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Ann Thorac Surg 2009;88:54-57. doi:10.1016/j.athoracsur.2009.03.019
© 2009 The Society of Thoracic Surgeons
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Original Articles: Adult Cardiac

Remodeling of Reconstructed Left Anterior Descending Coronary Arteries With Internal Thoracic Artery Grafts

Tomoki Shimokawa, MD*, Susumu Manabe, MD, Toshihiro Fukui, MD, Shuichiro Takanashi, MD

Department of Cardiovascular Surgery, Sakakibara Heart Institute, Tokyo, Japan

Accepted for publication March 10, 2009.

* Address correspondence to Dr Shimokawa, Department of Cardiovascular Surgery, Sakakibara Heart Institute, 3-16-1 Asahicho, Fuchu City, Tokyo, 183-0003, Japan (Email: tshimokawa-circ{at}umin.ac.jp).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background: The internal thoracic artery (ITA) remodels its diameter in response to flow requirements. The objective of this study was to elucidate the remodeling capacity of the reconstructed coronary artery using the ITA.

Methods: We evaluated coronary angiograms in 63 patients who had left anterior descending artery (LAD) segmental reconstruction with or without endarterectomy after off-pump coronary artery bypass graft surgery. The diameters of the ITA and reconstructed coronary artery were measured early and at 1 year after surgery.

Results: The mean diameter of the reconstructed LAD was significantly larger than that of the ITA, but significantly decreased 1 year after surgery (2.69 ± 0.53 mm versus 1.87 ± 0.39 mm; p > 0.0001). The proximal ratio, the ratio of the ITA to proximal reconstructed coronary artery, and the distal ratio, the ratio of the distal LAD to distal reconstructed coronary artery, increased to a value of almost 1.0 (0.77 ± 0.11 versus 1.05 ± 0.18, p < 0.0001, and 0.77 ± 0.14 versus 0.92 ± 0.12, p < 0.0001, respectively). Based on the mean diameter of the reconstructed coronary artery, there were no relationships between the use of endarterectomy and the degree of native coronary stenosis. The proximal ratio in the group with severe stenosis was significantly greater than that in the group with mild stenosis (1.08 ± 0.18 versus 0.95 ± 0.16; p = 0.036), although the distal ratio was not different between the two groups.

Conclusions: Vascular remodeling of the coronary artery reconstructed with the ITA is observed within 1 year after surgery.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Coronary artery bypass graft surgery (CABG) using the internal thoracic artery (ITA) has been clearly recognized to provide an excellent long-term patency rate and survival benefit [1]; however, extensive and calcified atheromatous lesions cannot be treated by conventional CABG. The incidence of diffuse coronary artery disease is likely to increase because of increasing age, associated comorbidities, and the increased use of percutaneous interventions. Therefore, we have developed a technique of left anterior descending artery (LAD) reconstruction using the ITA in which atheromatous plaques are excluded or removed outside the lumen of the reconstructed vessel [2, 3].

Although there is abundant evidence that arterial conduits will adjust their caliber and wall structure by vascular remodeling to adjust to the flow requirements of the distal vasculature [4], changes of the LAD reconstructed with the ITA have not been reported. The objective of this study was to elucidate the remodeling capacity of the reconstructed LAD using the ITA by angiography early and at 1 year after surgery.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Acknowledgments
 References
 
Patient Population
Between September 2004 and December 2006, isolated off-pump CABG was performed in 477 patients. Of these patients, 133 patients had segmental reconstruction (> 3 cm) of the LAD using the ITA. To evaluate the patency of the graft and anastomosis, 84 (63.2%) of 133 patients had postoperative coronary angiography before discharge and at 1 year of follow-up. Early angiography was not performed in 9 patients because of being elderly or having impaired renal function, and 40 patients declined 1-year follow-up angiography. For the purpose of this study, 17 patients with ITA-composite or sequential grafts and 4 patients with complications of the graft or segmental reconstruction were excluded. Finally, both the early (11.4 ± 7.2 days) and 1-year (373.3 ± 57.6 days) coronary angiograms in 63 patients were reviewed in this study. All angiograms were reviewed by a Board-certified cardiologist, and the patients were divided into two groups according to the degree of stenosis of the proximal native coronary artery: (1) a mild stenosis group with less than 90% stenosis, and (2) a severe stenosis group with 90% or greater stenosis. All patients signed informed consent forms before the operation and each angiography. The protocol of this study was approved by the Institutional Review Board, and the necessity for patient consent regarding this study was waived.

