Critical Limb Threatening Ischemia

- Recommendations

Recommendation	Strength of recommendation	Quality of evidence	References
1.Diagnosis
1.1 Use ABI to determine the presence and to quantify the severity of ischemia in all patients with suspected CLTI	strong	Low	[1] [2] [3]
1.2 Perform a detailed history to determine symptoms, past medical history, and cardiovascular risk factors in all patients with suspected CLTI.	Good practice statement
1.3 Perform a complete vascular physical examination of all patients with suspected CLTI, including palpation of carotid, upper extremity, aorta, and lower extremity pulses.	Good practice statement
1.4 Perform a complete examination of both feet, including a probe-to- bone test of any open ulcers using sterile equipment, in all patients with pedal tissue loss and suspected CLTI.	Good practice statement
1.5 We recommendDUS imaging, including assessment of Ankle Peak Systolic Velocity (APSV) as the first arterial imaging modality in patients with suspected CLTI.	Strong	Moderate	[4]
1.6 We recommendother noninvasive vascular imaging modalities (CTA, MRA) in patients with suspected CLTI who are candidates for revascularization, and who do not suffer impaired renal function.	strong	Moderate	[5] [6] [7] [8]
1.7 Obtain high-quality angiographic imaging of the lower limb using digital subtraction imaging (DSA). This should include the ankle and foot in all patients with suspected CLTI prior to proceeding to revascularization.	Good practice statement

2. Medical management
2.1 Evaluate cardiovascular risk factors in all patients with suspected CLTI.	strong	Moderate	[9]
2.2 Refer all patients with suspected CLTI to have all modifiable risk factors including hypertension, diabetes mellitus, dyslipidemia, controlled to recommended levels. Strongly advice smoking cessation.	strong	Moderate	[10], [11]
2.3 Treat all patients with CLTI with an antiplatelet agent.	strong	High	[12]
2.4 We recommendclopidogrel as the single antiplatelet agent of choice in patients with CLTI.	Conditional	Moderate	[13],[14]
2.5 We recommendlow-dose aspirin and rivaroxaban, 2.5 mg twice daily, to reduce adverse cardiovascular events and lower extremity ischemic events in patients with CLTI.	Conditional	Moderate	[15]
2.6 We recommend against usingsystemic vitamin K antagonists for the treatment of lower extremity atherosclerosis in patients with CLTI.	strong	Moderate	[15]
2.7 We recommend against usinglow molecular weight heparin for the treatment of lower extremity atherosclerosis in patients with CLTI, except if there is suspicion of acute thrombo-embolic event, or for bridging anticoagulation prior to an invasive procedure.	Good practice statement
2.8 Use moderate- or high-intensity statin therapy to reduce all-cause and cardiovascular mortality in patients with CLTI.	strong	High	[16] [17] [16] [18] [19]
2.9 Use medormin as the primary hypoglycemic agent in patients with type 2 DM and CLTI.	strong	High	[20]
2.10 We recommendwithholding medormin immediately before and for 24 to 48 hours after the administration of an iodinated contrast agent for diabetic patients, especially those with an estimated glomerular filtration rate <30 mL/min/1.73 m2.	Conditional	Low	[21] [22] [23]
2.11 Prescribe analgesics of appropriate strength for CLTI patients who have ischemic rest pain of the lower extremity and foot until pain resolves after revascularization.	Good practice statement

3. Evidence Based Revascularization (EBR)
3.1 Refer all patients with suspected CLTI to a vascular consultant for consideration of limb salvage unless major amputation is considered medically urgent.		Good practice statement
3.2 Offer primary amputation to patients with poor functional status (non-ambulatory), or an unsalvageable limb as judged by a qualified vascular consultant.		Good practice statement
3.3 Use an integrated threatened limb classification system (such as WIfI) to stage all CLTI patients who are candidates for limb salvage.		strong		Low	[24] [25] [26], [27], [28]
3.4 Perform urgent surgical drainage including minor amputation, if needed, and commence antibiotic treatment in all patients with suspected CLTI who present with deep space foot infection or wet gangrene. Perform urgent revascularization before or soon after foot surgery.		Good practice statement
3.5 Do not perform revascularization in the absence of significant ischemia (WIfI ischemia grade 0).		Good practice statement
3.6 Do not perform revascularization based on imaging alone in the absence of tissue necrosis or gangrene.		Good practice statement
3.7 Revascularization could be performed in the absence of significant foot ischemia in exceptional conditions such as isolated region of poor perfusion, which could be the target of angiosome revascularization, if the isolated region of poor perfusion is associated with major tissue loss (eg, WIfI wound grade 2 or 3), and the wound deteriorates despite appropriate infection control, wound care, and offloading.		Good practice statement

