concern. It has been widely accepted that the patients with severe atherosclerosis of the ascending aorta are the most suitable candidates for composite and sequential grafting [10,11]. We would suggest herein new patients’ selection criteria from a viewpoint of preventing competitive flow and maximizing durability of arterial grafts. According to the results of the present study and our previous investigations, the decisive risks of competitive and reverse flow are as follows: (1) a RCA branch with 51–75% stenosis, (2) a LCX branch with 51–75% stenosis, (3) a bypass conduit with four or more distal anastomoses, and (4) three high-risk situations reported in [9]. Of 677 patients in this study, 147 (21.7%) patients had none of these risks and/or all risky situations were successfully avoided. The actuarial graft patency rate of patients who have none of the above risks at 3 years was significantly higher than that of patients with any of the risks (92.6% vs 69.7%; p < 0.0001). They were the best candidates for this procedure. On the other hand, when competitive or reverse flow is highly predicted, alternative strategies, such as the aortocoronary bypass, which provides the highest bypass pressure [16], may be reasonable, especially for the non-LAD regions.

The present study had some limitations. First, the patients who underwent follow-up angiography were biased toward clinically evident graft failure. Second, the peripheral vascular resistance in the myocardial tissue, which has an important role in the coronary perfusion, was not taken into account. Third, the capacity of the ITA graft was not considered. The pressure and flow capacity as the blood source of the bypass conduit and potentiality of growth or thinning and adaptability to the graft flow may also play important roles in the occurrence of insufficient flow and resultant occlusion. At the beginning of 2004, we started to harvest ITA in a skeletonized fashion to maximize the capacity of the in-situ ITA graft [17,18]. This technique will extend the application of the bilateral ITA grafting to patients with a substantial operative risk [19]. Fourth, the effects of the luminal size of arterial conduits on the long-term patency remain unclear. Previously, the grading system of the luminal size at the narrowest portion, and intimal irregularity was reported [20,21]. It was reported useful for assessment of degeneration of bypass grafts in a conventional technique. However, the luminal size of the side-to-side anastomosis in the sequential fashion is not precisely measurable, especially when the angle between the graft and the coronary branch is near 90 degrees, or when the contrast medium only fills incompletely due to mixture with the blood flow from the native coronary artery. Moreover, the regression of stenosis and the increase of the diameter were relatively common findings in the arterial materials [22,23]. At last, high-pressure injection of contrast medium may induce reverse and competitive flow and may interfere with evaluation of graft flow direction. This may be a methodological limitation. This flow grading system is not necessarily practical for postoperative evaluation for each patient and each bypass graft. In the present study, flow grading was performed independently from the catheterization team. We utilized this grading system for comparison of graft configurations and optimizing the strategy for design of the arterial grafts, based on data of a considerable number of patients and bypass grafts, and examined significance of correlations between characteristics of the bypass grafts and the occurrence of competitive and reverse flow. For these purposes, flow grading is considered useful.

In conclusion, prediction and prevention of competitive and reverse flow may be necessary to enhance the advantage of multivessel revascularization using exclusively arterial materials because insufficiency of the antegrade flow would spoil the advantage of arterial grafts.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Maniar HS, Sundt TM, Barner HB, Prasad SM, Peterson L, Absi T, Moustakidis P. Effect of target stenosis and location on radial artery graft patency. J Thorac Cardiovasc Surg 2002;123:45-52.[Abstract/Free Full Text]
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