- Email: [email protected]
Percutaneous mechanical thrombolysis and thrombectomy
Percutaneous Mechanical Thrombolysis and Thrombectomy M a r t i n R. C r a i n , M D
Devices and methods for mechanically dissolving (thrombolysis) and removing (thrombectomy) thrombus using a percutaneous approach have been developed to address the deficiencies of the previously available methods of treating thrombus, namely Fogarty balloon thromboembolectomy and pharmacologic thrombolysis, Goals of percutaneous mechanical thrombectomy (PMT) include faster, safer, and less expensive treatment of vascular thrombosis, either alone or in conjunction with prior methods. PMT devices have rapidly assumed a role in declotting thrombosed hemodialysis access synthetic grafts, and may eventually play an integral part in many other thrombotic conditions. However, significant device refinement and modification, as well as properly conducted clinical trials, will be necessary before routine use in many applications can be advocated. In this article, each of the PMT devices currently (or soon to be) available in the United States are presented and compared. Each is approved by the Food and Drug Administration for use only in hemodialysis access at the present time. Copyright © 1998 by W.B. Saunders Company
n the search for methods to more rapidly, effectively, and safely remove thrombus compromising blood flow, it has become evident that mechanical fragmentation and dissolution is desirable as an adjunct to pharmacological thrombolysis or as stand-alone therapy. The first significant clinical experience with a mechanical method of thrombus liberation was with Fogarty-type compliant balloons in the operating room. By expanding to cover the entire circumference of a vessel, these balloons have allowed surgeons to rapidly and effectively clear emboli and thrombus from major vessels and grafts. However, balloons have several limitations, including need for open surgical introduction and thrombus removal, lack of directability, inability to clear thrombus from side branches, and significant trauma causing subsequent occlusion, especially in small vessels. 1,2 The other common method using mechanical fragmentation is so-called pharmacomechanical pulse-spray thrombolysis (PSPMT), a process by which small jets of fluid are forcefully ejected from multiple catheter sideholes to achieve both mechanical fragmentation and increasing the surface area to which thrombus is exposed to a thrombolytic agent. This method is particularly helpful in very acute thrombus, but in many arterial and venous thromboses, it produces insufficient maceration and fragmentation to replace
I
From the Department of Vascular/Interventional Radiology, Medical College of Wisconsin, Milwaukee, Wi. Address reprint requests to Martin R. Crain, MD, Assistant Professor of Radiology, Section of Vascular/Interventional Radiology, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, Room 2803, 9200 W Wisconsin Ave, Milwaukee, Wl 53226. Copyright © 1998 by W.B. Saunders Company 1089-2516/98/0104-001058.00/0
or substantially reduce the need for prolonged thrombolytic infusion. The inherent deficiencies of both methods have accelerated the evolution of devices and methods for fragmenting, mobilizing, and clearing thrombus inhibiting flow and causing disease. Defining the optimal characteristics of the "ideal" method to achieve thrombus dissolution (thrombolysis) and/or removal (thrombectomy) contributes to the understanding of the advantages and limitations of various devices emerging in the medical marketplace and outlines those areas of continued deficiency which will drive the future evolution and refinement of the mechanical thrombolysis field (Table 1). Unfortunately, the goals of mechanical thrombolysis are often at odds with each other. One primary goal is effective liberation and fragmentation of all thrombus within the vessel lumen and its branches, but at the same time, the native vessels should be protected from injury. Another goal is effective dispersion or removal of fragments, but hemolysis and significant embolization should be avoided. The device should be easily introduced into and negotiated within vessels (or otherwise applied) to rapidly treat thrombus, but should not cause injury at the introduction site or along its path. It becomes clear that there is probably a future for several device types if matched properly to the vessels treated. For instance, a device that vigorously macerates thrombus may be most appropriate for application in hemoaccess grafts and chronic thrombus, whereas a more delicate design may be safest for tibial and pedal arteries. Likewise, it is very unlikely that a device effective for tibial work would be as effective in debulking acute venous thromboembolism in the central pulmonary arteries. This article aims to provide an overview of each of the percutaneous mechanical thrombolytic and thrombectomy (PMT) devices currently in widespread use in the United States and Europe and to highlight features which make particular devices promising in some thrombotic circumstances and limited in others. Several other devices relying on variations of similar physical principles are undergoing bench and clinical evaluation and are not covered. The clinical experience to date in the major categories of thrombosis and embolism is also discussed. For a more detailed discussion of all aspects of mechanical thrombolysis and thrombectomy, the reader is referred to an excellent three-part review by Sharafuddin and Hicks. 3-5
Device Descriptions One of the more beneficial ways to categorize PMT devices is to differentiate those which expand within a vessel lumen to substantially contact the vessel wall (Group I) from others which produce thrombus fragmentation by induction of forces such as fluid penetration, suction, and recirculation (Group
Techniques in Vascular and Interventional Radiology, Vol 1, No 4 (December), 1998: pp 235-243
235
TABLE 1. Characteristics of the Ideal Mechanical Thrombolysis/Thrombectomy Device Remove all clot Replace (or reduce dose of) thrombolytic agent Effective against acute, chronic, and "arterial plug" thrombus Nontraumatic to native vessels No distal embolization (arterial and venous) Minimal blood loss; minimal hemolysis Wide range of vessel diameter applications Inexpensive Rapid Operator ease-of-use (simple, reliable) Flexible and directaNe Guidewire compatible Small diameter entry
II). 6 This categorization allows broad separation of those devices potentially exerting vigorous contact against the vessel wall and producing possible native vessel injury from the group of devices which rely on less direct methods of thrombus mobilization, but which may be limited in their ability to effectively fragment more organized material. By making contact with the entire luminal cross-section, Group I devices physically detach thrombus from the wall. Contents are often macerated into relatively large particles and require physical removal or adjunctive pharmacological thrombolysis if embolization avoidance is desired. Group II devices, on the other hand, use principles which tend to produce smaller particles which can either be easily suctioned or may be allowed to embolize without significant deleterious effect.
Group I Fogarty-type thrombectomy balloons. The Fogarty balloon (Baxter Healthcare, Santa Ana, CA) has been the mainstay of surgical thrombectomy and embolectomy. The technique requires open surgical exposure and blind passage of the catheter. For percutaneous, fluoroscopically guided work, several over-the-wire catheters are available (including the Fogarty ThruLumen catheter, Baxter Healthcare). These balloons use compliant materials such as latex which allow the balloon to expand to contact the entire circumference in a range of vessel diameters. Relatively noncompliant angioplasty balloons may also be used to dislodge thrombus and the "arterial plug" from hemoaccess grafts, but may leave adherent material when the balloon wings do not fully expand in instances when the balloon diameter exceeds the graft diameter. A primary limitation of balloon catheters is that they only dislodge material and do not adequately address further fragmentation in most instances. Therefore, their routine use in percutaneous procedures is mostly limited to dislodgment of the arterial plug in hemoaccess graft declotting (information to follow). Another significant limitation is the severe arteriaP ,2 and venous 7 injuries they can induce. Table 2 highlights advantages and disadvantages of compliant thrombectomy balloons. Arrow-Trerotola percutaneous thrombectomy device. The Arrow-Trerotola percutaneous thrombectomy device (PTD) (Arrow International, Inc, Reading, PA) (Fig 1), consists of a self-expanding nitinol cage basket deployed from its compressed state through a 5F catheter, s It is connected by a wire driveshaft to a battery-powered motor drive unit, which spins the basket at 3,000 rpm. It does not pass over a guidewire, but is flexible enough to be advanced through curves in synthetic
236
grafts. Thrombus is fragmented into particles less than 3 mm in diameter with the majority less than 1 mm. The device is placed through a 5F (minimum) sheath. The maximum open diameter of the basket is 9 ram. The PTD is approved by the Food and Drug Administration (FDA) for use in synthetic hemodialysis access grafts without concomitant administration of a thrombolytic agent. Aspiration of fragments is recommended but there is no significant blood loss. The hand-held device is easy to use, although may damage veins, crossing sheaths, and intravascular stents if not used with caution. Because of the relatively vigorous nature of the spinning cage, the device is also effective in removing adherent fibrotic material, which tends to line hemoaccess grafts. On the other hand, it has been shown to cause extensive endothelial denudation in veins and is more likely than Group II devices to cause permanent vascular injury and is not intended for use in native vessel segments. 7 The likelihood of distal embolization of sizeable fragments also limits its use in arteries. Table 3 highlights advantages and disadvantages of the PTD. Cragg/Castaneda thrombolytic brush catheter systems. Two spinning brush catheters are currently available from Micro Therapeutics, Inc. The original design (Cragg thrombolytic brush catheter system; Micro Therapeutics, Inc, San Clemente, CA) (Fig 2), consists of a "bottle brush" at the tip of a driveshaft which in turn is rotated by a hand-held battery-powered motor drive unit. The brush expands to a diameter of 6 mm when unconstrained. The bristles at the expandable tip are soft when deployed from the 6F catheter, but become resilient with spinning centrifugal force and effectively whisk the luminal surface of hemodialysis grafts. More recently released is the modified version (Castaneda brush) which possesses stiffer bristles and which can be advanced over a 0.035" guidewire. Concomitant urokinase (UK) administration is recommended in the FDA-approved instructions for use, but there is no reason to believe that the thrombolytic effect without UK would be any different from that produced by the Trerotola PTD. Like the PTD, the brush catheters are easy to use, but the same limitations of potential vascular injury and residual particle size limit their use outside of hemodialysis grafts. Table 4 highlights advantages and disadvantages of thrombectorny brush catheters.
