What You Should Know About Emerging Techniques In Revascularization

   Given the challenges of managing chronic wounds in patients with peripheral arterial disease, these authors offer a review of current concepts in revascularization and how these procedures may facilitate improved wound healing.

   Perfusion is the most fundamental requirement to heal a wound. According to current estimates, peripheral arterial disease (PAD) affects over 12 million people in the United States and more than half are asymptomatic.1,2

   As PAD progresses to advanced stages such as non-healing wounds or critical limb ischemia (CLI), the risk of lower limb amputation increases. For these patients, it is paramount to ensure a strong vascular supply to the lower extremity if one is to accomplish the goal of wound healing.3

   Multidisciplinary care is critical for these high-risk patients. Accordingly, it is incumbent upon podiatrists to be aware of emerging advances in revascularization in order to make appropriate referrals, when necessary, to vascular specialists.

A Pertinent Primer On Bypass Techniques

   Over the years, physicians have employed multiple techniques to overcome and treat vascular diseases of the lower extremity. Lower extremity bypass, angioplasty and stenting are just a few of the treatments vascular surgeons have utilized for the revascularization of a compromised limb.3 Autogenous grafts remain the gold standard for vascular conduits.

   The graft material is one of the most important factors in influencing long-term patency.2-6 The five-year patency rates for autogenous vein grafts reportedly range between 60 and 80 percent. The five-year patency rates of polytetrafluoroethylene (PTFE), the most common prosthetic material, are significantly less.

   Graft failure within 30 days is most commonly correlated with inadequate outflow, poor quality conduit or improper procedure selection. Progression of underlying atherosclerotic disease is the main contribution to graft failure after two years. Between these times, intimal hyperplasia is the predominant cause of graft failure. Intimal hyperplasia most commonly occurs at the distal anastomosis with higher failure rates occurring with longer grafts of small diameter.2-6 Intimal hyperplasia is responsible for 60 percent of graft failures following peripheral arterial reconstruction. Likewise, it is the predominant lesion when it comes to mid- to long-term failure of angioplasty and stenting.2-6

   The molecular basis for restenosis is not clearly defined but may share similar pathways as those identified for artherogenesis. These pathways include abnormalities of lipid metabolism and involvement of inflammatory cells. Evolving vascular strategies based on gene therapy techniques have been developed to prevent restenosis but there have not been sufficient results.

   When one performs an open procedure appropriately, it can follow an endovascular procedure that has failed. Similarly, an endovascular procedure can often follow an open procedure in the setting of a failing graft.4

What About Advances With Percutaneous Transluminal Angioplasty?

   Percutaneous transluminal angioplasty (PTA) with or without adjunctive stenting of iliac, femoral and popliteal and tibial lesions attempts to restore adequate perfusion to the lower extremity. The PTA involves a controlled injury to plaque in the arterial wall, which creates a localized dissection of the adventitial and medial layers with balloon angioplasty.

   One can measure the success of PTA via lesion location, length, plaque composition and morphology. Eccentric and ostial lesions do not respond well to PTA, nor do calcified circumferential lesions due to high vessel rupture rates.4 In regard to the success of PTA, researchers have reported average patency rates of 71 percent and 53 percent at one and five years respectively.2-7 Furthermore, there is a greater potential of distal embolization and perforation when vascular surgeons use balloon angioplasty for long or complex occlusions.5

   An outgrowth of PTA is CryoPlasty® therapy (Boston Scientific) for the treatment of limb ischemia. CryoPlasty utilizes a combination of mechanical dilation (balloon angioplasty) with cold therapy. Physicians achieve cooling with the use of nitrous oxide as the balloon inflation media. It is hypothesized that the cooling is beneficial because it causes apoptosis of the smooth muscle cells in the localized vessel wall and facilitates reduction of the elastic recoil of the media and plaque microfracture.

   This leads to a more uniform dilation during angioplasty and a decreased rate of flow limiting dissection. Apoptosis of smooth muscle cells may decrease proliferation rates, which may subsequently decrease intimal hyperplasia and thus reduce the risk of restenosis. However, there is no in vivo study at this time.5

   According to a multicenter registry of cryoplasty for the treatment of lesions in the superficial femoral artery (SFA) and popliteal artery with stenosis or occlusion up to 10 cm, vascular surgeons had a 94 percent procedural success rate with a need of bailout stenting in only 9 percent of cases. This compares favorably with the dissection rates of PTA.5,6 Researchers demonstrated a clinical patency rate of 75 percent at more than three years after the procedure in 70 patients from the multicenter registry.6,7

