Dr. Tan is a Fellow in Interventional Cardiology at the University of Maryland Medical Center, Baltimore, MD.

A major limitation of coronary artery bypass graft surgery (CABG) has been the progression of atheromatous disease in aortocoronary saphenous vein grafts (SVGs). SVG attrition is approximately 7% during the first week, 15% to 20% during the first year, 1% to 2% per year from 1 to 6 years, and 4% per year from 6 to 10 years after surgery. At 10 years, only 40% of patent grafts are free of significant stenosis. ¹ Repeat bypass surgery has higher risk than the initial procedure. Diseased SVG interventions are limited by distal embolization, which may arise from disruption of soft, friable atherosclerotic plaque and adherent thrombus. The reported incidence of distal embolization following balloon angioplasty of SVGs ranges from 2% to 42%, ² resulting in no reflow, myocardial infarction (MI), and death. These complications do not appear to be significantly reduced with glycoprotein (GP) IIb/IIIa inhibition.

Carotid stenting is being evaluated as an alternative to surgery for primary carotid occlusive disease. However, there is an important risk of periprocedural stroke, undoubtedly related to embolization. In carotid interventions, virtually every patient has acoustic and Doppler signal evidence of cerebral embolization. ³ Using transcranial Doppler ultrasound, the number of detected embolic particles during standard carotid endarterectomy correlated with the rate of subsequent neurologic events. ^4,5

In addition, renal artery stenting is currently an accepted treatment option for atherosclerotic renal artery stenosis. Atheroembolism during the procedure seems to be an important factor for subsequent decline in renal function in a subset of patients.

More recently, evidence from multiple fronts has underscored the frequency and prognostic importance of embolization during and acute coronary syndromes, which can be promoted by catheter-based therapy. ⁶

Therapeutic options

To overcome these problems, devices for containment of embolic material have been developed. There are two general types of distal protection devices: occlusive devices and filters. The occlusive device has a balloon that occludes the artery during intervention with aspiration of debris with a small catheter. Filters trap debris during intervention and are then collapsed and withdrawn from the artery with the trapped debris. Theoretically, occlusive devices allow more complete emboli capture. However, end-organ ischemia, vessel trauma, distal vessel thrombosis, and poor distal vessel visualization are limitations of these devices. The filter devices have the advantage of maintaining distal perfusion with the disadvantage of larger crossing profiles and their inability to capture the smallest particles. The practical lower limit for pore size appears to be 50 µm. Smaller microparticulate matter can still get through the filter, although particles that small may have no clinical significance. ⁶ Importantly, use of emboli protection devices adds procedural time and complexity to a technique in which manipulation should be minimized.

Occlusive devices

The concept of a distal balloon occlusive device was first described in 1987 by Theron et al ⁷ for cerebral protection during carotid angioplasty. In recent years, this notion has gained popularity.

PercuSurge

PercuSurge (Medtronic AVE, Santa Rosa, CA) is the device that has undergone the most clinical testing, and in almost all cases, embolic material was retrieved. This device has just been approved for general clinical use in the United States.

Device description -- The PercuSurge GuardWire temporary occlusion system (Medtronic Inc.) provides temporary vascular occlusion during percutaneous intervention. The PercuSurge System consists of 3 components ^2,8,9 : 1) GuardWire; 2) the MicroSeal Adapter; and 3) the Export aspiration catheter. The GuardWire is a 190-cm-long, 0.014-in hollow guidewire with a central lumen connected to a compliant distal occlusion balloon with a 0.41- to 0.43-in crossing profile and available inflated diameters of 3.5 to 5 mm (figure 1). Regular balloon catheters and stent delivery systems can be advanced over this wire to perform percutaneous interventions. A proprietary valve sealing system at the proximal end of the guidewire maintains distal balloon inflation despite disconnection of the inflation device. The MicroSeal Adapter is a device that controls the opening and closure of the proximal valve, allowing inflation and deflation of the distal balloon. The The Export aspiration catheter is a 5F monorail catheter connected to a 20-mL syringe, providing a low-pressure vacuum to remove debris and thrombus from the graft. The 135-cm-long aspiration catheter has a 35-cm-long distal monorail wire lumen. A schematic representation of the PercuSurge System is shown in figure 2.

Clinical trials -- The initial clinical experience with PercuSurge was limited to SVG interventions; however, the principles of its application can be extended to most vascular structures. It is particularly suited to vessels without major side branches, which helps to ensure that all emboli are contained by the inflated GuardWire.

