HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Mario Gaudino Nicola Luciani Franco Glieca Carlo Cellini Claudio Pragliola Gianfederico Possati Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gaudino, M. Articles by Possati, G. Search for Related Content PubMed PubMed Citation Articles by Gaudino, M. Articles by Possati, G. Related Collections Coronary disease Related Article

Ann Thorac Surg 2006;82:802-804
© 2006 The Society of Thoracic Surgeons

---

Original article: Cardiovascular

Patients With In-Stent Restenosis Have an Increased Risk of Mid-Term Venous Graft Failure

^a Department of Cardiac Surgery, Catholic University, Rome, Italy
^b Department of Cardiology, Catholic University, Rome, Italy

Accepted for publication April 25, 2006.

^_* Address correspondence to Dr Gaudino, Divisione di Cardiochirurgia, Policlinico Universitario A. Gemelli, Largo A. Gemelli 8, 00168 Rome, Italy. (Email: mgaudino{at}tiscali.it).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment References

 
BACKGROUND: This study was designed to evaluate if patients in whom in-stent restenosis developed had an higher risk of early venous graft failure compared with normal patients.

METHODS: The study cohort comprised 120 patients (60 with previous in-stent restenosis and 60 controls) who received a total of 165 complementary venous grafts on the circumflex or right coronary artery system (84 in the restenosis group and 81 in the control group). All patients were prospectively followed-up and underwent reangiography at 5-years follow-up.

RESULTS: In the restenosis group, 28 venous grafts (33.%) were perfectly patent, 10 showed major irregularities, and 46 were occluded. In the control patients, 50 grafts (61.7%) were perfectly patent (p < 0.001 compared with the restenosis series), 12 showed major irregularities (p = .74), and 19 were occluded (p < 0.0001). In contrast, the 5-year outcome of internal thoracic artery grafts was not affected by history of in-stent restenosis.

CONCLUSIONS: Patients who developed in-stent restenosis have an higher risk of early venous graft failure compared with the control patients. Arterial grafts should probably be preferred in these patients.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment References

 
In-stent restenosis identifies a subgroup of patients with aggressive coronary atherosclerosis in whom a second percutaneous intervention is more likely to result in failure compared with the general population [1–4]. In this setting, it can be hypothesized that different types of grafts can achieve different results and patency rates and that the modality of grafting adopted at the surgical procedure can have implications on patient outcome. Despite that, to date only limited information is available on the results of different revascularization strategies in this patient population.

This study was based on the same data set of a previously published report that compared arterial versus venous grafts in patients with in-stent restenosis [5] and was aimed at evaluating the mid-term results of venous bypass grafts in this particular patient population and comparing them with results of patients undergoing coronary artery bypass operations (controls). The main goal of this analysis is to furnish a benchmark for comparison for future research on this issue and to establish the current patency rates of saphenous vein grafts in a population of patients at extremely high risk of graft failure.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment References

 
This study protocol received local institutional review board approval and each patient gave informed consent to participate. This analysis was aimed at evaluating the angiographic results of venous bypass conduits in a patient population at high risk of graft failure: patients in whom a technically correct percutaneous stent implantation resulted in restenosis or occlusion.

Patient Population
A prospective study was carried out at our institution from January 1994 to October 1997 to compare the results of arterial versus venous conduits in patients with previous in-stent restenosis. The detailed methodology of this study has been published elsewhere [5]. In an initial report, we focused on the results of arterial versus venous grafts directed to the first obtuse marginal artery whereas in the present study (based on the same data set), we focus on the complementary venous grafts to non-obtuse marginal target coronary vessels.

Enrollment criteria included:

• primary elective isolated coronary artery bypass grafting;

• previous percutaneous coronary angioplasty with successful stent implantation in any coronary vessel 1.2 mm or more in diameter at least 1 month before the operation with preoperative angiographic demonstration of failed (n = 60; restenosis group) or patent (n = 60; control group) intracoronary stent;

• good preoperative left ventricular function (ejection fraction 0.50)

Patients who underwent stent implantation less than 1 month before the operation were excluded in the presumption that stent failure in such a limited time frame could have been technically related. Stent failure was defined as intrastent restenosis of 50% or more at the site of a previous stent implantation [4, 6]. The main features of the patients are summarized in Table 1.

Follow-Up
Each patient was scheduled for a follow-up clinical examination 6 months postoperatively and each year thereafter. At each time interval, the patients underwent a surface electrocardiogram, a transthoracic echocardiogram, and a stress myocardial nuclear scan for detection of clinical or instrumental ischemia recurrence. At the fifth postoperative year, all patients underwent control coronary and graft angiography.

