Review

Saphenous Vein Graft Intervention: Status Report 2014

Jonathan Soverow, MD, MPH and Michael S. Lee, MD

Jonathan Soverow, MD, MPH and Michael S. Lee, MD

Abstract: Given their frequent use as bypass conduits and high rates of degeneration, saphenous vein grafts (SVGs) will continue to require percutaneous coronary intervention. Due to their unique physiology, SVGs pose special challenges to the interventionalist. Preintervention evaluation of hemodynamic significance is hampered by limited data and uncertainty regarding the validity of fractional flow reserve. Intraprocedural complications, particularly distal embolization and no-reflow, are common but may be mitigated by various techniques. Despite advances in the field, SVG intervention is associated with worse outcomes — including increased rates of periprocedural myocardial infarction, restenosis, target vessel revascularization, non-target disease progression, and death — compared with native vessel intervention. This paper reviews the most recent data and techniques available to the interventionalist seeking to improve outcomes after SVG intervention.

J INVASIVE CARDIOL 2014;26(12):659-667

Key words: saphenous vein graft, embolic protection device, percutaneous coronary intervention

______________________________________

Following coronary artery bypass graft surgery, 10%-15% of saphenous vein grafts (SVGs) occlude within 1 year and 50% fail by 10 years, yet their use as conduits persists.1 Compared with arterial grafts, SVGs have more compliant vessel walls and unique anatomic characteristics, leading to higher rates of vessel failure.2 Loss of the vasa vasorum at harvesting, inflammatory mediators, and exposure to arterial pressures promote accelerated rates of atherosclerosis, neointimal hyperplasia, and thrombosis.1 In addition, SVGs suffer from increased lesion bulk with thinner, more friable fibrous caps compared with native arteries.3,4 These features render SVG intervention more susceptible to showering of debris. Combined with the release of neurohormonal mediators, embolization leads to microvascular plugging, vasospasm, and slow or no-reflow phenomenon in 10%-15% of SVG interventions.5 At the same time, SVG lesions have a high rate of deterioration, with 39% of intermediate (30%-60% angiographic diameter stenosis) lesions progressing to >70% stenosis during a median follow-up of 35 months in a recent analysis of the Stenting of Saphenous vein grafts (SOS) trial.6 

Lesion Selection

While early experience with SVG intervention was associated with an 8% mortality rate at 30 days, contemporary trials report 30-day mortality rates of <1%.7,8 That said, up to 15% of patients undergoing SVG intervention experience a periprocedural myocardial infarction (MI), defined as a CK-MB >5x the upper limit of normal, and those patients suffer from an associated 1.5x increase in 1-year mortality rates.9 Correlates of major adverse cardiovascular event (MACE)  occurrence include plaque volume, SVG angiographic severity score, presence of thrombus, female gender, and advanced age, with plaque volume estimates being the strongest consistent predictor in most studies and lesion length of >20 mm associated with >20% periprocedural MACE.8,10,11 

Give the relatively poor short- and long-term outcomes with SVG intervention, the decision to perform percutaneous revascularization should be based on strong clinical indications, including patient symptoms and non-invasive testing. Myocardial perfusion imaging (MPI) has good specificity but variable sensitivity in detecting angiographically significant graft stenosis and may detect disease in the native arterial bed where adequate grafting proves technically difficult.12 Coronary computed tomography shows promise, with one study of 51 patients demonstrating high sensitivity (96%) and specificity (95%) compared with coronary angiography, but with limited visualization of distal bypass anastomoses in 26% of the cases.13

Angiographic assessment of SVG lesion severity can be challenging. Intravascular ultrasound (IVUS) offers additional insights into plaque composition and objective, quantitative measurements of luminal diameter and percent stenosis. Compared with negative remodeling, the presence of positive remodeling on IVUS is a strong predictor of postprocedural no-reflow.14 However, IVUS has not been adequately evaluated in a prospective trial involving SVG intervention, and the decision to intervene based on IVUS characteristics alone is currently not supported.15 

Fractional flow reserve (FFR) has not been evaluated in large studies involving SVG. In small studies, FFR has high specificity (75%) and negative predictive value (70%), but poor sensitivity (50%) for identifying lesions associated with ischemia on (MPI) at a FFR cutoff of <0.75; correlation with angiographic severity is also low.16 Though FFR-guided treatment of native coronary lesions may prospectively improve revascularization rates, its validity and use in SVG is still debated.17,18 Vein grafts have different size and vessel wall attributes, and dosing of adenosine and the effects on the native distal coronary bed — which may provide competing flow within the graft — are unclear. However, angiographically guided pullback from the native artery to specifically test the pressure difference across lesions of interest should theoretically account for these differences. While applying FFR to treat stenotic lesions has not been fully validated in SVGs, deferring intervention in diseased areas known to rapidly progress has also not been studied. In the SOS trial, patients with an intermediate (30%-60%) lesion had high rates of acute coronary syndrome (64%) and/or required eventual percutaneous coronary intervention (PCI) of the lesion (74%) by 3 years of follow-up.19

The VELETI (Treatment of Moderate Vein Graft Lesions with Paclitaxel Drug-Eluting Stents) trial, which randomized 57 patients with moderate (30%-60%) SVG stenoses to medical therapy vs PCI, reported a reduction in 3-year MACE rate with PCI (3% vs 26%; P=.02).20 The larger, 450-patient VELETI II trial (Sealing Moderate Coronary Saphenous Vein Graft Lesions With Paclitaxel-Eluting Stents) (NCT0123443) is currently enrolling and will evaluate the hypothesis of prophylactically sealing intermediate lesions with drug-eluting stent (DES) implantation in a larger population. 

