Guideline sources The following summarized guidelines for the evaluation and management of chronic limb- threatening ischemia (CLTI) are prepared by our editorial team based on guidelines from the Canadian Cardiovascular Society (CCS 2022), the Society for Vascular Surgery (SVS 2019), the European Society of Cardiology (ESC/ESVS 2018), and the American Heart Association (AHA/ACC 2017). 1 2 3 4 Guidelines 1. Classification and risk stratification Classification and staging: Use an integrated, limb-based anatomic staging system, such as the GLASS, to define complexity of a preferred target artery path and to facilitate evidence-based revascularization in patients with CLTI. E https://web.pathway.md/diseases/recOr1qSws3E3mNyR 1/7 6/29/23, 3:54 AM Chronic limb-threatening ischemia Pathway Use an integrated threatened limb classification system, such as the WIfI, to stage all patients with CLTI being candidates for limb salvage. B Risk stratification: define patients with CLTI as average surgical risk if anticipated periprocedural mortality is < 5% and estimated 2-year survival is > 50%. B Show 2 more 2. Diagnostic investigations History and physical examination: As per SVS 2019 guidelines, elicit a detailed history to determine symptoms, past medical history, and cardiovascular risk factors in all patients with suspected CLTI. E Show 7 more As per ACC 2017 guidelines, consider obtaining toe-brachial index with waveforms, transcutaneous partial pressure of oxygen, or skin perfusion pressure for the diagnosis of critical limb ischemia in patients with normal ABI (1.00-1.40) or borderline ABI (0.91-0.99), in the setting of nonhealing wounds or gangrene. C Diagnostic imaging: As per SVS 2019 guidelines, consider obtaining duplex ultrasound as first-line arterial imaging in patients with suspected CLTI. C Show 5 more As per ESC 2018 guidelines, consider obtaining angiography including foot runoff in patients with CLTI with below-the-knee lesions before revascularization. C As per ACC 2017 guidelines, obtain invasive angiography in patients with critical limb ischemia being candidates for revascularization. B 3. Medical management Prostanoids: As per SVS 2019 guidelines, do not use prostanoids for limb salvage in patients with CLTI. Consider offering prostanoids in selected patients with rest pain or minor tissue loss, and if revascularization is not possible. D As per ACC 2017 guidelines, do not use prostanoids in patients with critical limb ischemia. D Vasoactive agents: do not use vasoactive drugs or defibrinating agents (ancrod) in patients with CLTI, if revascularization is not possible. D Angiogenic growth factors: restrict the use of therapeutic angiogenesis to patients with CLTI enrolled in a registered clinical trial. B Gene therapy: do not offer stem cell/gene therapy in patients with CLTI. D Antithrombotic therapy: initiate antiplatelet therapy in all patients with CLTI. A Show 3 more https://web.pathway.md/diseases/recOr1qSws3E3mNyR 2/7 6/29/23, 3:54 AM Chronic limb-threatening ischemia Pathway Statin therapy: initiate moderate- or high-intensity statin therapy to reduce all-cause and cardiovascular mortality in patients with CLTI. A Management of pain: Prescribe analgesics of appropriate strength in patients with CLTI with ischemic rest pain of the lower extremity and foot until pain resolves after revascularization. E Initiate acetaminophen in combination with opioids for pain control in patients with CLTI with chronic severe pain. E Management of comorbidities: As per SVS 2019 guidelines, manage all modifiable risk factors to recommended level in all patients with suspected CLTI. B Show 4 more As per ESC 2018 guidelines, ensure optimal glycemic control in patients with CLTI and diabetes. B As per ACC 2017 guidelines, consider optimizing glycemic control to reduce limb-related outcomes in patients with critical limb ischemia. C 4. Nonpharmacologic interventions Smoking cessation: offer smoking cessation interventions (pharmacotherapy, counseling, or behavior modification therapy) in all patients with CLTI smoking or using tobacco products. A 5. Therapeutic procedures Indications for revascularization: As per CCS 2022 guidelines, consider performing endovascular, open or hybrid revascularization on the basis of the anatomical pattern of disease, degree of ischemia, expected durability of the procedure, perioperative risk and patient life expectancy in patients with CLTI. B As per SVS 2019 guidelines, perform revascularization in all average-risk patients with advanced limb-threatening conditions (WIfI grade 4) and significant perfusion deficits (WIfI grade 2/3). B Show 11 more As per ESC 2018 guidelines, perform infrapopliteal revascularization for limb salvage in patients with CLTI. B Perform