Critical Limb Ischemia

Critical limb ischemia (CLI), defined as chronic ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease, is the most advanced form of peripheral arterial disease. Traditionally, open surgical bypass was the only effective treatment strategy for limb revascularization in this patient population. However, during the past decade, the introduction and evolution of endovascular procedures have significantly increased treatment options. In a certain subset of patients for whom either surgical or endovascular revascularization may not be appropriate, primary amputation remains a third treatment option. Definitive high-level evidence on which to base treatment decisions, with an emphasis on clinical and cost effectiveness, is still lacking. Treatment decisions in CLI are individualized, based on life expectancy, functional status, anatomy of the arterial occlusive disease, and surgical risk. For patients with aortoiliac disease, endovascular therapy has become first-line therapy for all but the most severe patterns of occlusion, and aortofemoral bypass surgery is a highly effective and durable treatment for the latter group. For infrainguinal disease, the available data suggest that surgical bypass with vein is the preferred therapy for CLI patients likely to survive 2 years or more, and for those with long segment occlusions or severe infrapopliteal disease who have an acceptable surgical risk. Endovascular therapy may be preferred in patients with reduced life expectancy, those who lack usable vein for bypass or who are at elevated risk for operation, and those with less severe arterial occlusions. Patients with unreconstructable disease, extensive necrosis involving weight-bearing areas, nonambulatory status, or other severe comorbidities may be considered for primary amputation or palliative measures.     

Critical limb ischemia

Opinion statement Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease (PAD). Without timely recognition, appropriate diagnosis, and revascularization, patients with CLI are at risk for amputation or potentially fatal complications. The past decade has seen substantial growth in endovascular CLI therapies and options now exist for treating long-segment lower-extremity arterial occlusive disease, but surgical bypass may yield more durable results. Patients who are younger, more active, and at low risk for surgery may have better outcomes with an operation. Surgical treatment is also indicated for failures of endovascular therapy, which may include early technical failures or later occlusion after placement of stents or other interventions.     

Drug-eluting stents for treatment of focal infrapopliteal lesions

We have investigated the role of drug-eluting stents on patency rates after treatment of focal infrapopliteal lesions in patients with intermittent claudication and critical limb ischemia. Reports indicate that drug-eluting stents reduce the risk of restenosis after percutaneous infrapopliteal artery revascularization. A Pub Med, EMBASE, Cochrane database review search of non-randomized studies investigating patency rates, target lesion revascularisation rates, limb salvage rates and mortality rates in an up to 3-year follow-up period after drug-eluting stent placement was conducted. In addition, preliminary results of randomized studies comparing drug-eluting stents with bare-metal stents and plain balloon angioplasty in treatment of focal infrapopliteal lesions were included in this review. A total of 1039 patients from 10 non-randomized and randomized studies were included. Most commonly used drug-eluting stents were sirolimus-eluting. The mean follow-up period was 12.6 (range 8 - 24). The mean 1-year primary patency rate was 86 ± 5 %. The mean target lesion revascularization rate and limb salvage rate was 9.9 ± 5 % and 96.6 %±4 %, respectively. Results from non-randomized and preliminary results from prospective, randomized trials show a significant advantage for drug-eluting stents in comparison to plain balloon angioplasty and bare-metal stents concerning target lesion patency and in parts target lesion revascularisation. No trial reveals an advantage for drug-eluting stents with regard to limb salvage and mortality.     

Peripheral arterial disease in the elderly

Smoking should be stopped and hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism treated in elderly patients with peripheral arterial disease (PAD) of the lower extremities. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in patients with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, angiotensin-converting enzyme inhibitors, and statins should be given to all elderly patients with PAD without contraindications to these drugs. Beta blockers should be given if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery are (1) incapacitating claudication in patients interfering with work or lifestyle; (2) limb salvage in patients with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and (3) vasculogenic impotence.     

Management of peripheral arterial disease

Peripheral arterial disease (PAD) may be asymptomatic, may be associated with intermittent claudication, or may be associated with critical limb ischemia. Coronary artery disease (CAD) and other atherosclerotic vascular disorders may coexist with PAD. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from CAD. Modifiable risk factors such as cessation of cigarette smoking and control of dyslipidemia, hypertension, and diabetes should be treated. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, and angiotensin-converting enzyme inhibitors should be given to all persons with PAD. beta-Blockers should be given if CAD is present. Exercise rehabilitation programs and cilostazol improve exercise time until intermittent claudication. Indications for lower-extremity angioplasty, preferably with stenting, or bypass surgery are 1) incapacitating claudication in persons interfering with work or lifestyle; 2) limb salvage in persons with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and 3) vasculogenic impotence. However, amputation should be performed if tissue loss has progressed beyond the point of salvage, if surgery is too risky, if life expectancy is very low, or if functional limitations diminish the benefit of limb salvage.     

