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September 2010
Endovascular Therapy for Acute Limb Ischemia
Current and future trends in percutaneous intervention for limb salvage.
By Raghav Gupta, MD, and Thomas A. Hennebry, MB BCH, BAO, FACC, FSCAI
Acute limb ischemia (ALI) is caused by a sudden decrease in limb perfusion, usually producing new or worsening symptoms and signs, threatening limb viability, and can lead to death if revascularization is not performed promptly.1 Devastating systemic effects include severe electrolyte disturbances resulting in a potentially fatal acid-base imbalance. The incidence of ALI has been reported to be approximately 0.014% per year in the United States.2
Current treatment modalities include open surgical interventions, pharmacologic catheter-directed thrombolysis (CDT), percutaneous mechanical thrombectomy (PMT), and percutaneous aspiration thrombectomy (PAT). Open surgical options include balloon catheter thrombectomy, endarterectomy with or without patch angioplasty, and intraoperative isolated limb thrombolysis. Unfortunately, ALI carries 9% and 15% in-hospital and 30-day mortality, respectively, and 15% and 25% amputation rates at discharge and 30 days, respectively.2,3 The 5-year survival rate after ALI caused by thrombosis approximates 45%.4 The basic treatment principle is restoration of uninterrupted pulsatile flow with a strategy that will provide the most complete revascularization with the lowest procedural risk. It has been suggested to consider computed tomographic angiography in patients with Rutherford class 1 or 2A ALI presentations, but this is associated with a potential major drawback of large volume contrast load, putting patients at high risk of contrast-induced nephropathy, especially if percutaneous treatment is chosen.1 Where the expertise for endovascular treatment strategy exists, it would be more judicious to resort to diagnostic invasive angiography in order to save valuable time and muscle in selected patients with limb-threatening ischemia.
Regardless of the technique, careful postprocedure follow- up is crucial, because ignoring compartment syndrome can lead to permanent nerve injury, paresis, or even death. Simple physical inspection, palpation of pulses with handheld Doppler confirmation, neurological exam of the affected limb, and assessment of pain with passive movement is generally effective. Pain that is out of proportion to the physical exam often denotes an early warning. Furthermore, judicious use of antiplatelet and anticoagulation drugs plays a pivotal role, not only in preventing further progression of disease, but especially in patients with cancer, atrial fibrillation, and hypercoaguable states. Use of aspirin, clopidogrel, warfarin, and cilostazol should be evaluated and tailored per each patient's indications.
CATHETER-DIRECTED THROMBOLYSIS
Catheter-directed, locally administered thrombolytic
agents were the first successful nonsurgical treatment
approach for ALI. CDT remains an initial treatment option
for patients presenting with Rutherford category l or 2 ALI
(Table 1).5 Thrombolytic therapy is administered through an
intra-arterial catheter placed within the thrombus to
achieve regional thrombus dissolution with relatively less
systemic fibrinolysis compared to what would occur with
systemically administered thrombolysis. However, time to
achieve reperfusion with thrombolytics can be as high as 1.5
days and may still eventually lead to limb loss.3,6,7 Moreover, thrombolytics are also associated with 5% to 15% risk of systemic
bleeding complications including major intracranial
hemorrhage.3,6-8 The Rochester trial showed a significant
mortality benefit at 1 year, with thrombolysis mostly due to
decreased complications compared to an open operative
procedure,6 and the STILE (Surgery versus Thrombolysis for
Ischemia of the Lower Extremity) trial showed modest
amputation-free survival with CDT compared with surgery7
but the largest of the three, TOPAS, failed to reveal any mortality
benefit over open embolectomy at 1-year follow-up.3
Although no statistical difference was noted in the rate of
amputation between the two groups in these three trials,
CDT did avoid the need for open surgery and can treat
smaller distal vessels. Drawbacks include increased overall
cost due to the need for prolonged infusion times combined
with intensive care requirements and possible repeat
catheterization procedures.
