Chronic Limb-Threatening Ischemia (CLTI)
Definition
CLTI is a severe clinical subset of entities/Peripheral-Artery-Disease characterised by chronic (>2 weeks) ischaemic rest pain, nonhealing wounds or ulcers, or gangrene attributable to objectively proven arterial occlusive disease. It has replaced the older term "critical limb ischaemia (CLI)" to emphasise the chronic nature and limb-threatening implications. sources/PVD-AHA-2024
Incidence among patients with known PAD: 11–20%. Historical 1-year mortality: 25–35%; 1-year amputation rate: up to 30%. More recent RCT data report lower rates with active revascularisation. Responsible for most major and minor PAD-related amputations. sources/PVD-AHA-2024
Key Concepts
Clinical Staging Systems
- WIfI (Wound, Ischaemia, foot Infection): Quantifies wound extent, degree of ischaemia, and severity of foot infection. Correlates with time to wound healing, amputation rate, and amputation-free survival. Used for both clinical staging and quality reporting. sources/PVD-AHA-2024
- GLASS (Global Limb Anatomic Staging System): Anatomic staging of infrainguinal disease; incorporated into CLTI revascularisation decision-making. sources/PVD-AHA-2024
- Fontaine and Rutherford classifications are used among vascular specialists to categorise CLTI severity. sources/PVD-AHA-2024
Diagnostic Approach
- ABI may be 0.90–1.40 in ~25% of CLTI patients — ABI alone is inadequate for CLTI assessment
- TBI ≤0.70 or absolute toe pressure <30 mmHg = severe ischaemia and risk of major amputation/poor wound healing
- TcPO₂ >30 mmHg or SPP >40 mmHg predicts wound healing
- Imaging (duplex US, CTA, MRA, or catheter angiography) COR 1 B-NR to determine revascularisation strategy sources/PVD-AHA-2024
Multispecialty Care Team (COR 1 B-NR)
The multispecialty care team for CLTI must include expertise in:
- Endovascular revascularisation (interventional cardiology, vascular surgery, IR)
- Surgical revascularisation
- Wound-healing therapies and foot surgery (podiatry, orthopaedic surgery)
- Medical evaluation and care (diabetes, infectious disease, nutrition, rehabilitation)
- Patients and family members are explicitly included as collaborators
Evaluation by multispecialty team before amputation is mandatory (except life-threatening sepsis). sources/PVD-AHA-2024
Revascularisation Strategy
Goals: Minimise tissue loss, heal wounds, relieve pain, preserve a functional limb (COR 1 B-R).
Key RCT evidence — BEST-CLI vs BASIL-2:
- BEST-CLI (patients with adequate single-segment great saphenous vein; Cohort 1): Surgical bypass was superior to endovascular revascularisation — composite death or MALE 42.6% vs 57.4% (HR 0.68 [95% CI 0.59–0.79]; P<0.001) over median 2.7 years. Difference driven by lower repeat revascularisation in bypass group. In Cohort 2 (inadequate saphenous vein), no significant difference (HR 0.79; P=0.12). sources/PVD-AHA-2024
- BASIL-2 (infrapopliteal-dominant disease): Endovascular was superior to bypass — major amputation or death 53% vs 63% (adjusted HR 1.35 [95% CI 1.02–1.80]; P=0.037) favouring endovascular. Difference driven by fewer deaths in the endovascular group. sources/PVD-AHA-2024
Individualisation factors (Table 16):
- Anatomy (multilevel CTOs, CFA/profunda involvement → favour surgery; infrapopliteal dominant → favour endovascular)
- Conduit availability (absent suitable saphenous vein → favour endovascular)
- Patient comorbidities (high perioperative risk → favour endovascular)
- Patient preferences
Conduit for surgical bypass:
- Single-segment great saphenous vein (≥3 mm diameter) is preferred for bypass to popliteal or infrapopliteal arteries: COR 1A — superior patency to all prosthetic conduits
- Ultrasound vein mapping before bypass: COR 1 B-R
- Alternative venous conduits (small saphenous, arm veins): acceptable when GSV unavailable
- Prosthetic/cadaveric grafts: secondary option when no suitable autogenous vein (COR 2a) sources/PVD-AHA-2024
Perfusion strategy:
- Direct revascularisation to wound bed (angiosome-directed) associated with lower amputation rates, superior wound healing, shorter time to healing vs indirect revascularisation
- In-line flow to named infrapopliteal artery still preferred where possible
- For ischaemic rest pain without tissue loss: address inflow disease first; outflow lesions can be staged sources/PVD-AHA-2024
Wound Care and Minimising Tissue Loss
Pressure offloading:
- Nonremovable devices superior to removable for diabetic foot ulcer healing: COR 1A
- Therapeutic footwear for patients with previous diabetic foot ulcers: COR 1 B-R
- Risk factors for ulcers: previous ulcer/amputation, Charcot deformity, diabetes with poor glycaemic control, CKD/ESKD, peripheral neuropathy, corns/calluses, ongoing smoking sources/PVD-AHA-2024
Wound care: Infection management (debridement, antibiotics) in conjunction with revascularisation is essential. Complete wound healing is the primary goal — the risk of limb-threatening infection persists until full healing.
"No-option" CLTI patients (no feasible revascularisation):
- Spinal cord stimulation: COR 2b — reduces ischaemic pain, may improve walking distance; does not reduce major amputation
- Intermittent pneumatic compression: COR 2b — may reduce pain and improve wound healing
- Percutaneous deep vein arterialization (pDVA/LimFlow): emerging technique — ALPS study: 78% 24-month limb salvage; PROMISE I: 70% amputation-free survival at 12 months sources/PVD-AHA-2024
Amputation for CLTI
- Multispecialty team should determine most distal level of amputation that heals and preserves maximal function: COR 1 B-NR
- Primary amputation indicated when life-over-limb is prevailing (sepsis, metabolic collapse, irreversible tissue loss): COR 1 C-EO
- WIfI/GLASS classification tools for objective documentation of no-option status
- Morbidity and mortality from amputation are high in elderly; mortality increases ~4% per year of age
- 20% reduction in nontraumatic amputation by 2030 is an explicit AHA advocacy goal sources/PVD-AHA-2024
Contradictions / Open Questions
- BEST-CLI vs BASIL-2 contrasting results: BEST-CLI favours surgery (saphenous vein available, mixed anatomy); BASIL-2 favours endovascular (infrapopliteal dominant). Patient population differences make direct comparison difficult. Individualisation is required; no universal strategy applicable to all CLTI patients. sources/PVD-AHA-2024
- Angiosome-directed revascularisation: Benefit primarily demonstrated for endovascular therapy in meta-analyses; benefit less clear for surgical bypass in the same analyses. Whether direct angiosome flow is truly superior to indirect via collaterals remains debated. sources/PVD-AHA-2024
- Optimal amputation level: No RCT evidence to guide selection of the level of amputation that heals in the setting of chronic ischaemia. Comparative studies of transmetatarsal vs Chopart vs Lisfranc vs below-knee amputation are conflicting. sources/PVD-AHA-2024
Connections
- Related to entities/Peripheral-Artery-Disease
- Related to concepts/Acute-Limb-Ischemia
- Related to concepts/Ankle-Brachial-Index
- Related to entities/Heart-Failure (CLTI patients often have polyvascular disease and HF)
- Related to entities/Chronic-Coronary-Disease (polyvascular disease)