What is Chronic Limb-Threatening Ischemia (CLTI)?

Definition of Chronic Limb-Threatening Ischemia (CLTI)

Chronic limb-threatening ischemia (CLTI) is a clinical syndrome defined by the presence of peripheral artery disease in combination with ischemic rest pain, non-healing lower limb ulceration of >2 weeks duration, or gangrene involving any portion of the foot or lower limb. 1

Key Characteristics of CLTI

• CLTI represents the end-stage form of peripheral arterial disease (PAD) with threatened limb viability related to several factors, not just severe ischemia 1
• The term CLTI is preferred over the former term "critical limb ischemia" for several important reasons:
  • "Critical" implies urgent treatment is needed to avoid limb loss, while some patients can maintain their limbs for extended periods even without revascularization 1
  • There is an increasing predominance of diabetes in these situations (present in 50-70% of cases), which often presents as neuro-ischemic diabetic foot ulcers 1
  • The risk of amputation depends not only on the severity of ischemia but also on the presence of wounds and infection 1

Diagnostic Criteria for CLTI

• Ischemic rest pain, typically in the forefoot with objectively confirmed hemodynamic studies 1:
  • Ankle-brachial index (ABI) <0.40
  • Ankle pressure <50 mmHg
  • Toe pressure <30 mmHg
  • Transcutaneous oxygen pressure (TcPO2) <30 mmHg
• Diabetic foot ulcer 1
• Non-healing lower limb or foot ulceration ≥2 weeks duration 1
• Gangrene involving any portion of the foot or lower limb 1

WIfI Classification System for CLTI

The WIfI (Wound, Ischemia, foot Infection) classification system is recommended for the initial assessment and risk stratification of all patients with CLTI 1, 2:

• Wound (W): Graded from 0 (none) to 3 (severe) based on ulcer depth and extent of tissue loss 1
• Ischemia (I): Graded from 0 (none) to 3 (severe) based on hemodynamic parameters 1
• foot Infection (fI): Graded from 0 (none) to 3 (severe) based on clinical signs of infection 1

Each factor is independently associated with the risk of amputation and helps guide treatment decisions 1, 2

Clinical Presentation

• Ischemic rest pain is typically described as a burning pain in the arch or distal foot that occurs while the patient is recumbent but is relieved when the feet are in a dependent position 3
• CLTI is associated with high risk of limb loss and mortality, similar to a terminal cancer disease, with significant impact on quality of life and healthcare costs 4
• Lower limb amputation associated with CLTI has 30-day mortality rates of up to 22% 1
• CLTI should be distinguished from acute limb ischemia (ALI), which has a duration of less than 2 weeks and is characterized by the "6 P's": pain, pallor, pulselessness, poikilothermia, paresthesias, and paralysis 1, 5

Management Considerations

• All patients with suspected CLTI should be urgently referred to a vascular specialist 2
• Management should be by a vascular team including at least a vascular physician, vascular surgeon, and radiologist 1
• Revascularization should be attempted to rapidly restore inline direct blood flow to the foot 1
• Best medical therapy should be provided to all patients with CLTI, including antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents 2
• In patients with diabetes, glycemic control is particularly important for improved limb-related outcomes 1

CLTI represents a significant clinical challenge requiring prompt diagnosis and multidisciplinary management to prevent limb loss and reduce mortality 4, 2.