The preoperative characteristics and operative data of the patients are shown in Tables 1 and 2. Go All patients had low-dose aspirin (81 mg/day) from the first postoperative day. Patients with extended segmental reconstruction (≥4 cm) were additionally given ticlopidine (200 mg/day) for 1 month and coumadin (maintained with a target international normalized ratio of 2.0 to 2.5) for 6 months after surgery.


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  		Table 1 Preoperative Patient Characteristics
 

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  		Table 2 Operative Data of Left Anterior Descending Artery Segmental Reconstruction
 
Surgical Technique
Details of the surgical indication and technique of the segmental reconstruction were previously reported [2, 3]. The method of segmental reconstruction consisted of either coronary artery reconstruction with plaque exclusion or with endarterectomy. Coronary artery reconstruction without endarterectomy was performed by covering the arteriotomy with an ITA onlay graft to exclude atheromatous plaques from the lumen of the coronary artery. The ITA wall made up 75% of the reconstructed vessel, and the native artery formed the posterior wall that gave rise to septal and diagonal branch arteries. In case the needle could not be passed through calcified plaques, an endarterectomy was performed with distal intimal suture fixation. The majority of the reconstructed lumen consisted of intact intima of the ITA.

Angiographic Measurement
Coronary angiograms were analyzed at an institutional QCA core laboratory by means of the Clinical Measurements Solutions System (QCA-CMS, version 5.1; MEDIS Imaging Systems, Leiden, Netherlands) by experienced technicians. For serial measurement of the graft and reconstructed coronary artery, great care was taken to obtain similar projections for the measurements early and at 1 year of follow-up, and to use the projection that best visualized both the ITA and LAD. An automatic edge detection program determined the vessel contours by assessing brightness along scan lines perpendicular to the vessel center. Five coronary dimensions were measured referenced to catheter sizes, as shown in Figure 1. All measurements were carried out separately by two different observers blinded to each other's assessments. The proximal matching ratio was defined as the diameter ratio of the ITA to proximal reconstructed LAD, and the distal matching ratio was defined as the diameter ratio of the distal LAD to distal reconstructed LAD.


Figure 1
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  		Fig 1. Five coronary dimensions were measured by the quantification system: A, the diameter of the internal thoracic artery about 5 mm proximal to the anastomosis; B, the diameter of the proximal reconstructed left anterior descending artery (LAD) approximately 5 mm from the heel; C, the diameter of the distal reconstructed LAD approximately 5 mm from the toe; D, the diameter of the distal LAD approximately 5 mm from the toe; and E, the mean diameter of the reconstructed LAD. (MRd = distal matching ratio [dashed line]; MRp = proximal matching ratio [solid line].)

 
Intraobserver and Interobserver Variability
Intraobserver and interobserver variability were assessed for the mean diameter of the reconstructed LAD. The measurement of the mean diameter of the reconstructed LAD showed a high degree of intraobserver reproducibility (2.68 ± 0.53 mm versus 2.69 ± 0.55 mm, r = 0.98; p < 0.0001) and interobserver reproducibility (2.68 ± 0.53 mm versus 2.70 ± 0.54 mm, r = 0.92; p < 0.0001).

Statistical Analysis
Statistical analyses were performed using SPSS software (SPSS Inc, Chicago, IL). All data were expressed as the mean ± SD. Differences in the variables between early postoperative and 1-year angiography were determined by using a Wilcoxon test. Differences in the variables within a group or between two groups were determined by using a Mann-Whitney U test or Fisher's exact test for categorical variables. All p values were two-tailed, and values less than 0.05 were taken as significant.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Acknowledgments
 References
 