Group II PSPMT catheters. Multisidehole catheters of various designs have been used extensively in assisting pharmacological thrombolysis. Thrombolytic agents are delivered through jets oriented perpendicularly within a thrombosed segment to fragment thrombus and increase the surface area to which the agent is exposed. Results and discussion of techniques are addressed in detail in other articles in this issue. It is also notable that heparinized saline has also been delivered with a similar technique in thrombosed hemodialysis grafts with TABLE 2. Fogarty-Type Balloon Summary Device strengths Addresses chronic thrombus and "arterial plug" Limitations Arterial and venous injury Inadequate thrombus fragmentation Promising applications Adjunct to hemodialysis graft declotting MARTIN R. CRAIN
Fig 1. Arrow-Trerotola PTD. Motor drive unit, catheter, and nitinol basket (A), (Reprinted with permission from Trerotola SO, Vesely TM, Lund GB, et ah Treatment of thrombosed hemodialysis access grafts: Arrow-Trerotola percutaneous thrombolytic device versus pulse-spray thrombolysis. Radiology 208:403-414, 1998.) Radiograph showing device deployment in a forearm dialysis access graft (B).
clinical efficacy equal to pulse-spray thrombolysis. 9 The advantages of PSPMT (ease of use, inexpensive catheters) are partially offset by the cost and minor risks of the thrombolytic agents. The principle deficiency, however, is the insufficient particle reduction and removal achieved with this method of thrombus fragmentation, 1° and thus the search for devices and methods to more completely pulverize thrombus has been undertaken, Amplatz thrombectomydevice. The Amplatz thrombectomy device (ATD) (Microvena Corporation, White Bear Lake, MN)
TABLE 3. Arrow-Trerotola PTD Summary Device strengths Ease-of-use; hand-held Vigorous thrombus clearance in hemodialysis grafts Limitations Potential for vascular injury Distal embolization in arteries Promising applications Hemodialysis grafts PMT AND THROMBECTOMY
(Fig 3) was the first of the PMT devices approved by the FDA for use in hemodialysis access grafts (approval August, 1996). It comprises a rapidly spinning helical screw impeller recessed within a short metal protective housing so as not to directly contact vessel wall. The impeller is driven by a cable connected to a small air turbine at the catheter base. The turbine is powered by compressed air (50 to 125 psi) from standard hospital air outlets in most angiographic rooms. The turbine is activated through sterile tubing by a foot pedal/regulator, which is in turn connected by tubing to the compressed air outlet. The turbine spins the impeller at approximately 100,000 rpm to create a vortex, which aspirates thrombus into the catheter housing where it is macerated and then ejected through a side port. Ejected particles are then subject to recirculation, which renders particle sizes between 13 to 1,000 llm, with less than 1% larger than 400 l~m.~1 The catheter currently sold is 8F and requires passage through an introducer sheath or guiding catheter. It is not guidewire-compatible and is limited by its inability to be directed. However, a 6F device and an over-the-wire design are close to release at the time of 237
Fig 2. Cragg/Castaneda thrombolytic brush catheter system. Magnified view of Castaneda brush over a wire with motor drive unit in background (A). The Cragg brush clearing thrombus and restoring flow (B).
this writing. Modification with an asymmetrical sideport to provide directability is also currently under evaluation. Unlike the other Group II devices, the ATD is a recirculation device with no effluent channel and thus no removal of fragments or net blood volume loss. Hemolysis has been shown to occur, and is directly related to cumulative device 238
activation time and more likely once flow has been reestablished} 2 Hemolysis is transient and usually well-tolerated, with no significant adverse effects yet reported. Nonetheless, as hemolysis has definitely been shown experimentally, caution is advised when treating patients at risk for anemia and nephrotoxicity due to free hemoglobin, including those with limited MARTIN R. CRAIN
TABLE 5. Amplatz ATD Summary Device strengths Best particle size reduction Recirculating (no volume Joss) Limitations Hemolysis Promising applications Hemodialysis grafts Arterial? DVT?
Fig 3, Amplatz thrombectomy device. Magnification of the impeller housings of the 6 and 8F devices (A). Impeller suction and recirculation vectors (B).
circulating blood volume (small children), compromised renal function, and preexisting hypoxemia. There are limited data available on the potential for the ATD to cause damage to native vessels. The effect on the arterial wall was studied in dogs, showing focal intimal disruption in two thirds of the vessels examined, but with very rare development of stenosis, x3 In veins, a recent abstract reported that endothelial denudation does occur after passage of the Amplatz ATD in veins of animals, 14 but in a similar experiment in the author's laboratory, gross inspection of valves under a dissecting microscope revealed little structural alteration of valve leaflets after ATD declotting when the device was passed in antegrade direction from below (unpublished data). Table 5 highlights advantages and disadvantages of the ATD. Angiojet rheolytic thrombectomy system. The Angiojet rheolytic thrombectomy system (Possis Medical, Minneapolis, MN) (Fig 4) is the only currently available FDA-approved PMT device based on suction and fragmentation generated by the Venturi effect (so-called "hydrodynamic" device). The original device consisted of two sets of water jets emitted from a small injection port, which terminated within a halo-shaped catheter TABLE 4. Cragg-Castaneda Brush Summary Device strengths Ease-of-use; hand-held Vigorous thrombus clearance in hemodialysis grafts Limitations Potential for vascular injury Distal embolization in arteries Promising applications Hemodialysis grafts
PMT AND THROMBECTOMY
tip. is The first set included a number of radially directed and retrogradely baffled jets for penetration and mobilization of thrombus near the catheter tip. The second high-pressure jet was ejected back into a larger exhaust lumen to create a local region of relative pressure negativity (technically called a stagnation pressure gradient, or the Bernoulli principle). These high-velocity jets produce thrombus suction (the Venturi effect), fragmentation, and removal. Subsequently, the number of jets directed at the exhaust lumen has been increased to produce more powerful suction, and the radially directed jets have been eliminated. Three catheters are currently sold for coronary, peripheral, and hemodialysis graft applications, each a variation of a 5F double lumen catheter with five to six jets. The system requires a special pump, which generates up to 30,000 psi within the pump to drive the water jets ejected at the catheter tip at 1,500 to 2,500 psi. A roller pump controls the removal of effluent into a collection bag. The catheters accommodate guidewires of 0.018" diameter through the exhaust lumen. A principle advantage of hydrodynamic catheters is their low potential for vascular injury when compared with Group I devices. The Angiojet proved to be safe in arterial passage in an animal model, producing only focal regions of minor endothelial denudation) 6 The biggest drawback of the Angiojet system to date has been the cost and size of the floor-standing pump unit, but a smaller pump, which may be mounted on an IV pole, is reportedly forthcoming. As with the Amplatz device, hemolysis can occur with prolonged activation times, especially after reestablishing flow. Venturi-based devices such as the Angiojet which exhaust thrombus, fluid, and blood may also result in blood volume loss, and close monitoring of infusion and evacuation volumes and hematocrit is recommended. Table 6 highlights advantages and disadvantages of the Angiojet device. Hydrolyser mechanical thrombectomy device. The initial version of the Hydrolyser mechanical thrombectomy device 0JIS-Cordis Endovascular, Warren, NJ) (Fig 5) is a 7F design with a small, asymmetrically located injection lumen inside a larger exhaust lumen) 7 The injection port terminates in a J-configuration in the closed distal tip of the catheter so as to provide a single high pressure, low volume jet that is oriented back into the exhaust lumen. As the jet passes a large (6 mm), asymmetrically placed thrombectomy side hole, it produces local pressure reduction which induces thrombus suction (the Venturi effect), fragmentation, and removal. The 7F catheter may be used over a 0.025" wire traversing the larger exhaust lumen. The single pressure jet is produced by connecting the injection lumen to a standard angiographic injector and infusing 4 mL/s at 750 psi. Effluent containing thrombus particles is exhausted into a collection bag. A 6F triple lumen catheter has also been designed with the third lumen accommo-
239
dating a 0.020" wire. The 7F catheter is designed for use in 5 to 9 mm vessels and the 6F catheter treats vessels 3 to 8 ram. Initial data suggest the Hydrolyser is relatively safe in the arterial system, inducing significantly less arterial intimal
TABLE 6. Angiojet RTC Summary Device strengths Low vessel injury potential Wire-compatible Particle evacuation Limitations Start-up costs for pump; cumbersome Promising applications Hemodialysis grafts Arterial use? DVT?