Management of peripheral arterial disease of the lower extremities in elderly patients

The prevalence of peripheral arterial disease (PAD) increases with age. PAD in elderly persons may be asymptomatic, may be associated with intermittent claudication, or may be associated with critical limb ischemia. Other atherosclerotic vascular disorders, especially coronary artery disease (CAD), may coexist with PAD. Elderly persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from CAD. Modifiable risk factors should be treated in persons with PAD such as cessation of cigarette smoking and control of hypertension, dyslipidemia, and diabetes. Statins have been shown to reduce the incidence of intermittent claudication and to improve treadmill exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, should be administered to all persons with PAD. Persons with PAD should be treated with angiotensin-converting enzyme inhibitors and also with beta blockers if CAD is present. Cilostazol should be given to persons with intermittent claudication to improve exercise capacity unless heart failure is present. Exercise rehabilitation programs improve exercise time until claudication. Indications for lower extremity angioplasty, preferably with stenting, or bypass surgery are 1) incapacitating claudication in persons interfering with work or lifestyle; 2) limb salvage in persons with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and 3) vasculogenic impotence. However, amputation should be performed if tissue loss has progressed beyond the point of salvage, if surgery is too risky, if life expectancy is very low, or if functional limitations obviate the benefit of limb salvage.     

Critical limb ischemia: endovascular strategies for limb salvage

Critical limb ischemia (CLI) represents the most severe clinical manifestation of peripheral arterial disease, defined as the presence of chronic ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease. The dominant pathology underlying CLI is atherosclerosis, distributed at multiple levels along the length of the lower extremity and with a propensity for involvement of the tibial vessels in the leg and the small vessels of the foot. To achieve limb salvage in patients with CLI, revascularization of the affected limb is generally required. In contemporary practice, endovascular techniques are rapidly replacing surgical bypass as the first option for revascularization for CLI based on high technical success rates and low rates of procedure-related morbidity and mortality. This review will describe the clinical strategy of the authors who have adopted an endovascular-first approach to revascularization in treating patients with CLI and summarize the clinical outcomes of endovascular therapy in this population.     

Anecdotal vs. evidence‐based,off label use of drug eluting stents for infrapopliteal disease: Abusus non tollit usum (Misuse does not nullify proper use)

Objectives: The purpose of this study was to assess the long‐term limb preservation and/or healing of ulcers in patients with critical limb ischemia (CLI) and severe infrapopliteal atherosclerotic disease treated with drug eluting stents (DES). Background: Percutaneous revascularization has become an effective treatment for CLI in patients with infrapopliteal atherosclerotic disease. Recent reports using DES in patients with CLI have documented excellent short‐term infrapopliteal vessel patency. Higher primary patency rates in infrapopliteal vessels treated with DES could translate into better long‐term clinical outcomes and improved limb salvage rates. Methods: Twenty‐four consecutive patients with CLI (defined as rest pain, nonhealing ulcers, or gangrene) because of severe infrapopliteal disease were treated with DES from August 2004 to June 2006. Results: Procedural success was achieved in 96% (27/28) of targeted lesions. There were no procedure‐related deaths, acute vessel thrombosis events, or need for urgent surgical intervention. There was one case of distal embolization. Clinical follow up, ranging 8–34 months, is available for 100% of patients of which 83% (20/24) achieved limb preservation and healing. Angiographic and/or sonographic follow up, ranging 6–34 months, is available in 79% (19/24) of patients of which 95% (18/19) had patent target vessels. Conclusions: DES is a safe and effective long‐term option for CLI due to severe infrapopliteal arterial disease. Long‐term vascular patency led to a high rate of limb preservation and low amputation rate. A multicenter trial should further elucidate the role of DES in the treatment of CLI. © 2008 Wiley‐Liss, Inc.     

Sirolimus for below the knee lesions: mid-term results of SiroBTK study.

