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Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study

BACKGROUND: It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart’s primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides i...

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Autores principales: Gabr, Refaat E., El-Sharkawy, AbdEl-Monem M., Schär, Michael, Panjrath, Gurusher S., Gerstenblith, Gary, Weiss, Robert G., Bottomley, Paul A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287363/
https://www.ncbi.nlm.nih.gov/pubmed/30526611
http://dx.doi.org/10.1186/s12968-018-0491-6
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author Gabr, Refaat E.
El-Sharkawy, AbdEl-Monem M.
Schär, Michael
Panjrath, Gurusher S.
Gerstenblith, Gary
Weiss, Robert G.
Bottomley, Paul A.
author_facet Gabr, Refaat E.
El-Sharkawy, AbdEl-Monem M.
Schär, Michael
Panjrath, Gurusher S.
Gerstenblith, Gary
Weiss, Robert G.
Bottomley, Paul A.
author_sort Gabr, Refaat E.
collection PubMed
description BACKGROUND: It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart’s primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides is reduced in human HF. However, the relationship between the CK energy supply and the mechanical energy expended has never been quantified in the human heart. This study tests whether reduced CK energy supply is associated with reduced mechanical work in HF patients. METHODS: Cardiac mechanical work and CK flux in W/kg, and mechanical efficiency were measured noninvasively at rest using cardiac pressure-volume loops, magnetic resonance imaging and phosphorus spectroscopy in 14 healthy subjects and 27 patients with mild-to-moderate HF. RESULTS: In HF, the resting CK flux (126 ± 46 vs. 179 ± 50 W/kg, p < 0.002), the average (6.8 ± 3.1 vs. 10.1 ± 1.5 W/kg, p  <0.001) and the peak (32 ± 14 vs. 48 ± 8 W/kg, p < 0.001) cardiac mechanical work-rates, as well as the cardiac mechanical efficiency (53% ± 16 vs. 79% ± 3, p < 0.001), were all reduced by a third compared to healthy subjects. In addition, cardiac CK flux correlated with the resting peak and average mechanical power (p < 0.01), and with mechanical efficiency (p = 0.002). CONCLUSION: These first noninvasive findings showing that cardiac mechanical work and efficiency in mild-to-moderate human HF decrease proportionately with CK ATP energy supply, are consistent with the energy deprivation hypothesis of HF. CK energy supply exceeds mechanical work at rest but lies within a range that may be limiting with moderate activity, and thus presents a promising target for HF treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00181259. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12968-018-0491-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-62873632018-12-14 Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study Gabr, Refaat E. El-Sharkawy, AbdEl-Monem M. Schär, Michael Panjrath, Gurusher S. Gerstenblith, Gary Weiss, Robert G. Bottomley, Paul A. J Cardiovasc Magn Reson Research BACKGROUND: It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart’s primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides is reduced in human HF. However, the relationship between the CK energy supply and the mechanical energy expended has never been quantified in the human heart. This study tests whether reduced CK energy supply is associated with reduced mechanical work in HF patients. METHODS: Cardiac mechanical work and CK flux in W/kg, and mechanical efficiency were measured noninvasively at rest using cardiac pressure-volume loops, magnetic resonance imaging and phosphorus spectroscopy in 14 healthy subjects and 27 patients with mild-to-moderate HF. RESULTS: In HF, the resting CK flux (126 ± 46 vs. 179 ± 50 W/kg, p < 0.002), the average (6.8 ± 3.1 vs. 10.1 ± 1.5 W/kg, p  <0.001) and the peak (32 ± 14 vs. 48 ± 8 W/kg, p < 0.001) cardiac mechanical work-rates, as well as the cardiac mechanical efficiency (53% ± 16 vs. 79% ± 3, p < 0.001), were all reduced by a third compared to healthy subjects. In addition, cardiac CK flux correlated with the resting peak and average mechanical power (p < 0.01), and with mechanical efficiency (p = 0.002). CONCLUSION: These first noninvasive findings showing that cardiac mechanical work and efficiency in mild-to-moderate human HF decrease proportionately with CK ATP energy supply, are consistent with the energy deprivation hypothesis of HF. CK energy supply exceeds mechanical work at rest but lies within a range that may be limiting with moderate activity, and thus presents a promising target for HF treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00181259. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12968-018-0491-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-10 /pmc/articles/PMC6287363/ /pubmed/30526611 http://dx.doi.org/10.1186/s12968-018-0491-6 Text en © The Author(s). 2018 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
Gabr, Refaat E.
El-Sharkawy, AbdEl-Monem M.
Schär, Michael
Panjrath, Gurusher S.
Gerstenblith, Gary
Weiss, Robert G.
Bottomley, Paul A.
Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study
title Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study
title_full Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study
title_fullStr Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study
title_full_unstemmed Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study
title_short Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study
title_sort cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287363/
https://www.ncbi.nlm.nih.gov/pubmed/30526611
http://dx.doi.org/10.1186/s12968-018-0491-6
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