hyperplasia at 3 weeks than balloon thrombectomy in an animal model38 The so-called hydrodynamic devices appear most effective in acute (<10 day) thrombus. 19 A distinct advantage of the Hydrolyser as compared with the Angiojet device is that the Hydrolyser runs off existing equipment in an interventional laboratory. At this time, the Hydrolyser is not approved by the FDA for use in the United States. Table 7 highlights advantages and disadvantages of the Hydrolyser device.
Clinical Experience
Hemodialysis Grafts
Fig 4. Angiojet rheolytic thrombectomy system. Magnification of catheter tip of the AV 60 dialysis device, Note several jets impinging on the large exhaust lumen (A), Schematic of the local Venturi effect producing thrombus suction and mobilization, Rounded catheter tip in this schematic depicts the longer devices intended for coronary and peripheral vascular applications (B). 240
To evaluate the role of the various methods of declotting thrombosed hemodialysis access sites, it is helpful to understand the pathophysiology leading to access thrombosis and the nature of the thrombotic material. Native arteriovenous access sites (Brescia-Cimino fistulae) fail late in their natural history by virtue of the resistance to thrombosis of native veins even in the presence of progressive outflow disease. Thus, there tends to be extensive stenotic and occlusive venous disease by the time these sites thrombose and attempts at salvage with declotting meet with diminished success. Arteriovenous "bridge" grafts, on the other hand, tend to be more appropriate for declotting procedures due to the predictability and locality of the outflow disease (80% of stenoses at the venous anastomosis) 2° and the relative prolongation of access survival achieved. When clotted, a minority of the graft volume (~25%) contains loose, soft thrombus, whereas most of the remainder contains predominantly serum. 21 The only firm substance in the graft is the "arterial plug" or "bullet" which is 5 mm to 3 cm long and composed of alternating and very compacted layers of red cells and fibrin and which is not platelet rich. ~I The compact arterial plug is relatively resistant to thrombolysis and often requires prolonged thrombolytic infusion to clear the leading segment of grafts. This is perhaps the strongest argument for addition of rapid mechanical techniques to graft declotting protocols and why crossingcatheter infusion thrombolysis has rapidly been phased out. The steps after puncture in hemodialysis graft declotting include outflow venography, thrombus removal, treatment of lesions responsible for thrombosis, and dislodgment of the arterial plug. There is general agreement that the outflow venogram be performed as the first step, because perhaps 10% to 15% of intended declotting sessions are abandoned on the basis of extent of outflow disease on the venogram. 22 Opinions regarding the order of the other three steps vary with proponents of declotting prior to angioplasty stressing the desire to adequately fragment thrombus before "prematurely" embolizMARTIN R. CRAIN
Fig 5. Hydrolyser mechanical thrombectomy device. Magnification of catheter tip over a wire (A). Local pressure gradient created by the Bernoulli principle which produces eccentric suction with this device (B).
ing to the lungs, while others favor angioplasty before declotting to avoid excessive intragraft pressure during PMT to protect against arterial embolization (especially with hydraulic devices). Techniques and results of many methods for rapid declotting have been published, including pulse-spray techniques withOUt 9 and with 2° UK, mechanical declotting with balloons alone, 23,24 and with the Hydrolyser,25 Amplatz, 26 and Trerotola 27 devices. Details of performance and outcome of the competing strategies are presented elsewhere in this issue; all produce similar results in experienced hands. Patency is determined by the ability to diagnose and correct responsible lesions rather than the method of declotting. Common to all the methods of declotting is the need to dislodge the arterial plug with a balloon catheter. After dislodgment, the plug is then either allowed to embolize to the pulmonary circulation or is fragmented within the graft. The fate of embolized fragments remains the subject of considerable debate. In series using balloon maceration and dislodgment alone without removal, the authors have pointed out how well deliberate pulmonary embolization of soft, macerated fragments is tolerated. 23,24In fact, it has been shown that PSPMT causes more significant pulmonary emboli (PE) than PMT. 1° On the other hand, others cite significant, if not frequent, morbidity and mortality from acute deliberate PE, and point out that the long-term effect of repeated intentional TABLE 7. Hydrolyser Summary Device strengths Low vessel injury potential Wire compatible Particle evacuation
Limitations Not FDA-approved (1998) Promising applications Hemodialysis grafts Arterial use? DVT? PMT AND THROMBECTOMY
pulmonary embolization in a population with limited cardiopulmonary reserve is not known. It should be clearly pointed out that PMT is contraindicated in patients with right-to-left shunts, severe cardiopulmonary compromise, and suspected graft infection (potential septic emboli), and in such cases surgical thrombectomy should be performed. 1°
Arterial Grafts and Native Arteries Series reporting the early arterial experience with Group I1 devices have been published for the Amplatz ATD in 14 patients, 2s the Angiojet in 50 patients, 29 and the Hydrolyser in 28 patients, 19 and 36 patients. 3° Because of the limits of device sizes~ use has been restricted predominantly to the superficial femoral artery and in synthetic and vein bypass grafts. The reported rates of complete success without concomitant thrombolytic infusion in these early series range from 50% to 70%. Embolization of thrombus fragments is a primary concern with PMT in arterial beds and was reported in 4% to 18%.19,2s Some of the embolic events were reportedly asymptomatic, but others required adjunctive thrombolysis, thromboaspiration, or operative embolectomy, and avoiding premature amputation remains a concern. Nonetheless, the early results are promising enough to warrant further investigation and it should be kept in mind that distal embolization may also occur with pharmacological thrombolysis or may be partially attributable to angioplasty itself.28 Several maneuvers have been recommended to avoid or minimize the risk of thrombus embolization in peripheral arterial applications. Undesired proximal displacement of thrombus can be minimized by initiating suction proximal to the occluded segment with Group II devices. 19 A blood pressure cuff applied distal to the treated segment and inflated to suprasystolic pressure has been recommended to protect the distal circulation from embolized debris. 28 The distal circulation can also be protected by inflating balloons to isolate thrombus during PMT, completing PMT before dilating out-
241
flow stenoses, and not traversing distal stenoses with the deviceJ 9 The acceptable limit of particle size produced by PMT and the target circulation at risk must also be considered if the technique is extended to other arterial applications. Although microemboli (angiographically occult, generally <500 lain) probably represent a low risk for ischemic injury in pulmonary and peripheral arteries, they may be significant in visceral and neurovascular territories. The other primary concern about use of PMT devices in peripheral arteries is the possibility of inducing arterial injury. Available animal work to date suggests that the Group II devices are relatively safe and certainly an improvement over balloon thromboembolectomy. Over-the-wire capability also minimizes the risk of subintimal passage and arterial perforation.
References
Pulmonary Emboli Rapid debulking of large proximal emboli with PMT and redistribution into the larger capacity peripheral pulmonary bed are theoretically attractive in reducing pulmonary arterial resistance, improving right heart hemodynamics, and improving oxygenation after acute, massive PE. Only case reports and small series with use of Group II devices in massive PE have been published. 3°-33 The published experience is too small to draw any definite conclusions on clinical efficacy. The major deficiencies which will probably significantly limit the applicability of current devices in acute PE are ineffectiveness in treating vessels larger than 8 to 10 mm and limited maneuverability. Although some individuals espouse creation of a "working channel" through large thrombus, there are no data yet to support the efficacy of the technique. Other prototypes of devices designed for the pulmonary artery have been described, one featuring a mechanically rotating pigtail catheter 34 and another an impeller (or small rotating basket) housed within a larger stationary basket for centering and protecting the pulmonary artery wall. 35 Very little human data are available, and it is clear that significant device modification and clinical experience is required before PMT can be routinely recommended in acute PE.