Intervention of chronically occluded SVGs is not recommended in the 2011 American College of Cardiology Foundation/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACCF/AHA/SCAI) guidelines.21 In a prospective study of 34 patients with chronic total SVG occlusion treated with PCI, procedural success was low (32%) and rates of in-stent restenosis (68%) and target vessel revascularization (TVR; 61%) were high, despite high use of embolic protection (78%) and DES (95%).22 On the other hand, a more recent retrospective study published in 2013 of a small number of patients (n = 27) undergoing occluded SVG intervention revealed a 79% success rate with no adverse events at 30 days and improvement in angina relief, suggesting that improved techniques may yield better outcomes. 23 By comparison, however, treatment of acute thrombotic occlusion and of native vessels suffering from chronic SVG occlusion have more favorable outcomes, and thus pursuing intervention of a chronically occluded SVG should only be undertaken when there are no other viable options, including medical therapy. 24,25

Stent Type 

Bare-metal stents vs drug-eluting stents. The SAVED (Saphenous Vein De Novo) trial demonstrated improved procedural success and MACE rates (26% vs 38% at 240 days; P=.04) with bare-metal stent (BMS) implantation compared with balloon angioplasty alone.26 Since then, SVG intervention has been performed consistently with stenting; however, comparison trials have favored DES implantation (Table 1). Multiple meta-analyses of randomized and prospective cohort trials comparing BMS and DES consistently report lower MACE and repeat revascularization rates with DES, but similar overall mortality rates.27-29 Of the four major randomized trials, ISAR-CABG (Prospective, Randomized Trial of Drug-Eluting Stents Versus Bare-Metal Stents for the Reduction of Restenosis in Bypass Grafts) is the largest and drives the results of the meta-analyses performed to date.30 ISAR-CABG randomized 610 patients to sirolimus-eluting stent (SES) or BMS and demonstrated a lower MACE event rate at 1 year (15% vs 22%; P=.02), driven primarily by a 50% relative reduction in TVR with non-significant differences in death and MI. Conversely, the RRISC (Reduction of Restenosis in Saphenous Vein Grafts with Cypher Sirolimus-Eluting Stent) trial enrolled 75 patients and showed similar TVR rates at 3 years, but significantly higher all-cause mortality with SES compared with BMS, although the study was small, underpowered to evaluate mortality rates, used a short (2-3 month) dual-antiplatelet regimen, and these results were borne out by a post hoc analysis.31 A more recent 2013 study of a large Dutch registry compared 510 DES-treated with 245 BMS-treated lesions over 3 years and found no significant differences in mortality or target lesion revascularization (TLR), while a smaller matched case-control study of 162 patients treated with DES or BMS found early reductions in TVR and MACE that did not persist beyond 3 years. 32,33

Few data are available regarding second-generation DESs, but suggest some possible advantages over first-generation stents. In the Xience V-SVG (Everolimus-Eluting Stent in Saphenous Vein Graft Atherosclerosis) study, a total of 40 patients received EES, with 15% experiencing in-stent restenosis requiring repeat revascularization.34 More recent evidence has become available within the last year. A single-center retrospective analysis of 88 patients receiving EES vs 243 patients receiving first-generation DES revealed a lower rate of TVR (6.8% vs 24.5%; P<.001) with EES over a 2-year period.35 However, another observational study comparing 127 EES with 230 paclitaxel-eluting stent (PES) or sirolimus-eluting stent (SES) SVG interventions found no difference in cardiac death, MI, or TVR with up to 4 years of follow-up.36 Another retrospective study comparing first-generation DES-treated lesions (n = 143) and second-generation DES-treated lesions (n = 100) showed similar rates of TVR (18.1% vs 14.2%; P=.46) and TLR (15% vs 10.7%; P=.37).37 Overall, the 2011 ACC/AHA guidelines on PCI note a “preference” for the use of DES over BMS in SVG intervention, but do not specify a class recommendation. 38

Covered stents. Stents wrapped in polytetrafluorethylene (PTFE) mesh theoretically prevent distal embolization by trapping atheroma on deployment. Despite this promising rationale for SVG intervention, multiple randomized trials have not shown any benefit. The RECOVERS (Randomized Evaluation of Polytetrafluoroethylene-Covered Stent in Saphenous Vein Grafts) trial randomized 301 patients to the PTFE-covered JoStent or BMS and demonstrated a higher rate of non-fatal MIs (10.3% vs 3.4%; P=.04) with the PTFE-covered stent; no difference in restenosis rate or 6-month MACE rate was observed; long-term follow-up data from this trial have not been published. 39 The BARRICADE (Barrier Approach to Restenosis: Restrict Intima to Curtail Adverse Events) trial also studied the JoStent, randomizing 243 patients to JoStent vs BMS; at 5 years, target vessel failure was higher with JoStent (68.3% vs 51.8% P<.001). 40

Despite promising initial results with the self-expanding PTFE-covered Symbiot stent (Boston Scientific Corporation), further studies have not demonstrated a benefit.41 The SYMBIOT III (A Prospective, Randomized Trial of a Self-Expanding PTFE Stent Graft During SVG Intervention) trial, which randomized 400 patients to Symbiot vs BMS, demonstrated no difference in MACE rate at 8 months (30.6% vs 26.6%; P=.43) or angiographic restenosis (30.9% vs 31.9%; P=.80).42 Additional studies of the Symbiot stent demonstrated no reduction in distal embolization compared with BMS.43

Two other covered stents have shown promise, but lack long-term follow-up in larger studies. The Sesame stent (Advanced Bioprosthetic Surfaces) is a nanosynthesized self-expanding all-metal stent and was tested in 20 patients with symptomatic SVG lesions; at 9 months, MACE rate was 14% with 3 patients undergoing repeat PCI.44 The Mguard stent (InspireMD), a BMS with a polymeric net covering, demonstrated no adverse events at 30 days in 16 patients undergoing SVG intervention; in a 1-year follow-up study of 30 patients enrolled in the trial, a total of 6 patients experienced ischemic-driven TLR with 2 MIs and no deaths.45,46 Bioabsorbable stents have been proposed to treat SVG lesions, but to date there is a paucity of data.47