   Stent-based revascularization of the SFA has special challenges that include: diffuse disease (often occluded); low flow/ high resistance conditions; coexistence of distal run-off disease; and involvement of the adductor canal. In addition to thrombosis and neointimal hyperplasia, failure of the stent can occur from stent fracture, incomplete stent expansion and malposition due to mechanical stresses and calcification. With restenosis rates as high as 75 percent, there is a need for improvement when it comes to stenting techniques.5

   Limitations of angioplasty have lead to the development of self expanding stents for primary or adjunctive techniques. Nitinol, a unique nickel titanium alloy, is not only superelastic but also has thermal shape memory. Nitinol is superior to previous generation stainless steel stents due to a greater resistance of external deformation. Therefore, nitinol is more ideally suited for areas of flexion and torsion such as the superficial femoral and popliteal arteries.4,5

   However, only one nitinol stent, the IntraCoil (ev3), has been approved by the U.S. Food and Drug Administration (FDA) for femoral and popliteal arterial disease.

   One- and two-year primary patency rates for nitinol stents have been promising as they show superiority to the rates of PTA and first-generation stents. However, the risk of restenosis after using nitinol stents and the potential for stent fracture remain limitations. A high incidence of nitinol stent fracture was confirmed in one study with 45 stent fractures out of 121 treated limbs (37.2 percent). Stent fracture may be associated with higher risks of restenosis and occlusion.5,9 More fracture-resistant and flexible nitinol stents, such as the Lifestent (C.R. Bard), are currently being developed to address these concerns.

   Efforts to duplicate the gold standard of femoropopliteal bypass have advanced the endoprosthesis. The Gore Viabahn® (W.L. Gore and Associates) is a self–expanding helical nitinol stent mounted to the outer surface of a PTFE expanded tube. Following predilation of the lesion, the PTFE membrane acts as a barrier to intimal hyperplasia. The Viabahn is approved by the FDA for symptomatic SFA lesions with vessel diameters of 4.8 to 7.5 mm.5 One study showed that primary patency of Viabahn (73.5 percent) at 12 months was not significantly different to that of a bypass with a synthetic graft (74.2 percent).10

   An additional covered stent is the iCAST (Atrium Medical Corp.), which vascular surgeons may use to help address aneurysmal iliac disease (5 to 12 mm). The iCAST is a balloon-expandable stent, which has stainless steel struts covered with microporous PTFE. It is designed for a more uniform radial expansion with improved deliverability. The Jostent Stent Graft Peripheral (Abbott Vascular) is also a balloon-expandable covered stent designed for the treatment of small vessel perforation (3 to 5 mm in diameter). Trials for iCAST and Jostent are pending.5

   There is no currently FDA-approved drug-eluting stent for the lower extremities. The use of drug eluting stents in the SFA have not shown the success of coronary drug eluting stents. Restenosis after stenting of the SFA, popliteal and tibial arteries remains high.

   One drug eluting stent currently available is the sirolimus-coated, nitinol self-expandable stent (Cordis), which vascular surgeons may employ in treating disease of the SFA. The stent has a thin uniform coating of 5 to 10 mm of sirolimus, which is equivalent to the dose used with coronary stents.

   Many issues still remain to be resolved with peripheral drug eluting stents. Key questions pertain to the ideal pharmacological agent, the release kinetics, the elimination of stent fractures and the cost-to-benefit ratio.5

Key Insights On Percutaneous Thrombectomy Procedures

   When peripheral arterial or graft occlusion occurs acutely, a thrombus is almost always present and either results from an in situ thrombosis from a ruptured plaque or from an embolus. When the collaterals are absent or minimal at best, acute limb ischemia may occur and jeopardize the limb unless there is swift treatment. Likewise, limbs may be at risk when distal thromboembolism occurs after peripheral intervention. Percutaneous rheolytic and aspiration thrombectomy catheters have been designed for these situations.

   The Angiojet Rheolytic Thrombectomy System (Possis Medical) is a device that delivers pressurized saline to the tip of the catheter in order to produce a series of retrograde high-velocity saline jets that will fragment the thrombus via hemodynamic forces and subsequently aspirate the fragments mechanically. The Angiojet has the ability to rapidly remove large amounts of de novo thrombus. This decreases the need for chemical thrombolysis and reduces the risk of bleeding. The disadvantages of the Angiojet are the inability to remove mural or chronic thrombus, and the possibility of causing distal embolization.