Deep Vein Thrombosis There is only anecdotal experience with the use of PMT in deep vein thrombosis (DVT). Nonetheless, methods for completely or adjunctively treating venous thrombosis are largely unexplored in this entity for which no definitive treatment is well-accepted, including catheter-directed thrombolytic therapy. The goals of PMT in lower extremity DVT are relief of thrombotic obstruction and preservation of valvular function for prevention of the postthrombotic syndrome, as well as removal of the source of PE. In treating DVT, it is imperative that PMT methods do not irreparably damage the vein walls or valves. Preliminary experimental work with the Amplatz ATD indicates that device-induced injury may be modest, keeping alive the concept that there may be a potential role for PMT in this vastly undertreated disorder.
Conclusion Devices for mechanical thrombectomy and thrombolysis have been rapidly accepted for treatment of thrombosed hemodialy-
242
sis grafts and have contributed to a further understanding of the process and pitfalls of rapid hemoaccess declotting. The devices approved for use by the FDA in the United States are not approved for use elsewhere in the body. Further design modification, extensive basic vascular research, and properly designed clinical trials will be necessary before recommending routine use in other less-forgiving vascular territories. The potential for PMT to provide faster, less expensive clearance of thrombosed vessels while shortening bedrest, minimizing intensive care unit stays, and reducing complications will continue to drive investigation of this technology at a rapid pace. A prominent role for PMT in arterial disease, venous thromboembolic disease, central venous thrombosis, and failed hemodialysis access in the future is almost certain.
1. Dobrin PB: Mechanisms and prevention of arterial injuries caused by balloon embolectomy. Surgery 106:457-466, 1989 2. Bowles CR, OIcott C, Pakter RL, et al: Diffuse arterial narrowing as a result of intimal proliferation: A delayed complication of embolectomy with the Fogarty balloon catheter. J Vasc Surg 7:487-494, 1988 3. Sharafuddin MJA, HicksME:Currentstatusof percutaneous mechanical thrombectomy. Part I. General principles. J Vasc Interv Radiol 8:911-921,1997 4. Sharafuddin MJA, Hicks ME: Current status of percutaneous mechanical thrombectomy. Part I1. Devices and mechanisms of action. J Vasc Interv Radiol 9:15-31, 1998 5. Sharafuddin MJA, Hicks ME: Current status of percutaneous mechanical thrombectomy. Part II1. Present and future applications. J Vasc Interv Radiol 9:209-224, 1998 6. Dolmatch B: New devices for mechanical thrombectomy of dialysis grafts, in SCVIR 98 Workshop Handout Book: 23rd annual scientific meeting of the Society of Cardiovascular and Interventional Radiology, February 28-March 5, 1998, San Francisco, pp 340-343 7. Lajvardi A, Trerotola SO, Strandberg JD, et al: Evaluation of venous injury caused by a percutaneous mechanical thrombectomy device. Cardiovasc Intervent Radiol 18:172-178, 1995 8. Trerotola SO, Davidson DD, Filo RS, et al: Preclinical in vivo testing of a rotational mechanical thrombectomy device. J Vasc Interv Radiol 7:717-723, 1996 9. Beathard GA: Mechanical versus pharmacomechanical thrombolysis for the treatment of thrombosed dialysis access grafts. Kidney Internat 45:1401-1406, 1994 10. Trerotola SO, Johnson MS, Schauwecker DS, et al: Pulmonary emboli from pulse-spray and mechanical thrombolysis: Evaluation with an animal dialysis graft model. Radiology 200:169-176, 1996 11. Yasui K, Qian Z, Nazarian GK, et al: Recirculation-type Amplatz clot macerator: Determination of particle size and distribution. J Vasc Interv Radiol 4:275-278, 1993 12. Nazarian GK, Qian Z, Coleman CC, et al: Hemolytic effect of the Amplatz thrombectomy device. J Vasc interv Radiol 5:155-160, 1994 13. Gomes MR, Pozza CH, Qian Z, et al: Radiographic and histopathologic evaluation of the vessel wall after using the Amplatz maceration aspiration thrombectomy device. Cardiovasc Interv Radiol 17:$112, 1994 (suppl 2) (abstr) 14. Sharafuddin MJA, Gu X, Urness M, et al: Lack of acute injury to venous valves by the Amplatz thrombectomy device during experimental antegrade venous thrombectomy. J Vasc Interv Radiol 9:203, 1998 (abstr) 15. Drasler W J, Jenson ML, Wilson GJ, et al: Rheolytic catheter for percutaneous removal of thrombus. Radiology 182:263-267, 1992 16. Sharafuddin MJ, Hicks ME, Jenson ML, et al: Rheolytic thrombectomy with use of the AngioJet F105 catheter: Preclinical evaluation of safety. J Vasc Interv Radiol 8:939-945, 1997 17. Reekers JA, Kromhout JG, van der Waal: Catheter for percutaneous thrombectomy: First clinical experience. Radiology 188:871-874, 1993 18. van Ommen VG, van der Veen FH, Geskes GG, et al: Comparison of arterial wall reaction after passage of the Hydrolyser device versus a MARTIN R. CRAIN
19.
20.
21.
22. 23.
24.
25,
26.
thrombectomy balloon in an animal model. J Vasc Interv Radiol 7:451-454, 1996 Reekers JA, Kromhout JG, Spithoven HG, et al: Arterial thrombosis below the inguinal ligament: Percutaneous treatment with a thrombosuction catheter. Radiology 198:49-53, 1996 Valji K, Bookstein J J, Roberts AC, et al: Pulse-spray pharmacomechanical thrombolysis of thrombosed hemodialysis access grafts: Long-term experience and comparison of original and current techniques. Am J Roentgeno1164:1495-1500, 1995 Winkler TA, Trerotola SO, Davidson DD, et al: Study of thrombus from thrombosed hemodialysis access grafts. Radiology 197:461-465, 1995 Vesely TM: Management of thrombosed dialysis grafts. J Vasc Interv Radiol 9:124-129, 1998 (suppl) Trerotola SO, Lund GB, Scheel PJ Jr, et al: Thrombosed dialysis access grafts: Percutaneous mechanical declotting without urokinase. Radiology 191:721-726, 1994 Middlebrook MR, Amygdalos MA, Soulen MC, et al: Thrombosed hemodialysis grafts: Percutaneous mechanical balloon declotting versus thrombolysis. Radiology 196:73-77, 1995 Vorwerk D, Sohn M, Schurmann K, et al: Hydrodynamic thrombectomy of hemodialysis fistulas: First clinical results. J Vasc Interv Radiol 5:813-821, 1994 Uflacker R, Ragagopalan PR, Vujic I, et al: Treatment of thrombosed dialysis access grafts: Randomized trial of surgical thrombectomy versus mechanical thrombectomy with the Amplatz device. J Vasc Interv Radiol 7:185-192, 1996
PMT AND THROMBECTOMY
27. Trerotola SO, Vesely TM, Lund GB, et al: Treatment of thrombosed hemodialysis access grafts: Arrow-Trerotola percutaneous device versus pulse-spray thrombolysis. Radiology 206:403-414, 1998 28. Tadavarthy SM, Murray PD, Inampudi S, et al: Mechanical thrombectomy with the Amplatz device. Human experience. J Vasc Interv Radiol 5:715-724, 1994 29. Wagner HJ, Muller-Hulsbeck S, Pitton MB, et al: Rapid thrombectomy with a hydrodynamic catheter: Results from a prospective, multicenter trial. Radiology 205:675-681, 1997 30. Henry M, Amor M, Henry I, et al: The Hydrolyser thrombectomy catheter: A single-center experience. J Endovasc Surg 5:24-31, 1998 31. Uflacker R, Strange C, Vujic I: Massive pulmonary embolism: Preliminary results of treatment with the Amplatz thrombectomy device. J Vasc Interv Radiol 7:519-528, 1996 32. Koning R, Cdbier A, Gerber L, et at: A new treatment for severe pulmonary embolism: Percutaneous rheolytic thrombectomy. Circulation 96:2498-2500, 1997 33. Michalis LK, Tsetis DK, Rees MR: Percutaneous removal of pulmonary artery thrombus in a patient with massive pulmonary embolism using the Hydrolyser catheter: The first human experience. Clin Radio152:158-161, 1997 34. Schmitz-Rode T, Guenther RW, Pfeffer JG, et al: Acute massive pulmonary embolism: Use of a rotatable pigtail catheter for diagnosis and fragmentation therapy. Radiology 197:157-162, 1995 35. Schmitz-Rode T, Adam G, Kilbinger M, et al: Fragmentation of pulmonary emboli: In vivo experimental evaluation of two high-speed rotating catheters. Cardiovasc Interv Radiol 19:165-169, 1996
243
Devices and methods for mechanically dissolving (thrombolysis) and removing (thrombectomy) thrombus using a percutaneous approach have been developed to address the deficiencies of the previously available methods of treating thrombus, namely Fogarty balloon thromboembolectomy and pharmacologic thrombolysis, Goals of percutaneous mechanical thrombectomy (PMT) include faster, safer, and less expensive treatment of vascular thrombosis, either alone or in conjunction with prior methods. PMT devices have rapidly assumed a role in declotting thrombosed hemodialysis access synthetic grafts, and may eventually play an integral part in many other thrombotic conditions. However, significant device refinement and modification, as well as properly conducted clinical trials, will be necessary before routine use in many applications can be advocated. In this article, each of the PMT devices currently (or soon to be) available in the United States are presented and compared. Each is approved by the Food and Drug Administration for use only in hemodialysis access at the present time. Copyright © 1998 by W.B. Saunders Company
