Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation,
and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on
definition, evaluation, and management of CLTI with the goals of improving evidence-based
care and highlighting critical research needs. The term CLTI is preferred over critical
limb ischemia, as the latter implies threshold values of impaired perfusion rather
than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral
artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration
>2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are
excluded. All patients with suspected CLTI should be referred urgently to a vascular
specialist. Accurately staging the severity of limb threat is fundamental, and the
Society for Vascular Surgery Threatened Limb Classification system, based on grading
of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic
testing, including toe pressures as the preferred measure, is required to assess CLTI.
Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk,
Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients
are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes
a new Global Anatomic Staging System (GLASS), which involves defining a preferred
target artery path (TAP) and then estimating limb-based patency (LBP), resulting in
three stages of complexity for intervention. The optimal revascularization strategy
is also influenced by the availability of autogenous vein for open bypass surgery.
Recommendations for EBR are based on best available data, pending level 1 evidence
from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced
limb threat and high complexity disease, while those with less complex anatomy, intermediate
severity limb threat, or high patient risk may be favored for endovascular intervention.
All patients with CLTI should be afforded best medical therapy including the use of
antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as
well as counseling on smoking cessation, diet, exercise, and preventive foot care.
Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization
therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric
oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene
therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical
trials. The GVG promotes standardization of study designs and end points for clinical
trials in CLTI. The importance of multidisciplinary teams and centers of excellence
for amputation prevention is stressed as a key health system initiative.