OBJECTIVES: To assess the safety and efficacy of sirolimus-eluting stents (SESs) in the treatment of severe intermittent claudication and critical limb ischaemia with "below-the-knee" lesions, unsuitable for surgery. BACKGROUND: Limited published evidence suggests that drug-eluting stents may offer significant improvements in the treatment of infrapopliteal lesions. METHODS: Thirty consecutive patients with either severe intermittent claudication or critical limb ischemia (CLI), category 3-6 of Rutherford classification, and multivessel disease of infrapopliteal arteries (> or = 2 vessels) were treated with SES. Sixty-two arteries were treated with 106 SES. Mean age was 73.9 years, 77% of patients were male and 36% diabetic. The primary endpoint was clinical improvement and healing of ulcers at short term (1 month) and mid term (7.7 months). The secondary endpoint was primary vessel patency rate (angiographic or duplex assessment). All patients received clopidogrel (75 mg daily) or ticlopidine (150 mg daily) for 2 months or longer. RESULTS: Angiographic and procedural success was achieved in all patients. At 7 months (7.7 +/- 5.8), it was necessary to amputate 1 toe in one patient and 1 mid-foot in another. Limb salvage was obtained in 100% of patients. Other events were: two cardiac deaths unrelated to CLI, one stroke with hemiparesia, one initial reperfusion syndrome, one contralateral CLI, and three recurrent homolateral claudication cases. All surviving patients had a mid-term clinical improvement with 97% of primary patency (56 patent arteries on 58 arteries). CONCLUSION: Treatment of "below-the-knee" lesions with SES may provide an alternative treatment for patients with CLI.     

膝下动脉闭塞腔内治疗与手术治疗效果的临床分析

目的:评价膝下动脉闭塞球囊扩张成形术和动脉旁路术的治疗效果。方法:回顾性分析2005年12月至2009年5月北京协和医院收治的膝下动脉闭塞重症下肢缺血病例,全部资料都是前瞻性收集并录入数据库,并将治疗结果进行回顾性分析。根据膝下动脉初次处理手段的不同分为2组:球囊扩张成形术(PTA)组、以膝下动脉为流出道行自体静脉旁路移植术(bypass surgery,BPS)组,比较2组手术及随访结果。结果:PTA组54例(61条肢体),男性37例,女性17例,平均年龄66岁;手术前后踝肱指数(ABI)由(0.43±0.27)增加至(0.86±0.21),随访期间一期通畅率63.8%,二期通畅率74.1%,救肢率88.3%。动脉旁路术组17例(17条肢体),男性12例,女性5例,平均年龄67岁,ABI由(0.21±0.19)增加至(0.73±0.38),手术通畅率60%,救肢率87.5%。2组治疗结果差异无统计学意义。结论:膝下动脉腔内成形术的临床治疗效果不次于膝下动脉旁路手术,可以作为膝下动脉闭塞首选的治疗方法。     

Endovascular Treatment of Peripheral Vascular Disease

Peripheral arterial disease (PAD) affects about 27 million people in North America and Europe, accounting for up to 413,000 hospitalizations per year with 88,000 hospitalizations involving the lower extremities and 28,000 involving embolectomy or thrombectomy of lower limb arteries. Many patients are asymptomatic and, among symptomatic patients, atypical symptoms are more common than classic claudication. Peripheral arterial disease also correlates strongly with risk of major cardiovascular events, and patients with PAD have a high prevalence of coexistent coronary and cerebrovascular disease. Because the prevalence of PAD increases progressively with age, PAD is a growing clinical problem due to the increasingly aged population in the United States and other developed countries. Until recently, vascular surgical procedures were the only alternative to medical therapy in such patients. Today, endovascular practice, percutaneous transluminal angioplasty with or without stenting, is used far more frequently for all types of lower extremity occlusive lesions, reflecting the continuing advances in imaging techniques, angioplasty equipment, and endovascular expertise. The role of endovascular intervention in the treatment of limb-threatening ischemia is also expanding, and its promise of limb salvage and symptom relief with reduced morbidity and mortality makes percutaneous transluminal angioplasty/stenting an attractive alternative to surgery and, as most endovascular interventions are performed on an outpatient basis, hospital costs are cut considerably. In this monograph we discuss current endovascular intervention for treatment of occlusive PAD, aneurysmal arterial disease, and venous occlusive disease.     

Awareness of anatomical variations for infrapopliteral intervention

With the tremendous advancement and accumulated expertise of endovascular techniques, infrapopliteal intervention is emerging as an alternative therapeutic option to distal bypass surgery for limb salvage in the setting of critical limb ischemia (CLI). However, though much attention has been given to infrapopliteal intervention, the importance of identifying preprocedural infrapopliteal variants remains underappreciated. Becoming more aware of these anatomical variants will translate to increased clinical effectiveness for the patient with infrapopliteal artery disease. Therefore, this review will highlight the fundamental aspects of infrapopliteal variant anatomy for the catheter‐based treatment of CLI patients with symptomatic infrapopliteal artery disease.© 2010 Wiley‐Liss, Inc.     

