Author + information
- Received July 28, 2018
- Revision received August 1, 2018
- Accepted August 1, 2018
- Published online September 7, 2018.
- Navneet Narula, MDa,b,∗ (, )@nyulangone,
- Andrew J. Dannenberg, MDa,
- Jeffrey W. Olin, DOc,
- Deepak L. Bhatt, MD, MPHd,
- Kipp W. Johnson, BSc,
- Girish Nadkarni, MDc,
- James Min, MDa,
- Sho Torii, MDe,
- Priti Poojary, MD, MPHc,
- Sonia S. Anand, MDf,
- Jeroen J. Bax, MD, PhDg,
- Salim Yusuf, MDf,
- Renu Virmani, MDe and
- Jagat Narula, MD, PhDc
- aNew York Presbyterian Hospital and Weill Cornell Medicine, New York, New York
- bNYU Langone Medical Center, New York, New York
- cMount Sinai Heart and Icahn School of Medicine at Mount Sinai, New York, New York
- dBrigham & Women’s Hospital and Harvard Medical School, Boston, Massachusettes
- eCardiovascular Pathology Inc., Gaithersburg, Maryland
- fPopulation Health Research Institute and McMaster University, Hamilton, Ontario, Canada
- gLeiden University Medical Center, Leiden, the Netherlands
- ↵∗Address for correspondence:
Dr. Navneet Narula, NYU Langone Medical Center, 550 First Avenue, Suite TH4 14A, New York, New York 10016.
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 thromboembolic 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.
- vascular calcification
Dr. Olin has served on the International Steering Committee for the Euclid Trial, sponsored by AstraZeneca; has served on the Medical Advisory Board of Janssen Pharmaceuticals; and has served on the Steering Committee of the TRAP 2 Prevention Trial sponsored by Merck. Dr. Deepak L. Bhatt has served on the advisory board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the board of directors of Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; has served as chair of American Heart Association Quality Oversight Committee; has served on the data monitoring committees for Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, and Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); has served as Deputy Editor of Clinical Cardiology; has served as chair of the NCDR-ACTION Registry Steering Committee and the VA CART Research and Publications Committee; has received research funding from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as Site Coinvestigator for Biotronik, Boston Scientific, St. Jude Medical (now Abbott), and Svelte; has served as a trustee for the American College of Cardiology; and has performed unfunded research for FlowCo, Merck, PLx Pharma, and Takeda. Dr. Johnson has received consulting fees from Pillar Health for work unrelated to this project; and has been partially supported by a National Institutes of Health Medical Scientist Training Program grant to Mount Sinai. Dr. Nadkarni has received operational funding from Goldfinch Bio; and has equity in, is cofounder of, and has served as a consultant for Renalytix AI. Dr. Min has served on the scientific advisory boards of Arineta and GE Healthcare; and has received funding from Dalio Foundation, National Institutes of Health, and GE Healthcare. Dr. Anand is supported by a Tier 1 Canada Research Chair in Ethnicity and Cardiovascular Disease, and the Michael G. DeGroote Heart and Stroke Foundation Chair in Population Health; and has received honoraria and consulting fees from Bayer. Dr. Yusuf has been supported by the Heart & Stroke Foundation/Marion W. Burke Chair in Cardiovascular Disease; has received research grants and honoraria and travel reimbursement for speaking from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, and Sanofi; and has received research grants from Cadilla. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received July 28, 2018.
- Revision received August 1, 2018.
- Accepted August 1, 2018.
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