CLTI Decision Frameworks and Limb-Preservation Strategy

39.1Definition and presentation

Chronic limb-threatening ischemia (CLTI) is peripheral artery disease presenting with rest pain, a non-healing wound, or gangrene of >= 2 weeks duration, combined with objective evidence of arterial occlusive disease GVG · 2019. Ischemic rest pain is corroborated hemodynamically by an ankle-brachial index below 0.40, an ankle pressure below 50 mmHg, a toe pressure below 30 mmHg, or a TcPO2 below 30 mmHg (WIfI ischemia grade 3), whereas ischemic tissue loss requires only a perfusion deficit of WIfI ischemia grade 1 or greater alongside the wound; the guideline treats these values as context-dependent rather than as a single defining cutoff. The condition requires urgent multidisciplinary evaluation, objective testing, limb staging, and expedited revascularization when feasible ACC/AHA/SVS 2024. Delay in specialist assessment acts as a limb-risk amplifier ESVS 2024.

39.2Risk factors and epidemiology

Patients with CLTI carry a high near-term risk of both limb loss and major adverse cardiovascular events Vemulapalli 2025 · VQI CLTI Survival · 2018. Best medical therapy is mandatory for every CLTI patient alongside any revascularization decision: antiplatelet monotherapy, a high-intensity statin, smoking cessation, and glycemic and blood-pressure control ACC/AHA/SVS 2024 · ESVS 2024 · GVG · 2019. After lower-extremity revascularization, add rivaroxaban 2.5 mg twice daily to low-dose aspirin: in VOYAGER PAD this dual-pathway regimen cut the composite of acute limb ischemia, major amputation, myocardial infarction, ischemic stroke, or cardiovascular death versus aspirin alone (HR 0.85), and the 2024 guideline recommends it for symptomatic PAD after revascularization, weighed against bleeding risk VOYAGER PAD · 2020. Registry data demonstrate a real-world 30-day mortality of 2 to 4 percent following lower-extremity revascularization, with a 1-year major amputation rate between 8 and 14 percent depending on comorbidity and initial limb stage VQI CLTI 2022. Baseline frailty, functional status, and life expectancy define whether complex revascularization preserves meaningful mobility or inappropriately delays necessary palliation Butala 2021.

39.3Clinical and anatomic staging

Patient and limb assessment follows the PLAN framework: Patient risk, Limb severity, and ANatomic complexity GVG 2019 · GVG · 2019.

• Wound, Ischemia, and foot Infection (WIfI): Grades each clinical domain from 0 to 3 and synthesizes them into stages 1 through 4 to estimate amputation risk and prioritize revascularization SVS WIfI 2014. One-year major amputation risk scales from less than 5 percent in stage 1 to greater than 30 percent in stage 4, validated across diabetic and non-diabetic cohorts WIfI Prognostic SR · 2019 · WIfI Validation · 2019 · WIfI Early Validation 2014. Active foot infection is more than a grading axis; it drives urgency and sequencing, with drainage and antibiotics before or concurrent with revascularization ESVS 2024 · GVG · 2019.
• Global Limb Anatomic Staging System (GLASS): Grades femoral-popliteal and infra-popliteal disease segments from 0 to 4 and integrates them into overall stages I through III GVG · 2019 · GLASS Methodology · 2021. The stage estimates anatomic feasibility and 1-year limb-based patency for a selected target-artery pathway, rather than predicting absolute success.

39.4Revascularization pathways

Treatment selection requires staging the limb, defining the anatomic pathway, and stratifying patient risk and conduit availability prior to intervention GVG 2019 · GVG · 2019. Open vein bypass confers a durability advantage for appropriate-risk patients with suitable single-segment great saphenous vein BEST-CLI · 2022. In BEST-CLI (2022) cohort 1, open vein bypass reduced the composite of major adverse limb event or death compared with endovascular therapy at a median 2.7 years (42.6 percent versus 57.4 percent; HR 0.68), driven by lower major reintervention and above-ankle amputation. This advantage is lost when suitable vein is absent; cohort 2 demonstrated no significant difference between bypass and endovascular therapy (42.8 percent versus 47.7 percent). Endovascular-first therapy is favored for high-surgical-risk patients, those with limited physiologic reserve, or predominant infra-popliteal disease where early operative mortality offsets limb benefit ESVS 2024 · BASIL-2 2023. In BASIL-2 (2023), patients requiring infra-popliteal revascularization experienced higher rates of above-ankle amputation or death with vein-bypass-first compared with endovascular-first therapy (63 percent versus 53 percent; HR 1.35), driven by higher early mortality in the bypass-first arm. Primary amputation is reserved for limbs without revascularization options or patients with severe baseline functional limitation ACC/AHA/SVS 2024.

1. Confirm CLTI via clinical symptoms (tissue loss, rest pain >= 2 weeks) and objective arterial testing.
2. Stage limb severity using WIfI to stratify amputation risk and urgency of wound healing.
3. Define anatomic complexity using GLASS to establish target-artery feasibility.
4. Assess cardiovascular risk, baseline frailty, and availability of usable single-segment great saphenous vein.
5. Assign revascularization modality (endovascular, open bypass, or hybrid), or pursue primary amputation or palliation if baseline functional limitations preclude meaningful limb salvage.

39.5Procedural and device outcomes

Device choice supplements the anatomic strategy but does not override patient-risk stratification GVG · 2019. Five-year randomized-trial meta-analyses of paclitaxel-coated devices demonstrate no increased signal for all-cause mortality or major amputation Paclitaxel Meta-analysis 2026. Sirolimus-coated balloons exhibit technical success and early wound-healing capability in complex infrainguinal lesions Sirolimus Registry 2024. Historically, BASIL-1 (2005) established that life expectancy fundamentally dictates strategy, showing similar 2-year survival and amputation-free survival between bypass and angioplasty, with a late survival advantage for bypass beyond 2 years among survivors BASIL-1 2005. Contemporary registry comparisons confirm that longitudinal outcomes for both bypass and endovascular interventions remain subject to confounding and competing mortality risks over time VQI Bypass vs PVI 2023.

39.6Areas of controversy

The synthesis of conflicting randomized trials remains unsettled. BEST-CLI supports bypass for suitable patients with adequate vein, while BASIL-2 favors an endovascular-first strategy for infra-popliteal disease, leaving the optimal approach for mixed anatomic patterns and intermediate surgical risk subject to active clinical debate BASIL-2 2023 · BEST-CLI · 2022. The application of WIfI and GLASS as deterministic predictors of revascularization success is similarly contested; they reliably estimate amputation risk and anatomic feasibility, but require integration with individualized patient frailty, cardiovascular risk, and functional goals to guide definitive decisions GVG · 2019 · Butala 2021 · SVS WIfI 2014.