Early and 1-Year Angiography
In 63 patients, the diameter of the ITA and the mean diameter of reconstructed LAD were 2.36 ± 0.36 mm and 2.69 ± 0.53 mm, respectively. There were no significant differences in the diameters and ratios between the groups with mild and severe stenosis. At 1 year after surgery, the diameter of the ITA and the mean diameter of the reconstructed LAD were significantly decreased (2.36 ± 0.36 mm versus 2.14 ± 0.35 mm, p < 0.0001, and 2.69 ± 0.53 mm versus 1.87 ± 0.39 mm, p < 0.0001, respectively). The diameter of the ITA in the severe stenosis group was significantly larger than that in the mild stenosis group (2.21 ± 0.33 mm [n = 49], versus 1.88 ± 0.31 mm [n = 14], p < 0.005). However, the two groups showed no significant difference in the mean diameter of the reconstructed LAD (1.85 ± 0.33 mm versus 1.88 ± 0.41 mm, p = 0.779). Early and 1-year angiographic measurements are shown in Table 3.


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  		Table 3 Findings of Early and One-Year Angiography
 
The diameter of the ITA and reconstructed LAD showed no relationship with the application of endarterectomy, although the diameter of the proximal reconstructed LAD was significantly greater in patients with endarterectomy (3.40 ± 0.61 mm [n = 23] versus 3.02 ± 0.73 mm [n = 40], p = 0.039) at early angiography.

Change in Matching Ratio
During the 1-year follow-up, proximal and distal matching ratio significantly increased (0.77 ± 0.11 versus 1.05 ± 0.18, p < 0.0001, and 0.77 ± 0.14 versus 0.92 ± 0.12, p < 0.0001, respectively), as shown in Figure 2. At early angiography, there were no significant differences in either proximal or distal ratio between the two groups. However, proximal ratio of the severe stenosis group was significantly greater than that of the mild stenosis group at the 1-year follow-up angiography (1.08 ± 0.18 versus 0.95 ± 0.16, p = 0.036), although distal ratio was not different between the two groups (1.11 ± 0.17 versus 1.15 ± 0.20, p = 0.667).


Figure 2
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  		Fig 2. Changes in the matching ratio. The proximal ratio and distal ratio increased during the 1-year follow-up.

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Acknowledgments
 References
 
The present study demonstrated following main findings: The diameter of the reconstructed LAD decreased to become equivalent to the diameters of the ITA and distal LAD at 1 year after surgery. Furthermore, the ratio of the ITA and proximal reconstructed LAD depended on the stenosis of the native coronary artery. These results suggest that the LAD reconstructed with the ITA remodels physiologically over time, in a manner similar to the ITA graft. This is a novel study demonstrating the remodeling capacity of the reconstructed LAD using the ITA.

Wall shear stress is the force induced by blood flow acting on the endothelium. This force modulates the levels of two potent endothelium-derived vasoactive mediators, the vasodilator nitric oxide [5] and the vasoconstrictor endothelin-1 [6]. Vascular remodeling of the arterial wall in response to changes in flow occurs over weeks to months and includes both cellular and noncellular elements. The end result of vascular remodeling is normalization of wall shear stress as detected by the endothelium. However, although healthy smooth muscle is highly responsive to dilators and constrictors, atherosclerotic vessels may not only have impaired endothelial responses but the smooth muscle can be destroyed or impaired by transmural sclerosis.

In this study, LAD reconstruction with endarterectomy was performed in 36.5% of the patients. Adaptive vascular remodeling after endarterectomy may be prevent by removal of the coronary endothelium and most of the smooth muscle, and is also influenced by inflammatory mediators, surface deposition of platelets and fibrin, occasional thrombosis, fibrosis, intimal hyperplasia, and endothelialization during the healing process. Moreover, nitric oxide, which has secondary effects on noncellular elements of the vessel wall, inhibits smooth muscle proliferation and neointimal hyperplasia. Despite of these situations, the diameter changes of the reconstructed LAD with endarterectomy were similar to those without endarterectomy. These responses must principally depend on the wall of the onlay grafting ITA. However, we guess that because the majority of the endarterectomized coronary arterial wall was excluded from the reconstructed coronary lumen in our technique, complete endothelial covering may be achieved rapidly and, thus, possibly decrease the risk of myofibrointimal proliferation.