Saphenous vein graft interventions -- In 1999, Webb et al ² reported the results of a pilot study of 22 patients who underwent 27 SVG stenting procedures using the PercuSurge system. Distal graft occlusion time averaged 150 ± 54 seconds and decreased as experience was gained. The procedure was well tolerated. The in-hospital event rates, including creatine kinase (CK) elevation (11.1%) and non-Q wave MI (3.7%), were lower than those in historic controls. Particulate material was retrieved in 91% of cases. Particle size was 204 ± 57 µm in the major axis and 83 ± 22 µm in the minor axis. Retrieved particulates consisted predominantly of soft acellular atheromatous material, such as is typically found under a fibrous cap. In no case was vessel wall damage seen as a result of the distal occlusive balloon, and late development of a stenosis at the distal occlusion was not apparent. Another PercuSurge registry, the SAFE trial ¹⁰ reported similarly low rates of in-hospital major adverse clinical events (MACEs) for SVG interventions. A total of 103 patients were enrolled in this multicenter registry and the in-hospital MACE rate was 4.9%. Visible material was removed in 95% of cases, and 81% of the material was less than 96 µm.

The Saphenous Vein Graft Angioplasty Free of Emboli Randomized (SAFER) trial ¹¹ (Transcatheter Cardiovascular Therapeutics meeting, 2000) was the first prospective multicenter randomized trial to determine if PercuSurge reduced the incidence of 30-day MACEs compared with unprotected stenting of SVGs. The study included lesions in SVGs 3 to 6 mm in diameter, more than 5 mm from the ostium and more than 20 mm from the distal anastomosis. Patients with ongoing myocardial infarction, ejection fraction <25%, serum creatinine >2.5, and planned use of atherectomy were excluded. A total of 801 patients were enrolled. Use of the PercuSurge system was technically successful in 91.6% of the patients. Procedural success was achieved in 90.7% of the patients in the PercuSurge group and in 84% of the control group.

In the PercuSurge group, there was a 49% reduction in the 30-day primary composite end point of MI, death, emergent bypass surgery, and target lesion revascularization (TLR) (9.0% vs. 17.8%, P = 0.001). Most of the difference was due to a significantly lower rate of non-Q wave MI in the PercuSurge group (6.9% vs. 14.5%, P = 0.003). In addition, there was a lower incidence of no-reflow in the PercuSurge group (3.3% vs. 8.3%, P = 0.005) with no significant difference in the incidence of perforation, dissection, or subacute closure. The Percu-Surge group had a lower incidence of postprocedure TIMI grade 2 flow (0.9% vs. 4.5%, P = 0.004), whereas the incidence of TIMI grade 0, 1, and 3 flow were similar among the two groups. GP IIb/IIIa inhibitors were used in >60% of cases in both arms. The MACE benefit of PercuSurge was independent of GP IIb/IIIa inhibitor use.

Evidently, the SAFER trial is a landmark trial that demonstrates the safety and efficacy of PercuSurge in recovering embolic debris, preserving normal flow, and reducing MACEs during SVG intervention.

Carotid interventions -- Using transcranial Doppler, Al-Mubarak et al ¹² studied the frequency of microembolic signals during carotid stenting. With PercuSurge protection, the frequency of the Doppler-detected microembolic signals was significantly reduced compared with the frequency of the signals with no protective device. Microembolic signals in the PercuSurge group occurred predominantly during sheath placement and wiring and during the occlusion balloon deflation.

Small studies of carotid interventions with PercuSurge have shown that cerebral protection with PercuSurge is feasible, safe and effective. Henry et al ^13,14 reported their single-center experience of 148 patients who underwent 164 internal carotid artery stenting procedures with PercuSurge protection. Immediate technical success was achieved in 99.4% of cases. Mean flow occlusion time was 422 seconds (range 125 to 1479 seconds) and the procedure was well tolerated in 95.1% of cases. Debris was retrieved in all patients. The in-hospital neurologic complication rate was 1.8%. The Carotid Angioplasty Free of Emboli (CAFE-USA) trial ¹⁵ reported similarly favorable results. This phase 1 multicenter registry evaluated the use of PercuSurge in 70 patients who underwent carotid stenting. Procedural success was 100%, and prolonged distal occlusion was well tolerated (mean time 12.5 minutes, range 3.4 to 35.6 minutes). Macroscopic debris was aspirated in all patients. The 30-day complication rate (stroke, transient ischemic attack [TIA], death) was 8.5%.

However, another single-center study ¹⁶ compared outcomes of carotid stenting with and without PercuSurge versus carotid endarterectomy and found disappointing results with carotid stenting despite protection. There were significantly more in-hospital complications (death, TIA, stroke) in all stent patients than with the surgical cohort patients (22.2% vs. 3%, P = 0.0077). Although PercuSurge decreased the in-hospital complication rate (15% vs. 27% for unprotected stenting), the outcomes were overwhelmingly worse than in the surgical group. Without question, the efficacy of PercuSurge in preventing neurological complication will require a large randomized trial comparing protected carotid stenting with surgical endarterectomy.

Percutaneous intervention in AMI -- A single-center series of 20 patients who underwent protected percutaneous intervention for AMI with PercuSurge in native coronary arteries suggested that this approach is feasible in selected cases. ¹⁷ Case selection consisted of patients with large thrombi in large vessels determined angiographically (proximal reference diameter 3.6 ± 0.7 mm), including: 7 left anterior descending, 11 right coronary, and 2 left circumflex. The procedure was successful in 18 of 20 patients. Macroscopically visible material was obtained in all successful cases, with histology demonstrating fresh and/or partial organizing thrombus. Angiographically evident embolization occurred in only 1 patient. Others reported improved angiographic, epicardial, and myocardial perfusion in AMI patients who underwent stenting of the infarct-related artery with PercuSurge protection. ¹⁸ Larger trials of primary angioplasty with distal protection are in progress.

