With an aging population and a changing diet, the incidence of Peripheral arterial disease (PAD) is increasing, especially in people with a high-calorie diet, diabetes, hypertension, hyperlipidemia, and smoking. The prevalence is as high as 70% in older adults older than 70 years. Most PAD is asymptomatic, while critical limb ischemia (CLI) refers specifically to PAD with the most severe symptoms, i.e., resting pain, limb ulcers, gangrene, etc., lasting at least 2-4 weeks.The main pathological lesion in CLI is atherosclerosis, a sclerotic occlusion of multiple segmental and multiplanar large and small leg arteries. The extent of the lesion is equivalent to Rutherford grade 4-6 or Fontaine stage III-IV. Compared to asymptomatic PAD, patients with CLI have a much higher incidence of cardiovascular events and related complications, with a natural course mortality rate of 15-20% per year and 40% of limb loss, so CLI must be treated promptly once diagnosed. In order to preserve the limb, timely revascularization is the main treatment for CLI. Revascularization methods include traditional open bypass diversion and percutaneous transluminal angioplasty (PTA). The era of endoluminal technology for CLI has arrived, but is it really expected to replace traditional surgery as the mainstream means of revascularization? This article will review this issue. In general, the overall goal of CLI treatment is to achieve arterial revascularization and limb preservation. However, clinical management must assess the risk-benefit and prognosis of the patient, and not all patients will have a positive clinical outcome with vascular surgery. In some cases, although proximal arterial revascularization has been completed, providing adequate blood supply to the distal tissues, the outcome may be compromised by ischemia-reperfusion injury, distal capillary injury or disease, or inadequate capillary perfusion. 40% of patients will require amputation within six months and 20% will die as a result of CLI revascularization failure. To ensure wound healing and maintain sufficient limb length to accommodate a prosthesis, the level of amputation must be chosen with great care. The likelihood of independent ambulation with an above-knee amputation is less than 50%, and the long-term prognosis for below-knee amputations is grim, with only 30% surviving after two years. These dismal prognoses have led to the advent of new and effective treatment options, and there has been a debate about which is more appropriate for CLI treatment strategies: bypass surgery or endoluminal techniques. Although infrainguinal autologous venous arterial bypass diversion has long been considered the most favorable treatment for CLI, in recent years the endoluminal technique, including PTA, has been improved with technical materials that allow for the treatment of patients who cannot undergo diversion surgery due to high risk factors. The advantages and disadvantages of these two treatment strategies have been more recently documented by evidence-based medicine. Evidence-based results for surgical bypass diversion Some studies have shown that open surgery using autologous saphenous vein as the diversion material results in the best long-term patency rate and can be the “gold standard” for CLI treatment. Currently, the BASIL trial remains the only prospective randomized comparison of open versus endoluminal treatment of CLI. 452 patients were admitted to BASIL and underwent endovascular lumpectomy or diversion surgery, respectively, with follow-up endpoints of above-ankle amputation or death occurring. at 12 months, only 107/216 cases (49.5%) in the endoluminal group maintained clinical success, compared with 110/195 in the surgical group The six-month amputation-free survival rate and quality of life were similar in both groups. However, in terms of long-term outcomes, surgery significantly increased the overall survival period by approximately seven months for patients expected to survive for more than two years. Despite the excellent efficacy, the number of patients who can tolerate this invasive procedure remains limited, and the BASIL trial concluded that only those patients with a life expectancy greater than two years could be candidates for bypass surgery and may realize a better survival benefit than endoluminal surgery. Similar clinical research trials evaluating diversion surgery include PREVENT III, a multicenter phase 3 study that showed patient one-year rates of phase I patency, phase I assisted patency, phase II patency, and limb preservation at 61%, 77%, 80%, and 88%, respectively. the PREVENT phase III study scored surgical risk based on age, comorbidities, and surgical indications Patients were classified into three groups: low, intermediate and high risk. For the high-risk group, outcomes remain unsatisfactory. Given the current data, open surgical treatment of CLI generally depends on the patient’s ability to tolerate an invasive procedure, the availability of an autologous saphenous vein, and the patient’s life expectancy. However, for the current complex healthcare environment, cost issues are also beginning to factor into clinical treatment decisions. It has been reported in the literature that open surgical procedures have more cost-benefit value than endoluminal procedures in terms of long-term course. Thus, open surgery has a better survival and cost-benefit ratio for patients with CLI with a life expectancy greater than 2 years. Evidence-based results for endoluminal angioplasty PTA as a minimally invasive technique is appropriate for patients without surgical conditions or for patients eligible for surgery with a life expectancy of less than 2 years. While endoluminal treatment reduces postoperative morbidity, length of stay, and initial surgical costs compared with bypass diversion, it still provides significantly less first-stage patency than open surgery. For example, PTA has mostly low first-stage patency rates of 20%-60% in the tibial artery of the lower