   Vascular surgeons can achieve aspiration of a thrombus via an aspiration catheter, sometimes in conjunction with chemical thrombolytic agent. These catheters are smaller in size than rheolytic catheters and allow access to smaller more distal vessels that are embolized. However, their ability to extract a thrombus is less efficient. This form of aspiration works via a vacuum system.

   Current devices available for peripheral vascular use are the Pronto V3 Extraction Catheter (Vascular Solutions), the Export XT catheter (Medtronic Vascular), the Rio Aspiration Catheter (Boston Scientific) and the Diver C.E. catheter (ev3 Inc.).5

   Historically, vascular surgeons have utilized embolic protection devices (EPDs) to reduce the cerebral morbidity and mortality associated with carotid artery stenting. When it came to incorporating these devices to the periphery, surgeons encountered difficulties because of the increased burden amount of thrombus and/or embolic material in the peripheral vessels versus the coronary/carotid vessels. Similarly, vessel diameters vary significantly. Therefore, not all vessels are suitable for the use of EPDs. Lastly, longer disease segments in the lower extremity make retrieving the filters with the captured debris more challenging.5

A Closer Look At The Options For Chronic Total Occlusion

   The ability to perform hand-controlled, catheter-based microdissection with a pair of miniature hinged jaws is known as controlled blunt microdissection. Vascular surgeons use the hinge jaws to create a channel to the true lumen. Researchers have reported success rates as high as 91 percent in total occlusions of the lower extremity.5

   When it comes to catheter-based microdissection, vascular surgeons may employ the FrontRunner XP chronic total occlusion catheter (Cordis). Once the surgeon has crossed the lesion, he or she can guide a Micro Guide catheter (Cordis) over the FrontRunner and subsequently withdraw the FrontRunner. The Micro Guide allows for further stenting or ballooning.5

   The CROSSER Chronic Total Occlusion Recanalization System (FlowCardia) is a unique device that uses high frequency mechanical vibration to penetrate through an occluded artery. The CROSSER catheter is a nitinol core wire with a stainless steel tip that vibrates at 20,000 cycles per second to a depth of 20 cm. However, the device is not recommended in vessel diameters of less than 2.5 mm.

   Today, there are multiple devices that allow passage of a guidewire beyond an occlusion or stenosis. However, this is usually in a subintimal fashion. Conventional guidewires are often unsuccessful in obtaining reentry into the true lumen in cases of heavily calcified occlusions. The Pioneer catheter (Medtronic) is one device which facilitates true lumen reentry, thereby reducing the risk of vessel perforation and procedure time.

   Vascular surgeons would advance these catheters subintimally beyond the occlusion to allow for the exchange of a 0.014-inch guidewire. They would then advance the reentry catheter over this guidewire and rotate it to its appropriate position, which one can view by either fluoroscopy or ultrasound (Pioneer). Lastly, the vascular surgeon can advance the wire into the true lumen. This allows for the delivery of conventional therapies (i.e. angioplasty stenting or atherectomy).5

Current Concepts With Atherectomy Procedures

   The concept of atherectomy has emerged since the limitations of balloon angioplasty and stenting have been recognized. Rather than stretching and compressing plaque in a narrow artery, atherectomy devices remove or sand away the plaque. Atherectomy devices have many different forms: laser, excisional, rotational and orbital.

This procedure may be beneficial for:
   • patients who are poor candidates for surgical revascularization because of diffuse distal disease;
   • patients who have poor targets for bypass;
   • patients who are devoid of a venous conduit; or
   • those with significant medical or cardiac comorbidities who are at high risk for complications.

   There has been a renewed interest in excisional laser atherectomy. Hot-tipped, continuous wave lasers were abandoned two decades earlier due to their thermal damage resulting in high complication rates.5,11

   Commercially available excimer laser assisted angioplasty has been present in Europe since 1994. Short bursts of ultraviolet energy are delivered via a 308 nm excisional laser using a flexible fiberoptic catheter. Molecular bonds are broken photochemically, not thermally, by the excisional laser catheter, which removes a 10 cm tissue layer with each burst. Subsequent ablation of thrombosis is done via contact only (as opposed to thermal degradation), thus inhibiting platelet aggregation.5,12 The advantages of this technique are the ability to treat large occlusions and complex disease with less stenting.

   In this technique, the vascular surgeon would advance a guide wire just proximal to the target lesion, allowing the excisional laser catheter to contact the occlusion’s fibrous cap. Then one would use short bursts of the laser until meeting the true lumen.