n the search for methods to more rapidly, effectively, and safely remove thrombus compromising blood flow, it has become evident that mechanical fragmentation and dissolution is desirable as an adjunct to pharmacological thrombolysis or as stand-alone therapy. The first significant clinical experience with a mechanical method of thrombus liberation was with Fogarty-type compliant balloons in the operating room. By expanding to cover the entire circumference of a vessel, these balloons have allowed surgeons to rapidly and effectively clear emboli and thrombus from major vessels and grafts. However, balloons have several limitations, including need for open surgical introduction and thrombus removal, lack of directability, inability to clear thrombus from side branches, and significant trauma causing subsequent occlusion, especially in small vessels. 1,2 The other common method using mechanical fragmentation is so-called pharmacomechanical pulse-spray thrombolysis (PSPMT), a process by which small jets of fluid are forcefully ejected from multiple catheter sideholes to achieve both mechanical fragmentation and increasing the surface area to which thrombus is exposed to a thrombolytic agent. This method is particularly helpful in very acute thrombus, but in many arterial and venous thromboses, it produces insufficient maceration and fragmentation to replace
I
From the Department of Vascular/Interventional Radiology, Medical College of Wisconsin, Milwaukee, Wi. Address reprint requests to Martin R. Crain, MD, Assistant Professor of Radiology, Section of Vascular/Interventional Radiology, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, Room 2803, 9200 W Wisconsin Ave, Milwaukee, Wl 53226. Copyright © 1998 by W.B. Saunders Company 1089-2516/98/0104-001058.00/0
or substantially reduce the need for prolonged thrombolytic infusion. The inherent deficiencies of both methods have accelerated the evolution of devices and methods for fragmenting, mobilizing, and clearing thrombus inhibiting flow and causing disease. Defining the optimal characteristics of the "ideal" method to achieve thrombus dissolution (thrombolysis) and/or removal (thrombectomy) contributes to the understanding of the advantages and limitations of various devices emerging in the medical marketplace and outlines those areas of continued deficiency which will drive the future evolution and refinement of the mechanical thrombolysis field (Table 1). Unfortunately, the goals of mechanical thrombolysis are often at odds with each other. One primary goal is effective liberation and fragmentation of all thrombus within the vessel lumen and its branches, but at the same time, the native vessels should be protected from injury. Another goal is effective dispersion or removal of fragments, but hemolysis and significant embolization should be avoided. The device should be easily introduced into and negotiated within vessels (or otherwise applied) to rapidly treat thrombus, but should not cause injury at the introduction site or along its path. It becomes clear that there is probably a future for several device types if matched properly to the vessels treated. For instance, a device that vigorously macerates thrombus may be most appropriate for application in hemoaccess grafts and chronic thrombus, whereas a more delicate design may be safest for tibial and pedal arteries. Likewise, it is very unlikely that a device effective for tibial work would be as effective in debulking acute venous thromboembolism in the central pulmonary arteries. This article aims to provide an overview of each of the percutaneous mechanical thrombolytic and thrombectomy (PMT) devices currently in widespread use in the United States and Europe and to highlight features which make particular devices promising in some thrombotic circumstances and limited in others. Several other devices relying on variations of similar physical principles are undergoing bench and clinical evaluation and are not covered. The clinical experience to date in the major categories of thrombosis and embolism is also discussed. For a more detailed discussion of all aspects of mechanical thrombolysis and thrombectomy, the reader is referred to an excellent three-part review by Sharafuddin and Hicks. 3-5
Device Descriptions One of the more beneficial ways to categorize PMT devices is to differentiate those which expand within a vessel lumen to substantially contact the vessel wall (Group I) from others which produce thrombus fragmentation by induction of forces such as fluid penetration, suction, and recirculation (Group
Techniques in Vascular and Interventional Radiology, Vol 1, No 4 (December), 1998: pp 235-243
235
TABLE 1. Characteristics of the Ideal Mechanical Thrombolysis/Thrombectomy Device Remove all clot Replace (or reduce dose of) thrombolytic agent Effective against acute, chronic, and "arterial plug" thrombus Nontraumatic to native vessels No distal embolization (arterial and venous) Minimal blood loss; minimal hemolysis Wide range of vessel diameter applications Inexpensive Rapid Operator ease-of-use (simple, reliable) Flexible and directaNe Guidewire compatible Small diameter entry
II). 6 This categorization allows broad separation of those devices potentially exerting vigorous contact against the vessel wall and producing possible native vessel injury from the group of devices which rely on less direct methods of thrombus mobilization, but which may be limited in their ability to effectively fragment more organized material. By making contact with the entire luminal cross-section, Group I devices physically detach thrombus from the wall. Contents are often macerated into relatively large particles and require physical removal or adjunctive pharmacological thrombolysis if embolization avoidance is desired. Group II devices, on the other hand, use principles which tend to produce smaller particles which can either be easily suctioned or may be allowed to embolize without significant deleterious effect.
Group I Fogarty-type thrombectomy balloons. The Fogarty balloon (Baxter Healthcare, Santa Ana, CA) has been the mainstay of surgical thrombectomy and embolectomy. The technique requires open surgical exposure and blind passage of the catheter. For percutaneous, fluoroscopically guided work, several over-the-wire catheters are available (including the Fogarty ThruLumen catheter, Baxter Healthcare). These balloons use compliant materials such as latex which allow the balloon to expand to contact the entire circumference in a range of vessel diameters. Relatively noncompliant angioplasty balloons may also be used to dislodge thrombus and the "arterial plug" from hemoaccess grafts, but may leave adherent material when the balloon wings do not fully expand in instances when the balloon diameter exceeds the graft diameter. A primary limitation of balloon catheters is that they only dislodge material and do not adequately address further fragmentation in most instances. Therefore, their routine use in percutaneous procedures is mostly limited to dislodgment of the arterial plug in hemoaccess graft declotting (information to follow). Another significant limitation is the severe arteriaP ,2 and venous 7 injuries they can induce. Table 2 highlights advantages and disadvantages of compliant thrombectomy balloons. Arrow-Trerotola percutaneous thrombectomy device. The Arrow-Trerotola percutaneous thrombectomy device (PTD) (Arrow International, Inc, Reading, PA) (Fig 1), consists of a self-expanding nitinol cage basket deployed from its compressed state through a 5F catheter, s It is connected by a wire driveshaft to a battery-powered motor drive unit, which spins the basket at 3,000 rpm. It does not pass over a guidewire, but is flexible enough to be advanced through curves in synthetic
236
grafts. Thrombus is fragmented into particles less than 3 mm in diameter with the majority less than 1 mm. The device is placed through a 5F (minimum) sheath. The maximum open diameter of the basket is 9 ram. The PTD is approved by the Food and Drug Administration (FDA) for use in synthetic hemodialysis access grafts without concomitant administration of a thrombolytic agent. Aspiration of fragments is recommended but there is no significant blood loss. The hand-held device is easy to use, although may damage veins, crossing sheaths, and intravascular stents if not used with caution. Because of the relatively vigorous nature of the spinning cage, the device is also effective in removing adherent fibrotic material, which tends to line hemoaccess grafts. On the other hand, it has been shown to cause extensive endothelial denudation in veins and is more likely than Group II devices to cause permanent vascular injury and is not intended for use in native vessel segments. 7 The likelihood of distal embolization of sizeable fragments also limits its use in arteries. Table 3 highlights advantages and disadvantages of the PTD. Cragg/Castaneda thrombolytic brush catheter systems. Two spinning brush catheters are currently available from Micro Therapeutics, Inc. The original design (Cragg thrombolytic brush catheter system; Micro Therapeutics, Inc, San Clemente, CA) (Fig 2), consists of a "bottle brush" at the tip of a driveshaft which in turn is rotated by a hand-held battery-powered motor drive unit. The brush expands to a diameter of 6 mm when unconstrained. The bristles at the expandable tip are soft when deployed from the 6F catheter, but become resilient with spinning centrifugal force and effectively whisk the luminal surface of hemodialysis grafts. More recently released is the modified version (Castaneda brush) which possesses stiffer bristles and which can be advanced over a 0.035" guidewire. Concomitant urokinase (UK) administration is recommended in the FDA-approved instructions for use, but there is no reason to believe that the thrombolytic effect without UK would be any different from that produced by the Trerotola PTD. Like the PTD, the brush catheters are easy to use, but the same limitations of potential vascular injury and residual particle size limit their use outside of hemodialysis grafts. Table 4 highlights advantages and disadvantages of thrombectorny brush catheters.