Evaluation of Graft Patency
We followed a method in use at our institution and previously described [7] in which graft morphology was graded according to a four-grade scale: perfectly patent graft, patent graft with irregularities, stringed graft, occluded graft. All angiograms were reviewed blindly by two expert observers, and in case of a disagreement, a third external blinded review was requested.

Statistical Analysis
Continuous data are presented as mean ± standard deviation (SD). The comparison of the two groups was performed with unpaired two-tailed t testing for continuous variables or ² test for categoric variables. Statistical significance was set at p = 0.05l. Analysis was conducted by using the statistical software SPSS 11.0 (SPSS, Chicago, IL) for Windows (Microsoft, Redmond, WA).

	Results

Top Abstract Introduction Patients and Methods Results Comment References

 
Follow-up was 100% complete, and mean follow-up time was 62 ± 7 months, without a difference between the study and control group (64 ± 6 versus 68 ± 5 months, p = 0.38)

Survival and Ischemia-Free Survival
No death occurred during the follow-up period. Freedom from clinical and instrumental evidence of ischemia recurrence was 17 of 60 in the study group versus 43 of 60 in the control patients (p < 0.0001).

Angiographic Data
Main angiographic results are summarized in Tables 2.

Arterial grafts
The respective internal thoracic artery patency and perfect patency rates were 95% (57/60) and 93.3% (56/60) in the restenosis group (p = 0.99) and 96.6% (58/60) for both in the control series (p = 0.67). The difference in perfect patency rate among arterial and venous grafts was more relevant in the restenosis group as a consequence of poorer outcome of venous grafts (p < 0.0001).

	Comment

Top Abstract Introduction Patients and Methods Results Comment References

 
There is consistent evidence that the percutaneous retreatment of in-stent restenosis leads to suboptimal clinical results and is associated with a high risk of further failure [1–4]. Although this issue has not been specifically investigated in surgical series, it is at least likely that even coronary bypass conduits can be damaged by the aggressive atherosclerotic process and develop accelerated graft disease and failure.

A number of biologic factors are potentially associated with both in-stent restenosis and venous graft failure. Reduced production of nitric oxide is a distinctive feature of diffused atherosclerotic disease [8] and has been implicated in venous graft failure in relation to established risk factors for atherosclerosis [9, 10]. Arterial grafts do not display reduced nitric oxide production, even in individuals with major atherosclerotic burden, which according to some authors, contributes to the superior outcome of such conduits [11]. In an analogous way, thrombin receptors are differently expressed in arterial and venous grafts [12] and disregulation of the same receptors is associated with in-stent restenosis [13]. All of these factors are traits of aggressive atherosclerotic processes.

Our data show that venous grafts implanted in this particular subset of patients have an extremely high incidence of failure and result in patency rates far lower than those achieved in the general population. Clinically, ischemia-free survival results were notably worse in the restenosis series. In contrast, internal thoracic artery grafts show practically the same behavior in patients with and without previous in-stent restenosis and do not seem to be affected by postimplantation graft disease [5].

The clinical benefits of total arterial grafting have yet to be definitely proven in the overall population of patients referred for surgical myocardial revascularization [14–17]. From our data, it is tempting to speculate that patients with in-stent restenosis can represent a subset of patients at very high risk of mid-term venous graft failure in whom the use of arterial revascularization can lead to better patency rates and possibly improve the clinical outcome. The amelioration in outcome associated with bilateral internal thoracic artery grafting [18] can be even more evident among patients with previous in-stent restenosis. Tailored investigations with a larger number of patients are needed to address the role of grafting with the radial artery or bilateral mammary artery.

A minor limitation of the present study was that the two patients groups were not exactly matched in terms of preoperative characteristics, in particular in regard to the incidence of diabetes mellitus. In fact, as obvious, diabetes (a strong risk factor for restenosis) is by far more frequent in the restenosis group. However, this difference reflects the intrinsic higher atherosclerotic risk profile of patients of this group (that, in fact, result in the failure of the stenting procedure) and does not reduce the importance of our observations.

	References

Top Abstract Introduction Patients and Methods Results Comment References

 

