Infrapopliteal Endovascular Balloon Technology
New interventional options for treating critical limb ischemia have shown promising results to date.
Perhaps nowhere in medicine has the landscape changed so dramatically in such a short period of time as with the management of critical limb ischemia (CLI). Although open bypass remains the gold standard because of its excellent durability, alternative strategies now exist for limb salvage. As modern medicine allows sicker patients to live longer, it is increasingly important to balance durable vessel patency against surgical morbidity. Conditions are ripe for a major paradigm shift within the arena of CLI; as demand for limb salvage increases, physicians representing separate vascular disciplines evolve from competitors to collaborators, and the synergy between demand and emerging technology continues to aggressively fuel innovation.
Although many tools are available for the endovascular specialist, the cornerstone of intraluminal revascularization remains the angioplasty balloon. Despite few prospective, randomized trials, there are indeed many prospective and retrospective series reporting feasible results with angioplasty alone below the popliteal artery for limb salvage. The BASIL trial was a prospective, multicenter trial that randomized 452 eligible patients with CLI into angioplasty-first (n=224) or surgery-first (n=228) treatment groups. These patients were not exclusively limited to below-the-knee interventions, however, the majority in the angioplasty group (62%) required some treatment below the superficial femoral artery. Based on intent-to-treat analysis, the primary endpoint was amputation-free survival, with a secondary endpoint of all-cause mortality. Survival to the primary endpoint (amputation-free survival) at 1 year was 68%, and at 3 years, it was 57% for those assigned to the surgery-first group; survival at 1 year was 71% and at 3 years was 52% for those randomized to the angioplasty-first group. There were no significant differences in survival to either endpoint by randomized group.1
Dorros et al reported a prospective, nonrandomized series of tibioperoneal angioplasty with 95% technical success in 270 of 284 critically ischemic limbs, including 92% success at the tibioperoneal level.2 They reported a clinical success rate of 95% in limbs at risk, with an aggregate 91% limb salvage rate during a mean 5-year follow-up. Perhaps as equally revealing as the success of the procedure is the poor overall survival of the patients in this and similar series. In the Dorros et al prospective registry, the overall survival of the group was only 56% over the period of the study, including a low 33% survival rate for the most severely diseased (Fontaine class IV) patients. Ingle et al presented a retrospective review of 67 consecutive patients with isolated infrageniculate arterial disease and ischemia undergoing exclusively subintimal angioplasty.3 Technical and clinical success (eg, relief of rest pain or wound healing) were 86% and 80%, respectively, with a mortality rate of 19% at 1 year, 43% at 2 years, and 51% at 3 years.
Balmer et al presented a review of 60 consecutive CLI patients (65% had disease involving or isolated to the infrapopliteal arteries), and although primary restenosis rates were high, limb salvage was achieved overall in 90% of the survivors, with a 25% mortality rate in the group at 1 year.4 Kudo et al presented a 10-year review of infrainguinal angioplasty patients, including 52 patients with below-the-knee disease.5 They reported an overall limb salvage rate of 77% in these patients at 36 months. This excellent result, however, did require a significant number of secondary interventions (assisted primary and secondary patency) to achieve the reported success. In 2003, Clair et al presented a review of 19 nonsurgical candidates (no conduit options or scheduled amputations) with limb-threatening ischemia.6 These patients underwent infrapopliteal angioplasty, including a mix of subintimal and laser recanalizations prior to angioplasty for long occlusions. The angiographic success was 96%, with 84% limb salvage in a short mean follow-up period of 3 months.
THE INFRAPOPLITEAL CHALLENGE
When developing new technology for use in infrapopliteal arteries, we must acknowledge that these vessels represent a challenge to the endovascular specialist for a variety of reasons. It is essential to the future success of minimally invasive limb salvage that the inherent unique anatomic and physiological challenges posed by the infrapopliteal vessels must be overcome for balloon therapy to succeed as a viable option for limb salvage.