Wireless laser-assisted angioplasty of the superficial femoral artery in patients with critical limb ischemia who have failed conventional percutaneous revascularization.

Percutaneous revascularization has become an effective treatment for patients suffering from chronic critical limb ischemia (CLI) due to chronic atherosclerotic obstructions, including total occlusions. Unlike other vascular beds, total chronic occlusions of the femoropopliteal arteries are frequently found in patients with severe claudication or CLI. As a consequence, patients with long chronic total occlusions of the femoropopliteal arteries are generally not considered optimal candidates for percutaneous revascularization and are frequently referred for surgical revascularization. In the present study, we sought to evaluate the feasibility, safety, and outcome of a modified wireless laser ablation technique to recanalize total occlusions in patients with CLI who had failed conventional percutaneous techniques for limb salvage. Procedural success, complications, actuarial freedom of limb loss, and surgical revascularization were evaluated in 25 patients after a mean follow-up of 13 +/- 8 months. Procedural success was achieved in 21 patients (84%). Actuarial freedom from surgical revascularization or limb loss was 72%. There was one vascular perforation. No deaths or distal embolization occurred. Three patients (12%) required limb amputation during follow-up, whereas four patients (16%) had surgical revascularization in the presence of feasible vascular targets. Limb salvage was achieved in 88% of patients when laser recanalization was combined with surgical revascularization. These results suggest that the use of laser ablation is safe and facilitates angioplasty and stenting in patients with CLI that failed conventional endovascular revascularization. This technique might prevent limb loss in patients with CLI due to femoropopliteal total occlusions, particularly in patients with unsuitable anatomy for surgical revascularization.     

Bypass Surgery for Lower Extremity Limb Salvage: Vein Bypass

Bypass surgery for limb salvage in cases of chronic limb ischemia is a well-established treatment modality. Use of an autogenous vein provides the best conduit for infrainguinal arterial bypass procedures, particularly for bypass to the infrapopliteal arteries. In this article, we discuss infrainguinal vein bypass surgery including indications, perioperative care, and long-term follow up. We also discuss the outcomes of the procedure with regard to patient survival and limb salvage. The autogenous vein continues to be the best available conduit with the highest patency rate and the best treatment option. Compared to all other revascularization options for infrainguinal disease, the vein bypass has the best limb salvage and long-term survival in patients appropriately selected for the procedure.     

Limb salvage following laser-assisted angioplasty for critical limb ischemia: results of the LACI multicenter trial.

PURPOSE: To evaluate the effectiveness of laser-assisted angioplasty for patients with critical limb ischemia (CLI) who were poor candidates for surgical revascularization. METHODS: A prospective registry at 14 sites in the US and Germany enrolled 145 patients with 155 critically ischemic limbs; the patients were poor candidates for bypass surgery owing to inadequate target vessel or saphenous vein, prohibitive cardiac disease, or significant comorbidities (ASA class 4). Additional comorbid risk factors included diabetes in 66%, hypertension in 83%, previous stroke in 21%, and myocardial infarction in 23%. Endovascular treatment included guidewire traversal and excimer laser angioplasty followed by balloon angioplasty with optional stenting. RESULTS: Occlusions were present in 92% of limbs. A mean of 2.7+/-1.4 lesions were treated per limb; the total median treatment length was 11 cm (mean 16.2, range 0.2-123). Stents were implanted in 45% of limbs. Procedural success, defined as <50% residual stenosis in all treated lesions, was seen in 86% of limbs. At 6-month follow-up, limb salvage was achieved in 110 (92%) of 119 surviving patients or 118 (93%) 127 limbs. CONCLUSION: Excimer laser-assisted angioplasty for CLI offers high technical success and limb salvage rates in patients unfit for traditional surgical revascularization.     

Stadiengerechte medikament?se Therapie bei arterieller Verschlusskrankheit

Peripheral arterial occlusive disease (PAOD) is a manifestation of atherothrombosis with severe mortality. Regardless of the severity of the disease all patients have to be treated with basic therapy (management of classical risk factors in combination with inhibitors of platelet function with consistent physical activity). Specific vascular therapy has to be indicated in correlation to the severity of disease. In the case of intermittent claudication (CI), which belongs to the domain of conservative treatment, exercise training and drug therapy are combined. Cilostazol is indicated with the highest recommendation due to its superior grade of evidence. In severe cases, parenteral therapy with prostaglandins can be attempted. In critical limb ischemia (CLI), amputation can only be avoided by immediate revascularization; therefore, CLI is in the domain of invasive therapy. Evidence-based vasoactive drugs (PGE-1) can only be indicated as an additional measure, or as an ultimate therapy if limb salvage is reasonable. The indication and performance of invasive and non-invasive therapy must be offered on an interdisciplinary basis by vascular specialists taking all aspects of the varying but complementary therapeutic methods into consideration.     