   Despite high technical success rates, primary patency rates at one year have been disappointing, thereby requiring surveillance and early re-intervention.13 One limiting factor that remains with the laser catheter technology is the inability to create a channel much larger than the diameter of the catheter.5

   The Silverhawk Plaque Excision System (ev3) is a forward-cutting arthrectomy device that uses a high-speed cutting blade to create a ribbon of plaque that is collected into the nose cone of the catheter. The vascular surgeon must make multiple passes with the catheter, redirecting it to each quadrant of the lumen. One can achieve debulking of the lesion without the barotrauma associated with previous cutting devices that used a balloon opposite to the blade to maximize plaque removal.

   Currently, there are no prospective, randomized trials comparing the Silverhawk catheter to balloon angioplasty or stenting. Femoropopliteal atherectomy may warrant the use of embolic protection devices (EPD) due to high rate of distal embolization.5

   Chronic total occlusions often cause CLI or claudication when the collaterals are jeopardized by a more proximal occlusion. Traditional guidewire and balloon angioplasty fail in approximately 20 percent of heavy calcified lesions. To address the need to effectively recanalize and treat these chronic total occlusions including calcific lesions, a new rotational atherectomy technology has emerged.

   The Diamondback 360° Orbital Atherectomy System (Cardiovascular Systems) utilizes an eccentrically mounted, diamond-coated crown that creates an “orbital” motion to efficiently sand away plaque. When the vascular surgeon rotates this device at adjustable high speeds, the abrasive crown orbits within the artery to create a lumen up to twice the diameter of the crown. (One may achieve a 1:2 crown to lumen ratio.) The vast majorities of the fine particles generated are smaller than a red blood cell, and are effectively absorbed by the blood stream and macrophage process.

   The Diamondback 360° Orbital Atherectomy System (OAS) has some similarities and many differences from rotational atherectomy. It is similar in that it uses a diamond covered “crown” similar to a “burr” and is powered by a high-pressure air or nitrogen. The difference lies in the system’s unique mechanism of action. The system operates on the principles of centripetal force, utilizing an eccentrically mounted crown to create the orbital motion. This differs from the concentric rotation of conventional rotational technology. As the speed increases, the orbital motion allows the crown to contact and efficiently sand the plaque away with each orbit.

   There are many advantages with this device. As the crown contacts only one part of the vessel wall at a time, it allows for continuous blood and saline flow, and may minimize the risk of barotraumas or thermal damage. The OAS sanding action continually washes away the plaque in the blood stream, rather than building up into a large bolus.

   Particulate size measured in animal and cadaver studies averages 1.96 microns with 98.8 percent of the particulate being smaller than the size of a typical capillary (9.5 microns). As the particulate is dispersed into the distal vascular bed, macrophages from the reticuloendothelial system metabolize the microparticulates.14

   The properties of the diamond coating create a “differential sanding” action, which allows the healthy media layer to “flex away” from the crown. This potentially reduces the incidence of complications such as dissection or perforation. Results of one trial of 350 cases showed low rates of complication (dissection 2 percent, perforation 2.3 percent and embolization 2 percent).14

   The unique offset eccentric crown allows the operator to maximize arterial lumen diameter by adjusting the speed. This allows for a possible single insertion technique, thus reducing procedure time and cost.

   The OAS has a variety of available crown sizes: 1.23, 1.5, 1.75, 2.0 and 2.25 mm in diameter. These are compatible with a 0.014-inch guide wire. There are two styles of crowns available. There is a smaller, more flexible Classic Crown for tight lesions in smaller below-the-knee vessels and the larger mass Solid Crown for the larger vessels above the knee.

   The device treats complex plaque morphologies including calcified lesions. The device is advantageous in that it effectively treats calcium even in narrow or totally occluded section of arteries.

   Orbital atherectomy achieves stent like results without the additional barotraumas, reducing the risk of restenosis.15 The OAS was approved by the FDA in August of 2007.14

Final Notes

   Peripheral arterial disease (PAD) affects nearly 27 million individuals in Europe and North America alone with 16.5 million being asymptomatic.16 Without lifestyle risk modifications or judicious pharmacotherapies, individuals with lower extremity PAD may require endovascular treatments, bypass or amputations.17

   While there has been unprecedented advancement in revascularization techniques, the complex and diffuse nature of peripheral vascular disease complicates the endovascular approach to revascularization. Long-term patency remains suboptimal, making long-term post-op surveillance with adjunctive imaging crucial. There is still a need for more research in regard to improving these techniques.

Dr. Hafner is a third-year resident with the Yale Podiatric Surgical Program in New Haven, Conn.