Intervention Technique

Predilation versus direct stenting. Direct stenting may trap debris and prevent distal embolization that occurs with balloon inflation alone. In a study of 527 patients undergoing SVG intervention, direct stenting was associated with decreased CK-MB release (9.5% vs 19.6%; P<.01) and decreased TLR at 1 year (odds ratio, 0.47; P=.01) compared with angioplasty first without distal protection.48 However, in another retrospective study including 188 patients who underwent direct stenting without distal protection vs angioplasty followed by stenting and distal embolic protection, the rate of CK-MB rise >2x the upper limit of normal (ULN) and the rate of MACE (death, Q-wave MI, and TVR) were no different in-hospital or at 30 days.49 Direct stenting resulted in CK-MB elevation >5x ULN in only 3% of cases, a marked reduction compared to rates >10% generally reported with angioplasty when distal protection is not used. 

Small stent diameter. In a retrospective analysis of 226 patients undergoing SVG intervention, aggressive stent expansion beyond 100% of the reference lumen was associated with higher rates of postprocedural CK-MB elevation (29% vs 17%; P=.05), MI (26% vs 8%; P=.01) at 1 year, and no reduction in TVR at 1 year.50 Undersized stents may thus theoretically decrease embolization by limiting the amount of luminal plaque intrusion through stent struts. A retrospective study of 209 patients undergoing DES treatment demonstrated that the amount of tissue extrusion by IVUS through stent struts was smallest in stents with a relative reference diameter <0.89% and associated with a lower incidence of CK-MB elevation >3x ULN.51 However, both TLR and TVR were similar at 1 year. Given the risk of possibly higher rates of restenosis and stent thrombosis in undersized stents, this technique merits further evaluation before routine adoption; nonetheless, some authors argue it may play a role in cases where embolic protection cannot be used for technical reasons.52

Embolic Protection Devices

Despite high rates of distal embolization and a class Ib recommendation for their use in the 2011 ACCF/AHA/SCAI guidelines, embolic protection devices (EPDs) were used in 22% of 19,546 SVG intervention cases in the National Cardiovascular Data Registry.53 Embolic protection devices include: (1) distal balloon-occlusion; (2) distal filter-based; (3) proximal occlusion; and (4) excimer laser (Table 2). However, in a study of 624 SVG interventions, only 77% were eligible for either distal or proximal protection, with 57% eligible for distal protection, suggesting a real-world limitation to their use.54

Distal occlusion devices. Distal balloon occlusion devices create a stagnant column of blood beyond the lesion, preventing initial plaque embolization beyond the occlusive balloon. Prior to balloon deflation, the debris and neurohumoral mediators contained within the blood column are aspirated. However, this technique requires: (1) a 3 cm disease-free distal landing zone; (2) crossing the lesion with a guidewire prior to occlusion; (3) temporary cessation of blood flow; (4) possible trauma to the SVG with balloon inflation; and (5) limited contrast visualization of the lesion. The PercuSurge GuardWire (Medtronic) is the only FDA-approved device currently available in the United States (US) (Figure 1).

The GuardWire uses a 0.014˝ wire with either a 0.028˝ or 0.036˝ balloon crossing profile for occlusion of 2.5-5.0 mm or 3.0-6.0 mm vessels, respectively, with a built-in aspiration system. In the SAFER (Saphenous Vein Graft Angioplasty Free of Emboli Randomized) trial, the GuardWire reduced 30-day MACE rates, driven primarily by less MI (8.6% vs 14.7%; P=.01) and “no-reflow” (3% vs 9%; P=.02) (Table 3).55 The GuardWire was also evaluated in native coronary artery interventions in the EMERALD (Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris) trial, which randomized 501 patients with ST-elevation MI to GuardWire vs standard angioplasty and did not show any benefit in procedural success, infarct size, or survival, but importantly did not demonstrate any serious adverse events during a rapidly-performed, emergency intervention.56

The TriActiv device (Kensey Nash Corporation) was a previously available, Food and Drug Administration (FDA)-approved distal occlusion device with a similar profile to GuardWire. TriActiv utilized a heparin-saline flush system in place of an aspiration device and was evaluated in PRIDE (A Prospective Randomized Controlled Trial of Distal Protection), which randomized 631 patients to Triacti, GuardWire, or FilterWire and met non-inferiority endpoints, but had more hemorrhagic complications (10.9% vs 5.4%; P=.01).57 The product is no longer available in the US.

Distal filter devices. Retractable filter systems are easy to use and permit antegrade blood flow as well as contrast opacification of the lesion. Disadvantages include incomplete entrapment of particles and neurohumoral mediators, need for an adequate distal landing zone, a high profile (3-4 Fr), possible filter occlusion, and possible filter entrapment. Currently available FDA-approved products include FilterWire EZ (Boston Scientific) (Figure 2) and SpideRX (ev3). 

The FilterWire EX and the GuardWire had similar 30-day and 6-month MACE rates in the FIRE (FilterWire EX Randomized Evaluation) trial.58 The second-generation FilterWire EZ system has a lower crossing profile (3.2 vs 3.9 Fr), smaller pore size, improved wall apposition, and easier maneuverability than FilterWire EX. In the BLAZE (Embolic Protection Transluminally With the FilterWire EZ Device in Saphenous Vein Grafts) and BLAZE II registries, which enrolled 90 and 131 patients, respectively, the combined 30-day MACE rate was 5.0%.59

The SpideRX filter is advanced over any 0.014˝ wire once across the lesion and requires a 30-70 mm diameter vessel for placement. In the 700-patient SPIDER (Saphenous Vein Graft Protection in a Distal Embolic Protection Randomized) trial, the SpideRX filter was non-inferior to FilterWire and GuardWire, with comparable 30-day MACE rates (9.1% vs 8.4%; P=.01 for non-inferiority).60