Group II PSPMT catheters. Multisidehole catheters of various designs have been used extensively in assisting pharmacological thrombolysis. Thrombolytic agents are delivered through jets oriented perpendicularly within a thrombosed segment to fragment thrombus and increase the surface area to which the agent is exposed. Results and discussion of techniques are addressed in detail in other articles in this issue. It is also notable that heparinized saline has also been delivered with a similar technique in thrombosed hemodialysis grafts with TABLE 2. Fogarty-Type Balloon Summary Device strengths Addresses chronic thrombus and "arterial plug" Limitations Arterial and venous injury Inadequate thrombus fragmentation Promising applications Adjunct to hemodialysis graft declotting MARTIN R. CRAIN
Fig 1. Arrow-Trerotola PTD. Motor drive unit, catheter, and nitinol basket (A), (Reprinted with permission from Trerotola SO, Vesely TM, Lund GB, et ah Treatment of thrombosed hemodialysis access grafts: Arrow-Trerotola percutaneous thrombolytic device versus pulse-spray thrombolysis. Radiology 208:403-414, 1998.) Radiograph showing device deployment in a forearm dialysis access graft (B).
clinical efficacy equal to pulse-spray thrombolysis. 9 The advantages of PSPMT (ease of use, inexpensive catheters) are partially offset by the cost and minor risks of the thrombolytic agents. The principle deficiency, however, is the insufficient particle reduction and removal achieved with this method of thrombus fragmentation, 1° and thus the search for devices and methods to more completely pulverize thrombus has been undertaken, Amplatz thrombectomydevice. The Amplatz thrombectomy device (ATD) (Microvena Corporation, White Bear Lake, MN)
TABLE 3. Arrow-Trerotola PTD Summary Device strengths Ease-of-use; hand-held Vigorous thrombus clearance in hemodialysis grafts Limitations Potential for vascular injury Distal embolization in arteries Promising applications Hemodialysis grafts PMT AND THROMBECTOMY
(Fig 3) was the first of the PMT devices approved by the FDA for use in hemodialysis access grafts (approval August, 1996). It comprises a rapidly spinning helical screw impeller recessed within a short metal protective housing so as not to directly contact vessel wall. The impeller is driven by a cable connected to a small air turbine at the catheter base. The turbine is powered by compressed air (50 to 125 psi) from standard hospital air outlets in most angiographic rooms. The turbine is activated through sterile tubing by a foot pedal/regulator, which is in turn connected by tubing to the compressed air outlet. The turbine spins the impeller at approximately 100,000 rpm to create a vortex, which aspirates thrombus into the catheter housing where it is macerated and then ejected through a side port. Ejected particles are then subject to recirculation, which renders particle sizes between 13 to 1,000 llm, with less than 1% larger than 400 l~m.~1 The catheter currently sold is 8F and requires passage through an introducer sheath or guiding catheter. It is not guidewire-compatible and is limited by its inability to be directed. However, a 6F device and an over-the-wire design are close to release at the time of 237
Fig 2. Cragg/Castaneda thrombolytic brush catheter system. Magnified view of Castaneda brush over a wire with motor drive unit in background (A). The Cragg brush clearing thrombus and restoring flow (B).
this writing. Modification with an asymmetrical sideport to provide directability is also currently under evaluation. Unlike the other Group II devices, the ATD is a recirculation device with no effluent channel and thus no removal of fragments or net blood volume loss. Hemolysis has been shown to occur, and is directly related to cumulative device 238
activation time and more likely once flow has been reestablished} 2 Hemolysis is transient and usually well-tolerated, with no significant adverse effects yet reported. Nonetheless, as hemolysis has definitely been shown experimentally, caution is advised when treating patients at risk for anemia and nephrotoxicity due to free hemoglobin, including those with limited MARTIN R. CRAIN
TABLE 5. Amplatz ATD Summary Device strengths Best particle size reduction Recirculating (no volume Joss) Limitations Hemolysis Promising applications Hemodialysis grafts Arterial? DVT?
Fig 3, Amplatz thrombectomy device. Magnification of the impeller housings of the 6 and 8F devices (A). Impeller suction and recirculation vectors (B).
circulating blood volume (small children), compromised renal function, and preexisting hypoxemia. There are limited data available on the potential for the ATD to cause damage to native vessels. The effect on the arterial wall was studied in dogs, showing focal intimal disruption in two thirds of the vessels examined, but with very rare development of stenosis, x3 In veins, a recent abstract reported that endothelial denudation does occur after passage of the Amplatz ATD in veins of animals, 14 but in a similar experiment in the author's laboratory, gross inspection of valves under a dissecting microscope revealed little structural alteration of valve leaflets after ATD declotting when the device was passed in antegrade direction from below (unpublished data). Table 5 highlights advantages and disadvantages of the ATD. Angiojet rheolytic thrombectomy system. The Angiojet rheolytic thrombectomy system (Possis Medical, Minneapolis, MN) (Fig 4) is the only currently available FDA-approved PMT device based on suction and fragmentation generated by the Venturi effect (so-called "hydrodynamic" device). The original device consisted of two sets of water jets emitted from a small injection port, which terminated within a halo-shaped catheter TABLE 4. Cragg-Castaneda Brush Summary Device strengths Ease-of-use; hand-held Vigorous thrombus clearance in hemodialysis grafts Limitations Potential for vascular injury Distal embolization in arteries Promising applications Hemodialysis grafts
PMT AND THROMBECTOMY
tip. is The first set included a number of radially directed and retrogradely baffled jets for penetration and mobilization of thrombus near the catheter tip. The second high-pressure jet was ejected back into a larger exhaust lumen to create a local region of relative pressure negativity (technically called a stagnation pressure gradient, or the Bernoulli principle). These high-velocity jets produce thrombus suction (the Venturi effect), fragmentation, and removal. Subsequently, the number of jets directed at the exhaust lumen has been increased to produce more powerful suction, and the radially directed jets have been eliminated. Three catheters are currently sold for coronary, peripheral, and hemodialysis graft applications, each a variation of a 5F double lumen catheter with five to six jets. The system requires a special pump, which generates up to 30,000 psi within the pump to drive the water jets ejected at the catheter tip at 1,500 to 2,500 psi. A roller pump controls the removal of effluent into a collection bag. The catheters accommodate guidewires of 0.018" diameter through the exhaust lumen. A principle advantage of hydrodynamic catheters is their low potential for vascular injury when compared with Group I devices. The Angiojet proved to be safe in arterial passage in an animal model, producing only focal regions of minor endothelial denudation) 6 The biggest drawback of the Angiojet system to date has been the cost and size of the floor-standing pump unit, but a smaller pump, which may be mounted on an IV pole, is reportedly forthcoming. As with the Amplatz device, hemolysis can occur with prolonged activation times, especially after reestablishing flow. Venturi-based devices such as the Angiojet which exhaust thrombus, fluid, and blood may also result in blood volume loss, and close monitoring of infusion and evacuation volumes and hematocrit is recommended. Table 6 highlights advantages and disadvantages of the Angiojet device. Hydrolyser mechanical thrombectomy device. The initial version of the Hydrolyser mechanical thrombectomy device 0JIS-Cordis Endovascular, Warren, NJ) (Fig 5) is a 7F design with a small, asymmetrically located injection lumen inside a larger exhaust lumen) 7 The injection port terminates in a J-configuration in the closed distal tip of the catheter so as to provide a single high pressure, low volume jet that is oriented back into the exhaust lumen. As the jet passes a large (6 mm), asymmetrically placed thrombectomy side hole, it produces local pressure reduction which induces thrombus suction (the Venturi effect), fragmentation, and removal. The 7F catheter may be used over a 0.025" wire traversing the larger exhaust lumen. The single pressure jet is produced by connecting the injection lumen to a standard angiographic injector and infusing 4 mL/s at 750 psi. Effluent containing thrombus particles is exhausted into a collection bag. A 6F triple lumen catheter has also been designed with the third lumen accommo-
239
dating a 0.020" wire. The 7F catheter is designed for use in 5 to 9 mm vessels and the 6F catheter treats vessels 3 to 8 ram. Initial data suggest the Hydrolyser is relatively safe in the arterial system, inducing significantly less arterial intimal
TABLE 6. Angiojet RTC Summary Device strengths Low vessel injury potential Wire-compatible Particle evacuation Limitations Start-up costs for pump; cumbersome Promising applications Hemodialysis grafts Arterial use? DVT?
hyperplasia at 3 weeks than balloon thrombectomy in an animal model38 The so-called hydrodynamic devices appear most effective in acute (<10 day) thrombus. 19 A distinct advantage of the Hydrolyser as compared with the Angiojet device is that the Hydrolyser runs off existing equipment in an interventional laboratory. At this time, the Hydrolyser is not approved by the FDA for use in the United States. Table 7 highlights advantages and disadvantages of the Hydrolyser device.