PERCUTANEOUS MECHANICAL THROMBECTOMY
Percutaneous removal of a thrombus today is a wellestablished
modality and is often used as first-line therapy
for ALI patients. There are several percutaneous devices that
can remove thrombus from peripheral arteries using a rapid
stream of fluid and hydrodynamic forces. The AngioJet rheolytic
thrombectomy system (Medrad Interventional/Possis,
Minneapolis, MN) (Figure 1) is a US Food and Drug
Administration–approved device for infrainguinal arterial
interventions in the United States. It is a dual-lumen
catheter, one lumen of which accommodates either a
0.014- to 0.035-inch guidewire depending on model, and
the smaller lumen delivers a high-velocity, pulsatile saline
flow to the catheter tip via a high-pressure stainless steel
hypotube connected to an external piston pump and drive
unit. The hypotube forms a closed loop at the catheter tip,
which contains multiple jets aimed retrograde into the larger
effluent lumen that is used for both guidewire passage
and evacuation of thrombus debris. The jets fragment and
dislodge the thrombus, creating a localized low-pressure
zone (Bernoulli/Venturi effect) that draws the thrombus
into the catheter tip and then out of the vessel through the
catheter's effluent lumen (Figure 1).9,10 The catheter, in theory,
works isovolumetrically; that is, the volume of saline
infused via the jets is approximately equal to the volume of
thrombus debris evacuated from the catheter.11
The AngioJet catheter has been reported to aspirate more than 75% of the thrombus in patients presenting with ALI involving native vessels and grafts.10 A multicenter registry of 99 patients treated with rheolytic thrombectomy reported 70% substantial or complete revascularization (< 50% residual defect) and < 5% in-hospital and 30-day mortality related to limb ischemia.11 Primary patency rates of 74% and 69% have been reported at 3 months and 1 year respectively. 9 Another approach with the AngioJet catheter is called the power-pulse spray technique and has been reported to have 90% success rates.10 This technique involves thrombolytic drug infusion through the PMT catheter while occluding the outflow port and is followed by thrombus aspiration.
An important consideration is the potential to induce distal embolization.10 The efficacy of the device is limited by the size of the effluent lumen, a property that is dependent on the size of the device. This limitation, however, must be balanced by the convenience of placing the device through a relatively small-bore sheath, as well as the increased safety associated with the use of a smaller device in the tibial vessels. Another limitation is that a significant amount of red blood cell hemolysis resulting in hemoglobinemia and hemoglobinuria can occur with repeated passes of the device with fatal consequences, especially in patients with renal insufficiency.9,11 This, along with potential for fluid overload due to intravascular irrigation, is a concern because on an average, four passes with a PMT catheter have been reported to be required to achieve good results.11 Although volume overload and hemolysis have not been reported to be a problem in preliminary clinical trials, we have witnessed fatalities from hyperkalemia and recommend caution in children and patients with chronic renal failure. Other potential pitfalls are early and late recurrent thrombosis resulting from vessel wall damage.11
PERCUTANEOUS ASPIRATION THROMBECTOMY
PAT is based on the simple concept of applying suction
by a syringe to a specially designed aspiration catheter in
order to achieve thrombus aspiration. The Pronto extraction
catheter (Vascular Solutions, Inc., Minneapolis, MN)
(Figure 2) is a low-profile, dual-lumen, rapid-exchange aspiration
thrombectomy catheter compatible with a 6-F guiding
catheter and a 0.014-inch wire. It has an atraumatic
spherical distal tip and sloped extraction lumen designed
to protect the vessel wall while advancing the catheter during
aspiration, which is completed by 30-mL locking vacuum
syringes that are provided.10 It has a 0.053-inch crossing
profile for vessels as small as 1.5 mm and a hydrophilic
coating for smooth navigation. Although the efficiency and
volume of thrombus extracted with these catheters are not
equivalent to those of rheolytic catheters, the advantages of these catheters include ease of use and deliverability to
small-caliber distal vasculature. PAT has been reported to
be a successful and safe aid during coronary interventions
for acute myocardial infarction and for mesenteric arterial
interventions due to its flexibility.12,13 The Pronto catheter's
success in ALI has mostly been anecdotal, limiting its application
in primarily managing embolization during peripheral
interventions.14
The apparent benefits of the device are minimal risk for distal embolization, the ability to intervene within smallercaliber vessels, quick set up, and no evidence of hemolysis to date. However, prospective data on rapidity of thrombus removal, native vessel injury, distal embolization, blood loss, flexibility, maneuverability, ease of operation, primary patency rates, impact on total fluoroscopy time and complications in regards to the Pronto catheter are limited in the medical literature. The Export catheter (Medtronic, Inc., Minneapolis, MN) is a similar catheter, but we are unaware of published reports of its use in ALI. Our experience with the Pronto catheter in 16 patients with ALI revealed 6% mortality (one patient died due to severe mechanical valve thrombosis resulting in severe heart failure) and a 12% amputation rate at 30 days. Although approximately 75% achieved complete or substantial response, more than 65% of the patients required additional use of rheolytic thrombectomy, and most of them required either angioplasty or stenting for residual defects.