Many other filter-based devices have been tested, but are not available for use in the US. The Interceptor (Medtronic) is a low-profile (2.7 Fr) filter-based device with larger open-pore size than FilterWire EZ and higher in vitro flow rates. The AMEthyst (Assessment of the Medtronic AVE Interceptor Saphenous Vein Graft Filter System) trial, which randomized 797 SVG-intervention patients to Interceptor or control (GuardWire or FilterWire EX), reported similar 30-day MACE rates (8% vs 7.3%; P=.02 for non-inferiority).61 The product received the CE mark of approval, but has not been made available in the US for PCI. The Rubicon Embolic Filter (Rubicon) has one of the lowest crossing profiles (2.1 Fr) and received the CE mark for PCI based on small safety trials; however, it is not available in the US. The CardioShield (MedNova, Ltd), another filter-based device, had higher 30-day MACE rates (10.1% vs 8.8%; P=.02) than GuardWire in the CAPTIVE (A Prospective, Randomized, Controlled Trial of Distal Protection With the Third-Generation Mednova Emboshield Compared to the GuardWire or FilterWire) trial.62 The TRAP Vascular Filtration System (Microvena) was evaluated in a trial randomizing 467 patients to TRAP vs angioplasty alone; the trial was terminated early due to slow enrollment and did not show a difference in 30-day MACE events.63

Proximal occlusion devices. The FDA-approved Proxis device (St. Jude Medical) is no longer available in the US, but merits discussion given its potential benefits. It utilizes a proximal inner balloon to seal the device sheath to the guide catheter and a distal outer balloon to seal the device sheath to the SVG upstream from the lesion. This prevents any distal embolization of debris by crossing the lesion and allows aspiration of debris prior to restoration of flow. The catheter permitted multiple guidewire options and did not require a distal landing zone; however, it did require a 15 mm proximal landing zone and was cumbersome to use. The PROXIMAL (Proximal Protection During Saphenous Vein Graft Intervention) trial randomized 594 SVG-intervention cases to Proxis vs FilterWire/GuardWire and demonstrated non-inferiority in 30-day MACE (9.2% vs 10.0%; P=.01 for non-inferiority).64

Excimer laser. Laser atherectomy has the potential to debulk lesions by vaporizing thrombus. In a single case-control trial published in 2013 comparing excimer laser and SpideRX or Filterwire EZ in 71 patients with non-ST elevation MI due to SVG lesion, there was a trend toward improved angiographic flow and a statistically significant decrease in the occurrence of type IVa MI with excimer laser (21% vs 49%; P=.04).65 Further investigation is warranted prior to widespread adoption of this technology.

Adjunctive Pharmacotherapy

Antithrombotic and antiplatelet medications. No dedicated trials have demonstrated the superiority of a specific intravenous antiplatelet or antithrombin agent for SVG intervention. A pooled analysis of 5 randomized glycoprotein IIb/IIIa inhibitor trials (EPIC, EPILOG, EPISTENT, IMPACT II, and PURSUIT) showed no benefit with their use in SVG intervention, although these studies were not powered to specifically assess their role and did not routinely employ EPDs.66 Similar results were found in a subset analysis of ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy Trial), with the exception of lower minor bleeding complications with bivalirudin vs heparin plus a glycoprotein IIb/IIIa inhibitor (26% vs 38%; P=.05).67 The use of IIb/IIIa inhibitors in SVG intervention carries a class III (no benefit) recommendation in the ACCF/AHA/SCAI 2011 guidelines.68 

In a subgroup analysis of 1133 patients with prior coronary artery bypass graft surgery in the PLATO (PLATelet inhibition and patient Outcomes) trial, 31% of whom underwent SVG intervention, MACE were not significantly reduced by ticagrelor compared with clopidogrel (19.6% vs 21.4%; hazard ratio, 0.90; 95% confidence interval [CI], 0.69-0.17). However, prehospital use of any dual-antiplatelet therapy has been associated with improved MACE after SVG intervention, while discontinuation of clopidogrel within 90 days of SVG intervention in a cohort of 603 patients has been associated with a significant increase in death (relative risk [RR], 2.33; 95% CI, 1.32-4.11) in a study published this past year, arguing for early and sustained use of dual-antiplatelet therapy.69

Pharmacological treatment of slow or no-reflow. The slow or no-reflow phenomena complicates 10%-15% of SVG interventions and has been associated with presence of probable thrombus, acute coronary syndrome, degenerated SVG, and lesion ulceration.70 No clinical trials have compared pharmacological agents; however, observational studies of vasodilators have demonstrated improved procedural success and reversal of no-reflow with several agents. These agents are best delivered distal to the lesion using a microcatheter, such as an aspiration thrombectomy catheter (Figure 3). 

Adenosine. Adenosine causes vasodilation of arteries and arterioles, as well as platelet inhibition, at the cost of potentially severe, transient bradycardia. In a retrospective study of 143 SVG interventions, of which 70 received preprocedure intragraft adenosine, there appeared to be no benefit with pretreatment with adenosine as the rates of slow or no-reflow were similar (14.2% vs 13.6%; P=.90).71 However, in those patients who developed slow or no-reflow, high-dose adenosine (≥5 boluses of 24 µg each) vs low-dose adenosine (<5 boluses) resulted in reestablishment of flow (91% vs 33%; P=.02), a finding seen in one other smaller trial.72 A randomized 2013 study of 22 patients receiving either pretreatment with 2000 µg intragraft adenosine or saline led to improved angiographic results; although 4 patients in the saline arm developed no-reflow, no patients in the adenosine group did.73 

Nitroprusside. Nitroprusside is a nitric oxide promoter and a potent arterial and vasodilator. A case-control study of 64 patients who received pretreatment with nitroprusside (50-300 µg) demonstrated a significant reduction in periprocedural CK-MB elevation >3x and >5x ULN (6.3% vs 16.4% [P=.049] and 1.6% vs 10.9% [P=.02], respectively), but no effect on prevention of slow or no-reflow.74 In a study of 19 patients undergoing SVG intervention, a total of 9 patients developed slow or no-reflow, and intragraft administration of nitroprusside (median dose, 200 µg) improved angiographic flow without significant adverse events.75 Although neither of these studies reported serious adverse events, nitroprusside can cause profound hypotension, particularly in patients with borderline blood pressure.