3.7 Offer revascularization to all average-risk patients with severe ischemia and tissue necrosis or gangrene	strong		Low	[29]
3.8 We recommendrevascularization to all average-risk patients with moderate ischemia and extensive wounds or extensive tissue necrosis	Conditional		Low	[25] [26],[27], [28]
3.9 Perform ultrasound vein mapping in all CLTI patients who are candidates for surgical bypass.	strong		Low	[30], [31], [32]
3.10 Do not classify a CLTI patient as being unsuitable for revascularization without review of adequate-quality imaging studies and clinical evaluation by a qualified vascular consultant.	Good practice statement

4.0 Combined inflow and outflow disease
4.1 Correct inflow disease first when both inflow and outflow diseases are present in a patient with CLTI.	Good practice statement
4.2 Base the decision for staged vs combined inflow and oudlow revascularization on patient risk and the severity of limb threat (eg, WIfI stage).	strong	Low	[30] [33]
4.3 Correct inflow disease alone in CLTI patients with multilevel disease and low-grade ischemia (eg, WIfI ischemia grade 1) or limited tissue loss (eg, WIfI wound grade 0/1) and in any circumstance in which the riskbenefit of additional oudlow reconstruction is high or initially unclear.	strong	Low	[30] [33]
4.4 Restage the limb and repeat the hemodynamic assessment after performing inflow correction in CLTI patients with inflow and oudlow disease	strong	Low	[34]
4.5 We recommendsimultaneous inflow and oudlow revascularization in CLTI patients with a high limb risk (eg, WIfI stages 3 and 4), or in patients with severe ischemia (eg, WIfI ischemia grades 2 and 3).	Conditional	Low	[35]

5.0 Aorto-iliac disease
5.1 Use an endovascular-first approach for treatment of CLTI patients with moderate to severe aorto-iliac disease.	strong	Moderate	[36], [37], [38]
5.2 We recommendsurgical reconstruction for the treatment of average-risk CLTI patients with extensive aorto- iliac disease, or after failed endovascular intervention.	Conditional	Low	[39],[40],[41]

6.0 Common femoral artery disease
6.1 Perform open CFA endarterectomy with patch angioplasty, with or without extension into the PFA, in CLTI patients with hemodynamically significant (>50% stenosis) disease of the common and deep femoral arteries.	strong	Low	[42],[43]
6.2 We recommenda hybrid procedure combining open CFA endarterectomy and endovascular treatment of aorto-iliac disease with concomitant CFA involvement.	Conditional	Low	[44]
6.3 We recommendendovascular treatment of significant CFA disease in selected patients who are deemed to be at high surgical risk or to have a hostile groin.	Conditional	Low	[45], [46], [47], [48]
6.4 Avoid stents in the CFA and do not place stents across the origin of a patent deep femoral artery.	Good practice statement
6.5 Correct hemodynamically significant (>50% stenosis) disease of the proximal deep femoral artery whenever technically feasible.	Good practice statement

7.0 endovascular vs surgical bypass
7.1 In surgically average-risk CLTI patients with infrainguinal disease, base decisions of endovascular intervention vs open surgical bypass on the severity of limb threat (eg, WIfI), the anatomic pabern of disease, and the availability of autologous vein.	strong	Low	[49]
7.2 Offer endovascular revascularization when technically feasible for surgically high-risk patients with advanced limb threat and significant perfusion deficits (eg, WIfI ischemia grades 2 and 3).	Conditional	Low	[29],[26],[27], [28]
7.3 We recommendangiosome-guided revascularization in patients with significant wounds (eg, WIfI wound grades 3 and 4), particularly those involving the midfoot or hindfoot, and when the appropriate target arterial path is available.	Conditional	Low	[50],[51],[52], [53], [54]
7.4 In treating femoro-popliteal (FP) disease in CLTI patients by endovascular means, We recommendadjuncts to balloon angioplasty (eg, stents, covered stents, or drug- eluting technologies) when appropriate.	Conditional	Moderate	[55], [56], [57], [58],[49]
7.5 Use autologous vein as the preferred conduit for infrainguinal bypass surgery in CLTI.	strong	Moderate	[49]
7.6 Avoid using a non-autologous conduit for infrainguinal bypass unless there is no endovascular option and no adequate autologous vein.	2(Conditional)	C (Low)	[49]

7.7 We recommendperforming intraoperative imaging (angiography, DUS, or both) on completion of open bypass surgery for CLTI and correct significant technical defects if feasible during the index operation.		strong	Low	[59], [60]