revascularization for limb salvage whenever feasible. B As per ACC 2017 guidelines: Perform revascularization when possible to minimize tissue loss in patients with critical limb ischemia. B Evaluate for revascularization options by an interdisciplinary care team before commencing amputation in patients with critical limb ischemia. B https://web.pathway.md/diseases/recOr1qSws3E3mNyR 3/7 6/29/23, 3:54 AM Chronic limb-threatening ischemia Pathway Endovascular revascularization: As per CCS 2022 guidelines, perform endovascular therapy in appropriately selected patients with CLTI. B As per SVS 2019 guidelines, perform endovascular revascularization when technically feasible in high-risk patients with advanced limb threat (WIfI stage 4) and significant perfusion deficits (WIfI grade 2/3). B Show 7 more As per ESC 2018 guidelines, consider performing endovascular therapy for revascularization of infra-popliteal arteries in patients with CLTI. C As per ACC 2017 guidelines, perform endovascular procedures to establish in-line blood flow to the foot in patients with nonhealing wounds or gangrene. Show 4 more Balloon angioplasty: consider performing adjunct balloon angioplasty (such as stents, covered stents, or drug-eluting technologies), when treating femoropopliteal disease in patients with CLTI by endovascular means, if there is a technically inadequate result (residual stenosis or flow- limiting dissection) or in the setting of advanced lesion complexity (such as GLASS femoropopliteal grade 2-4). C Intermittent pneumatic compression therapy: As per SVS 2019 guidelines, consider offering intermittent pneumatic compression therapy in carefully selected patients (such as rest pain, minor tissue loss) with CLTI, if revascularization is not possible. C As per ACC 2017 guidelines, consider offering intermittent pneumatic compression therapy to augment wound healing and/or ameliorate severe ischemic rest pain in patients with critical limb ischemia. C Spinal cord stimulation: consider performing spinal cord stimulation to reduce the risk of amputation and to decrease pain in carefully selected patients (such as rest pain, minor tissue loss) with CLTI, if revascularization is not possible. C Lumbar sympathectomy: do not perform lumbar sympathectomy for limb salvage in patients with CLTI, if revascularization is not possible. D Hyperbaric oxygen therapy: As per SVS 2019 guidelines, do not offer hyperbaric oxygen therapy to improve limb salvage in patients with severe, uncontrolled CLTI (WIfI grade 2/3). D As per ACC 2017 guidelines, insufficient evidence to recommend hyperbaric oxygen therapy for wound healing in patients with critical limb ischemia. I 6. Perioperative care Periprocedural risk assessment: estimate periprocedural risk and life expectancy in patients with CLTI being candidates for revascularization. B https://web.pathway.md/diseases/recOr1qSws3E3mNyR 4/7 6/29/23, 3:54 AM Chronic limb-threatening ischemia Pathway Postprocedural restaging: Repeat limb staging after surgical drainage, debridement, minor amputations, or correction of inflow disease (aortoiliac, common and deep femoral artery disease) and before the next major treatment decision. E Repeat limb staging and repeat the hemodynamic assessment after performing inflow correction in patients with inflow and outflow disease. B 7. Surgical interventions Wound care: As per SVS 2019 guidelines, provide optimal wound care until the lower extremity wound is completely healed or the patient undergoes amputation. E As per ACC 2017 guidelines: Evaluate and provide comprehensive care with the help of an interdisciplinary care team to achieve complete wound healing and a functional foot in patients with critical limb ischemia and tissue loss. B Provide wound care after revascularization with the goal of complete wound healing in patients with critical limb ischemia. B Surgical debridement: As per CCS 2022 guidelines, perform wound debridement and/or minor amputation simultaneously with revascularization or in a staged manner depending on the degree of tissue loss, gangrene and/or infection. B As per SVS 2019 guidelines, perform urgent surgical drainage and debridement (including minor amputation if needed) and commence antibiotic treatment in all patients with suspected CLTI presenting with deep space foot infection or wet gangrene. E Surgical revascularization: As per CCS 2022 guidelines: Perform surgical bypass to the popliteal or infrapopliteal arteries with an autogenous vein in patients with CLTI. A Consider using prosthetic material for bypass to the below-knee popliteal and tibial arteries as a last resort in cases of limb salvage in patients with CLTI, if endovascular revascularization is not feasible and a suitable autogenous vein is not available. B As per