The success of percutaneous intervention has historically been predicated on selecting short lesions with large-diameter or high-flow vessels for catheter-based treatment. In this regard, the tibial vessels are quite different than other vessel families. The limb salvage patient presents commonly with long segments of disease, frequently serial stenosis or occlusions, and often densely calcified arteries. The vessels are small in diameter and usually have multiple levels of stenosis within the artery, in addition to supervening inflow disease and compromised runoff beds. These segmental lesions act as resistors in series, dramatically altering flow dynamics both during and immediately after intervention. In addition to the anatomic challenges of tibial revascularization, there are frequently unfavorable physiologic conditions, such as low cardiac output, renal insufficiency limiting contrast volume, diabetes impacting both wound healing and wall compliance, and coexistent medical contraindications to the best adjuvant pharmacotherapy. Under these austere conditions, it becomes evident that the technology used elsewhere in the body is not so readily exportable to the tibial arteries.
The foundation of technology that has made tibial interventions possible are the smaller .018-inch and .014-inch platforms developed for delivery of balloons, stents, and various recanalization and plaque excision devices to the coronary arteries. In addition to smaller delivery platforms and specialized support wires, technical success in the infrapopliteal vessels requires a diverse set of tools, including novel devices for crossing stenoses and re-entering the true lumen of long occlusions. In comparison with the first-generation, high-pressure balloons of the 1970s, the new-generation balloons achieving success in the tibial arteries have thinner walls, higher material strength, and smaller profiles, with an increasing variety of lengths, diameters, shapes, pushability, hydrophilic coatings, and novel additions such as cutting microtomes or the ability to deliver topical cold or heat energy to successfully treat stenosis and occlusion while minimizing dissection, avoiding perforation, and limiting restenosis.
A primary requisite for tibial intervention is the need for small-diameter and extra-long balloons up to 12 cm in length. This design is unique to the requirements of successful tibial angioplasty due to the pattern of disease prevalent in patients with CLI. The Cordis Savvy and the ev3 Amphirion (ev3 Inc, Plymouth, MN) are two examples of popular balloons available in small diameters and long lengths that are especially well-designed for tibial angioplasty.
The Cordis Savvy balloon (Figure 1) demonstrates excellent trackability through long segments of diseased tibial arteries courtesy of several unique design features. The catheter has a low-profile shaft that tapers from 3.5 F to a distal 3-F diameter. The tapered tip also provides a smooth tip-to-wire transition, and the inner wire lumen has a lubricious coating to enhance movement on the wire. The available diameters range from 2 mm to 6 mm, with balloon lengths up to 10 cm. The catheters are .018-inch wire compatible and the shafts are available up to 120 cm in length.
The ev3 Amphirion is another small-diameter, long balloon with excellent trackability, designed specifically for the tibial arteries. The Amphiron is available in diameters ranging from 1.5 mm to 4 mm with lengths up to 12 cm, and it is the only .014-inch platform balloon catheter.
Another promising tool for tibial intervention adding novel technology to balloon angioplasty is the cutting balloon (Boston Scientific Corporation, Natick, MA). The cutting balloon has microtome blades in each quadrant. This particular balloon was designed originally for complex calcified coronary lesions. For the tibial vessels, the design feature allows the plaque to be broken at lower pressure, avoiding overdilation and barotrauma in an attempt to limit dissection, avoiding perforation, and minimizing the recoil and flow-limiting dissections that might obligate bailout stenting. Ansel et al reported a limb salvage rate of 89.5% in 73 patients with threatened limbs during a mean follow-up of 1 year.7 There were no perforations or target lesion revascularization during the period, and only 20% required adjuvant stenting for inadequate dilation or significant dissection.