Critical limb ischemia: medical and surgical management

AbstractChronic critical limb ischemia (CLI), defined as > 2 weeks of rest pain, ulcers, or tissue loss attributed to arterial occlusive disease, is associated with great loss of both limb and life. Therapeutic goals in treating patients with CLI include reducing cardiovascular risk factors, relieving ischemic pain, healing ulcers, preventing major amputation, improving quality of life and increasing survival. These aims may be achieved through medical therapy, revascularization, or amputation. Medical therapy includes administration of analgesics, local wound care and pressure relief, treatment of infection, and aggressive therapy to modify atherosclerotic risk factors. For patients who are not candidates for revascularization, and who are unwilling or unable to undergo amputation, treatments such as intermittent pneumatic compression or spinal cord stimulation may offer symptom relief and promote wound healing. Revascularization offers the best option for limb salvage. The decision to perform surgery, endovascular therapy, or a combination of the two modalities ('hybrid' therapy) must be individualized. Patients who are relatively fit and able to withstand the rigors of an open procedure may benefit from the long-term durability of surgical repair. In contrast, frail patients with a limited life expectancy may experience better outcomes with endovascular reconstruction. Hybrid therapy is an attractive option for patients with limited autologous conduit, as it permits complete revascularization with a less extensive procedure, shorter duration of operation, and decreased risk of peri-operative complications. Amputation should be considered for patients who are non-ambulatory, demented, or unfit to undergo revascularization.     

Functional outcomes and quality of life in peripheral arterial disease: current status

This review examines current evidence for baseline functional impairment and changes with therapy in patients with peripheral arterial disease (PAD)--ranging from patients without claudication or critical limb ischemia (CLI) but other exertional leg symptoms (erroneously referred to as asymptomatic in the Fontaine classification system), to patients with claudication and those with CLI. The review points out that the status of functional outcomes research is markedly different in focus and development in the different levels of disease severity--paradoxically less studied in the more severe CLI population than in patients with claudication, for example.     

Sirolimus-eluting versus bare stents after suboptimal infrapopliteal angioplasty for critical limb ischemia: enduring 1-year angiographic and clinical benefit.

PURPOSE: To report the 1-year angiographic and clinical outcome from a prospective single-center study investigating the infrapopliteal application of sirolimus-eluting versus bare metal stents in patients with critical limb ischemia (CLI) who underwent below-the-knee endovascular revascularization. METHODS: Stenting was performed as a bailout procedure for suboptimal angioplasty results (flow-limiting dissection, elastic recoil, or postangioplasty residual stenosis >30%). In the first 29 patients, infrapopliteal stenting was performed with bare metal stents (group B) and with sirolimus-eluting stents in the other 29 patients (group S). RESULTS: Below-the-knee angioplasty and stenting involved 65 lesions in 40 infrapopliteal arteries of 29 limbs in group B and 66 lesions in 41 infrapopliteal arteries of 29 limbs in group S. Baseline comorbidities (hyperlipidemia and symptomatic cardiac and carotid disease) were more pronounced in group S (p<0.05). At 6 months, sirolimus-eluting stents demonstrated significantly higher primary patency (OR 5.625, 95% CI 1.711 to 18.493, p = 0.004) and decreased in-stent binary restenosis (OR 0.067, 95% CI 0.021 to 0.017, p<0.001) and in-segment binary restenosis (OR 0.229, 95% CI 0.099 to 0.533, p = 0.001). After 1 year, sirolimus-eluting stents were steadily associated with increased primary patency (OR 10.401, 95% CI 3.425 to 31.589, p<0.001) and significantly less in-stent (OR 0.156, 95% CI 0.060 to 0.407, p<0.001) and in-segment (OR 0.089, 95% CI 0.023 to 0.349, p = 0.001) binary restenosis. In addition, sirolimus-eluting stents were associated with significantly fewer cumulative target lesion reinterventions at 6 months (OR 0.057, 95% CI 0.008 to 0.426, p = 0.005) and 1 year (OR 0.238, 95% CI 0.067 to 0.841, p = 0.026). No significant differences between groups B and S were noted at 1 year with respect to mortality (10.3% versus 13.8%, respectively), minor amputation (17.2% versus 10.3%), or limb salvage (100% versus 96%). CONCLUSION: The application of sirolimus-eluting stents reduces the restenosis rate in the infrapopliteal arteries and the rate of repeat endovascular procedures the first year after treatment.