SVS 2019 guidelines, consider performing surgical reconstruction in average-risk patients with CLTI with extensive aortoiliac disease or after failed endovascular intervention. C Show 5 more As per ESC 2018 guidelines, perform bypass surgery using the great saphenous vein for revascularization of infrapopliteal arteries in patients with CLTI. A Amputation: https://web.pathway.md/diseases/recOr1qSws3E3mNyR 5/7 6/29/23, 3:54 AM Chronic limb-threatening ischemia Pathway As per CCS 2022 guidelines, perform primary major amputation in patients with CLTI with non- reconstructible disease, non-salvageable limb, non-ambulatory status, severe sepsis or for palliation of patients with a short life expectancy and unfit for revascularization. B As per SVS 2019 guidelines, offer primary amputation or palliation in patients with limited life expectancy, poor functional status (such as non-ambulatory) or an unsalvageable limb after shared decision-making. E Show 5 more As per ESC 2018 guidelines, assess the risk of amputation in patients with CLTI. B 8. Follow-up and surveillance Indications for specialist referral: As per CCS 2022 guidelines, refer all patients with CLTI urgently to vascular specialists for consideration of revascularization. B As per SVS 2019 guidelines, refer all patients with suspected CLTI to a vascular specialist for consideration of limb salvage, unless major amputation is deemed medically urgent. E As per ESC 2018 guidelines, ensure early recognition of tissue loss and/or infection and refer to the vascular team to improve limb salvage. B Serial clinical assessment: observe patients undergone lower extremity vein or prosthetic bypass for CLTI on a regular basis for at least 2 years with a clinical surveillance program consisting of interval history, pulse examination, and measurement of resting ankle pressures and toe pressures. E Show 2 more Serial imaging assessment: Consider obtaining duplex ultrasound, where available, in the follow-up of patients undergone lower extremity vein bypass for CLTI. E Consider obtaining additional imaging to detect vein graft stenosis in patients undergone infrainguinal revascularization for CLTI with lower extremity vein grafts with a decrease in ABI 0.15 and recurrence of symptoms or change in pulse status. E Post-revascularization care (general principles): Continue best medical therapy for PAD including long-term antiplatelet and statin therapies in all patients undergone lower extremity revascularization. A Advise smoking cessation in all patients with CLTI undergone lower extremity revascularization. A Post-revascularization care (foot care): Provide mechanical offloading as a primary component of care after infrainguinal revascularization in all patients with CLTI with pedal wounds. A Provide counseling on continued protection of the healed wound and foot to include appropriate shoes, insoles, and monitoring of inflammation in patients undergone infrainguinal https://web.pathway.md/diseases/recOr1qSws3E3mNyR 6/7 6/29/23, 3:54 AM Chronic limb-threatening ischemia Pathway revascularization. A Post-revascularization care (dual antiplatelet therapy): consider initiating dual antiplatelet therapy (aspirin plus clopidogrel) for 6-24 months to maintain graft patency in patients undergone infrainguinal prosthetic bypass. C Show 2 more Management of restenosis: offer intervention for duplex ultrasound-detected vein graft lesions with an associated PSV of > 300 cm/s and a PSV ratio > 3.5 or grafts with low velocity (midgraft PSV < 45 cm/s) to maintain patency in patients undergone infrainguinal revascularization. B Show 3 more Clinical findings Symptoms Past medical history Claudication of lower limb PAD Leg pain Integument exam Muscle cramps Numbness of feet Leg ulcer Skin atrophy Vascular exam Skin dryness Diminished pedal pulses ABI toe pressure References 1. Conte MS, Bradbury AW, Kolh P et al. Global Vascular Guidelines on the Management of Chronic Limb- Threatening Ischemia. J Vasc Surg. 2019 Jun;69 6S 3S 125S.e40. Open 2. Victor Aboyans, Jean-Baptiste Ricco, Marie-Louise E L Bartelink et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery ESVS Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization ESO The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology ESC and of the European Society for Vascular Surgery ESVS . Eur Heart J. 2018 Mar 1;39 9 763 816. Open 3. Marie D Gerhard-Herman, Heather L Gornik, Coletta Barrett et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017 Mar 21;135 12):e686-e725. Open 4. Beth L. Abramson, MD Co-Chair) Mohammed Al-Omran, MD Co-Chair) Sonia S. Anand et al. Canadian Cardiovascular Society 2022 Guidelines for Peripheral Arterial Disease. CCS. 2022 May. Open https://web.pathway.md/diseases/recOr1qSws3E3mNyR 7/7