Pathological Basis of Critical Limb Ischemia

Study Questions:

What is the pathology of peripheral artery disease (PAD) in below- and above-knee amputation specimens in patients presenting with critical limb ischemia (CLI)?


The investigators examined peripheral arteries from 95 patients (121 amputation specimens); 75 patients had presented with CLI, and the remaining 20 had amputations performed for other reasons. The pathological characteristics were separately recorded for femoral and popliteal arteries (FEM-POP), and infrapopliteal arteries (INFRA-POP). The authors used mixed-effect regression models to analyze the data, controlling for fixed effects of age, sex, hypertension, hyperlipidemia, diabetes, renal disease, smoking history, ischemic heart disease history, cerebrovascular disease history, and heart failure disease history.


A total of 299 arteries were examined. In the 239 arteries from CLI patients, atherosclerotic plaques were more frequent in FEM-POP (23 of 34, 67.6%) compared with INFRA-POP (79 of 205, 38.5%) arteries (adjusted odds ratio [OR], 5.47; p = 0.003). Of these 239 arteries, 165 (69%) showed ≥70% stenosis, which was due to significant pathological intimal thickening, fibroatheroma, fibrocalcific lesions, or restenosis in 45 of 165 (27.3%), or was due to luminal thrombi with (39 of 165, 23.6%) or without (81 of 165, 49.1%) significant atherosclerotic lesions. Presence of chronic luminal thrombi was more frequently observed in arteries with insignificant atherosclerosis (OR, 16.7; p = 0.0002), more so in INFRA-POP compared with FEM-POP (OR, 2.14; p = 0.0041) arteries. Acute thrombotic occlusion was less frequently encountered in INFRA-POP than FEM-POP arteries (OR, 0.27; p = 0.0067). Medial calcification was present in 170 of 239 (71.1%) large arteries.


The authors concluded that thrombotic luminal occlusion associated with insignificant atherosclerosis is commonly observed in CLI and suggests the possibility of thromboembolic disease.


This study reports that evaluation of arteries with ≥70% luminal stenosis from amputation specimens demonstrated significantly more atherosclerosis in FEM- than INFRA-POP arteries. Furthermore, the luminal compromise in the INFRA-POP arteries was more commonly secondary to a thrombotic occlusion, and more likely to occur in absence of significant atherosclerosis. The usual therapeutic options in CLI management include open or endovascular revascularization with or without adjunctive mechanical thrombectomy and/or thrombolysis. If the thromboembolic hypothesis of CLI in lower legs is confirmed, then catheter-based therapy (mechanical thrombectomy and low-dose thrombolytic therapy) or surgical thrombectomy may provide rapid restoration of blood flow and improve leg salvage. In addition, there may be a role for antithrombotic agents for prevention of CLI, which however, needs to be verified in prospective studies with hard clinical endpoints.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and Arrhythmias, Interventions and Vascular Medicine

Keywords: ESC Congress, ESC18, Amputation, Anticoagulants, Atherosclerosis, Constriction, Pathologic, Coronary Occlusion, Fibrinolytic Agents, Myocardial Revascularization, Peripheral Arterial Disease, Plaque, Atherosclerotic, Popliteal Artery, Primary Prevention, Thrombectomy, Thrombolytic Therapy, Thrombosis, Vascular Diseases

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