An Embolization Containment Device

ABSTRACT: A coaxial catheter system for containment of distal embolization is described. Utilizing a novel 0.014" hypotube with a distal elastomeric occlusion balloon, the PercuSurge GuardWire functions as a guidewire while trapping distal embolization resulting from more proximal intervention. The particulate debris is evacuated with a single operator exchange aspiration catheter (Export catheter) prior to deflation of the distal occlusion balloon. This animal study confirmed the feasibility of concept. The system was easily delivered through tortuous coronary anatomy. The GuardWire served as an adequate rail for delivery of dilatation balloons and a multitude of stents. There was no evidence of deep wall damage from low-pressure inflation and apposition of the distal occlusion balloon. Distal embolization is a frequent complication of aortocoronary vein graft interventions. No reflow, myocardial infarction and death can directly result from graft embolization. The threat of embolization has not been mitigated by the selection of device; in vein grafts, it is observed following balloon angioplasty, atherectomy and stenting. Although less frequently encountered in the context of carotid interventions, the neurological consequences of cerebral embolization can be catastrophic. We have developed a percutaneous coaxial device with the potential to prevent distal embolization and thus improve the safety of catheter-based intervention within vein grafts and other diseased vascular segments. This article describes the rationale for and prototype development of an emboli containment device. A demonstration of feasibility in an animal model is presented. Methods Device description. The PercuSurge emboli containment system (PercuSurge, Sunnyvale, California) is schematically depicted in Figure 1. The system derives from a series of coaxial devices. Standard 8 and 9 French (Fr) angioplasty guiding catheters are used to access the target vessel. A novel distal occlusion wire (GuardWire) is used as the primary guidewire for delivery of angioplasty and stent devices. The GuardWire is constructed from a 0.014" nitinol hypotube. The terminal end of this exchange length guidewire has a flexible coil design and can be shaped and torqued in a manner comparable to conventional coronary guidewires. An elastomeric balloon (5 mm working length) is mounted 3.5 cm proximal to the flexible coils (Figure 2) and is inflated and deflated at low pressure by dilute contrast delivered through the hypotube. The deflated low-profile “balloon on a wire” system is passed beyond the area to be treated and the distal occlusion balloon is then inflated at low pressure (Inflation of the distal elastomeric occlusion balloon occurs through the nitinol hypotube. Inflation through the hypotube is facilitated by an inflation device (Figure 3) that can inflate and deflate the distal balloon while allowing angioplasty devices to come on and off the GuardWire. Inflation and deflation are accomplished through a small side hole in the proximal hypotube. The prototype inflation device is used to slide a coaxial wire “plug” in and out of this location, sealing or unsealing the hypotube. The exchange length GuardWire is then used as a conventional guidewire or rail, facilitating passage of most balloon catheters and stents. Following treatment with one or more therapeutic devices, a side hole catheter (Export, PercuSurge) is delivered up to the distal occlusion balloon to facilitate aspiration of debris into a closed vacuum container. The aspiration catheter has a single large oval side hole that allows passage of relatively large debris. It is designed with a short length of guidewire lumen, facilitating rapid single operator exchange. Following 10–15 seconds of aspiration, the distal occlusion balloon is deflated and debris-free blood flow is returned to the distal vessel. The prototype PercuSurge emboli containment system relies on the use of a 20 cc syringe, locked with full vacuum, and attached to the aspiration catheter through a one-way valve. The early PercuSurge embolization containment systems included custom guiding catheters with an elastomeric balloon at their tip. Following deep intubation with the guiding catheter, simultaneous inflation of the GuardWire and the guiding catheter balloon created a closed chamber whereby both distal and proximal embolization could be prevented. Particle retrieval in this closed-chamber system was compared to a simplified sump system that was subsequently used for the majority of animal investigations. With the sump system, standard nonoccluding 8 and 9 Fr guiding catheters are used in conjunction with the GuardWire. In this sump system, the gradient of positive pressure from the aorta to the distal occlusion balloon (as aspiration occurs) results in passive prevention of proximal