SIMULTANEOUS ANGIOPLASTY WITH
THROMBOLYTIC IRRIGATION
Mostly used as a bailout technique after failed/inadequate
PMT or PAT, simultaneous angioplasty with thrombolytic
irrigation (SATI) combines a low-pressure (2 atm)
balloon angioplasty with simultaneous in situ thrombolysis
using the Clearway irrigation balloon (Atrium Medical
Corporation, Hudson, NH). The balloon creates a fluid layer
over its surface, allowing local delivery of thrombolytics while
a low-atmosphere angioplasty is accomplished (Figure 3).
We have reported three cases of ALI treated with SATI as a
bailout.15 Only one of those required additional CDT and
none had any hemorrhagic complications. Drawbacks include a relatively large profile, requiring a 7- or 8-F sheath,
increasing the risk of vascular access complications, and a
small balloon length requiring several balloon inflations in
case of large thrombus distribution; however, recent availability
of 50-mm-length balloons should improve its applicability.
Hopefully, the ongoing randomized trial comparing
SATI to PMT (Use of Clearway Balloon vs. Mechanical
Thrombectomy as Initial Treatment for Acute Limb
Ischemia) will further define its role.
ISOLATED PHARMACOMECHANICAL
THROMBOLYSIS-THROMBECTOMY SYSTEM
In our practice, a relatively novel device has proven
extremely useful in urgent management of patients presenting
with ALI. In some subgroups, CDT, PMT, and PAT systems
show modest improvements in mortality compared
to surgery but with important disadvantages of major
bleeding, distal embolization, recurrent thrombosis, prolonged
thrombolytic infusion, and increased overall cost.
Prolonged infusion times combined with intensive care
requirement and possible repeat catheterization procedure
are the main factor in the increased cost.
The relatively novel, isolated (site-specific) pharmacomechanical thrombolysis-thrombectomy (IPMT) system, Trellis (Covidien, Mansfield, MA) (Figure 4), is designed to improve on the shortcomings of both mechanical thrombectomy and catheter-based thrombolysis. The Trellis PIS is a 510(k) Food and Drug Administration–approved device. This hybrid catheter device uniquely isolates the thrombolytic agent between two balloons (diameter, 3–10 mm) inflated proximal and distal to the thrombotic lesion. For arterial use, it is available in a 6-F multilumen catheter that is passed over a 0.035-inch guidewire with treatment zone lengths (length between two balloons for isolation of the desired lesion from systemic circulation) of 10 and 30 cm (Figure 5).
When inflated (distal balloon is inflated first using a 3:1 ratio of saline to angiographic contrast), the balloons isolate the treatment zone and maintain the concentration of the thrombolytic agent in the affected area. Next, a batterypowered, flexible sinusoidal wire is inserted through the catheter (replacing the guidewire) and produces oscillations at 500 to 3,000 rpm only in the isolated zone (Figure 6). This process mechanically mixes the clot with the thrombolytic agent (typically 1 mg recombinant tissue plasminogen activator per minute to a total of 10 mg) and enhances rapid dissolution of the thrombus by increasing the surface area of clot exposed to the lytic agent. Lysed thrombus is then aspirated via an integral port as the proximal balloon is deflated while the inflated distal balloon prevents distal embolization. This reduces systemic dispersion of the thrombolytic agent, thereby also reducing bleeding complications while achieving rapid revascularization and avoiding prolonged infusions.