Verapamil. In a randomized trial of 22 patients undergoing SVG intervention, preprocedure administration of verapamil tended to reduce no-reflow compared with placebo (0% vs 33%; P=.10) and increased flow rate by Thrombolysis in Myocardial Infarction (TIMI) frame count (53.3 ± 22.4% vs 11.5 ± 38.9%; P=.02) without any significant effect on biomarker release.76 In one case-control study of 163 cases of SVG intervention, the combination of abciximab and verapamil decreased the incidence of slow or no-reflow (1% vs 18%, P<.001) compared with placebo.77 In 32 episodes of no-flow, intragraft verapamil (100-500 µg) improved flow in all cases and reestablished TIMI-3 flow in 88%, where initial treatment with intragraft nitroglycerin had no effect.78

Nicardipine. Nicardipine is a dihydropyridine calcium-channel blocker with enhanced selectivity for cerebral and coronary blood vessels compared with other dihydropyridine agents (eg, amlodipine and felodipine) and a more potent coronary vasodilator than diltiazem or verapamil.79 Pretreatment with intragraft nicardipine in 83 cases of degenerated SVG intervention resulted in CK-MB >3x ULN in 4.4%, transient slow or no-reflow in 2.4% of patients, and a MACE rate of 4.4% at 30 days.80 

Conclusion

Saphenous vein graft interventions pose unique challenges, including high rates of slow or no-reflow, distal embolization, periprocedural MI and restenosis. Available data suggest a possible benefit with prophylactic treatment of intermediate lesions with further clarification coming when the results of VELETI II are published. DESs reduce restenosis rates compared with BMS, while covered stents provide no known advantage. There is weak evidence to support direct stenting and undersized stenting, but significant data reinforce the use of EPDs, which carry a class Ib recommendation for SVG intervention. Currently, GuardWire, FilterWire, and SpideRX are available for use in the US. No pharmacological agent has been shown to consistently prevent slow or no-reflow, but several (nitroprusside, verapamil, adenosine) delivered distally via microcatheter successfully improve flow once the phenomena occurs. When SVG intervention is required, careful planning with attention to device selection and anticipation of adverse events, as well as close patient follow-up, are warranted. 

