Saphenous vein graft

Saphenous vein graft
Saphenous vein grafts for coronary arteries

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Associate Editors-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Jason C. Choi, M.D., Xin Yang, M.D.

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Overview

Since Rene Favaloro first described it in 1967, coronary artery revascularization with saphenous veins (saphenous vein grafts or SVGs) has become a surgical standard for treatment of coronary artery disease. When a native coronary artery is obstructed, the sutured graft provides a connection between the aorta and the coronary artery beyond the area of obstruction. The procedure is repeated on all the coronary artery segments that are significantly diseased.

The vein is often removed by cardiac surgeons and used for autotransplantation in coronary artery bypass operations, when arterial grafts are not available or many grafts are required, such as in a triple bypass or quadruple bypass.

Diagnosis and Evaluation of SVG Disease

Coronary Angiography

Use of Coronary Angiography of Saphenous Vein Graft Disease as Endpoint in Clinical Trials Evaluating Pharmacotherapy and Device Based Therapies

SVG Patency and SVG Narrowing as a Surrogate Endpoint for Clinical Events

One issue that arises is the suitability of SVG patency, and SVG narrowing as a surrogate endpoint for clinical events.

There are multiple studies demonstrating that SVG closure or failure is associated with clinical events. The association of SVG failure or narrowing with clinical events is complex and should be interpreted in light of the following nuances:

1. The SVG may close and the native artery may remain open minimizing the symptoms associated with SVG failure. SVG failure may therefore by clinically "silent" or may not be closely associated with "hard endpoints" such as myocardial infarction(MI).
2. Placement of SVGs has been associated with improved survival over medical therapy particularly in patients with left main disease and three vessel disease. In so far as the mechanism of clinical benefit of SVGs is predicated upon their ongoing patency, this supports the relevance of SVG patency as a surrogate endpoint.
3. Despite the native artery remaining open after SVG failure, it should be realized that placement of an SVG is associated with more rapid disease progression in the grafted native coronary artery. SVG placement therefore exposes the patient to a risk of more rapid native disease progression. There is a 4 to 6 fold increase in the risk of proximal native vessel occlusion following the placement of an SVG, while there is limited impact upon disease progression downstream from the SVG . While long-term studies demonstrate that as many as 22/23 grafted vessels occlude proximal to the SVG insertion site, the patency beyond the SVG insertion remains better (only 8 of 39 segments failed). Progression of native disease is more rapid in segments bypassed by and SVG than those bypassed by an arterial conduit (p = 0.001, odds ratio = 2.03). In summary, if the SVG fails, the patient most often is left with greater progression of the underlying native vessel disease than they would have had had they not had an SVG placed. It is difficult to ascertain the impact of native vessel disease acceleration given the limited duration of follow-up in trials of SVGs. The impact of disease progression may not be apparent for many years and may be underestimated in current trials and analyses.
4. As a nuance of the above, the impact of SVG failure may depend in part upon when it occurs.
5. SVG failure not only leads to a potential reduction in antegrade blood flow to the bypassed segment as a result of vessel closure, there is also the potential for embolizaiton from a large occluded conduit into the downstream native circulation. SVGs do not have sidebranches and there is therefore no capacity for alternate run off when occlusion occurs. As a result, SVGs often occlude back to the origin of the SVG. Furthermore, the diameter of SVG often exceeds that of native arteries. As a result of the fact that the SVG occludes back to the ostium and is of a larger volume than a native coronary artery, there is a much larger embolic burden associated with a SVG.
6. Consistent with the embolic hazard cited above, is the fact that dilation of an SVG failure does not lead to improved clinical outcomes. The fact that opening a closed SVG does not lead to improved outcomes may lead to inappropriate confusion surrounding SVG failure as a relevant clinical outcome. While it may be intuitive that opening an occluded or failed SVG would lead to improved outcomes (consistent with SVG failure being a surrogate), opening the occluded SVG may instead lead to embolizaiton of a large amount of the thrombotic material downstream. Preventing SVG occlusion may be related to improved outcomes, but treating SVG occlusion after it occurs may not be related to improved outcomes. The failure of reopening an occluded SVG to improve outcomes should not detract from the importance and relevance of preventing SVG occlusion in the first place as a valid surrogate endpoint.
7. The patient is the unit of randomization, but the SVG is the unit most closely related to clinical events.

