Despite major advances in catheter-based therapy and adjunctive pharmacology, percutaneous revascularisation of diseased saphenous vein bypass grafts (SVGs) remains a critical challenge for the interventional cardiologist. Degeneration and occlusion of vein grafts is a common problem with an incidence of 15% to 30% in year one after surgery, 1% to 2% annual occlusion rates in years one to six and 4% to 5% beyond year six. Ten years after surgery, up to 50% of SVGs are expected to be significantly diseased or occluded. Options for revascularisation in cases of SVG disease include either percutaneous coronary interventions (PCI) or repeat coronary artery bypass graft surgery (CABG). Due to a significantly higher risk of redo CABG, PCI is the preferred method of treating patients with SVG lesions.
Currently, almost irrespective of the lesion morphology and the extension of the disease, percutaneous interventions primarily result in implantation of coronary stents. Compared with balloon angioplasty, the use of coronary stents in patients with SVG lesions is associated with a high rate of procedural success, reduced angiographic restenosis and a favourable late clinical outcome. The overall results remain inferior to those obtained with stent implantations in native coronary arteries, given a 30-day major adverse cardiac event (MACE) rate of 6% to 15% and six month restenosis rates of 17% to more than 50%. This finding is mainly attributable to the structural differences between SVG and native coronary artery lesions.
Compared with native coronary artery disease (CAD), vein graft lesions are frequently associated with considerable plaque burden and intracoronary thrombus, which increases the risk of peri-interventional adverse events. In addition, a unique pathophysiology and histomorphology of SVG lesions with typically friable degenerated plaques result in a different vessel response to endoluminal interventions and a high risk of debris embolisation. Finally, patients with diseased SVGs frequently have additional conditions including advanced age, more extensive atherosclerosis and reduced left ventricular function, which predicts a worse outcome after peri-interventional complications compared with 'healthier' patients; thus, optimised approaches that minimise complications and maximise the efficacy in patients undergoing vein graft PCI are of specific importance.
Distal embolisation, being the main complication of PCI with stenting of degenerated SVGs, results in 'slow-flow'/'no-reflow' secondary to diffuse microvascular occlusion, mainly caused by debris arising from manipulation of the friable lesion within a diseased vein graft.
Although the use of glycoprotein (GP) IIb/IIIa inhibitors have enhanced the safety of PCI, these drugs have no significant impact on patient outcome after distal embolisation in interventions of diseased SVGs due to the specific composition of vein graft emboli, which are primarily based on atherofibrotic particles. Pooled data of 627 patients (32% abciximab and 31% eptifibatide) from five trials (a randomized double-blind evaluation of the efficacy and safety of two dosing regimens of Integrelin versus Placebo for Reducing Mortality and Myocardial Infarction (PURSUIT), Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis II (IMPACT II), Evaluation of c7E3 for the Prevention of Ischemic Complications (EPIC), Evaluation of PTCA to Improve Long-Term Outcomes by c7E3 Glycoprotein IIb/IIIa Receptor Blockade (EPILOG) and Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT)) involving SVG treatment failed to show clinical efficacy of IIb/IIIa inhibitors in this lesion subset; therefore, SVG lesion patients remain at high risk for peri-procedural embolisation with consecutive development of non-Q-wave/Q-wave myocardial infarctions (MIs).
In the past decade, several techniques and devices have been developed to limit distal embolisation (intracoronary administration of urokinase, directional coronary atherectomy, laser angioplasty, or ultrasound thrombolysis), but failed to prove efficacy. Studies on a thrombectomy device (X-Sizer) revealed similar 30-day and one-year MACE rates compared with a control, proving the non-superiority of this device. Direct stenting without prior balloon inflation is believed to be beneficial in order to minimise peri-interventional complications, but it is still not sufficient to lower complication rates substantially.
A new class of devices have been shown to successfully reduce the incidence of embolisations and subsequent major complications in patients with SVG disease - the distal protection devices. Distal protection devices are specifically designed to capture atherosclerotic debris mobilised during the intervention. Basically, there are two types of distal protection devices - balloon occlusion techniques and filter systems.
First evidence of safety and efficacy of these techniques was obtained by the non-randomised multicentre Saphenous Vein Graft Angioplasty Free of Emboli (SAFE) study, evaluating the Percusurge GuardWire balloon occlusion device in treatment of SVG lesions. The subsequent Saphenous Vein Graft Angioplasty Free of Emboli Randomized (SAFER) trial confirmed the initial findings and demonstrated a significant 42% reduction in adverse ischaemic events, including MI and no-reflow using the GuardWire device in SVG interventions (9.6% GuardWire compared with 16.5% control).
In the following FilterWire During Transluminal Intervention of Saphenous Vein Grafts (FIRE) study, patients undergoing SVG interventions were randomised to either the GuardWire or the FilterWire Ex - a filter-based distal protection device. Similar success and MACE rates at 30 day follow-up (9.9% GuardWire, 11.6% FilterWire, p=ns) demonstrated equivalence of both techniques.
Due to these studies with demonstration of superior safety outcomes compared with unprotected interventions, the use of distal protection devices has been established as a standard of care in treatment of diseased vein graft lesions. New products with technical improvements to ease device placement and increase the capture capabilities are currently under development and will further improve the efficacy of these techniques. In summary, this class of devices has provided substantial progress in PCI safety for SVG lesions, but there is no impact on mid- and long-term efficacy. In order to improve both safety and efficacy, covered coronary stents have been developed to seal the lesion on the one hand, thereby potentially reducing the incidence of debris dislocation, and to reduce restenosis by providing a solid artificial barrier for neointimal growth on the other.
Initial studies of expanded polytetrafluoroethylene (ePTFE) membrane-covered coronary stents for treatment of SVG disease indicated high restenosis rates due to exaggerated focal restenoses at the stent edges (Randomized evaluation of a polytetra-fluoroethylene- covered stent in saphenous vein grafts (RECOVER) and Stents in Grafts (STING) study). These investigations were conducted with a balloon-expandable stent design, in which a single PTFE membrane was inserted between two layers of stent struts. Due to this design, appropriate stent expansion required use of high inflation pressures, which increased the risk of a peri-stent trauma leading to excessive initimal proliferation as healing response.
In contrast to these findings, recently published registry data on a nitinol self-expanding ePTFE membrane-covered stent (Symbiot) suggested an improved outcome compared with a bare metal historical control with a 30-day MACE rate of 5.2% and a six-month in-segment restenosis rate of 8.6%. In a total of 77 patients, there was no evidence of no-reflow, even though thrombus was present in 22.7% of the lesions at baseline; however, these data need to be confirmed in larger randomised trials.
A true breakthrough in efficacy improvements might be the introduction of drug-eluting stents (DES) for the treatment of stenotic SVGs. Sirolimus- as well as Paclitaxel-eluting stents have been proven to be safe and remarkably effective in suppression of plaque progression and lumen renarrowing in the treatment of native coronary lesions. With treatment effects of 50% to 90% in various lesion subsets, DES are likely to reduce the incidence of restenosis in SVG interventions as well. Although there are no randomised data available so far, initial reports are promising.
Overall, these results demonstrate that technical developments over the past few years have had a substantial impact on the outcome of PCIs in SVG lesions. Distal protection devices improve safety while modern stent designs improve both efficacy and safety. The combination of both is certainly the key for optimal patient care in this specific lesion subset.