Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia

Abstract

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.

Keywords: Bypass surgery; Chronic limb-threatening ischemia; Critical limb ischemia; Diabetes; Endovascular intervention; Evidence-based medicine; Foot ulcer; Peripheral artery disease; Practice guideline.

Fig 2.1.

Prevalence of peripheral artery disease (PAD; ankle-brachial index [ABI] <0.9) by age and sex in high-income countries (HICs) and in low- and middle-income countries (LMICs).

Fig 2.2.

Odds ratios (ORs) for peripheral artery disease (PAD) in high-income countries (HICs) and low- and middle-income countries (LMICs). BMI, Body mass index; CRP, C-reactive protein; CVD, cardiovascular disease; HDL, high-density lipoprotein. (Reprinted from Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res 2015;116:1509–26.)

Fig 2.3.

Association of risk factors with the level of atherosclerotic target lesions. The red overlay on the anatomic cartoon illustrates the association of risk factor with patterns of atherosclerotic disease. (Reprinted from Diehm N, Shang A, Silvestro A, Do DD, Dick F, Schmidli J, et al. Association of cardiovascular risk factors with pattern of lower limb atherosclerosis in 2659 patients undergoing angioplasty. Eur J Vasc Endovasc Surg 2006;31:59–63.)

Fig 3.1.

Flow diagram for the investigation of patients presenting with suspected chronic limb-threatening ischemia (CLTI). ABI, Ankle-brachial index; PAD, peripheral artery disease; TBI, toe-brachial index; WIfI, Wound, Ischemia, and foot Infection.

Fig 3.2.

Suggested algorithm for anatomic imaging in patients with chronic limb-threatening ischemia (CLTI) who are candidates for revascularization. In some cases, it may be appropriate to proceed directly to angiographic imaging (computed tomography angiography [CTA], magnetic resonance angiography [MRA], or catheter) rather than to duplex ultrasound (DUS) imaging.

Fig 5.1.

Inframalleolar (IM)/pedal disease descriptor in Global Limb Anatomic Staging System (GLASS). Representative angiograms of P0 (left), P1 (middle), and P2 (right) patterns of disease.

Fig 5.2.

Femoropopliteal (FP) disease grading in Global Limb Anatomic Staging System (GLASS). Trifurcation is defined as the termination of the popliteal artery at the confluence of the anterior tibial (AT) artery and tibioperoneal trunk. CFA, Common femoral artery; CTO, chronic total occlusion; DFA, deep femoral artery; Pop, popliteal; SFA, superficial femoral artery.

Fig 5.3.

Infrapopliteal (IP) disease grading in Global Limb Anatomic Staging System (GLASS). AT, Anterior tibial; CTO, chronic total occlusion; TP, tibioperoneal.

Fig 5.4.

Representative angiograms of Global Limb Anatomic Staging System (GLASS) stage I disease patterns. The target arterial path (TAP) is outlined in yellow. Left panel, TAP includes the anterior tibial (AT) artery. Femoropopliteal (FP) grade is 0. Infrapopliteal (IP) grade is 2 (3-cm chronic total occlusion; chronic total occlusion of AT artery and total length of disease <10 cm). Right panel, TAP includes the peroneal artery. FP grade is 2 (chronic total occlusion <10 cm; total length of disease <²/₃). IP grade is 0.

Fig 5.5.

Representative angiograms of Global Limb Anatomic Staging System (GLASS) stage II disease patterns. The target arterial path (TAP) is outlined in yellow. Left panel, TAP includes the anterior tibial (AT) artery. Femoropopliteal (FP) grade is 1 (superficial femoral artery [SFA] occlusion <5 cm). Infrapopliteal (IP) grade is 2 (two focal stenoses of AT artery, total length <10 cm). Right panel, TAP includes the peroneal artery. FP grade is 0 (no significant stenosis). IP grade is 3 (chronic total occlusion of peroneal artery, 3–10 cm).

Fig 5.6.

Representative angiograms of Global Limb Anatomic Staging System (GLASS) stage III disease patterns. The target arterial path (TAP) is outlined in yellow. Left panel, TAP includes the peroneal artery. Femoropopliteal (FP) grade is 4 (superficial femoral artery [SFA] disease length, 10–20 cm; popliteal stenosis <5 cm; heavily calcified). Infrapopliteal (IP) grade is 2 (stenosis of tibioperoneal trunk and proximal peroneal <10 cm). Right panel, TAP includes the anterior tibial (AT) artery. FP grade is 4 (popliteal chronic total occlusion extending into trifurcation). IP grade is 3 (chronic total occlusion of target artery origin).

Fig 5.7.

Flow chart illustrating application of Global Limb Anatomic Staging System (GLASS) to stage infrainguinal disease pattern in chronic limb-threatening ischemia (CLTI). FP, Femoropopliteal; IP, infrapopliteal; PLAN, patient risk estimation, limb staging, anatomic pattern of disease; TAP, target arterial path; WIfI, Wound, Ischemia, and foot Infection.

Fig 6.1.

Paradigm for evidence-based revascularization (EBR) in the treatment of chronic limb-threatening ischemia (CLTI). Patient risk, Limb severity, and ANatomic stage are integrated in the PLAN approach. WIfI, Wound, Ischemia, and foot Infection.

Fig 6.2.

PLAN framework of clinical decision-making in chronic limb-threatening ischemia (CLTI); infrainguinal disease. Refer to Fig 6.4 for preferred revascularization strategy in standard-risk patients with available vein conduit, based on limb stage at presentation and anatomic complexity. Approaches for patients lacking suitable vein are reviewed in the text. GLASS, Global Limb Anatomic Staging System; WIfI, Wound, Ischemia, and foot Infection.

Fig 6.3.

The benefit of performing revascularization in chronic limb-threatening ischemia (CLTI) increases with degree of ischemia and with the severity of limb threat (Wound, Ischemia, and foot Infection [WIfI] stage). WIfI stage 1 limbs do not have advanced ischemia grades, denoted as not applicable (N/A).

Fig 6.4.

Preferred initial revascularization strategy for infrainguinal disease in average-risk patients with suitable autologous vein conduit available for bypass. Revascularization is considered rarely indicated in limbs at low risk (Wound, Ischemia, and foot Infection [WIfI] stage 1). Anatomic stage (y-axis) is determined by the Global Limb Anatomic Staging System (GLASS); limb risk (x-axis) is determined by WIfI staging. The dark gray shading indicates scenarios with least consensus (assumptions—inflow disease either is not significant or is corrected; absence of severe pedal disease, ie, no GLASS P2 modifier).

Fig 12.1.

The elevating risk of the “stairway to an amputation” or the natural history of diabetes-related amputations. (Adapted from Rogers LC, Armstrong DG. Podiatry care. In: Cronenwett JL, Johnston KW, editors. Rutherford’s vascular surgery. 7th ed. Philadelphia: Saunders Elsevier; 2010. p. 1747–60.)

Fig 12.2.

A schematic on how to organize the diabetic foot care within a multidisciplinary team.

Fig 12.3.

An example of using the organized care model for peripheral artery disease (PAD) screening in diabetic foot ulcers (DFUs). CPG, Clinical practice guideline; CPP, clinical practice pathway; P&P, policies and procedures; PI, performance improvement; QA, quality assurance.

Fig 13.1.

International Diabetes Federation global diabetes projections. (From the International Diabetes Federation. IDF diabetes atlas. 7th ed. Brussels, Belgium: International Diabetes Federation; 2015.)