Clinical Experience
Hemodialysis Grafts
Fig 4. Angiojet rheolytic thrombectomy system. Magnification of catheter tip of the AV 60 dialysis device, Note several jets impinging on the large exhaust lumen (A), Schematic of the local Venturi effect producing thrombus suction and mobilization, Rounded catheter tip in this schematic depicts the longer devices intended for coronary and peripheral vascular applications (B). 240
To evaluate the role of the various methods of declotting thrombosed hemodialysis access sites, it is helpful to understand the pathophysiology leading to access thrombosis and the nature of the thrombotic material. Native arteriovenous access sites (Brescia-Cimino fistulae) fail late in their natural history by virtue of the resistance to thrombosis of native veins even in the presence of progressive outflow disease. Thus, there tends to be extensive stenotic and occlusive venous disease by the time these sites thrombose and attempts at salvage with declotting meet with diminished success. Arteriovenous "bridge" grafts, on the other hand, tend to be more appropriate for declotting procedures due to the predictability and locality of the outflow disease (80% of stenoses at the venous anastomosis) 2° and the relative prolongation of access survival achieved. When clotted, a minority of the graft volume (~25%) contains loose, soft thrombus, whereas most of the remainder contains predominantly serum. 21 The only firm substance in the graft is the "arterial plug" or "bullet" which is 5 mm to 3 cm long and composed of alternating and very compacted layers of red cells and fibrin and which is not platelet rich. ~I The compact arterial plug is relatively resistant to thrombolysis and often requires prolonged thrombolytic infusion to clear the leading segment of grafts. This is perhaps the strongest argument for addition of rapid mechanical techniques to graft declotting protocols and why crossingcatheter infusion thrombolysis has rapidly been phased out. The steps after puncture in hemodialysis graft declotting include outflow venography, thrombus removal, treatment of lesions responsible for thrombosis, and dislodgment of the arterial plug. There is general agreement that the outflow venogram be performed as the first step, because perhaps 10% to 15% of intended declotting sessions are abandoned on the basis of extent of outflow disease on the venogram. 22 Opinions regarding the order of the other three steps vary with proponents of declotting prior to angioplasty stressing the desire to adequately fragment thrombus before "prematurely" embolizMARTIN R. CRAIN
Fig 5. Hydrolyser mechanical thrombectomy device. Magnification of catheter tip over a wire (A). Local pressure gradient created by the Bernoulli principle which produces eccentric suction with this device (B).
ing to the lungs, while others favor angioplasty before declotting to avoid excessive intragraft pressure during PMT to protect against arterial embolization (especially with hydraulic devices). Techniques and results of many methods for rapid declotting have been published, including pulse-spray techniques withOUt 9 and with 2° UK, mechanical declotting with balloons alone, 23,24 and with the Hydrolyser,25 Amplatz, 26 and Trerotola 27 devices. Details of performance and outcome of the competing strategies are presented elsewhere in this issue; all produce similar results in experienced hands. Patency is determined by the ability to diagnose and correct responsible lesions rather than the method of declotting. Common to all the methods of declotting is the need to dislodge the arterial plug with a balloon catheter. After dislodgment, the plug is then either allowed to embolize to the pulmonary circulation or is fragmented within the graft. The fate of embolized fragments remains the subject of considerable debate. In series using balloon maceration and dislodgment alone without removal, the authors have pointed out how well deliberate pulmonary embolization of soft, macerated fragments is tolerated. 23,24In fact, it has been shown that PSPMT causes more significant pulmonary emboli (PE) than PMT. 1° On the other hand, others cite significant, if not frequent, morbidity and mortality from acute deliberate PE, and point out that the long-term effect of repeated intentional TABLE 7. Hydrolyser Summary Device strengths Low vessel injury potential Wire compatible Particle evacuation
Limitations Not FDA-approved (1998) Promising applications Hemodialysis grafts Arterial use? DVT? PMT AND THROMBECTOMY
pulmonary embolization in a population with limited cardiopulmonary reserve is not known. It should be clearly pointed out that PMT is contraindicated in patients with right-to-left shunts, severe cardiopulmonary compromise, and suspected graft infection (potential septic emboli), and in such cases surgical thrombectomy should be performed. 1°
Arterial Grafts and Native Arteries Series reporting the early arterial experience with Group I1 devices have been published for the Amplatz ATD in 14 patients, 2s the Angiojet in 50 patients, 29 and the Hydrolyser in 28 patients, 19 and 36 patients. 3° Because of the limits of device sizes~ use has been restricted predominantly to the superficial femoral artery and in synthetic and vein bypass grafts. The reported rates of complete success without concomitant thrombolytic infusion in these early series range from 50% to 70%. Embolization of thrombus fragments is a primary concern with PMT in arterial beds and was reported in 4% to 18%.19,2s Some of the embolic events were reportedly asymptomatic, but others required adjunctive thrombolysis, thromboaspiration, or operative embolectomy, and avoiding premature amputation remains a concern. Nonetheless, the early results are promising enough to warrant further investigation and it should be kept in mind that distal embolization may also occur with pharmacological thrombolysis or may be partially attributable to angioplasty itself.28 Several maneuvers have been recommended to avoid or minimize the risk of thrombus embolization in peripheral arterial applications. Undesired proximal displacement of thrombus can be minimized by initiating suction proximal to the occluded segment with Group II devices. 19 A blood pressure cuff applied distal to the treated segment and inflated to suprasystolic pressure has been recommended to protect the distal circulation from embolized debris. 28 The distal circulation can also be protected by inflating balloons to isolate thrombus during PMT, completing PMT before dilating out-
241
flow stenoses, and not traversing distal stenoses with the deviceJ 9 The acceptable limit of particle size produced by PMT and the target circulation at risk must also be considered if the technique is extended to other arterial applications. Although microemboli (angiographically occult, generally <500 lain) probably represent a low risk for ischemic injury in pulmonary and peripheral arteries, they may be significant in visceral and neurovascular territories. The other primary concern about use of PMT devices in peripheral arteries is the possibility of inducing arterial injury. Available animal work to date suggests that the Group II devices are relatively safe and certainly an improvement over balloon thromboembolectomy. Over-the-wire capability also minimizes the risk of subintimal passage and arterial perforation.
References
Pulmonary Emboli Rapid debulking of large proximal emboli with PMT and redistribution into the larger capacity peripheral pulmonary bed are theoretically attractive in reducing pulmonary arterial resistance, improving right heart hemodynamics, and improving oxygenation after acute, massive PE. Only case reports and small series with use of Group II devices in massive PE have been published. 3°-33 The published experience is too small to draw any definite conclusions on clinical efficacy. The major deficiencies which will probably significantly limit the applicability of current devices in acute PE are ineffectiveness in treating vessels larger than 8 to 10 mm and limited maneuverability. Although some individuals espouse creation of a "working channel" through large thrombus, there are no data yet to support the efficacy of the technique. Other prototypes of devices designed for the pulmonary artery have been described, one featuring a mechanically rotating pigtail catheter 34 and another an impeller (or small rotating basket) housed within a larger stationary basket for centering and protecting the pulmonary artery wall. 35 Very little human data are available, and it is clear that significant device modification and clinical experience is required before PMT can be routinely recommended in acute PE.