embolization. Prototype development in animal model. Early animal work concentrated on refining the GuardWire so that the tip had sufficient flexibility and torque response within the coronary circulation of anesthetized pigs. The distal occlusion balloon was developed to maintain a low deflated profile with rapid low-pressure inflation and deflation characteristics. A variety of aspiration catheters were tested to assure efficient aspiration of particles up to 1,000 microns. In the absence of surrogate models of human vein graft disease, we relied on injection and retrieval of exogenous particles following inflation of the GuardWire in isolated vascular segments of porcine and canine models. To ensure the “closed conduit” characteristics of a vein graft, particle retrieval studies were carried out in isolated coronary and peripheral arterial segments without angiographically evident sidebranches. Assessment of vessel wall trauma. The potential for denudation and vessel wall damage from the distal occlusion balloon and passage of the aspiration catheter led to quantitative and qualitative pathological assessments as follows. The distal occlusion balloon was inflated at 2 atm in an isolated coronary segment of a normal porcine coronary artery. An angioplasty device was inflated proximal to the inflated occlusion balloon and then exchanged for the aspiration catheter. Coronary arteries subjected to distal balloon occlusion were removed from the heart, cut into 3–5 mm segments, and processed for paraffin embedding. Selected arterial segments were examined by scanning electron microscopy. Coronary aspirates (7 ml) were collected in tubes containing EDTA-citrate buffer and stored at 4 °C for preparation. Aspirates were pooled and centrifuged at 500 x g for 10 minutes. The plasma was removed and the remaining material was resuspended in Hank’s balanced salt solution (HBSS). Interfering red blood cells were lysed with 1% saponin (Calbiochem, La Jolla, California). Samples were again centrifuged and then fixed in 10% neutral buffered formalin for histologic processing. Fixed aspirate and coronary artery samples were prepared for light microscopy using routine procedures. Sections (4 µg) were cut and placed on high-adhesive slides (SuperFrost/Plus, Fisher) and stained with hematoxylin and eosin or Movat pentachrome methods. In selected aspirates, the presence of endothelial cells was evaluated by localization of von Willebrand factor (vWF), a constitutively expressed endothelial cell marker, using a polyclonal rabbit antihuman antibody that reacts with swine vWF. For antibody detection, slides were incubated with a biotin-conjugated secondary antibody, goat antirabbit IgG (Vector Laboratories, Burlingame, California). Immunostains were then visualized using an avidin-peroxidase-substrate system (Vectastain ABC Kit, Vector Laboratories) and the chromogenic substrate diaminobenzidine that generate a brown-colored product. Scanning electron microscopy was performed on aspirate and coronary samples to detect fragments of smooth-muscle cells and to assess the degree of focal endothelial disruption. Both the internal elastic lamina and the media are left intact following the occlusion and aspiration procedures. For these studies, specimens were dehydrated in a graded series of ethanols. After critical-point drying, samples were sputter-coated with gold; specimens were visualized using a Zeiss scanning electron microscope (model DSM 960 A, Oberkochen, Germany). Results Results from animal testing. Following a series of modifications in the emboli containment system, we were able reliably and repetitively to deliver the GuardWire, inflate the elastomeric distal occlusion balloon, deliver and inflate an angioplasty balloon, exchange for an aspiration catheter, evacuate the chamber and deflate the GuardWire. This series of steps could usually be completed within 3–4 minutes. We anticipate that this duration of ischemia should be tolerated by most patients. Pathology. Morphologic examination of coronary arteries after an aspiration procedure showed focal loss of endothelium (Figures 4 and 5); a thin layer of platelets covered areas devoid of endothelial cells. There was no injury to the internal or external elastic lamina and medial layer. Aspirate samples showed fragments of tissue consistent with endothelium. The presence of both endothelial cells and platelets was confirmed by immunostaining of aspirate samples with an antibody directed against vWF (data not shown). The simple 20 cc aspiration syringe and catheter system were able to readily retrieve particles up to 1,000 microns. There was no measurable difference in the amount of particle retrieval between the sump and closed systems during bench-top testing. Discussion Aortocoronary vein grafts have limited durability because of progressive degeneration with atherosclerosis.