References

  1. Harskamp RE, Lopes RD, Baisden CE, de Winter RJ, Alexander JH. Saphenous vein graft failure after coronary artery bypass surgery: pathophysiology, management, and future directions. Ann Surg. 2013;257(5):824-833.
  2. Desai ND, Cohen EA, Naylor CD, Fremes SE. A randomized comparison of radial-artery and saphenous-vein coronary bypass grafts. N Engl J Med. 2004;351(22):2302-2309.
  3. Cox JL, Chiasson DA, Gotlieb AI. Stranger in a strange land: the pathogenesis of saphenous vein graft stenosis with emphasis on structural and functional differences between veins and arteries. Prog Cardiovasc Dis. 1991;34(1):45-68.
  4. Murphy GJ, Angelini GD. Insights into the pathogenesis of vein graft disease: lessons from intravascular ultrasound. Cardiovasc Ultrasound. 2004;2:8.
  5. Sdringola S, Assali AR, Ghani M, et al. Risk assessment of slow or no-reflow phenomenon in aortocoronary vein graft percutaneous intervention. Catheter Cardiovasc Interv. 2001;54(3):318-324.
  6. Abdel-Karim AR, Da Silva M, Lichtenwalter C. Prevalence and outcomes of intermediate saphenous vein graft lesions: findings from the stenting of saphenous vein grafts randomized-controlled trial. Int J Cardiol. 2013;168(3):2468-2473. Epub 2013 Apr 3.
  7. Keeley EC, Velez CA, O’Neill WW. Long-term clinical outcome and predictors of major adverse cardiac events after percutaneous interventions on saphenous vein grafts. J Am Coll Cardiol. 2001;38(3):659-665.
  8. Kirtane AJ, Heyman ER, Metzger C. Correlates of adverse events during saphenous vein graft intervention with distal embolic protection: a PRIDE substudy. JACC Cardiovasc Interv. 2008;1(2):186-191.
  9. Hong MK, Mehran R, Dangas G, et al. Creatine kinase-MB enzyme elevation following successful saphenous vein graft intervention is associated with late mortality. Circulation. 1999;100(24):2400–2405.
  10. Naidu SS, Turco MA, Mauri L. Contemporary incidence and predictors of major adverse cardiac events after saphenous vein graft intervention with embolic protection (an AMEthyst trial substudy). Am J Cardiol. 2010;105(8):1060-1064. Epub 2010 Feb 20.
  11. Ahmed JM, Dangas G, Lansky AJ. Influence of gender on early and one-year clinical outcomes after saphenous vein graft stenting. Am J Cardiol. 2001;87(4):401–405.
  12. Lakkis NM, Mahmarian JJ, Verani MS. Exercise thallium-201 single photon emission computed tomography for evaluation of coronary artery bypass graft patency. Am J Cardiol. 1995;76(3):107-111.
  13. Schlosser T, Konorza T, Hunold P, Kuhl H, Schmermund A, Barkhausen J. Non-invasive visualization of coronary artery bypass grafts using 16-detector row computed tomography. J Am Coll Cardiol. 2004;44(6):1224-1229.
  14. Hong YJ, Jeong MH, Ahn Y, et al. Intravascular ultrasound analysis of plaque characteristics and postpercutaneous coronary intervention catheterization outcomes according to the remodeling pattern in narrowed saphenous vein grafts. Am J Cardiol. 2012;110(9):1290-1295. Epub 2012 Jul 25.
  15. Murphy GJ, Angelini GD. Insights into the pathogenesis of vein graft disease: lessons from intravascular ultrasound. Cardiovasc Ultrasound. 2004;2:8.
  16. Aqel R, Zoghbi GJ, Hage F, Dell’Italia L, Iskandrian AE. Hemodynamic evaluation of coronary artery bypass graft lesions using fractional flow reserve. Catheter Cardiovasc Interv. 2008;72(4):479-485.
  17. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367(11):991-1001.
  18. Kern MJ. Is the coronary physiology of bypass grafts different from that of the native coronary artery? Comment on the “hemodynamic evaluation of coronary artery bypass graft lesions using fractional flow reserve.” Catheter Cardiovasc Interv. 2008;72(4):486-487.
  19. Abdel-Karim AR, Da Silva M, Lichtenwalter C, et al. Prevalence and outcomes of intermediate saphenous vein graft lesions: findings from the stenting of saphenous vein grafts randomized-controlled trial. Int J Cardiol. 2013;168(3):2468-2473. Epub 2013 Apr 3.
  20. Rodés-Cabau J, Bertrand OF, Larose E, et al. Comparison of plaque sealing with paclitaxel-eluting stents versus medical therapy for the treatment of moderate non-significant saphenous vein graft lesions: the moderate vein graft lesion stenting with the taxus stent and intravascular ultrasound (VELETI) pilot trial. Circulation. 2009;120(20):1978-1986.
  21. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44-e122. Epub 2011 Nov 7.
  22. Al-Lamee R, Ielasi A, Latib A, et al. Clinical and angiographic outcomes after percutaneous recanalization of chronic total saphenous vein graft occlusion using modern techniques. Am J Cardiol. 2010;106(12):1721-1727.
  23. Garg N, Hakeem A, Gobal F, Uretsky BF. Outcomes of percutaneous coronary intervention of chronic total saphenous vein graft occlusions in the contemporary era. Catheter Cardiovasc Interv. 2014;83(7):1025-1032. Epub 2013 Oct 19.
  24. Abdel-Karim AR, Banerjee S, Brilakis ES. Percutaneous intervention of acutely occluded saphenous vein grafts: contemporary techniques and outcomes. J Invasive Cardiol. 2010;22(6):253-257.
  25. Meliga E, García-García HM, Kukreja N, et al. Chronic total occlusion treatment in post-CABG patients: saphenous vein graft versus native vessel recanalization — long-term follow-up in the drug-eluting stent era. Catheter Cardiovasc Interv. 2007;70(1):21-25.
  26. Savage MP, Douglas JS Jr, Fischman DL, et al. Stent placement compared with balloon angioplasty for obstructed coronary bypass grafts. Saphenous Vein De Novo Trial Investigators. N Engl J Med. 1997;337(11):740-747.
  27. Alam M, Bandeali SJ, Virani SS, et al. Clinical outcomes of percutaneous interventions in saphenous vein grafts using drug-eluting stents compared to bare-metal stents: a comprehensive meta-analysis of all randomized clinical trials. Clin Cardiol. 2012;35(5):291-296. Epub 2012 Apr 6.
  28. Wiisanen ME, Abdel-Latif A, Mukherjee D, Ziada KM. Drug-eluting stents versus bare-metal stents in saphenous vein graft interventions: a systematic review and meta-analysis. JACC Cardiovasc Interv. 2010;3(12):1262-1273.
  29. Lee MS, Yang T, Kandzari DE, Tobis JM, Liao H, Mahmud E. Comparison by meta-analysis of drug-eluting stents and bare metal stents for saphenous vein graft intervention. Am J Cardiol. 2010;105(8):1076-1082.