Deep Vein Thrombosis There is only anecdotal experience with the use of PMT in deep vein thrombosis (DVT). Nonetheless, methods for completely or adjunctively treating venous thrombosis are largely unexplored in this entity for which no definitive treatment is well-accepted, including catheter-directed thrombolytic therapy. The goals of PMT in lower extremity DVT are relief of thrombotic obstruction and preservation of valvular function for prevention of the postthrombotic syndrome, as well as removal of the source of PE. In treating DVT, it is imperative that PMT methods do not irreparably damage the vein walls or valves. Preliminary experimental work with the Amplatz ATD indicates that device-induced injury may be modest, keeping alive the concept that there may be a potential role for PMT in this vastly undertreated disorder.
Conclusion Devices for mechanical thrombectomy and thrombolysis have been rapidly accepted for treatment of thrombosed hemodialy-
242
sis grafts and have contributed to a further understanding of the process and pitfalls of rapid hemoaccess declotting. The devices approved for use by the FDA in the United States are not approved for use elsewhere in the body. Further design modification, extensive basic vascular research, and properly designed clinical trials will be necessary before recommending routine use in other less-forgiving vascular territories. The potential for PMT to provide faster, less expensive clearance of thrombosed vessels while shortening bedrest, minimizing intensive care unit stays, and reducing complications will continue to drive investigation of this technology at a rapid pace. A prominent role for PMT in arterial disease, venous thromboembolic disease, central venous thrombosis, and failed hemodialysis access in the future is almost certain.
1. Dobrin PB: Mechanisms and prevention of arterial injuries caused by balloon embolectomy. Surgery 106:457-466, 1989 2. Bowles CR, OIcott C, Pakter RL, et al: Diffuse arterial narrowing as a result of intimal proliferation: A delayed complication of embolectomy with the Fogarty balloon catheter. J Vasc Surg 7:487-494, 1988 3. Sharafuddin MJA, HicksME:Currentstatusof percutaneous mechanical thrombectomy. Part I. General principles. J Vasc Interv Radiol 8:911-921,1997 4. Sharafuddin MJA, Hicks ME: Current status of percutaneous mechanical thrombectomy. Part I1. Devices and mechanisms of action. J Vasc Interv Radiol 9:15-31, 1998 5. Sharafuddin MJA, Hicks ME: Current status of percutaneous mechanical thrombectomy. Part II1. Present and future applications. J Vasc Interv Radiol 9:209-224, 1998 6. Dolmatch B: New devices for mechanical thrombectomy of dialysis grafts, in SCVIR 98 Workshop Handout Book: 23rd annual scientific meeting of the Society of Cardiovascular and Interventional Radiology, February 28-March 5, 1998, San Francisco, pp 340-343 7. Lajvardi A, Trerotola SO, Strandberg JD, et al: Evaluation of venous injury caused by a percutaneous mechanical thrombectomy device. Cardiovasc Intervent Radiol 18:172-178, 1995 8. Trerotola SO, Davidson DD, Filo RS, et al: Preclinical in vivo testing of a rotational mechanical thrombectomy device. J Vasc Interv Radiol 7:717-723, 1996 9. Beathard GA: Mechanical versus pharmacomechanical thrombolysis for the treatment of thrombosed dialysis access grafts. Kidney Internat 45:1401-1406, 1994 10. Trerotola SO, Johnson MS, Schauwecker DS, et al: Pulmonary emboli from pulse-spray and mechanical thrombolysis: Evaluation with an animal dialysis graft model. Radiology 200:169-176, 1996 11. Yasui K, Qian Z, Nazarian GK, et al: Recirculation-type Amplatz clot macerator: Determination of particle size and distribution. J Vasc Interv Radiol 4:275-278, 1993 12. Nazarian GK, Qian Z, Coleman CC, et al: Hemolytic effect of the Amplatz thrombectomy device. J Vasc interv Radiol 5:155-160, 1994 13. Gomes MR, Pozza CH, Qian Z, et al: Radiographic and histopathologic evaluation of the vessel wall after using the Amplatz maceration aspiration thrombectomy device. Cardiovasc Interv Radiol 17:$112, 1994 (suppl 2) (abstr) 14. Sharafuddin MJA, Gu X, Urness M, et al: Lack of acute injury to venous valves by the Amplatz thrombectomy device during experimental antegrade venous thrombectomy. J Vasc Interv Radiol 9:203, 1998 (abstr) 15. Drasler W J, Jenson ML, Wilson GJ, et al: Rheolytic catheter for percutaneous removal of thrombus. Radiology 182:263-267, 1992 16. Sharafuddin MJ, Hicks ME, Jenson ML, et al: Rheolytic thrombectomy with use of the AngioJet F105 catheter: Preclinical evaluation of safety. J Vasc Interv Radiol 8:939-945, 1997 17. Reekers JA, Kromhout JG, van der Waal: Catheter for percutaneous thrombectomy: First clinical experience. Radiology 188:871-874, 1993 18. van Ommen VG, van der Veen FH, Geskes GG, et al: Comparison of arterial wall reaction after passage of the Hydrolyser device versus a MARTIN R. CRAIN
19.
20.
21.
22. 23.
24.
25,
26.
thrombectomy balloon in an animal model. J Vasc Interv Radiol 7:451-454, 1996 Reekers JA, Kromhout JG, Spithoven HG, et al: Arterial thrombosis below the inguinal ligament: Percutaneous treatment with a thrombosuction catheter. Radiology 198:49-53, 1996 Valji K, Bookstein J J, Roberts AC, et al: Pulse-spray pharmacomechanical thrombolysis of thrombosed hemodialysis access grafts: Long-term experience and comparison of original and current techniques. Am J Roentgeno1164:1495-1500, 1995 Winkler TA, Trerotola SO, Davidson DD, et al: Study of thrombus from thrombosed hemodialysis access grafts. Radiology 197:461-465, 1995 Vesely TM: Management of thrombosed dialysis grafts. J Vasc Interv Radiol 9:124-129, 1998 (suppl) Trerotola SO, Lund GB, Scheel PJ Jr, et al: Thrombosed dialysis access grafts: Percutaneous mechanical declotting without urokinase. Radiology 191:721-726, 1994 Middlebrook MR, Amygdalos MA, Soulen MC, et al: Thrombosed hemodialysis grafts: Percutaneous mechanical balloon declotting versus thrombolysis. Radiology 196:73-77, 1995 Vorwerk D, Sohn M, Schurmann K, et al: Hydrodynamic thrombectomy of hemodialysis fistulas: First clinical results. J Vasc Interv Radiol 5:813-821, 1994 Uflacker R, Ragagopalan PR, Vujic I, et al: Treatment of thrombosed dialysis access grafts: Randomized trial of surgical thrombectomy versus mechanical thrombectomy with the Amplatz device. J Vasc Interv Radiol 7:185-192, 1996
PMT AND THROMBECTOMY
27. Trerotola SO, Vesely TM, Lund GB, et al: Treatment of thrombosed hemodialysis access grafts: Arrow-Trerotola percutaneous device versus pulse-spray thrombolysis. Radiology 206:403-414, 1998 28. Tadavarthy SM, Murray PD, Inampudi S, et al: Mechanical thrombectomy with the Amplatz device. Human experience. J Vasc Interv Radiol 5:715-724, 1994 29. Wagner HJ, Muller-Hulsbeck S, Pitton MB, et al: Rapid thrombectomy with a hydrodynamic catheter: Results from a prospective, multicenter trial. Radiology 205:675-681, 1997 30. Henry M, Amor M, Henry I, et al: The Hydrolyser thrombectomy catheter: A single-center experience. J Endovasc Surg 5:24-31, 1998 31. Uflacker R, Strange C, Vujic I: Massive pulmonary embolism: Preliminary results of treatment with the Amplatz thrombectomy device. J Vasc Interv Radiol 7:519-528, 1996 32. Koning R, Cdbier A, Gerber L, et at: A new treatment for severe pulmonary embolism: Percutaneous rheolytic thrombectomy. Circulation 96:2498-2500, 1997 33. Michalis LK, Tsetis DK, Rees MR: Percutaneous removal of pulmonary artery thrombus in a patient with massive pulmonary embolism using the Hydrolyser catheter: The first human experience. Clin Radio152:158-161, 1997 34. Schmitz-Rode T, Guenther RW, Pfeffer JG, et al: Acute massive pulmonary embolism: Use of a rotatable pigtail catheter for diagnosis and fragmentation therapy. Radiology 197:157-162, 1995 35. Schmitz-Rode T, Adam G, Kilbinger M, et al: Fragmentation of pulmonary emboli: In vivo experimental evaluation of two high-speed rotating catheters. Cardiovasc Interv Radiol 19:165-169, 1996
243