¹ Angioplasty and stenting of saphenous vein graft disease are associated with frequent adverse clinical events.^2–8 Though rarely seen in catheter treatment of native coronary arteries,^9,10 embolization of plaque debris is common in vein graft angioplasty. It is also associated with stent implantation, particularly following high-pressure deployment.^11–17 No reflow, myocardial infarction and death are unpredictable consequences that occur in discretely as well as diffusely diseased vein grafts. Embolization is frequently associated with major myocardial infarction and is a common cause of angioplasty-related death. There is minimal benefit from emergency surgical revascularization in this context; hence, prevention or containment is imperative. Embolization, abrupt closure, no reflow and CK elevations are most commonly associated with interventions in the body of vein grafts. Stenoses of the proximal and distal anastomoses are invariably fibrotic and less prone to embolization. No reflow and CK elevations are thought to reflect embolization of particulate debris. Small-vessel spasm may attend such embolization, potentiating the perturbation in flow. In the absence of preventive therapy, treatment of no reflow has focused on the local delivery of calcium channel blockers.^18–21 Lesion-specific devices have been designed to mitigate the risks of vein graft intervention. The transluminal extraction catheter (TEC; Interventional Technologies, Irvine, California) is an atherectomy device that relies on continuous aspiration behind rotating twin cutting blades to remove atheromatous debris. Although of some value in the hands of select operators, the TEC device is fundamentally limited by its maximum working diameter (2.5 mm); its use has had minor impact on the routine treatment of vein graft disease.^22–24 The AngioJet Rapid Thrombectomy System (Possis Medical, Minneapolis, Minnesota) uses the Bernoulli effect to aspirate friable pathology, such as poorly organized thrombus.²⁵ This device has demonstrable success in extracting thrombus from both diseased vein grafts and native coronary arteries. In its current configuration, the AngioJet is not capable of efficient removal of atheromatous material from the vein graft wall, nor does it prevent distal embolization and no reflow. In a small pilot study of the AngioJet, there was a 13% incidence of no reflow while attempting proximal thrombectomy.²⁶ Although there is clear potential for this device to be of therapeutic value as a thrombectomy instrument, there are no data to suggest that it will adequately contain the distal embolization associated with its application. Covered stents have the potential to entrap debris that would otherwise embolize during deployment.²⁷ Such stents with suitable lengths and compatible coverings are anticipated but untried. Even if this method eliminates emboli during stent deployment, emboli still might occur with wire manipulation, predilatation PTCA or delivery of the covered stent system. In a study of carotid stenting with transcranial Doppler monitoring, up to 55% of emboli occurred with wire placement and predilatation alone.²⁸ Selective infusion of thrombolytic agents has been used in a strategy designed to debulk the thrombotic burden of diffusely diseased or totally occluded aortocoronary vein grafts.^29–33 Although urokinase and tPA may have some role in attenuating the extent of thrombus, there is no evidence that these drugs have an important effect on attendant atheroma; thus, the threat of embolization remains. Bolus infusion of the platelet antagonist abciximab (ReoPro) has been advocated for pretreatment in vein graft interventions.^34–36 Although glycoprotein IIb/IIIa receptor inhibitors have theoretical appeal for reducing no reflow associated with embolization, they cannot effectively prevent atheromatous embolization itself. The PercuSurge containment system is a simple coaxial catheter solution for the prevention of distal embolization. Its initial use is anticipated in vein graft intervention; however, the principles of its application can be extended to most vascular structures. It is particularly suited to vessels without major sidebranches, ensuring that all emboli are contained by the inflated GuardWire; vein grafts, prosthetic graft conduits, carotid and superficial femoral arteries are attractive targets. We believe there is compelling rationale to implement an emboli containment system for most vein graft interventions not involving the anastomoses. A similar argument can be made for carotid angioplasty and stenting where embolic stroke remains a clear concern. The PercuSurge emboli containment system is a simple coaxial device that can serve the additional purpose of a primary guidewire for most cases. This pilot animal study demonstrated the ease of application and the potential benefit of this emboli containment device.