In summary there are multiple mechanisms whereby SVG patency is related to clinical outcomes.

1. Closure of the conduit may reduce antegrade blood flow
2. There may be embolization into the native vessel from the thrombosed SVG conduit, the diameter of which often exceeds the native coronary artery
3. The SVG may have accelerate native vessel disease which predisposes the patient to adverse outcomes when the vessel occludes

Is the timing of SVG failure relevant? If an anticoagulant (either antiplatelet or antithrombin) is undergoing evaluation of its efficacy in the prevention of thrombotic graft closure, then it is irrelevant if this thrombotic closure is early (in the immediate peri-operative period) or late. It could be hypothesized that the clinical benefit of the anticoagulant agent would be operative during both the early and late follow-up periods.

Potential for Ascertainment Bias

There are several issues that arise with respect to ascertainment bias in the use of coronary angiograms as an endpoint.

1. The patient may not return for follow-up angiography. Maybe the patient is feeling so well they don't feel compelled to return for repeat angiography (you missed a positive treatment effect), or maybe they are so sick they can't show up (you missed a negative treatment effect). If patients died, traditionally they are counted or imputed as having SVG failure on both a per patient and a per SVG conduit basis. The percent of patients who returned for follow-up angiography was 80% in the PREVENT 4 study
2. The patient may return for follow-up angiography, but one or more of the SVGs cannot be engaged and selectively injected. As stated above, in the PREVENT 4 study, the use of saphenous vein graft markers improved the odds of finding SVGs in particular occluded SVGs . However, the SVG stenosis 70% or greater at follow-up did not differ by use of markers (25.8% with marker vs 24.4% without marker, p = not significant). In other words, there does not seem to be ascertainment bias whereby failure to find the SVG results in a different outcome (the outcomes in patients with SVG markers with a greater degree of ascertainment of the endpoint were no different).

Per Patient versus Per SVG as the Unit of Analysis

Analyses should be presented on both a per patient basis (the unit of randomization) and a per SVG basis (the unit that is associated with clinical events). Because the behavior of multiple SVGs may be correlated, and this within patient correlation may reduce the estimate of the variance in the population, an adjustment for the within patient correlation must be provided when presenting the results on a per SVG basis. The within patient conocrdance can be adjusted for using a General Linear Model of Intraclass Correlation (GLIMIC) .

Clinical Trials

• Radial Artery Versus Saphenous Vein Grafts in Coronary Artery Bypass Surgery
• The RETRIEVE Study: Use of the FiberNet Embolic Protection System in Saphenous Vein Grafts
• The SOS (Stenting Of Saphenous Vein Grafts) Trial
• Symbiot III: A Prospective Randomized Trial Evaluating the Symbiot Covered Stent System in Saphenous Vein Grafts
• Comparison of Safety and Efficacy of Two Different Drug Eluting Stents Implanted Into Saphenous Vein Grafts
• Evaluating the Role of Thrombin in Saphenous Vein Graft Failure After Heart Bypass Surgery
• Acupuncture and Post-Surgical Wound Healing
• RRISC Study: Reduction of Restenosis In Saphenous Vein Grafts With Cypher Sirolimus-Eluting Stent.
• Treatment of Moderate Vein Graft Lesions With Paclitaxel Drug Eluting Stents: The VELETI Trial
• Trial of Clopidogrel After Surgery for Coronary Artery Disease (CASCADE Trial)
• Multicentre Radial Artery Patency Study: 5 Year Results
• Study to Test the Efficacy and Safety of Drug Eluting vs. Bare-Metal Stents for Saphenous Vein Graft Interventions (BASKETSAVAGE)
• Vein-Coronary Atherosclerosis And Rosiglitazone After Bypass Surgery: The VICTORY Trial
• Copenhagen Arterial Revascularization Randomized Patency and Outcome Trial (CARRPO)
• The SOS (Stenting Of Saphenous Vein Grafts) Trial
• The eSVS (TM) Mesh External Saphenous Vein Support Trial