Trellis PIS has been extensively described in treating deep venous thrombosis,16 and there are reports for treatment of either de novo suprainguinal arterial lesions or infrainguinal peripheral arterial bypass graft occlusion.17-19 Initial case studies on Trellis PIS have been extremely successful, with 97% 30-day survival and no reports of major hemorrhage or death, even though more than half of the patients presented with ALI (15 out of 26 patients).17 The distal embolization rate was less than 10%, while 15% of patients required an adjunctive surgical procedure, and 54% required an adjunctive interventional procedure (angioplasty with or without stenting).17 The aspiration mechanism of the device has been changed to enable aspiration of larger thrombotic debris since then.
Cost analysis of using Trellis PIS has been found to be 0.7 times less expensive than using CDT and is driven by decreased hospital/intensive care unit monitoring, decreased angiographic suite time, lower dose of thrombolytic agent used, and less bleeding complications.17 Combining the known benefits of local lytic infusion with mechanical fragmentation, the Trellis PIS allows rapid revascularization, a significant advantage over the standard multihour thrombolytic infusion protocols. Hemolysis and hyperkalemia have not been reported to be a problem even in the larger deep vein thrombosis treatment registries. At present, the Trellis PIS is the only device that has the ability to isolate lytic infusion in combination with mechanical thrombus fragmentation while preventing major bleeding, prolonged intensive care unit stay, and distal embolization.
The availability of the 6-F Trellis PIS with treatment lengths of 10 and 30 cm has increased its utilization in arterial occlusions. Our experience with the Trellis PIS is growing rapidly and has revealed excellent results in native (both de novo and pretreated) suprainguinal (Figure 6) and infrainguinal arteries (Figure 7). We have also reported one of the first cases with successful utilization of the Trellis PIS for aortofemoral graft thrombosis presenting with ALI.20 We have had excellent outcomes with the Trellis PIS in 34 vessels in 20 patients treated with ALI, with 19 out of 20 patients experiencing successful results.21 Only one patient required additional CDT, and none experienced distal embolization.
CONCLUSION
Percutaneous intervention can offer limb-salvage success
rates that rival those for surgical management for ALI, and a
strong consideration for endovascular management of ALI
can be made where the skilled personnel and facilities
exist (Figure 8). IPMT is an indispensable tool in the current
armamentarium for endovascular treatment of ALI
(includes CDT, PMT, PAT) with successful clinical outcomes
achievable in up to 95% of cases. Successful endovascular
treatment of ALI also requires careful postprocedure observation
for compartment syndrome or any other complications
and a patient-centered approach toward discharge
medications guided by etiology and treatment technique
remain important milestones of management.
Raghav Gupta, MD, is from the Cardiovascular Section, University of Oklahoma in Oklahoma City. Dr. Gupta has disclosed that he holds no financial interest in any product or manufacturer mentioned herein.
Thomas A. Hennebry, MB BCh, BAO, FACC, FSCAI, is Director, EndoVascular Interventions, Robert Glenn Rapp Foundation Presidential Professor, and Associate Professor of Medicine at the University of Oklahoma in Oklahoma City, Oklahoma. He has disclosed that he is principal investigator for the Local Paclitaxel Delivery for SFA Disease (IRRITAX) trial, and that he receives grant/research funding from Atrium Medical Corporation, Medtronic, and Bristol-Myers Squibb. He further disclosed that he is coprincipal investigator of the trial Use of Clearway Balloon vs. Mechanical Thrombectomy as Initial Treatment for Acute Limb Ischemia trial. In both trials, Atrium Medical Corporation provides the Clearway angioplasty and in situ thrombolysis balloon. Other financial disclosures of Dr. Hennebry include that he is a proctor for carotid stenting for Abbott Vascular. He is also an investigator for the CHOICE carotid stent registry sponsored by Abbott Vascular and for the ORION study for iliac stents sponsored by Boston Scientific Corporation. Dr. Hennebry may be reached at (405) 271-4742; thomas-hennebry@ouhsc.edu.
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