An aging population with an increasing prevalence of diabetes and metabolic syndrome is developing in the United States. Associated critical limb ischemia (CLI) is thus poised to be a major health concern and potential burden to this health care system. The development of advanced reperfusion techniques, with the integration of multiple specialties, will be necessary for successful clinical outcomes. Economically sensible, safe, and successful therapeutic treatments will need to become better defined.

Critical limb ischemia includes patients with rest pain, digital ulcerations and gangrene. It is not simply an abnormal ankle brachial index, as this does not truly evaluate tissue oxygenation or limb status. The natural history based on conservative care is poor, with a short-term mortality rate of 10%. Other risks include myocardial infarction (MI) and stroke (2%), amputation (12%), and persistent CLI (18%).¹ It is well-known that the amount of blood flow required to heal damaged tissue is severalfold higher than that required to maintain an intact limb. Successful reperfusion techniques are based upon providing improvement in straight-line crural blood flow to the foot for a sufficient time interval to allow for wound healing. However, patients who present with CLI are at exceedingly high procedural risk from both cardiovascular mortality and disease-based morbidity.

Treatment of these critical limbs includes restoration of perfusion and local wound care, which includes pressure off-loading, infection control, and meticulous debridement as needed. Prior to undertaking any definitive therapy, proper evaluation and documentation of the status of any infection, including osteomyelitis, must be undertaken. The anatomic obstructions that are present in patients with CLI are usually multilevel, or in the case of tibial vessels, multi-segment. Healing variables that will need to be evaluated include the number of vascular levels that are obstructed, the patency of the plantar arch, the amount of tissue destruction that has occurred, the need for debridement or skin grafting, the potential conduit (such as vein) available for the patient, comorbidities, and finally, the nutritional status of the patient, as tissue healing requires significant caloric intake. The techniques for increasing perfusion to the threatened limb can be completed either with open surgical or percutaneous endovascular means in the appropriately selected populations.

Surgical bypass to the infrainguinal and infrapopliteal segments has a documented history with reliable outcomes. Five-year patencies for saphenous vein may be approximated at 66% (limb salvage rates of 80–90%) in patients with CLI. The use of in-situ vein bypass has led to the advancement of bypass grafting to more distal tibial vessels. However, if an adequate venous conduit is not present, prosthetic graft patency is < 50%.² More complex procedures have been created, such as short-segment venous hoods combined with prosthetic bypass material, popliteal to venous bypass, and venous bypass to the tarsal vessels, which have shown some early success.^3–6 However, with any of these surgical techniques, extensive vascular calcification leads to significant surgical challenges. The adjunctive use of ticlopidine and antiplatelet therapy with the surgical procedures has been shown to have some benefit, although larger trials are necessary.⁷ Despite these adjunctive pharmacologic measures, surgical revision remains quite common, occurring in up to 20% of the patients in the first two years.⁸ Although open surgical procedures are reliable, they subject the patient to significant perioperative risk, including wound infection (10–30%), myocardial infarction (1.9 to 3.4%), and an operative mortality rate of 1.3–6%.⁹ In this issue, Trotter et al¹⁰ offers the potential for a less invasive, though still open surgical bypass approach. However, the risk of infection still stands out.

Because of the significant comorbidities that are often present with this patient population, the use of endovascular techniques for revascularization has started to increase. Certainly, endovascular procedures have clearly not demonstrated the long-term patency of the open surgical procedures, but the clinical outcomes as measured by limb salvage appear to be similar, and the percutaneous procedures are often easily repeatable. The recently published Bypass Versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial,¹¹ which randomized patients with CLI to surgery and angioplasty, showed a cost benefit to angioplasty at one year with similar clinical outcomes. With the improvement in low-profile percutaneous transluminal angioplasty (PTA) balloon technology, even diffuse tibial occlusive disease can be effectively dilated. Recent results of a large series (n = 993) of tibial angioplasty patients have shown five-year limb salvage rates of 88%, which certainly challenge those of surgical bypass (Figure 1). The reintervention rate of only 13% was certainly acceptable.¹² Though plain balloon angioplasty certainly is the cornerstone for endovascular care, there are other niche techniques that may be utilized for successful outcomes. Cutting balloon angioplasty has been evaluated in registry format and has shown promise with complex disease such as bifurcation lesions.¹³ This registry of 73 limbs showed an almost 90% limb salvage rate at one year, with a 30-day mortality rate of only 1.5%. Other techniques that have shown utility in small series including subintimal angioplasty¹⁴ and directional atherectomy.¹⁵ The application of coronary stents is certainly feasible and early hemodynamic and limb salvage have been excellent in a recent series.16 The only technology that has been evaluated in a prospective multicenter study utilizing core lab documentation has been excimer laser technology. Over 145 patients deemed poor surgical candidates underwent excimer laser treatment for CLI. The six-month survival with limb salvage rate was 93%.¹⁷ Even though each of these technologies has its own benefits and drawbacks, comparison data are not available between the different technologies to show an advantage over plain balloon angioplasty.

Long total occlusions have often been challenging to traverse with a guidewire. However, even as surgical techniques have advanced for distal pedal or crural anastomosis, endovascular techniques have started to take advantage of any patent pedal vessels for successful retrograde wire access, adding another avenue for success.¹⁸

Summary
Patients with CLI are at risk for both limb loss and premature death, but as refinements of endovascular devices and techniques mature, the need for open surgical procedures will likely diminish, unless much less invasive techniques, such as those outlined in the Trotter et al article, are refined. This paradigm shift in revascularization strategy will be occurring at a time when we will be treating an older, more complex patient population. Coupled with an epidemic of metabolic syndrome and diabetes, this will make endovascular revascularization attractive, since these procedures appear to be emerging as a low-risk, often outpatient, successful treatment strategy. Successful outcomes rely on adequate initial diagnostic testing, including comprehensive cardiac evaluation, followed by a thoughtful plan for revascularization and limb care.