Many patients who develop graft disease are poor candidates for repeat bypass surgery, because they are older and more likely to have comorbid illnesses, such as congestive heart failure, diabetes mellitus, and renal insufficiency. The percutaneous treatment of older vein grafts thus may be preferred, but remains problematic due to the high risk of embolization. Compared to the treatment of native coronary arteries, balloon angioplasty of saphenous vein graft (SVG) lesions is associated with poorer acute and long-term outcomes, with a high incidence of procedural complications and restenosis rates as high as 40% to 70% (3). Vein-graft stenting has become the preferred treatment, due to the higher procedural success rates, low risk of subacute thrombosis, and significantly less restenosis when compared to balloon angioplasty (BA) (4, 5, 6).

A major limitation of vein-graft stenting, however, is the continued high incidence of periprocedural ischemic events. When serial cardiac enzymes are systematically collected in all patients following SVG stenting, the incidence of periprocedural CPK-MB elevation may be as high as 48%, with CPK-MB elevation >5 times normal in 15% (7). Failure to restore TIMI grade 3 flow (a marker of profound distal embolization or so-called “no reflow”) is associated with a 32% incidence of Q-wave or large non-Q myocardial infarction (MI) and an 8% in-hospital mortality (8). The propensity for distal embolization following SVG stenting is multifactorial, but it is probably best explained by larger vessel size and more diffuse atherosclerosis, as well as by the friable nature of the vein-graft atheroma, which renders it prone to dislodgement following the barotrauma associated with stent deployment and expansion (9).

No reflow is a phenomenon in which myocardial ischemia and reduced antegrade flow occur despite the absence of proximal stenosis, spasm, dissection, or embolic cutoff of major distal branches. Several mechanisms have been proposed for the no reflow phenomenon (Table 12.1). In the animal laboratory, experimental no reflow has been shown to be due to the plugging of capillaries by red cells and
neutrophils, myocyte contracture, and local intracellular and interstitial edema (10,11). A loss of capillary autoregulation and severe microvascular dysfunction are the ultimate physiologic consequences of these microscopic anatomic alterations.

Early work by Hori et al. demonstrated that embolization of an increasing number or sizes of particles (100 to 300 micron) caused significant impairment of flow reserve and ultimately decreased resting flow (12). In addition to such atheroembolization, microvascular vasoconstriction, due to the release of soluble vasoconstrictors such as serotonin and thromboxane A₂, also may contribute. The mechanism of no reflow may differ depending on the clinical scenario (Table 12.1).

Pharmacologic and mechanical strategies to address the problem of intragraft thrombosis and embolism have included the use of thrombolytic agents, platelet glycoprotein IIb/IIIa receptor antagonists, rheolytic thrombectomy, extraction and excisional atherectomy, and local vasodilators. Thrombolytic drugs, such as urokinase, have not been shown to reduce the risk of embolic complications and are associated with a high incidence of major hemorrhagic complications (10%) (13). Likewise, Gp IIb/IIIa antagonist use prior to intervention has not been shown to reduce early ischemic complications in vein grafts (14). Mechanical thrombectomy, using devices such as AngioJet (Possis Medical, Minneapolis), has been developed to achieve effective thrombectomy without inducing a systemic lytic state. In a randomized comparison with urokinase, AngioJet treatment was associated with greater procedural success, reduced incidence of major adverse events, and shorter length and cost of hospitalization. However, 11% of the patients still had periprocedural infarction, thus supporting the concept that atheroembolism is a major culprit despite effective thrombectomy (15). Intracoronary vasodilators, ranging from calcium channel blockers to nitroprusside and adenosine, have been used to treat no reflow, but each of these drugs has only about an 80% response rate in improving slow flow (16, 17, 18, 19).

Based on the theory that most cases of no reflow during SVG intervention are primarily related to the distal embolization of atherosclerotic debris or platelet aggregates, devices have been designed to trap these particles within the vein graft and avoid their dispersion into the microcirculation. Current devices that have been approved or are under clinical investigation include either occlusion balloons or micropore filters. The most convincing evidence of microparticle embolization contributing to no reflow, as opposed to the isolated effects of vasoactive molecules, comes from the early clinical evaluation of the Percusurge GuardWire (Medtronic, Santa Rosa, California) distal occlusion balloon (4). Webb et al. reported significant atheroembolic material in 21 of 23 analyzable specimens and demonstrated that the debris consisted predominantly of necrotic core with cholesterol clefts, lipid-rich macrophages, and fibrin, with an average size of 204 ± 57 microns in the major axis and 83 ± 22 microns in the minor axis. Liberation of such particles into the myocardial circulation would account for poor distal flow with or without the presence of vasoconstrictor mediators.

Distal occlusion balloons offer the potential advantage of trapping the smallest of these microparticles, including those that might be smaller than the size of the filter pores. An effective distal occlusion protection system must provide complete distal occlusion and cessation of flow. This strategy must therefore provide for ease of use, so that occlusion time may be minimized, and for the ability to perform sequential steps with intermittent occlusion in those patients who cannot tolerate longer occlusion times. Most important, successful occlusion must be followed by an aspiration mechanism to remove the suspended particles and blood column before antegrade flow is restored. The distal occlusion balloon systems in use or under development have in common an elastomeric balloon, placed distal to the target lesion to occlude the vessel, and an aspiration mechanism for removal of the blood column. Several potential concerns that have emerged in conjunction with either the distal occlusion balloon or the aspiration mechanism have been considered or addressed during the early development and testing of these devices.