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Value of the First Post-Transplant Biopsy for Predicting Long-Term Cardiac Allograft Vasculopathy (CAV) and Graft Failure in Heart Transplant Patients
BACKGROUND: Cardiac allograft vasculopathy (CAV) is the principal cause of long-term graft failure following heart transplantation. Early identification of patients at risk of CAV is essential to target invasive follow-up procedures more effectively and to establish appropriate therapies. We evaluat...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338502/ https://www.ncbi.nlm.nih.gov/pubmed/22558345 http://dx.doi.org/10.1371/journal.pone.0036100 |
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author | Labarrere, Carlos A. Woods, John R. Hardin, James W. Campana, Gonzalo L. Ortiz, Miguel A. Jaeger, Beate R. Baldridge, Lee Ann Pitts, Douglas E. Kirlin, Philip C. |
author_facet | Labarrere, Carlos A. Woods, John R. Hardin, James W. Campana, Gonzalo L. Ortiz, Miguel A. Jaeger, Beate R. Baldridge, Lee Ann Pitts, Douglas E. Kirlin, Philip C. |
author_sort | Labarrere, Carlos A. |
collection | PubMed |
description | BACKGROUND: Cardiac allograft vasculopathy (CAV) is the principal cause of long-term graft failure following heart transplantation. Early identification of patients at risk of CAV is essential to target invasive follow-up procedures more effectively and to establish appropriate therapies. We evaluated the prognostic value of the first heart biopsy (median: 9 days post-transplant) versus all biopsies obtained within the first three months for the prediction of CAV and graft failure due to CAV. METHODS AND FINDINGS: In a prospective cohort study, we developed multivariate regression models evaluating markers of atherothrombosis (fibrin, antithrombin and tissue plasminogen activator [tPA]) and endothelial activation (intercellular adhesion molecule-1) in serial biopsies obtained during the first three months post-transplantation from 172 patients (median follow-up = 6.3 years; min = 0.37 years, max = 16.3 years). Presence of fibrin was the dominant predictor in first-biopsy models (Odds Ratio [OR] for one- and 10-year graft failure due to CAV = 38.70, p = 0.002, 95% CI = 4.00–374.77; and 3.99, p = 0.005, 95% CI = 1.53–10.40) and loss of tPA was predominant in three-month models (OR for one- and 10-year graft failure due to CAV = 1.81, p = 0.025, 95% CI = 1.08–3.03; and 1.31, p = 0.001, 95% CI = 1.12–1.55). First-biopsy and three-month models had similar predictive and discriminative accuracy and were comparable in their capacities to correctly classify patient outcomes, with the exception of 10-year graft failure due to CAV in which the three-month model was more predictive. Both models had particularly high negative predictive values (e.g., First-biopsy vs. three-month models: 99% vs. 100% at 1-year and 96% vs. 95% at 10-years). CONCLUSIONS: Patients with absence of fibrin in the first biopsy and persistence of normal tPA in subsequent biopsies rarely develop CAV or graft failure during the next 10 years and potentially could be monitored less invasively. Presence of early risk markers in the transplanted heart may be secondary to ischemia/reperfusion injury, a potentially modifiable factor. |
format | Online Article Text |
id | pubmed-3338502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33385022012-05-03 Value of the First Post-Transplant Biopsy for Predicting Long-Term Cardiac Allograft Vasculopathy (CAV) and Graft Failure in Heart Transplant Patients Labarrere, Carlos A. Woods, John R. Hardin, James W. Campana, Gonzalo L. Ortiz, Miguel A. Jaeger, Beate R. Baldridge, Lee Ann Pitts, Douglas E. Kirlin, Philip C. PLoS One Research Article BACKGROUND: Cardiac allograft vasculopathy (CAV) is the principal cause of long-term graft failure following heart transplantation. Early identification of patients at risk of CAV is essential to target invasive follow-up procedures more effectively and to establish appropriate therapies. We evaluated the prognostic value of the first heart biopsy (median: 9 days post-transplant) versus all biopsies obtained within the first three months for the prediction of CAV and graft failure due to CAV. METHODS AND FINDINGS: In a prospective cohort study, we developed multivariate regression models evaluating markers of atherothrombosis (fibrin, antithrombin and tissue plasminogen activator [tPA]) and endothelial activation (intercellular adhesion molecule-1) in serial biopsies obtained during the first three months post-transplantation from 172 patients (median follow-up = 6.3 years; min = 0.37 years, max = 16.3 years). Presence of fibrin was the dominant predictor in first-biopsy models (Odds Ratio [OR] for one- and 10-year graft failure due to CAV = 38.70, p = 0.002, 95% CI = 4.00–374.77; and 3.99, p = 0.005, 95% CI = 1.53–10.40) and loss of tPA was predominant in three-month models (OR for one- and 10-year graft failure due to CAV = 1.81, p = 0.025, 95% CI = 1.08–3.03; and 1.31, p = 0.001, 95% CI = 1.12–1.55). First-biopsy and three-month models had similar predictive and discriminative accuracy and were comparable in their capacities to correctly classify patient outcomes, with the exception of 10-year graft failure due to CAV in which the three-month model was more predictive. Both models had particularly high negative predictive values (e.g., First-biopsy vs. three-month models: 99% vs. 100% at 1-year and 96% vs. 95% at 10-years). CONCLUSIONS: Patients with absence of fibrin in the first biopsy and persistence of normal tPA in subsequent biopsies rarely develop CAV or graft failure during the next 10 years and potentially could be monitored less invasively. Presence of early risk markers in the transplanted heart may be secondary to ischemia/reperfusion injury, a potentially modifiable factor. Public Library of Science 2012-04-25 /pmc/articles/PMC3338502/ /pubmed/22558345 http://dx.doi.org/10.1371/journal.pone.0036100 Text en Labarrere et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Labarrere, Carlos A. Woods, John R. Hardin, James W. Campana, Gonzalo L. Ortiz, Miguel A. Jaeger, Beate R. Baldridge, Lee Ann Pitts, Douglas E. Kirlin, Philip C. Value of the First Post-Transplant Biopsy for Predicting Long-Term Cardiac Allograft Vasculopathy (CAV) and Graft Failure in Heart Transplant Patients |
title | Value of the First Post-Transplant Biopsy for Predicting Long-Term Cardiac Allograft Vasculopathy (CAV) and Graft Failure in Heart Transplant Patients |
title_full | Value of the First Post-Transplant Biopsy for Predicting Long-Term Cardiac Allograft Vasculopathy (CAV) and Graft Failure in Heart Transplant Patients |
title_fullStr | Value of the First Post-Transplant Biopsy for Predicting Long-Term Cardiac Allograft Vasculopathy (CAV) and Graft Failure in Heart Transplant Patients |
title_full_unstemmed | Value of the First Post-Transplant Biopsy for Predicting Long-Term Cardiac Allograft Vasculopathy (CAV) and Graft Failure in Heart Transplant Patients |
title_short | Value of the First Post-Transplant Biopsy for Predicting Long-Term Cardiac Allograft Vasculopathy (CAV) and Graft Failure in Heart Transplant Patients |
title_sort | value of the first post-transplant biopsy for predicting long-term cardiac allograft vasculopathy (cav) and graft failure in heart transplant patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338502/ https://www.ncbi.nlm.nih.gov/pubmed/22558345 http://dx.doi.org/10.1371/journal.pone.0036100 |
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