1. Mehran R, Dangas G, Abizaid A, et al. Treatment of focal in-stent restenosis with balloon angioplasty alone versus stentingShort- and long- term results. Am Heart J 2001;141:610-614.[Medline]
2. Alfonso F, Zueco J, Cequier A, et al. Restenosis Intra-stent: Balloon Angioplasty Versus Elective Stenting(RIBS) Investigators A randomized comparison of repeat stenting with balloon angioplasty in patients with in-stent restenosis J Am Coll Cardiol 2003;42:796-805.[Abstract/Free Full Text]
3. Elezi S, Kastrati A, Hadamitzky M, Dirschinger J, Neumann FJ, Schomig A. Clinical and angiographic follow-up after balloon angioplasty with provisional stenting for coronary in-stent restenosis Catheter Cardiovasc Intervent 1999;48:151-156.[Medline]
4. Alfonso F, Cequier A, Zueco J, et al. Stenting the stentinitial results and long term clinical and angiographic outcome of coronary stenting for patients with in-stent restenosis. Am J Cardiol 2000;65:327-332.
5. Gaudino M, Cellini C, Pragliola C, et al. Arterial versus venous bypass grafts in patients with in-stent restenosis Circulation 2005;112(suppl I):265-269.
6. Mc Alpine WA. Heart and coronary arteries. Berlin, Heidelberg, New York: Springer Verlag; 1975. pp. 163-168.
7. Possati G, Gaudino M, Prati F, et al. Long-term angiographic results of radial artery grafts used as coronary artery bypass conduit Circulation 2003;108:1350-1354.[Abstract/Free Full Text]
8. Harrison O. Endothelial dysfunction in the coronary microcirculationa new clinical entity or an experimental finding?. J Clin Invest 1993;1:1-2.[Medline]
9. Metcalfe BL, Sellers KW, Jeng MJ, Huentelman MJ, Katovich MJ, Raizada MK. Gene therapy for cardiovascular disordersis there a future?. Ann N Y Acad Sci 2001;953:31-42.[Medline]
10. West N, Quian H, Guzik T, et al. Nitric oxide synthase gene transfer modifies venous bypass graft remodeling – Effects on vascular smooth muscle cells differentiation and superoxide production Circulation 2001;104:1526-1532.[Abstract/Free Full Text]
11. Tarr FI, Sasvari M, Tarr M, Racz R. Evidence of nitric oxide produced by the internal mammary artery graft in venous drainage of the recipient coronary artery Ann Thorac Surg 2005;80:1728-1731.[Abstract/Free Full Text]
12. Yang Z, Ruschitzka F, Rabelink TJ, et al. Different effects of thrombin receptor activation on endothelium and smooth muscle cells of human coronary artery bypass vessel. Implications for venous bypass graft failure Circulation 1997;95:1870-1876.[Abstract/Free Full Text]
13. Takamori N, Azuma H, Kato M, et al. High plasma heparin cofactor II activity is associated with reduced incidence of in-stent restenosis after percutaneous coronary intervention Circulation 2004;109:481-486.[Abstract/Free Full Text]
14. Erbel R, Haude M, Hopp HW, et al. Coronary-artery stenting compared with balloon angioplasty for restenosis after initial balloon angioplasty N Engl J Med 1998;339:1672-1678.[Abstract/Free Full Text]
15. Grandjean JG, Boonstra PW, Den Heyer P, Ebels T. Arterial revascularization with the right gastroepiploic artery and internal mammary arteries in 300 patients J Thorac Cardiovasc Surg 1994;107:1309-1315.[Abstract/Free Full Text]
16. Sergeant P, Blackstone E, Meyns B, Stockman B, Jashari R. First cardiological or cardiosurgical reintervention for ischemic heart disease after primary coronary artery bypass grafting Eur J Cardiothorac Surg 1998;14:480-487.
17. Sergeant P, Blackstone E, Meyns B. Does arterial revascularization decrease the risk of infarction after coronary artery bypass grafting? Ann Thorac Surg 1998;66:1-10.[Abstract/Free Full Text]
18. Lytle BW, Blackstone EH, Loop FD, et al. Two internal thoracic artery grafts are better than one J Thorac Cardiovasc Surg 1999;117:855-872.[Abstract/Free Full Text]

This article has been cited by other articles:

				R. Atoui, S. Mohammadi, and D. Shum-Tim Surgical extraction of occluded stents: when stenting becomes a problem Interactive CardioVascular and Thoracic Surgery, October 1, 2009; 9(4): 736 - 738. [Abstract] [Full Text] [PDF]

				H. L. Lazar Detrimental effects of coronary stenting on subsequent coronary artery bypass surgery: is there another flag on the field? J. Thorac. Cardiovasc. Surg., August 1, 2009; 138(2): 276 - 277. [Full Text] [PDF]

				M. Gaudino and G. Possati Invited commentary Ann. Thorac. Surg., September 1, 2007; 84(3): 799 - 800. [Full Text] [PDF]

				B. Goldman Invited commentary. Ann. Thorac. Surg., September 1, 2006; 82(3): 805 - 805. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Mario Gaudino Nicola Luciani Franco Glieca Carlo Cellini Claudio Pragliola Gianfederico Possati Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gaudino, M. Articles by Possati, G. Search for Related Content PubMed PubMed Citation Articles by Gaudino, M. Articles by Possati, G. Related Collections Coronary disease Related Article