The AngioSculpt scoring balloon (AngioScore Inc., Fremont, CA) represents another variation on the theme of cutting balloon technology (Figure 2). The AngioSculpt has been used in Europe and was recently approved by the FDA for the treatment of infrapopliteal peripheral disease. The AngioSculpt is a two-component system with over-the-wire or rapid-exchange semicompliant balloon surrounded by a spiral, three-wire nitinol cage. The profile is extremely low (2.7 F), and the catheter is delivered on a .014-inch wire through a 5-F sheath or 6-F guiding catheter. The nitinol ring additionally enhances deflation, improving balloon rewrapping and allowing multiple inflations with preserved trackability. The balloon diameters are available in widths of 2 mm to 3.5 mm and lengths of 10 mm to 20 mm.
Early data on use of the AngioSculpt looks promising as detailed in a European prospective, multicenter registry, which included 56 lesions treated in 43 patients at five participating institutions.8 The patients included were scheduled for percutaneous intervention in infrapopliteal arteries or a planned amputation. Patient demographics included an average age of 74 years, and 39 of the total patients (90.1%) were CLI patients (Rutherford class >4). Vessel profile characteristics included a diameter range from 1.5 mm to 3.5 mm; 73% of the lesions were characterized as moderately to severely calcified. The AngioSculpt was successfully deployed in 98.2% of the lesions and was the sole therapy required in 89.3% of patients. The dissection rate was only 10.7%, and most were characterized as minor, with no perforations. Based on these early results, AngioScore plans the future development of larger catheters with larger diameters and longer length balloons, more aggressive scoring with additional and larger nitinol wires, and the possibility of novel drug coatings on the balloons.
Balloon cryoplasty is an additional novel therapy for balloon revascularization that is gaining momentum. The cryoballoon not only serves as a mechanical dilation device but is also a vehicle for delivery of cold energy to the vessel wall to induce a secondary effect with therapeutic implications beyond simple angioplasty (Figure 3). The Polarcath (Boston Scientific Corporation) simultaneously dilates and cools the vessel wall by inflating the balloon with nitrous oxide in place of saline and contrast. This topical cooling to subzero temperature has been reported in clinical studies to limit dissection and reduce vessel wall recoil and, most significantly, reduce restenosis through inducement of apoptosis as frozen smooth muscle cells are rehydrated. The interim results from the CHILL study were recently reported.9 The study presented 111 patients from 16 sites with chronic CLI (Rutherford class 4-6 or Fontaine class III or IV), >50% stenosis or occlusive lesions below the popliteal artery, and vessel reference diameter >2.5 mm but <5 mm. Heavily calcified lesions were excluded. The average follow-up was 173 days, with an acute procedural success rate of 97%. There was only one case of clinically significant dissection and seven cases of nonclinically significant dissections. The freedom from major revascularization was 94%, with 14% target limb revascularization at a mean of 112 days and only eight (7%) major amputations, five at less than 6 months and three at more than 6 months from the initial angioplasty.
Infrapopliteal revascularization represents a very viable option for CLI patients as evidenced by the high rate of procedural success in these often critically ill patients with limited life expectancy. Acute technical failures do not seem to affect the prospect of future surgery and durability issues can likely be overcome by an aggressive surveillance program with a diligent vascular lab and close clinical follow-up. The options for treatment vary, with each modality proposing its own merits, and no general consensus exists. The key elements seem to be re-establishing flow with minimal inducement of injury as a stimulus of premature restenosis while avoiding dissection and perforation so that stents may be avoided in the tibial vessels. In conjunction with the expanding role of plaque excision devices, the future of percutaneous limb salvage is a very promising yet unwritten text. As our collective experience grows with the latest technology, and appropriate prospective trials are designed and patiently completed, we look ahead to application of the best data-driven decisions, employing the latest technology under the most appropriate circumstances for each individual patient with limb-threatening critical ischemia.
Neal C. Hadro, MD, FACS, is from the Cleveland Clinic Foundation, Cleveland, Ohio. He has disclosed that he holds no financial interest in any product or manufacturer mentioned herein. Dr. Hadro may be reached at (216) 587-4280; email@example.com.