Saphenous Vein Graft Intervention: A Review


Vindhya Hindnavis, MD, Sung-Hae Cho, MD, Sheldon Goldberg, MD

Abstract: Saphenous vein grafts are prone to degeneration and occlusion. Vein graft disease continues to be a significant problem in maintaining long-term benefits after coronary artery bypass surgery. The neointimal hyperplasia and aggressive atherosclerosis that occur in saphenous vein grafts make interventions particularly challenging due to plaque embolization and the no-reflow phenomenon. This review discusses the pathophysiology of vein graft disease and the various percutaneous strategies that have been applied to manage vein grafts. We review the issues surrounding stent selection and various approaches to embolic protection devices. Finally, we discuss the technical steps that optimize success in treating this challenging patient subset.

J INVASIVE CARDIOL 2012;24:64-71

Key words: embolic protection devices, saphenous vein grafts, plaque embolization, no-reflow


Degeneration and occlusion of saphenous vein grafts (SVG) continue to be significant problems in maintaining long-term benefit in patients who have undergone coronary artery bypass graft (CABG) surgery. SVG occlusion during the first year is high at 15%, and 10-year patency is only 60%.1-4 SVG failure is associated with a significant increase in major adverse cardiovascular events (MACE), including death, myocardial infarction (MI), and the need for repeat revascularization.5 Predictors of vein graft occlusion include tobacco use, hypertension, dyslipidemia, and small target vessel diameter (<2 mm).6 SVG percutaneous coronary intervention (PCI) comprises an important subset of interventions in the cardiac catheterization laboratory. According to the American College of Cardiology National Cardiovascular Data Registry, there were over 90,000 patients (5.7% of all PCIs) who underwent SVG PCI between 2004 and 2009.8

SVG disease occurs in 3 phases: early (before hospital discharge); intermediate (1 month to 1 year); and late (beyond 1 year). Early graft failure is due to thrombotic closure, usually at the site of anastomosis, as a result of endothelial injury and the release of inflammatory cytokines during surgery. Technical factors, such as poor distal runoff, graft kinking, and small target vessel diameter, predispose grafts to early occlusion.6,7 After the first month, exposure of the vein grafts to arterial pressure results in neointimal hyperplasia. This pathophysiologic process causes intimal damage, fibrosis, platelet aggregation, the release of growth factors, and smooth muscle cell proliferation.6 After the first year, aggressive atherosclerotic narrowing occurring over the already abnormal endothelium is the main mechanism for graft failure.

Atherosclerotic plaques in SVGs are more diffuse, friable, contain more foam and inflammatory cells, have absent or small fibrous caps, and little or no calcification in comparison to native coronary atherosclerosis.6 These characteristics predispose SVGs to extensive thrombotic burden and distal embolization during coronary graft interventions, resulting in the no-reflow phenomenon, and hence, more periprocedural MI. Grafts particularly susceptible to these effects are those of an older age with more ectasia and greater plaque burden.9


Various strategies have been applied in the treatment of patients with SVG failure. Redo-CABG surgery is associated with a marked increase in morbidity and mortality compared with initial surgery10-12 and is therefore used as a last resort. Percutaneous transluminal coronary angioplasty (PTCA) alone also proved to be inadequate therapy with unacceptably high rates of restenosis and MACE.13-15

The Saphenous Vein De Novo (SAVED) trial was the seminal study that compared balloon angioplasty with bare-metal stents (BMS) in SVG lesions.16 This demonstrated that the use of BMS had a better composite outcome of freedom from death, MI, repeat CABG, and target lesion revascularization (TLR).

The advent of drug-eluting stents (DES) dramatically reduced restenosis in native coronaries. With the high rates of restenosis in SVGs,17 DES were also applied in the treatment of SVG stenosis.

Some observational studies comparing DES to BMS in SVG PCI suggest that DES was associated with reduction in TLR and death.18-21 Other studies, however, showed no difference between DES and BMS in terms of death, MI, and target vessel revascularization (TVR).22-25

Randomized prospective studies comparing BMS to DES in SVG PCI are less conclusive because of the small number of studies available and their small sample size. The Reduction in Restenosis in Saphenous Vein Grafts with Cypher (RRISC) trial and the Stenting of Saphenous Vein Graft (SOS) trial compared DES to BMS and found a significant reduction in restenosis and TLR, but no difference in mortality.26,28 RRISC also found a reduction in TVR. However, at 3-year follow-up from the RRISC trial (DELAYED RRISC), there were more deaths in the DES compared with the BMS group.27 In addition, the decrease in TVR seen at 6 months was not noted at follow-up. In contrast, a 3-year follow-up from the SOS trial demonstrated continued benefit with DES, with lower rates of MI and target vessel failure as well as a trend toward less stent thrombosis.29 There were no differences in all-cause mortality or cardiac mortality. Recent meta-analyses have shown that DES had lower TVR and TLR in the observational studies, but this was not confirmed in the randomized studies.30-35

The moderate VEin graft LEsion stenting with the Taxus stent and Intravascular ultrasound (VELETI) trial poses an interesting consideration in the future management of SVG disease. This study showed that stenting moderate SVG lesions with DES showed better luminal area, no progression to occlusion, and a trend toward lower incidence of MACE compared to medical treatment alone.36 A 3-year follow-up confirmed that the incidence of MACE was significantly lower in the stented group.37 Further studies are required to determine if this preventive approach leads to long-term benefit.