Additional Resources

• S. A. Hassantash, B. Bikdeli, S. Kalantarian, M. Sadeghian, and H. Afshar Pathophysiology of Aortocoronary Saphenous Vein Bypass Graft Disease Asian Cardiovasc Thorac Ann, August 1, 2008; 16(4): 331 - 336.

• A. Coolong, D. S. Baim, R. E. Kuntz, A. J. O'Malley, S. Marulkar, D. E. Cutlip, J. J. Popma, and L. Mauri. Saphenous Vein Graft Stenting and Major Adverse Cardiac Events: A Predictive Model Derived From a Pooled Analysis of 3958 Patients. Circulation, February 12, 2008; 117(6): 790 - 797.

• R. F. Padera Jr. and F. J. Schoen. Pathology of Cardiac Surgery Card. Surg. Adult, January 1, 2008; 3(2008): 111 - 178.

• E. Gongora and T. M. Sundt III. Myocardial Revascularization with Cardiopulmonary Bypass. Card. Surg. Adult, January 1, 2008; 3(2008): 599 - 632.

• P. Widimsky, Z. Straka, P. Stros, K. Jirasek, J. Dvorak, J. Votava, L. Lisa, T. Budesinsky, M. Kolesar, T. Vanek, et al. One-Year Coronary Bypass Graft Patency: A Randomized Comparison Between Off-Pump and On-Pump Surgery Angiographic Results of the PRAGUE-4 Trial Circulation, November 30, 2004; 110 (22): 3418 - 3423.

• M. A. Hlatky, D. B. Boothroyd, K. A. Melsop, M. M. Brooks, D. B. Mark, B. Pitt, G. S. Reeder, W. J. Rogers, T. J. Ryan, P. L. Whitlow, et al. Medical Costs and Quality of Life 10 to 12 Years After Randomization to Angioplasty or Bypass Surgery for Multivessel Coronary Artery Disease Circulation, October 5, 2004; 110 (14): 1960 - 1966.

• J. G. Lobo Filho, M. C. d. A. Leitao, and A. J. d. V. Forte Studying the lumen in composite Y internal thoracic artery-saphenous vein grafts J. Thorac. Cardiovasc. Surg., September 1, 2004; 128(3): 490 - 491.

• E. McGregor, L. Kempster, R. Wait, M. Gosling, M. J. Dunn, and J. T. Powell. F-actin Capping (CapZ) and Other Contractile Saphenous Vein Smooth Muscle Proteins Are Altered by Hemodynamic Stress: a proteomic approach Mol. Cell. Proteomics, February 1, 2004; 3(2): 115 - 124.

• M. Endo, Y. Tomizawa, and H. Nishida Bilateral Versus Unilateral Internal Mammary Revascularization in Patients with Diabetes Circulation, September 16, 2003; 108(11): 1343 - 1349.

• T. D. Rea, M. Crouthamel, M. S. Eisenberg, L. J. Becker, and A. R. Lima. Temporal Patterns in Long-Term Survival After Resuscitation From Out-of-Hospital Cardiac Arrest Circulation, September 9, 2003; 108(10): 1196 - 1201.

• M. Hilker, T. Langin, U. Hake, F.-X. Schmid, W. Kuroczynski, H.-A. Lehr, H. Oelert, and M. Buerke Gene expression profiling of human stenotic aorto-coronary bypass grafts by cDNA array analysis Eur. J. Cardiothorac. Surg., April 1, 2003; 23(4): 620 - 625.

