Chronic Limb-Threatening Ischemia

Publication Date: June 3, 2019

Key Points

Key Points

Chronic limb-threatening ischemia (CLTI) represents the end stage of peripheral artery disease (PAD), a problem of growing prevalence and increased health care costs around the globe. CLTI is a highly morbid disease, incurring significant mortality, limb loss, pain, and diminished health-related quality of life.

Vascular specialists evaluate patients with CLTI across a broad range of disease severity. This guideline promotes the use of the SVS Threatened Limb Classification System (WIfI) for clinical staging and proposes the Global Anatomic Staging System (GLASS) for defining the extent and complexity of PAD along the Target Artery Pathway (TAP).

Objective measurement of perfusion (eg, ankle, toe pressures) is essential for accurate staging of CLTI. The presence and degree of ischemia is an important determinant of risk of limb loss and treatment approach.

Optimum medical therapy reduces overall mortality as well as major adverse cardiovascular and limb-related events. All vascular specialists treating CLTI should assess and provide evidence-based recommendations on lifestyle and medical therapies.

The goals of limb treatment in CLTI are to prevent amputation, maintain function, reduce pain, and heal wounds. Selection of appropriate candidates for revascularization depends on careful assessment of patient risk, functional status, clinical severity and salvageability of the affected foot.

Structured decision-making in CLTI follows the PLAN concept, assessing (in order) Patient risk, Limb stage, and ANatomic complexity of disease to define appropriate candidates for, and the best approach to revascularization in individual patients.

The effectiveness of non-revascularization treatments for CLTI including pharmacotherapies, hyperbaric oxygen, pneumatic compression, spinal cord stimulation, cell and gene therapies appears limited and further research is needed to establish their role, if any.

Patients with CLTI require long-term surveillance for disease recurrence/progression and should be maintained on appropriate risk factor modification and cardiovascular protective medications.

Future clinical trials in CLTI should exclude patients with intermittent claudication, incorporate stratification by disease stage, employ meaningful clinical and patient-oriented outcomes, and have appropriate follow up duration to better define clinical and cost effectiveness.

Diagnosis

...iagnos...

...diagram for the investigation of patients...


...uggested algorithm for anatomic imagi...


...framework of clinical decision-ma...


Diagnosis – Limb Staging

...gnosis – Limb Sta...

...Wound grading in Wound, Ischemia, an...


...ble 2. Ischemia grading in Wound, Ische...


...nfection grading in Wound, Ischemia, and f...


...SVS WIfI Clinical Limb Stage (Based on esti...


...e benefit of performing revascularization in CLTI...


Diagnosis – Global Anatomic Staging System (GLASS)

...s – Global Anatomic Staging System...

...Femoropopliteal (FP) disease gradi...


...ure 7. Infrapopliteal (IP) disease grading...


...nment of GLASS stageHaving trouble vi...


.... Flow chart illustrating application...


...nframalleolar (IM)/pedal disease de...


...scriptive summary of GLASS stages of inf...


...ferred initial revascularization strateg...


Recommendations

...ommendations...

...tions and nomenclature...

...a lower extremity threatened limb classifica...

...hemodynamic tests to determine the presence...


...miology and risk factors for CLTI

...ommendations (, )6...


...and limb staging in CLTI...

...orm a detailed history to determine sym...

...te cardiovascular physical examinati...

...plete examination of the foot, including a...

...sure AP and ABI as the first-line noninvasive test...

...TBI in all patients with suspected CLTI an...

Consider using alternative methods fo...

Consider DUS imaging as the first a...

...r noninvasive vascular imaging modalities (DUS, C...

...tain high-quality angiographic ima...


...l management...

...ardiovascular risk factors in all patients wi...

...nage all modifiable risk factors to r...

...patients with CLTI with an antiplatelet agent. (...

...ider clopidogrel as the single ant...

...er low-dose aspirin and rivaroxaban, 2.5 mg twic...

...se systemic vitamin K antagonists for the treatme...

...erate- or high-intensity statin therapy to redu...

Control hypertension to target l...

...l of type 2 DM in CLTI patients to ac...

...metformin as the primary hypoglycemic agent in pa...

...er withholding metformin immediately...

...ssation interventions (pharmacother...

...LTI patients who are smokers or former smoke...