Pharmacologic and Mechanical Strategies to Minimize Complications During SVG PCI

The increased incidence of plaque embolization and platelet aggregation presents unique and significant procedural challenges during SVG intervention.38,39 Plaques that develop in SVG are friable and bulky, making them technically difficult during interventions. Vein grafts also have no side branches, and plaque embolization often leads to “slow-flow” or “no-reflow” phenomena where there is diminished or loss of antegrade blood flow to the distal vasculature without angiographic evidence of obstruction. The exact mechanism of the no-reflow phenomenon is unclear, but it is thought to be associated with endothelial swelling, neutrophil infiltration, and platelet aggregation causing obstruction and spasm in the microvasculature.40,41

Various pharmacological and mechanical strategies have been developed in an attempt to decrease complications in SVG PCI. Some of the pharmacologic strategies that have been utilized include the use of glycoprotein (GP) IIb/IIIa inhibitors and vasodilators.

GP IIb/IIIa inhibitors. Adjunctive treatment with platelet GP IIb/IIIa inhibitors in primary PCI for acute ST-elevation myocardial infarction (STEMI) has been shown to improve epicardial blood flow and microvascular perfusion, along with decreasing mortality.42,43 However, the same benefits with GP IIb/IIIa inhibitors were not observed in SVG interventions. One of the reasons for this might include the sheer excessive atheroembolic and thrombotic burden present during SVG interventions. No clinical benefit in terms of reduction in MACE was seen in 2 retrospective studies44,45 and a pooled analysis of 5 studies.46 While the Evaluation of IIb/IIa platelet receptor antagonist 7E3 in Preventing Ischemic Complication (EPIC) trial did find a reduction in the rate of distal embolization and a trend toward reduction in early large non-Q wave MI in patients treated with GP IIb/IIIa inhibitors, the 30-day and 6-month clinical endpoints were similar in both groups.47 A post hoc analysis of the FilterWire EX Randomized Evaluation (FIRE) trial77 showed that GP IIb/IIIa inhibitors in conjunction with FilterWire embolic protection device had better outcomes, with better flow through the filter, and reduced procedural ischemia, as well as less abrupt closure, no reflow, or distal embolization.48 However, similar results were not seen with GP IIb/IIIa inhibitors and the PercuSurge GuardWire embolic protection system in the Saphenous Vein Graft Angioplasty Free of Emboli Randomized (SAFER) trial.75 In fact, in this trial, the patients who were preselected to receive GP IIb/IIIa inhibitors had a higher incidence of MACE. The reason for this increased incidence of MACE may partly be due to selection bias, as operators gave GP IIb/IIIa inhibitors to higher-risk patients who had the most unfavorable lesion morphologies. To date, there are no prospective randomized trials clearly demonstrating the benefits of GP IIb/IIIa inhibitors in SVG PCI. However, while GP IIb/IIIa inhibitors have not been shown to reduce mortality or myonecrosis in SVG PCI, there may be a role in their usage as adjuncts with certain embolic protection devices, such as the distal filtration devices.

Vasodilators. Vasodilators that have been studied in the no-reflow phenomenon include adenosine, verapamil, and nicardipine. Adenosine is a very short-acting, endogenous nucleoside that vasodilates arteries and arterioles and prevents platelet aggregation and thrombus formation. Pretreatment with intracoronary adenosine has been shown to decrease the incidence of MI after elective PCI.49,50 Intracoronary adenosine has also been studied in acute MI and was found to improve myocardial flow51,52 and lower the incidence of the no-reflow phenomenon51,53 and reduce CK elevation.51 The Acute Myocardial Infarction Study of Adenosine (AMISTAD) trials showed adjunctive adenosine infusion reduced the infarct size in patients with anterior ST-elevation MI.54,55

Although there are some data showing benefits of adenosine in elective PCI and acute MI, there are only limited data on the use of adenosine in SVG PCI. There are no studies confirming that adenosine prevents no-reflow, but there are a few small studies showing that adenosine aids in reversing the no-reflow phenomenon. Fischell et al showed promising results with adenosine in reversing slow-flow and no-reflow phenomenon among patients undergoing SVG PCI.56 This finding was later confirmed when repeated boluses of high-dose adenosine reversed no-reflow and improved final Thrombolysis In Myocardial Infarction (TIMI) flow grade.57

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