Previous reports showed the ITA diameter had a particularly strong correlation with the degree of LAD stenosis within 1 month of CABG [7, 8]. In the present study, the stenosis of the native coronary artery significantly affected the proximal ratio but not affected the distal ratio. Moreover, the proximal ratio was larger at 1 year. There is substantial evidence that the reconstructed LAD dilate or narrow when flow dictates this response, although the posterior wall remains severely disease coronary artery. These findings suggest that shear stress in the entire reconstructed artery normalizes, and this may provide the best long-term patency, because lower shear stress is associated with the development of atherosclerosis.

There are a few limitations of this study that must be recognized. First, in our analysis, no data on flow velocity with a Doppler wire or intimal thickness measurements with an intravascular ultrasonography catheter were included. We only elucidated the anatomic change in the reconstructed LAD using the ITA early and at 1 year after surgery, and this anatomic change was defined as vascular remodeling. Second, long-term patency of the reconstructed LAD using the ITA has not been evaluated. There is some evidence that the patency rate ranged from 56% to 90% at 1 year using the vein graft with endarterectomy [9, 10]. Moreover, the patency rate was 92.5% using the ITA anastomosed to the vein patch [11], and ranged from 94.6% to 98.6% using the ITA in LAD reconstruction with or without endarterectomy [3, 12]. Third, the percent diameter stenosis is not always the best predictor of native coronary flow. Fourth, the number of patients enrolled was relatively small because the complexity of the study protocol made it difficult to recruit patients, especially the need for angiography at 1 year.

In conclusion, vascular remodeling of the reconstructed LAD is obtained angiographically within 1 year after segmental reconstruction using the ITA. Endarterectomy does not affect the remodeling. These results suggest that the LAD that has been reconstructed with the ITA over a long segment remodels over time, and that may provide the high long-term patency rate in the severely diseased coronary artery.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
References
 
The authors thank Kazuya Takeda, RT, for radiographic contribution to this study.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Lytle BW, Loop FD. Superiority of bilateral internal thoracic artery grafting: it's been a long time comin' Circulation 2001;104:2152-2154.[Free Full Text]
  2. Takanashi S, Fukui T, Hosoda Y, Shimizu Y. Off-pump long onlay bypass grafting using left internal mammary artery for diffusely diseased coronary artery Ann Thorac Surg 2003;76:635-637.[Abstract/Free Full Text]
  3. Fukui T, Takanashi S, Hosoda Y. Long segmental reconstruction of diffusely diseased left anterior descending coronary artery with left internal thoracic artery with or without endarterectomy Ann Thorac Surg 2005;80:2098-2105.[Abstract/Free Full Text]
  4. Barner HB. Remodeling of arterial conduits in coronary grafting Ann Thorac Surg 2002;73:1341-1345.[Abstract/Free Full Text]
  5. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology Pharmacol Rev 1991;43:109-142.[Medline]
  6. Resnick N, Gimbrone MA. Hemodynamic forces are complex regulators of endothelial gene expression FASEB J 1993;9:874-882.
  7. Seki T, Kitamura S, Kawachi K, et al. A quantitative study of postoperative luminal narrowing of the internal thoracic artery graft in coronary artery bypass surgery J Thorac Cardiovasc Surg 1992;104:1532-1538.[Abstract]
  8. Nakayama Y, Sakata R, Ura M. Growth potential of left internal thoracic artery grafts: analysis of angiographic findings Ann Thorac Surg 2001;71:142-147.[Abstract/Free Full Text]
  9. Brenowitz JB, Kayser KL, Johnson WD. Results of coronary artery endarterectomy and reconstruction J Thorac Cardiovasc Surg 1988;95:1-10.[Abstract]
  10. Goldstein J, Cooper E, Saltups A, Boxall J. Angiographic assessment of graft patency after coronary endarterectomy J Thorac Cardiovasc Surg 1991;102:539-545.[Abstract]
  11. Beretta L, Lemma M, Vanelli P, et al. Coronary "open" endarterectomy and reconstruction: short- and long-term results of the revascularization with saphenous vein versus IMA-graft Eur J Cardiothorac Surg 1992;6:382-387.[Abstract/Free Full Text]
  12. Barra JA, Bezon E, Mondine P, et al. Surgical angioplasty with exclusion of atheromatous plaques in case of diffuse disease of the left anterior descending artery: 2 years' follow-up Eur J Cardiothorac Surg 2000;17:509-514.[Abstract/Free Full Text]

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