Pathology of Peripheral Artery Disease in Patients With Critical Limb Ischemia

Navneet Narula, Andrew J. Dannenberg, Jeffrey W. Olin, Deepak L. Bhatt, Kipp W. Johnson, Girish Nadkarni, James Min, Sho Torii, Priti Poojary, Sonia S. Anand, Jeroen J. Bax, Salim Yusuf, Renu Virmani, Jagat Narula

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Background: Critical limb ischemia (CLI) is the most serious complication of peripheral artery disease (PAD). Objectives: The purpose of this study was to characterize pathology of PAD in below- and above-knee amputation specimens in patients presenting with CLI. Methods: Peripheral arteries from 95 patients (121 amputation specimens) were examined; 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). Results: 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. 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. Conclusions: Thrombotic luminal occlusion associated with insignificant atherosclerosis is commonly observed in CLI and suggests the possibility of atherothromboembolic disease. The pathological characteristics of arteries in CLI suggest possible mechanisms of progression of PAD to CLI, especially in INFRA-POP arteries, and may support the preventive role of antithrombotic agents.

Original languageEnglish (US)
Pages (from-to)2152-2163
Number of pages12
JournalJournal of the American College of Cardiology
Issue number18
StatePublished - Oct 30 2018


  • DOAC
  • amputation
  • atherosclerosis
  • calciphylaxis
  • gangrene
  • revascularization
  • thromboembolism
  • vascular calcification

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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