  30. Mehilli J, Pache J, Abdel-Wahab M, et al. Drug-eluting versus bare-metal stents in saphenous vein graft lesions (ISAR-CABG): a randomized controlled superiority trial. Lancet. 2011;378(9796):1071-1078.
  31. Vermeersch P, Agostoni P, Verheye S, et al. Increased late mortality after sirolimus-eluting stents versus bare-metal stents in diseased saphenous vein grafts: results from the randomized DELAYED RRISC trial. J Am Coll Cardiol. 2007;50(3):261-267.
  32. Hougaard M, Thayssen P, Kaltoft A, et al. Long-term outcome following percutaneous coronary intervention with drug-eluting stents compared with bare-metal stents in saphenous vein graft lesions: from Western Denmark heart registry. Catheter Cardiovasc Interv. 2014;83(7):1035-1042. Epub 2013 Dec 5.
  33. Ybarra LF, Ribeiro HB, Pozetti AH, et al. Long-term follow-up of drug eluting versus bare metal stents in the treatment of saphenous vein graft lesions. Catheter Cardiovasc Interv. 2013;82(7):E856-E863. 
  34. Brilakis ES, Papayannis AC, Abdel-Karim AR, et al. TCT abstract 219: prospective evaluation of the Xience V everolimus-eluting stent in saphenous vein graft atherosclerosis: the Xience V-SVG Angiographic Study. J Am Coll Cardiol. 2011;58:B59.
  35. Kitabata H, Loh JP, Pendyala LK, et al. Two-year follow-up of outcomes of second-generation everolimus-eluting stents versus first-generation drug-eluting stents for stenosis of saphenous vein grafts used as aortocoronary conduits. Am J Cardiol. 2013;112(1):61-67.
  36. Taniwaki M, Räber L, Magro M, et al. Long-term comparison of everolimus-eluting stents with sirolimus- and paclitaxel-eluting stents for percutaneous coronary intervention of saphenous vein grafts. Eurointervention. 2014;9(12):1432-1440. 
  37. Costopoulos C, Latib A, Naganuma T, et al. Comparison of first- and second-generation drug-eluting stents in saphenous vein grafts used as aorto-coronary conduits. Am J Cardiol. 2013;112(3):318-322. Epub 2013 Apr 30.
  38. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44-e122. Epub 2011 Nov 7.
  39. Stankovic G, Colombo A, Presbitero P, et al. Randomized evaluation of polytetrafluoroethylene-covered stent in saphenous vein grafts: the Randomized Evaluation of polytetrafluoroethylene COVERed stent in Saphenous vein grafts (RECOVERS) trial. Circulation. 2003;108(1):37-42. Epub 2003 Jun 23.
  40. Stone GW, Goldberg S, O’Shaughnessy C, et al. 5-year follow-up of polytetrafluoroethylene-covered stents compared with bare-metal stents in aortocoronary saphenous vein grafts the randomized BARRICADE (barrier approach to restenosis: restrict intima to curtail adverse events) trial. JACC Cardiovasc Interv. 2011;4(3):300-309.
  41. Laarman GJ, Kiemeneij F, Mueller R, Guagliumi G, Cobaugh M, Serruys PW. Feasibility, safety, and preliminary efficacy of a novel ePTFE-covered self-expanding stent in saphenous vein graft lesions: the Symbiot II trial. Catheter Cardiovasc Interv. 2005;64(3):361-368.
  42. Turco MA, Buchbinder M, Popma JJ, et al. Pivotal, randomized U.S. study of the Symbiot covered stent system in patients with saphenous vein graft disease: eight-month angiographic and clinical results from the Symbiot III trial. Catheter Cardiovasc Interv. 2006;68(3):379-388.
  43. Blackman DJ, Choudhury RP, Banning AP, Channon KM. Failure of the Symbiot PTFE-covered stent to reduce distal embolization during percutaneous coronary intervention in saphenous vein grafts. J Invasive Cardiol. 2005;17(11):609-612.
  44. Abizaid A, Weiner B, Bailey SR, Londero H. Use of a self-expanding super-elastic all-metal endoprosthesis; to treat degenerated SVG lesions: the SESAME first in man trial. Catheter Cardiovasc Interv. 2010;76(6):781-786.
  45. Maia F, Costa JR Jr, Abizaid A, et al. Preliminary results of the INSPIRE trial with the novel MGuard stent system containing a protection net to prevent distal embolization. Catheter Cardiovasc Interv. 2010;76(1):86-92.
  46. Costa JR Jr, Abizaid A, Feres F, et al. One-year results of the INSPIRE trial with the novel MGuard stent: serial analysis with QCA and IVUS. Catheter Cardiovasc Interv. 2011;78(7):1095-1100. Epub 2011 Jul 22.
  47. Ong PJ, Jafary FH, Ho HH. “First-in-man” use of bioresorbable vascular scaffold in saphenous vein graft. Eurointervention. 2013;9(1):165. 
  48. Leborgne L, Cheneau E, Pichard A, et al. Effect of direct stenting on clinical outcome in patients treated with percutaneous coronary intervention on saphenous vein graft. Am Heart J. 2003;146(3):501-506.
  49. Okabe T, Lindsay J, Torguson R, et al. Can direct stenting in selected saphenous vein graft lesions be considered an alternative to percutaneous intervention with a distal protection device? Catheter Cardiovasc Interv. 2008;72(6):799-803.
  50. Iakovou I, Dangas G, Mintz GS, et al. Relation of final lumen dimensions in saphenous vein grafts after stent implantation to outcome. Am J Cardiol. 2004;93(8):963-968.
  51. Hong YJ, Pichard AD, Mintz GS, et al. Outcome of undersized drug-eluting stents for percutaneous coronary intervention of saphenous vein graft lesions. Am J Cardiol. 2010;105(2):179-185. Epub 2009 Nov 14.
  52. Maluenda G, Alfonso F, Pichard AD. Percutaneous intervention of a thrombotic-occluded saphenous vein graft successfully treated using the undersized stent approach to prevent distal embolization. Catheter Cardiovasc Interv. 2011;78(1):65-69. Epub 2011 Feb 16.
  53. Mehta SK, Frutkin AD, Milford-Beland S, et al. Utilization of distal embolic protection in saphenous vein graft interventions (an analysis of 19,546 patients in the American College of Cardiology-National Cardiovascular Data Registry). Am J Cardiol. 2007;100(7):1114-1118. Epub 2007 Jul 18.
  54. Webb LA, Dixon SR, Safian RD, O’Neill WW. Usefulness of embolic protection devices during saphenous vein graft intervention in a non-selected population. J Interv Cardiol. 2005;18(2):73-75.
  55. Baim DS, Wahr D, George B, et al. Randomized trial of a distal embolic protection device during percutaneous intervention of saphenous vein aorto-coronary bypass grafts. Circulation. 2002;105(11):1285-1290.
  56. Stone GW, Webb J, Cox DA, et al. Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial. JAMA. 2005;293(9):1063-1072.