Renal artery interventions-- Henry et al ¹⁹ reported a pilot study of 26 patients who underwent protected renal angioplasty and stenting with the PercuSurge device. Immediate technical success was achieved in all cases. Visible debris was extracted from all patients. At 6 months, there was no renal function deterioration in any patient. These preliminary data suggest that protected renal artery revascularization is feasible and safe.

Parodi Anti-Emboli System

Parodi et al ²⁰ have developed a circulatory control device system, the Parodi Anti-Emboli System (PAES), which creates temporary blood flow reversal from the carotid artery into a suctioning catheter positioned proximal to the carotid artery target lesion. This device, specifically designed for the carotid system, is quite complicated and bulky.

Device description-- The PAES device consists of two components: a 7F or 8F guiding catheter with an inverted pear-shaped balloon at the tip for occlusion of the common carotid artery through which the low-profile, guidewire-based, balloon-type device is used for occlusion of the external carotid artery. The guiding catheter lumen is then connected externally to the contralateral femoral vein introducer with an interposed blood filter, which achieves inversion of the internal carotid blood flow. During angioplasty and stenting, additional suction is used to capture embolic debris.

Clinical trials -- A multicenter registry of 60 patients using the PAES during carotid stenting showed no in-hospital strokes, TIA, loss of consciousness, or seizures. ²¹ There were 3 patients who were intolerant to flow reversal without sequelae.

Filters

The concept of a filter device was first introduced in 1991 by Gunther and Vorwerk ²² for use in peripheral arterial intervention. Recently, several other filters have been designed and are in various stages of testing, although they have not been approved for general clinical use in the United States. This section will review the filter devices that have preliminary experience in humans.

AngioGuard

The AngioGuard Guidewire system (Cordis J&J, Warren, NJ) has undergone the most clinical evaluation of the filter device systems.

Device description-- The AngioGuard Guidewire system uses a distal guidewire-based filter that traps debris. The filter device is a flexible olive-shaped Nitinol structure, distally covered by a polyurethane filter connected to a long, 0.014-in wire. The closed device's crossing profile is 3.4F and is available in 50-µm and 100-µm pores. After crossing the target lesion, the basket (4 to 7 mm in diameter) is expanded by removal of the delivery sheath, and the intervention can be performed in a standard manner. Plaque debris is captured within the distal basket, and at the end of the procedure, the filter is closed and retrieved. The filter membrane allows normal blood flow during the procedure.

Clinical trials-- In a small number of patients, AngioGuard has been tested in percutaneous coronary, SVGs, and carotid and renal interventions, with a resulting retrieval of atherosclerotic material in almost all of those patients. ^23-25 Two randomized trials are in progress to evaluate the clinical impact of the AngioGuard device. The SAPPHIRE trial is a randomized trial of protected carotid stenting versus surgical carotid endarterectomy. The GUARD trial compares SVG interventions randomized to be performed with or without AngioGuard.

TRAP Vascular Filtration System

Device description -- The TRAP Vascular Filtration System (VFS) (Microvena, White Bear Lake, MN) consists of a specially treated nitinol braided basket that captures embolic material during percutaneous intervention. The basket diameters are available from 2.5 to 7 mm, in 0.5-mm increments.

Clinical trials-- In Europe, 32 patients with de novo SVG lesions were treated successfully with the TRAP VFS. ²⁶ Debris was captured in all but one basket. There were no device-related MACEs at 30 days.

EPI FilterWireEX device

Device description-- EPI FilterWireEX device (Boston Scientific/EP Technologies, San Jose, CA) is a temporary intra-arterial filtration system using a standard 0.014-in guidewire that incorporates a round nitinol wire loop structure that supports a thin, 75-µm porous filter membrane at the distal end. The filter is made of polyethylene and rotates freely on the end of the guidewire.

Clinical trials -- A small number of patients have been treated for SVG, native coronary, and carotid stenosis with the EPI FilterWireEX device. ²⁷ No in-hospital complications were reported.

Conclusion

Embolic particulate matter is commonly induced by percutaneous revascularization. This particulate matter may play a pivotal role in the pathogenesis of distal embolization and microvascular obstruction following percutaneous intervention. Use of innovative emboli protection devices to shield the microvasculature may improve short- and long-term outcome. It is still early in the development of these novel devices. Making them simple and easy to use and as atraumatic as possible, with the lowest profile and highest torqueability, will require further refinements. Randomized controlled trials for each distal protection device and each vascular bed are warranted in order to prove that interventions are accomplished more safely. Undoubtedly, a safe and effective device will become available and, ultimately, will be incorporated into the daily practice of percutaneous coronary and peripheral revascularization.