• J. L. Sperry, C. B. Deming, C. Bian, P. L. Walinsky, D. A. Kass, F. D. Kolodgie, R. Virmani, A. Y. Kim, and J. J. Rade Wall Tension Is a Potent Negative Regulator of In Vivo Thrombomodulin Expression Circ. Res., January 10, 2003; 92(1): 41 - 47.

• F. J. Schoen and R. F. Padera Jr. Cardiac Surgical Pathology Card. Surg. Adult, January 1, 2003; 2(2003): 119 - 185.

• A. Y. Kim, P. L. Walinsky, F. D. Kolodgie, C. Bian, J. L. Sperry, C. B. Deming, E. A. Peck, J. G. Shake, G. B. Ang, R. H. Sohn, et al. Early Loss of Thrombomodulin Expression Impairs Vein Graft Thromboresistance: Implications for Vein Graft Failure Circ. Res., February 8, 2002; 90(2): 205 - 212.

• K. B. Kim, C. Lim, C. Lee, I.-H. Chae, B.-H. Oh, M.-M. Lee, and Y.-B. Park Off-pump coronary artery bypass may decrease the patency of saphenous vein grafts Ann. Thorac. Surg., September 1, 2001; 72(3): S1033 - 1037.

• Z. Yang, T. Kozai, B. van de Loo, H. Viswambharan, M. Lachat, M. I. Turina, T. Malinski, and T. F. Luscher. HMG-CoA reductase inhibition improves endothelial cell function and inhibits smooth muscle cell proliferation in human saphenous veins J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1691 - 1697.

• H. Hirose, A. Amano, S. Yoshida, A. Takahashi, N. Nagano, and T. Kohmoto Coronary Artery Bypass Grafting in the Elderly Chest, May 1, 2000; 117(5): 1262 - 1270.

• D. R. Holmes Jr and P. B. Berger. Percutaneous Revascularization of Occluded Vein Grafts : Is It Still a Temptation to Be Resisted? Circulation, January 12, 1999; 99(1): 8 - 11.

• Y. K. Wong, M. Thomas, V. Tsang, P. J. Gallagher, and M. E. Ward. The prevalence of Chlamydia pneumoniae in atherosclerotic and nonatherosclerotic blood vessels of patients attending for redo and first time coronary artery bypass graft surgery. J. Am. Coll. Cardiol., January 1, 1999; 33(1): 152 - 156.

• F. D. Loop Coronary artery surgery: the end of the beginning Eur. J. Cardiothorac. Surg., December 1, 1998; 14(6): 554 - 571.

• Z. G. Zhu, H.-H. Li, and B.-R. Zhang. Expression of Endothelin-1 and Constitutional Nitric Oxide Synthase Messenger RNA in Saphenous Vein Endothelial Cells Exposed to Arterial Flow Shear Stress Ann. Thorac. Surg., November 1, 1997; 64(5): 1333 - 1338.

• A. Y. Kim, P. L. Walinsky, F. D. Kolodgie, C. Bian, J. L. Sperry, C. B. Deming, E. A. Peck, J. G. Shake, G. B. Ang, R. H. Sohn, et al. Early Loss of Thrombomodulin Expression Impairs Vein Graft Thromboresistance: Implications for Vein Graft Failure. Circ. Res., February 8, 2002; 90(2): 205 - 212.

See Also

• CABG
• Hybrid bypass
• Off-pump coronary artery bypass surgery (OPCAB)
• Minimally invasive direct coronary artery bypass surgery (MIDCAB)

External Links

• Advances in Cardiovascular Surgery and Cardiothoracic Surgical Procedures
• CTSNet: The Cardiothoracic Surgery Network
• Yale: Introduction to Cardiothoracic Imaging

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