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Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy

BACKGROUND: Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which there is no cure. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejecti...

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Autores principales: Soslow, Jonathan H., Damon, Stephen M., Crum, Kimberly, Lawson, Mark A., Slaughter, James C., Xu, Meng, Arai, Andrew E., Sawyer, Douglas B., Parra, David A., Damon, Bruce M., Markham, Larry W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722665/
https://www.ncbi.nlm.nih.gov/pubmed/26795569
http://dx.doi.org/10.1186/s12968-016-0224-7
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author Soslow, Jonathan H.
Damon, Stephen M.
Crum, Kimberly
Lawson, Mark A.
Slaughter, James C.
Xu, Meng
Arai, Andrew E.
Sawyer, Douglas B.
Parra, David A.
Damon, Bruce M.
Markham, Larry W.
author_facet Soslow, Jonathan H.
Damon, Stephen M.
Crum, Kimberly
Lawson, Mark A.
Slaughter, James C.
Xu, Meng
Arai, Andrew E.
Sawyer, Douglas B.
Parra, David A.
Damon, Bruce M.
Markham, Larry W.
author_sort Soslow, Jonathan H.
collection PubMed
description BACKGROUND: Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which there is no cure. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejection fraction must be found. The hypothesis of this study is that T1 and extracellular volume fraction (ECV) mapping using cardiovascular magnetic resonance (CMR) can detect diffuse extracellular matrix expansion in DMD patients with normal left ventricular ejection fraction (LVEF) and without myocardial late gadolinium enhancement (LGE). METHODS: Thirty-one DMD and 11 healthy control participants were prospectively enrolled. CMR using a modified Look-Locker (MOLLI) sequence was performed in all participants before and after contrast administration. T1 and ECV maps of the mid left ventricular myocardium were generated and regions of interest were contoured using the standard 6-segment AHA model. Global and segmental values were compared between DMD and controls using a Wilcoxon rank-sum test. RESULTS: The DMD participants had significantly higher mean native T1 compared with controls (1045 ms vs 988 ms, p = 0.001). DMD participants with normal LVEF and without evidence of LGE also demonstrated elevated mean native T1 (1039 ms vs 988 ms, p = 0.002, and 1038 ms vs 988 ms, p = 0.011). DMD participants had a significantly greater mean ECV than controls (0.31 vs 0.24, p < 0.001), even in the settings of normal LVEF (0.28 vs 0.24, p < 0.001) and negative LGE (0.29 vs 0.24, p = 0.001). CONCLUSIONS: DMD participants have elevated LV myocardial native T1 and ECV, even in the setting of normal LVEF and in the absence of LGE. T1 and ECV mapping in DMD have potential to serve as surrogate cardiomyopathy outcome measures for clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12968-016-0224-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-47226652016-01-23 Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy Soslow, Jonathan H. Damon, Stephen M. Crum, Kimberly Lawson, Mark A. Slaughter, James C. Xu, Meng Arai, Andrew E. Sawyer, Douglas B. Parra, David A. Damon, Bruce M. Markham, Larry W. J Cardiovasc Magn Reson Research BACKGROUND: Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which there is no cure. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejection fraction must be found. The hypothesis of this study is that T1 and extracellular volume fraction (ECV) mapping using cardiovascular magnetic resonance (CMR) can detect diffuse extracellular matrix expansion in DMD patients with normal left ventricular ejection fraction (LVEF) and without myocardial late gadolinium enhancement (LGE). METHODS: Thirty-one DMD and 11 healthy control participants were prospectively enrolled. CMR using a modified Look-Locker (MOLLI) sequence was performed in all participants before and after contrast administration. T1 and ECV maps of the mid left ventricular myocardium were generated and regions of interest were contoured using the standard 6-segment AHA model. Global and segmental values were compared between DMD and controls using a Wilcoxon rank-sum test. RESULTS: The DMD participants had significantly higher mean native T1 compared with controls (1045 ms vs 988 ms, p = 0.001). DMD participants with normal LVEF and without evidence of LGE also demonstrated elevated mean native T1 (1039 ms vs 988 ms, p = 0.002, and 1038 ms vs 988 ms, p = 0.011). DMD participants had a significantly greater mean ECV than controls (0.31 vs 0.24, p < 0.001), even in the settings of normal LVEF (0.28 vs 0.24, p < 0.001) and negative LGE (0.29 vs 0.24, p = 0.001). CONCLUSIONS: DMD participants have elevated LV myocardial native T1 and ECV, even in the setting of normal LVEF and in the absence of LGE. T1 and ECV mapping in DMD have potential to serve as surrogate cardiomyopathy outcome measures for clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12968-016-0224-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-21 /pmc/articles/PMC4722665/ /pubmed/26795569 http://dx.doi.org/10.1186/s12968-016-0224-7 Text en © Soslow et al. 2016 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
Soslow, Jonathan H.
Damon, Stephen M.
Crum, Kimberly
Lawson, Mark A.
Slaughter, James C.
Xu, Meng
Arai, Andrew E.
Sawyer, Douglas B.
Parra, David A.
Damon, Bruce M.
Markham, Larry W.
Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy
title Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy
title_full Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy
title_fullStr Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy
title_full_unstemmed Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy
title_short Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy
title_sort increased myocardial native t1 and extracellular volume in patients with duchenne muscular dystrophy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722665/
https://www.ncbi.nlm.nih.gov/pubmed/26795569
http://dx.doi.org/10.1186/s12968-016-0224-7
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