Dr. Han is a third-year resident with the Yale Podiatric Surgical Program in New Haven, Conn.

Dr. Aruny is an Assistant Professor and Co-Chief of Vascular and Interventional Radiology at the Yale University School of Medicine in New Haven, Conn.
Dr. Key is an Assistant Clinical Professor of Orthopedics and Rehabilitation at the Yale University School of Medicine in New Haven, Conn.

Dr. Indes is an Assistant Professor and Director of the Vein Center and Vascular Laboratory at the Yale University School of Medicine in New Haven, Conn.

Dr. Muhs is an Assistant Professor and Co-Director of the Endovascular Program at the Yale University School of Medicine in New Haven, Conn.

Dr. Sumpio is the Chief of the Section of Vascular Surgery at the Yale University School of Medicine in New Haven, Conn.

Dr. Blume is an Assistant Clinical Professor of Surgery, Anesthesia and Orthopedics and Rehabilitation at the Yale University School of Medicine in New Haven, Conn.

References:

1. Blume PA. Percutaneous transluminal cryoplasty therapy. Podiatry Management. 2005 (9) 208-210. 2. Blume PA, Sumpio BE, Sarage AL, Aruny JE, Yui W. Aggressive Revascularization salvage options for patients referred for leg amputation by using atherectomy and cryoangioplasty technology. Peripheral Vascular Disease of the Lower Extremity, 2007. p1-10 3. Blume PA. The appropriateness of referral for cryoplasty therapy from podiatric physicians and wound care specialists. Referral Management. 60-61. 4. Perera GB, Lyden SP. Current trends in lower extremity revascularization. Surg Clin N Am 2007; 87:1135-1147. 5. Rogers JH, Laird JR. Overview of new technologies for lower extremity revascularization. Circulation. 2007; 116:2072-2085. 6. Laird J, Jaff MR, Biamino G, McNamara T, Scheinert D, Zetterland P, Moen E, Joyce JD. Cryoplasty for the treatment of femoropopliteal arterial disease: results of a prospective, multicenter registry. J Vasc Interv Radiol. 2005; 16: 1067-1073. 7. Laird J, Biamino G, McNamara T, Scheinert D, Zetterland P, Moen E, Joyce JD. Cryoplasty for the treatment of femoropopliteal arterial disease: extended follow-up results. J Endovasc Ther. 2006; 13(suppl 2): II-52-II59. 8. Das T. 1-year results from the below-the-knee (BTK) Chill study. Presented at: 56th Annual American College of Cardiology Scientific Session; March 26, 2007; New Orleans, La. 9. Schienert D, Schienert S, Sax J, Piorkowski C, Braunlich S, Ulrich M, Biaminio G, Schmidt A. Prevalence and Clinical impact of stent fractures after femoropopliteal stenting. J Am Coll Cardiol. 2005; 45:312-315. 10. Kedora J, Hohmann S, Garrett W, Munschaur C, Theune B, Gable D. Randomized comparison of percutaneous Viabhan stent grafts vs. prosthetic femoral-popliteal bypass in the treatment of superficial femoral arterial occlusive disease. J Vasc Surg. 2007; 45:10-16. 11. Wollenek G, Laufer G. Comparative study of different laser systems with special regard to angioplasty. Thorac Cardiovasc Surg. 1988; 36(suppl 2):126-132. 12. Lawrence JB, Prevosti LG, Kramer WS, Smith PD, Bonner RF, Lu DY, Leon MB. Pulsed laser and thermal ablation of atherosclerotic plaque: morphometrically defined surface thrombogenicity in studies using an annular perfusion chamber. J Am Coll Cardiol. 1992; 19:1091-1100. 13. Schienert D, Laird JR Jr, Schroder M, Steinkamp H, Balzer JO, Biamino G. Excimer laser-assisted recanalization of long, chronic superficial femoral artery occlusions. J Endovasc Ther. 2001; 8:156-166. 14. Weinstock B, Dulas D. A new treatment option for treating peripheral vascular stenosis: orbital atherectomy. Vascular Disease Management. May/June 2008. 15. Dave R. Orbital atherectomy: a new treatment for complex peripheral arterial disease. Cath Lab Digest. April 2008. 16. Jill J, Belch F, Topol EJ, et al. Critical issues in peripheral arterial disease detection and management: a call to action. Arch Intern Med. 2003; 163, 884-892. 17. Heuser RR. Treatment of lower extremity vascular disease: The diamond back 3600 Orbital Atherectomy System. Expert Rev Med Devices 5(3):279-286, 2008.