...lgesics of appropriate strength for...

...CLTI patients with chronic severe pain, use p...


...he GLASS for...

...integrated, limb-based anatomic staging syste...


Strategies for EBR

...fer all patients with suspected CLTI...

...r primary amputation or palliation to patient...

...te periprocedural risk and life expectancy in...

...tient as average surgical risk when anticip...

...CLTI patient as high surgical risk when a...

...an integrated threatened limb classification s...

...gent surgical drainage and débrid...

...imb staging after surgical drainage, d...

...T perform revascularization in the absenc...

...T perform revascularization in very-low–ris...

...fer revascularization to all average-risk p...

...sider revascularization for average-risk...

...r revascularization in average-risk patie...

...scularization in average-risk patients...

Obtain high-quality angiographic imaging wit...

...tegrated limb-based staging system (eg, GLASS) to...

...nd vein mapping when available in all CL...

...ilateral GSV and small saphenous vein for pl...

...classify a CLTI patient as being unsuitab...

...rrect inflow disease first when both inflow and ou...

...e decision for staged vs. combined...

...orrect inflow disease alone in CLTI pati...

...he limb and repeat the hemodynamic a...

...ider simultaneous inflow and outflo...

...dovascular-first approach for treatment of CL...

...der surgical reconstruction for the treatment of a...

...FA endarterectomy with patch angioplasty, with o...

...er a hybrid procedure combining ope...

Consider endovascular treatment of signif...

...tents in the CFA and do NOT place stents acr...

...hemodynamically significant (≥50%...

...ge-risk CLTI patients with infraingu...

...scular revascularization when technically feasi...

...nsider endovascular revascularization for high-...

...der endovascular revascularization for high-ris...

...ascular revascularization for high-risk pati...

...open surgery in selected high-risk patients with...

...der angiosome-guided revascularization in patien...

...isease in CLTI patients by endovascular mea...

...ogous vein as the preferred conduit for infraingu...

...oid using a nonautologous conduit for infra...

...perative imaging (angiography, DUS, or both) o...


...larization treatments of the l...

...onsider SCS to reduce the risk of amputation an...

...NOT use LS for limb salvage in CLTI patients in...

...IPC therapy in carefully selected patien...

...stanoids for limb salvage in CLTI pati...

...oactive drugs or defibrinating agent...

...T offer HBOT to improve limb salvage in CLTI pa...

...ue to provide optimal wound care unti...


...ogic and regenerative medicine approaches in CLTI...

...of therapeutic angiogenesis to CLTI patients wh...


...of minor and major amputations...

...er transmetatarsal amputation of the for...

...r primary amputation to CLTI patients who have...

...ary amputation for patients with CLTI w...

...sider revascularization to improve the...

Consider a TKA or AKA in patients who are nonam...

...lve a multidisciplinary rehabilitation te...

...observe CLTI patients who have unde...


...care and surveillance after infrainguin...

...est medical therapy for PAD, including the long-te...

...ing cessation in all CLTI patients who hav...

...(aspirin plus clopidogrel) in patie...

...er DAPT (aspirin plus clopidogrel) i...

...or 1–6 months in patients undergoing...

...ents who have undergone lower extremity vein...

...e patients who have undergone lower extremity...

...s who have undergone infrainguinal endovascular...

...rforming additional imaging in patients with low...

...rvention for DUS-detected vein graft lesions wit...

...-term surveillance after surgical or ca...

...terial imaging after endovascular intervention f...

...reintervention for patients with DUS-detected re...

...mechanical offloading as a primary...

...rovide counseling on continued protection...


...s and trial end points in CLTI...

...research framework such as the IDEAL for gathe...

...funders, journal reviewers, and edit...

...n RCTs are not feasible, use the OPG...

...e sufficient enrollment, limit RCT exclusi...

...gn RCTs, prospective cohort studies, and...

...integrated, limb-based threatened limb classific...

...outcomes in CLTI trials using a combin...

...quire regulatory trials aimed at obtai...

...atients in trials for a time sufficient...

...ntegrated measure of clinical diseas...

...CLTI trial protocols together with the f...

...postmarketing surveillance data collection...

...trial data to allow subsequent individual patien...

...e quality of evidence in CLTI research usin...