8.0 Non-revascularization treatment of the limb
8.1 We recommend against usinglumbar sympathectomy for limb salvage in CLTI patients in whom revascularization is not possible.	Conditional	Low	[61]
8.2 We recommendintermibent pneumatic compression therapy in carefully selected patients (eg, rest pain, minor tissue loss) in whom revascularization is not possible.	Conditional	Moderate	[29]
8.3 Do not offer prostanoids for limb salvage in CLTI patients. We recommendoffering selectively for patients with rest pain or minor tissue loss and in whom revascularization is not possible.	Conditional	Moderate	[62]
8.4 Do not offer vasoactive drugs in patients in whom revascularization is not possible.	strong	Low	[63]
8.5 Do not offer hyperbaric oxygen therapy to improve limb salvage in CLTI patients with severe, uncorrected ischemia (eg, WIfI ischemia grade 2/3).	strong	Moderate	[64], [65], [66]
8.6 The patient should be provided with optimal wound care until the lower extremity wound is completely healed or the patient undergoes amputation.	Good practice statement
8.7 Restrict use of therapeutic angiogenesis to CLTI patients who are enrolled in a registered clinical trial.	strong	Moderate	[29], [67]

9.0 The role of minor and major amputations
9.1 We recommendtransmetatarsal amputation of the forefoot in CLTI patients who would require more than two digital ray amputations to resolve distal necrosis, especially when the hallux is involved.	Conditional	Low	[68]
9.2 Offer primary amputation to CLTI patients who have a pre-existing dysfunctional or unsalvageable limb, a poor functional status (eg, bedridden), after shared decision- making with the patient and health care team.	strong	Low	[69],[70]
9.3 We recommendsecondary amputation for patients with CLTI who have a failed or ineffective reconstruction and in whom no further revascularization is possible and who have incapacitating pain, nonhealing wounds, or uncontrolled sepsis in the affected limb after shared decision-making with the patient and health care team.	Conditional	Low	[71]
9.4 We recommendrevascularization to improve the possibility of healing an amputation at a more distal functional amputation level (eg, AKA to BKA), particularly for patients with a high likelihood of rehabilitation and continued ambulation.	Conditional	Low	[72]
9.5 We recommenda BKA or AKA in patients who are non-ambulatory for reasons other than CLTI (ie, bedridden patients with flexion contracture, dense hemiplegia, cancer) and are unlikely to undergo successful rehabilitation to ambulation after shared decision- making with the patient and health care team	Conditional	Low	[73] [74]
9.7 Patients who have undergone amputation for CLTI are instructed to seek medical advice to monitor progression of disease in the contralateral limb and to maintain optimal medical therapy and risk factor management.	strong	Low	[75] [76]
10.0 Postprocedural care and surveillance after infrainguinal revascularization for CLTI
10.1 Continue best medical therapy for PAD, including the long-term use of antiplatelet and statin therapies, in all patients who have undergone lower extremity revascularization.	strong	High	[77], [78], [79], [80], [81]
10.2 We strongly advise smoking cessation in all CLTI patients who have undergone lower extremity revascularization.	strong	High	[82], [83]
10.3 We recommendDAPT (aspirin plus clopidogrel) in patients who have undergone infrainguinal prosthetic bypass for CLTI for a period of 6 to 24 months to maintain graft patency.	Conditional	Moderate	[79], [84], [85], [80]
10.4 We recommendDAPT (aspirin plus clopidogrel) in patients who have undergone infrainguinal endovascular interventions for CLTI for a period of at least 1 month, alternatively We recommendAspirin and Rivaroxiban 2.5mg bd.	Conditional	Low	[86], [86], [87], [88]
10.5 We recommendDAPT for a period of 1 to 6 months in patients undergoing repeated catheter based interventions, or alternatively We recommendAspirin and Rivaroxiban 2.5mg bd, if they are at low risk for bleeding.	Conditional	Low	[89], [87], [88]
10.6 Patients who have undergone lower extremity vein or prosthesis bypass for CLTI are advised to have a check up on a regular basis for at least 2 years. We recommendDUS scanning where available.	Good practice statement
10.7 We recommendperforming additional imaging in patients with lower extremity grafts who have a decrease in ABI or a decrease in APSV or recurrence of symptoms or change in pulse status to detect vein graft stenosis.	Good practice statement
10.8 Offer intervention for DUS- detected vein graft lesions with an associated PSV of >300 cm/s and a PSV ratio >3.5 or grafts with low velocity (mid-graft PSV <45 cm/s), which may be further documented by CTA, to maintain graft patency.	strong	Moderate	[90],138 2001
10.9 Patient is strongly advised to maintain long-term surveillance after surgical or catheter-based revision of a vein graft, including DUS graft scanning where available, to detect recurrent graft-threatening lesions.	strong	Moderate	[91], [92]
10.10 Refer for mechanical offloading as a primary component for care of all CLTI patients with plantar wounds, and for continued protection of the healed wound and the foot to include appropriate shoes, insoles, and monitoring of inflammation.	strong	High	[93]