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Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery
BACKGROUND: The objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome. METHODS: Voluntary participants undergoing heart surgery were enrolled...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905054/ https://www.ncbi.nlm.nih.gov/pubmed/31822289 http://dx.doi.org/10.1186/s12967-019-02162-5 |
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author | Aguiar, Christie M. Gawdat, Kareem Legere, Stephanie Marshall, Jean Hassan, Ansar Kienesberger, Petra C. Pulinilkunnil, Thomas Castonguay, Mathieu Brunt, Keith R. Legare, Jean-Francois |
author_facet | Aguiar, Christie M. Gawdat, Kareem Legere, Stephanie Marshall, Jean Hassan, Ansar Kienesberger, Petra C. Pulinilkunnil, Thomas Castonguay, Mathieu Brunt, Keith R. Legare, Jean-Francois |
author_sort | Aguiar, Christie M. |
collection | PubMed |
description | BACKGROUND: The objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome. METHODS: Voluntary participants undergoing heart surgery were enrolled in the study and blood samples were collected prior to surgery, and right atrium samples were harvested intraoperatively. Blood samples were analyzed by flow cytometry and complete blood counts. Atrial samples were divided for fixed fibrosis analysis, homogenized for cytokine analysis and digested for single cell suspension flow cytometry. RESULTS: A total of 18 patients were enrolled and samples assessed. Isolated cells from the atria revealed a CD45+ population of ~ 20%, confirming a large number of leukocytes. Further characterization revealed this population as 57% lymphocytes and 26% monocyte/macrophages (MoΦ), with the majority of the latter cells being classical (CD14++/CD16−). Interstitial fibrosis was present in 87% of samples and correlated significantly with patient age. Older patients (> 65) had significantly more atrial fibrosis and cellular inflammation. AFib patients had no distinguishing feature of atrial fibrosis and had significantly greater CD45+ MoΦ, increased expression of MMP9 and presented with a significant correlation in length of stay to CCL-2/MCP-1 and NLR (neutrophil-to-lymphocyte ratio). CONCLUSION: Atrial fibrosis is correlated with age and not determinate to AFib. However, severity of atrial leukocyte infiltration and markers of matrix degradation are determinant to AFib. This also correlated with CCL2 (or MCP-1) and NLR-indicative of marked inflammation. These data show the potential importance of diagnostic and prognostic assessments that could inform clinical decision making in regard to the intensity of AFib patient management. |
format | Online Article Text |
id | pubmed-6905054 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69050542019-12-19 Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery Aguiar, Christie M. Gawdat, Kareem Legere, Stephanie Marshall, Jean Hassan, Ansar Kienesberger, Petra C. Pulinilkunnil, Thomas Castonguay, Mathieu Brunt, Keith R. Legare, Jean-Francois J Transl Med Research BACKGROUND: The objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome. METHODS: Voluntary participants undergoing heart surgery were enrolled in the study and blood samples were collected prior to surgery, and right atrium samples were harvested intraoperatively. Blood samples were analyzed by flow cytometry and complete blood counts. Atrial samples were divided for fixed fibrosis analysis, homogenized for cytokine analysis and digested for single cell suspension flow cytometry. RESULTS: A total of 18 patients were enrolled and samples assessed. Isolated cells from the atria revealed a CD45+ population of ~ 20%, confirming a large number of leukocytes. Further characterization revealed this population as 57% lymphocytes and 26% monocyte/macrophages (MoΦ), with the majority of the latter cells being classical (CD14++/CD16−). Interstitial fibrosis was present in 87% of samples and correlated significantly with patient age. Older patients (> 65) had significantly more atrial fibrosis and cellular inflammation. AFib patients had no distinguishing feature of atrial fibrosis and had significantly greater CD45+ MoΦ, increased expression of MMP9 and presented with a significant correlation in length of stay to CCL-2/MCP-1 and NLR (neutrophil-to-lymphocyte ratio). CONCLUSION: Atrial fibrosis is correlated with age and not determinate to AFib. However, severity of atrial leukocyte infiltration and markers of matrix degradation are determinant to AFib. This also correlated with CCL2 (or MCP-1) and NLR-indicative of marked inflammation. These data show the potential importance of diagnostic and prognostic assessments that could inform clinical decision making in regard to the intensity of AFib patient management. BioMed Central 2019-12-10 /pmc/articles/PMC6905054/ /pubmed/31822289 http://dx.doi.org/10.1186/s12967-019-02162-5 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Aguiar, Christie M. Gawdat, Kareem Legere, Stephanie Marshall, Jean Hassan, Ansar Kienesberger, Petra C. Pulinilkunnil, Thomas Castonguay, Mathieu Brunt, Keith R. Legare, Jean-Francois Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery |
title | Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery |
title_full | Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery |
title_fullStr | Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery |
title_full_unstemmed | Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery |
title_short | Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery |
title_sort | fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905054/ https://www.ncbi.nlm.nih.gov/pubmed/31822289 http://dx.doi.org/10.1186/s12967-019-02162-5 |
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