  57. Carrozza JP Jr, Mumma M, Breall JA, Fernandez A, Heyman E, Metzger C. Randomized evaluation of the TriActiv balloon-protection flush and extraction system for the treatment of saphenous vein graft disease. J Am Coll Cardiol. 2005;46(9):1677-1683.
  58. Stone GW, Rogers C, Hermiller J, et al. Randomized comparison of distal protection with a filter-based catheter and a balloon occlusion and aspiration system during percutaneous intervention of diseased saphenous vein aorto-coronary bypass grafts. Circulation. 2003;108(5):548-553.
  59. Sturm E, Goldberg D, Goldberg S. Stenting in saphenous vein grafts with distal protection using a second generation filter-based catheter: the combined BLAZE I and II registries. Presented at Transcatheter Cardiovascular Therapeutics, Oct 2005: Washington DC.
  60. Dixon S. Saphenous vein graft protection in a distal embolic protection randomized trial. Presented at Transcatheter Cardiovascular Therapeutics, Oct 2005: Washington DC.
  61. Kereiakes DJ, Turco MA, Breall J, et al. A novel filter-based distal embolic protection device for percutaneous intervention of saphenous vein graft lesions: results of the AMEthyst randomized controlled trial. JACC Cardiovasc Interv. 2008;1(3):248-257.
  62. Holmes DR, Coolong A, O’Shaughnessy C, et al. Comparison of the CardioShield filter with the guardwire balloon in the prevention of embolisation during vein graft intervention: results from the CAPTIVE randomised trial. EuroIntervention. 2006;2(2):161-168.
  63. Dixon SR, Mann JT, Lauer MA, et al. A randomized, controlled trial of saphenous vein graft intervention with a filter-based distal embolic protection device: TRAP trial. J Interv Cardiol. 2005;18(4):233-241.
  64. Mauri L, Cox D, Hermiller J, et al. The PROXIMAL trial: proximal protection during saphenous vein graft intervention using the Proxis Embolic Protection System: a randomized, prospective, multicenter clinical trial. J Am Coll Cardiol. 2007;50(15):1442-1449. Epub 2007 Sep 24.
  65. Niccoli G, Belloni F, Cosentino N. Case-control registry of excimer laser coronary angioplasty versus distal protection devices in patients with acute coronary syndromes due to saphenous vein graft disease. Am J Cardiol. 2013;112(10):1586-1591.
  66. Roffi M, Mukherjee D, Chew DP, et al. Lack of benefit from intravenous platelet glycoprotein IIb/IIIa receptor inhibition as adjunctive treatment for percutaneous interventions of aortocoronary bypass grafts: a pooled analysis of five randomized clinical trials. Circulation. 2002;106(24):3063-3067.
  67. Kumar D, Dangas G, Mehran R, et al. Comparison of bivalirudin versus bivalirudin plus glycoprotein IIb/IIIa inhibitor versus heparin plus glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes having percutaneous intervention for narrowed saphenous vein aorto-coronary grafts (the ACUITY trial investigators). Am J Cardiol. 2010;106(7):941-945.
  68. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44-e122. Epub 2011 Nov 7.
  69. Harskamp RE, Beijk MA, Damman P, Tijssen JG, Lopes RD, de Winter RJ. Prehospitalization antiplatelet therapy and outcomes after saphenous vein graft intervention. Am J Cardiol. 2013;111(2):153-158. Epub 2012 Oct 24.
  70. Sdringola S, Assali AR, Ghani M, et al. Risk assessment of slow or no-reflow phenomenon in aortocoronary vein graft percutaneous intervention. Catheter Cardiovasc Interv. 2001;54(3):318-324.
  71. Sdringola S, Assali A, Ghani M, et al. Adenosine use during aortocoronary vein graft interventions reverses but does not prevent the slow-no reflow phenomenon. Catheter Cardiovasc Interv. 2000;51(4):394-399.
  72. Fischell TA, Carter AJ, Foster MT, et al. Reversal of “no reflow” during vein graft stenting using high velocity boluses of intracoronary adenosine. Cathet Cardiovasc Diagn. 1998;45(4):360-365.
  73. Kapoor N, Yalamanchili V, Siddiqui T, Raza S, Leesar MA. Cardioprotective effect of high-dose intragraft adenosine infusion on microvascular function and prevention of no-reflow during saphenous vein grafts intervention. Catheter Cardiovasc Interv. 2014;83(7):1045-1054. Epub 2014 Jan 31.
  74. Zoghbi GJ, Goyal M, Hage F, et al. Pretreatment with nitroprusside for microcirculatory protection in saphenous vein graft interventions. J Invasive Cardiol. 2009;21(2):34-39. 
  75. Hillegass WB, Dean NA, Lial L, Rhinehart RG, Myers PR. Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous coronary interventions: initial human clinical experience. J Am Coll Cardiol. 2001;37(5):1335-1343. 
  76. Michaels AD, Appleby M, Otten MH, et al. Pretreatment with intragraft verapamil prior to percutaneous coronary intervention of saphenous vein graft lesions: results of the randomized, controlled vasodilator prevention on no-reflow (VAPOR) trial. J Invasive Cardiol. 2002;14(6):299-302.
  77. Sharma S. Intra-graft abciximab and verapamil combined with direct stenting is a safe and effective strategy to prevent slow-flow and no-reflow phenomenon in saphenous vein graft lesions not associated with thrombus. Recent Pat Cardiovasc Drug Discov. 2012;7(2):152-159. 
  78. Kaplan BM, Benzuly KH, Kinn JW, et al. Treatment of no-reflow in degenerated saphenous vein graft interventions: comparison of intracoronary verapamil and nitroglycerin. Cathet Cardiovasc Diagn. 1996;39(2):113-118.
  79. Fugit MD, Rubal BJ, Donovan DJ. Effects of intracoronary nicardipine, diltiazem and verapamil on coronary blood flow. J Invasive Cardiol. 2000;12(2):80-85.
  80. Fischell TA, Subraya RG, Ashraf K, Perry B, Haller S. “Pharmacologic” distal protection using prophylactic, intragraft nicardipine to prevent no-reflow and non-Q wave myocardial infarction during elective saphenous vein graft intervention. J Invasive Cardiol. 2007;19(2):58-62.

____________________________________________

From the David Geffen School of Medicine at University of California, Los Angeles (Division of Cardiology), Los Angeles, California.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted April 10, 2014, provisional acceptance given May 14, 2014, final version accepted June 30, 2014.

Address for correspondence: Michael S. Lee, MD, 100 Medical Plaza, Suite 630, Los Angeles, CA 90095. Email: mslee@mednet.ucla.edu

/sites/invasivecardiology.com/files/wm%20JIC_659-667%20Soverow%20JIC%20Dec%202014.pdf