leg. Of course, new endovascular techniques may result in higher patency rates than traditional PTA techniques. In a comparative study of endoluminal and surgical procedures for severe aortoiliac occlusive disease, surgical procedures were found to have higher first-stage patency rates at three years (89% vs 100%), while second-stage patency rates were similar (96% vs 96%). kedora et al. presented results comparing self-expanding stents with suprapopliteal femoral N bypass diversion, with one-year first-stage patency rates (73.5% vs 74.2%) and second-stage patency rates (83.9% vs. 83.7%) were not significantly different. However, Lepantalo et al. reported a significantly lower patency rate and a 2.7% perioperative mortality rate with the laminated stent compared to bypass surgery, which led to the premature termination of the randomized clinical trial. Other studies have reported that, despite the low rate of first-stage PTA patency, the rate of limb preservation is relatively acceptable compared with bypass surgery, reaching 74% at five years and 84.7% at eight years. In a recent meta?? analysis, CLI with distal N artery angioplasty had lower 36-month first-stage patency, second-stage patency, and limb preservation rates than sub-N bypass diversion. However, this meta-analysis also showed that PTA still had some clinical benefit, as the 3-year limb preservation rate was up to 82%, comparable to the surgical group. In addition, the superiority of endovascular surgery over bypass diversion is characterized by the possibility of frequent repeat interventions, which are less feasible. The recent drug-eluting stent trial (PaRADISE), the largest published clinical trial of CLI treatment to date, primarily received BTK (below the knee) drug-eluting stent implantation. The results at 3 years postoperatively were encouraging, with an amputation rate of only 6±2%, an amputation survival rate of 68±5%, and an overall survival rate of 71±5%. In addition, PaRADISE showed a 13±3.6% improvement in the three-year limb preservation rate compared to BASIL. Another study used assisted laser angioplasty (Spectranetics, USA) to treat 145 patients with CLI who were ineligible for surgery. After laser rotation, PTA was performed in 110 limbs and stenting was performed in 70 limbs. Postoperatively, 86% of the limbs had residual stenosis of less than 50%, with 6-month patient survival and limb preservation rates of 92% and 93%, respectively. Recent literature has demonstrated that the indications for endoluminal techniques continue to expand and have begun to challenge complex subtrochanteric lesions of the femoral N knee that were previously considered difficult to accomplish endolumetrically. Given the encouraging results of endoluminal treatment, Conrad et al. proposed a new treatment concept of performing a less invasive endoluminal procedure in one stage and maintaining continuous vascular patency by performing secondary interventions. This multi-stage approach is largely suitable for patients who are elderly and not suitable for open surgery. Accordingly, the treatment strategy for CLI has shifted to a one-stage palliative stent implantation combined with secondary interventions to maintain patency, while open surgery is limited to those with poor expected angioplasty results or who are simply not eligible for endoluminal treatment. Management of BTK disease in CLI The treatment of below-knee BTK vessel occlusions is usually complex. Diversion surgery is generally not used in CLI in the middle-aged and elderly because of significantly increased surgical morbidity and mortality, the high incidence of graft failure, and worsening CLI conditions after failure. Limb preservation is the main goal of CLI treatment, and success depends on the patency of dilatation of all key inflow tracts and the opening of one or more tibial artery outflow tracts communicating with the foot vessels. Recently, the Angiosome concept, originally proposed by Taylor and Palmer in 1987, has been increasingly applied to the treatment of CLI, improving limb preservation rates, healing rates, and amputation disease-free survival. Taylor and Palmer later defined the concept of angiosome specifically for the lower leg, by opening a specific vascular and collateral vascular supply of the angiosome to aid in the healing of a wound or amputation stump. However, despite the application of these concepts, the patency rate of BTK remains low, with a minimum of 58% at 1 year. In addition, it was thought that stenting was reserved due to the very high restenosis rate in the calf artery, residual stenosis or entrapment formation after PTA. in 2004, Feiring et al. applied stents in BTK patients with 95% efficiency, relieving ischemic pain and aiding tissue healing. Recent studies have also shown that balloon PTA in BTK can achieve a technical success rate of 77%-100%. In addition, long distance low-pressure angioplasty balloons and microguide systems have recently emerged to improve intravascular passage rates and prolong the extent of lesion treatment. Studies have shown that 58 patients treated with low-pressure long balloons (80 – 120 mm) had a 100% limb preservation rate at 15 months. Technical skill, device type, and access point all influence the success rate of BTK endovascular treatment. In addition, the short-term tissue healing benefit outweighed the long-term vascular patency rate. Other newer techniques, such as cryoballoon and laser-assisted recanalization, are not yet fully accepted. There is a growing trend toward the use of endarterectomy in the infrapopliteal artery. Several device companies are producing spinotomy devices proposed for use in the calf tibial vessels and even in the foot circulation. Long-term patency data for these devices are not yet known. New Techniques and Products for Endoluminal Angioplasty For lesions that cannot be treated with normal balloons, such as due to heavy vascular calcification, special balloons may be required, including the cutting balloon (Boston Scientifi, Natic??k, Mass) and the new generation of AngioSculpt balloons (AngioScore, Fremont, Calif ) and VascuTrak 2 (Bard, Tempe, Ariz). The cutting balloon has 3 (1.5 to 4 mm diameter balloons) or 4 (5 to 8 mm diameter balloons) microscopic blades that are fixed longitudinally to the surface of the balloon and can extend more than 0.127 mm to produce a longitudinal incision to expand the plaque during balloon expansion. The AngioSculpt balloon catheter uses a laser-cut, highly flexible nickel-titanium alloy composition made with 3 spiral struts surrounding the balloon, which allows the balloon expansion force to extend along the edge of the lesion. the VascuTrak 2 balloon has 2 guidewires placed outside the balloon to give longitudinal pressure on the plaque during expansion. One of the main drawbacks of balloon dilatation shaping is the possibility of entrapment at the tibial vessel site. These occur infrequently and the application of a stent can successfully alleviate the acute hemodynamic abnormalities caused by entrapment. Currently, the most widely used stents for the calf segment include coronary balloon-expandable stents (bare or drug-eluting stents) and small vessel self-expanding XPERT stents (Abbott Vascular, ST Paul, MN). the main advantage of the Xpert stent is the option of using 40 and 60 mm lengths for diffuse calf vascular lesions. In general, the typical CLI patient with severe infrapopliteal calf vasculopathy, drug-eluting balloon-expandable stents may compromise blood flow and increase the risk of in-stent thrombosis. Intra-arterial spinotomy and ablation techniques have trended towards a substantial increase in the calf field over the past 5 years. Current plaque spinning devices are, SilverHawk (ev3, Plymouth, MN) or Jetstream (Pathway Medical Technologies, Inc, Kirkland, WA) catheters, Turbo Elite Laser (Spectranetics, Inc. Colorado Springs, CO), Rotablator (Boston Scientific, Natick, MA), or Diamondback (Cardiovascular Systems Inc, Plymouth, MN) catheters. In general, angioplasty and stenting in the calf vasculature have the expected high success rate to achieve angioplasty and stenting and do not require the aggressive use of these techniques, which are only used to assist in opening the vessel in certain specific circumstances. When using these techniques, the use of a filter-type embolic protection device is necessary to prevent distal artery embolization during PTA. Patients with CLI do not receive any clinical benefit if embolism occurs in the distal circulation after hemodynamic reconstruction. In angulated vessels such as the proximal segment of the anterior tibial artery, the use of these devices can increase the risk of perforation. Despite these risks, the use of these techniques for the treatment of continuous N tibial vascular disease can avoid stenting because the knee area is, after all, a non-stenting zone. CLI Microcirculation Concept The concept of microcirculation is a holistic system that includes small arteries, capillaries, small veins, lymphatics, and cutaneous microvasculature and is useful as an indicator for the evaluation of systemic vascular disease, including CLI. notably, patients with CLI often present with edema, possibly due to impaired capillary vasodilatory response resulting in high capillary pressure and excess fluid leakage. After dealing with the revascularization of the main artery, it is important to focus on the protection of the peripheral microcirculatory state to reduce its damage by ischemia-reperfusion and to protect the function of the endothelium. Vascular endothelial cells, lining the intimal surface, play a crucial role in maintaining vascular function, and their dysfunction leads to common vascular diseases such as atherosclerosis, inflammation and thrombosis. Under normal conditions, endothelial cells are in a resting state and have a normal morphology. When blood flow is normal, leukocytes and platelets are in a secretory and non-adherent state. However, in patients with symptomatic intermittent claudication, exercise can cause a decrease in blood flow to the ischemic zone, and a subsequent decrease in acute perfusion pressure. Endothelial cells respond to ischemia by becoming prethrombotic, activating the coagulation cascade and proplatelet adhesion, and secreting adhesion molecules that favor the accumulation of leukocytes, erythrocytes, and platelets, leading to increased blood viscosity. In addition, while leukocyte and platelet activation may cause microcirculatory obstruction, activated leukocytes can also release toxic substances, including protein hydrolases, oxygen radicals, and leukotrienes, which further promote endothelial damage, thereby increasing vascular permeability and causing plasma overflow. As a result, continuous circulation of all participants promotes endothelial damage, increases vascular permeability, leads to fluid leakage, interstitial edema, and local capillary collapse, further exacerbating damage to the capillary hemodynamic system. Endothelial dysfunction also leads to impairment of endothelial-mediated mechanisms of vascular tension regulation, such as reduced nitric oxide synthesis. In conclusion, the endothelium is the initiating factor for alterations in the microcirculatory system. The relationship between macroangiographic manifestations and microcirculation, and how to facilitate the healing of CLI by improving microcirculation, is still poorly understood and needs to be further investigated. Conclusions Severe lower extremity ischemia must be treated aggressively with revascularization, and endoluminal therapy is increasingly used. However, there is no definite conclusion whether endoluminal treatment is always preferred, because after all, the long-term patency rate of angioplasty is still lower than that of autologous venous bypass diversion. The key to successful treatment of CLI is individualized treatment based on multiple factors such as age, comorbidities, quality of life, and life expectancy.