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Obesity modifies the energetic phenotype of dilated cardiomyopathy

AIMS: We sought to determine if myocardial energetics could distinguish obesity cardiomyopathy as a distinct entity from dilated cardiomyopathy. METHODS AND RESULTS: Sixteen normal weight participants with dilated cardiomyopathy (DCM(NW)), and 27 with DCM and obesity (DCM(OB)), were compared to 26 n...

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Autores principales: Rayner, Jennifer J, Peterzan, Mark A, Clarke, William T, Rodgers, Christopher T, Neubauer, Stefan, Rider, Oliver J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885325/
https://www.ncbi.nlm.nih.gov/pubmed/34542592
http://dx.doi.org/10.1093/eurheartj/ehab663
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author Rayner, Jennifer J
Peterzan, Mark A
Clarke, William T
Rodgers, Christopher T
Neubauer, Stefan
Rider, Oliver J
author_facet Rayner, Jennifer J
Peterzan, Mark A
Clarke, William T
Rodgers, Christopher T
Neubauer, Stefan
Rider, Oliver J
author_sort Rayner, Jennifer J
collection PubMed
description AIMS: We sought to determine if myocardial energetics could distinguish obesity cardiomyopathy as a distinct entity from dilated cardiomyopathy. METHODS AND RESULTS: Sixteen normal weight participants with dilated cardiomyopathy (DCM(NW)), and 27 with DCM and obesity (DCM(OB)), were compared to 26 normal weight controls (CTL(NW)). All underwent cardiac magnetic resonance imaging and (31)P spectroscopy to assess function and energetics. Nineteen DCM(OB) underwent repeat assessment after a dietary weight loss intervention. Adenosine triphosphate (ATP) delivery through creatine kinase (CK flux) was 55% lower in DCM(NW) than in CTL(NW) (P = 0.004), correlating with left ventricular ejection fraction (LVEF, r = 0.4, P = 0.015). In contrast, despite similar LVEF (DCM(OB) 41 ± 7%, DCM(NW) 38 ± 6%, P = 0.14), CK flux was two-fold higher in DCM(OB) (P < 0.001), due to higher rate through CK [median k(f) 0.21 (0.14) vs. 0.11 (0.12) s(−1), P = 0.002]. During increased workload, the CTL(NW) heart increased CK flux by 97% (P < 0.001). In contrast, CK flux was unchanged in DCM(NW) and fell in DCM(OB) (by >50%, P < 0.001). Intentional weight loss was associated with positive left ventricular remodelling, with reduced left ventricular end-diastolic volume (by 8%, P < 0.001) and a change in LVEF (40 ± 9% vs. 45 ± 10%, P = 0.002). This occurred alongside a fall in ATP delivery rate with weight loss (by 7%, P = 0.049). CONCLUSIONS: In normal weight, DCM is associated with reduced resting ATP delivery. In obese DCM, ATP demand through CK is greater, suggesting reduced efficiency of energy utilization. Dietary weight loss is associated with significant improvement in myocardial contractility, and a fall in ATP delivery, suggesting improved metabolic efficiency. This highlights distinct energetic pathways in obesity cardiomyopathy, which are both different from dilated cardiomyopathy, and may be reversible with weight loss.
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spelling pubmed-88853252022-03-01 Obesity modifies the energetic phenotype of dilated cardiomyopathy Rayner, Jennifer J Peterzan, Mark A Clarke, William T Rodgers, Christopher T Neubauer, Stefan Rider, Oliver J Eur Heart J Clinical Research AIMS: We sought to determine if myocardial energetics could distinguish obesity cardiomyopathy as a distinct entity from dilated cardiomyopathy. METHODS AND RESULTS: Sixteen normal weight participants with dilated cardiomyopathy (DCM(NW)), and 27 with DCM and obesity (DCM(OB)), were compared to 26 normal weight controls (CTL(NW)). All underwent cardiac magnetic resonance imaging and (31)P spectroscopy to assess function and energetics. Nineteen DCM(OB) underwent repeat assessment after a dietary weight loss intervention. Adenosine triphosphate (ATP) delivery through creatine kinase (CK flux) was 55% lower in DCM(NW) than in CTL(NW) (P = 0.004), correlating with left ventricular ejection fraction (LVEF, r = 0.4, P = 0.015). In contrast, despite similar LVEF (DCM(OB) 41 ± 7%, DCM(NW) 38 ± 6%, P = 0.14), CK flux was two-fold higher in DCM(OB) (P < 0.001), due to higher rate through CK [median k(f) 0.21 (0.14) vs. 0.11 (0.12) s(−1), P = 0.002]. During increased workload, the CTL(NW) heart increased CK flux by 97% (P < 0.001). In contrast, CK flux was unchanged in DCM(NW) and fell in DCM(OB) (by >50%, P < 0.001). Intentional weight loss was associated with positive left ventricular remodelling, with reduced left ventricular end-diastolic volume (by 8%, P < 0.001) and a change in LVEF (40 ± 9% vs. 45 ± 10%, P = 0.002). This occurred alongside a fall in ATP delivery rate with weight loss (by 7%, P = 0.049). CONCLUSIONS: In normal weight, DCM is associated with reduced resting ATP delivery. In obese DCM, ATP demand through CK is greater, suggesting reduced efficiency of energy utilization. Dietary weight loss is associated with significant improvement in myocardial contractility, and a fall in ATP delivery, suggesting improved metabolic efficiency. This highlights distinct energetic pathways in obesity cardiomyopathy, which are both different from dilated cardiomyopathy, and may be reversible with weight loss. Oxford University Press 2021-09-20 /pmc/articles/PMC8885325/ /pubmed/34542592 http://dx.doi.org/10.1093/eurheartj/ehab663 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Research
Rayner, Jennifer J
Peterzan, Mark A
Clarke, William T
Rodgers, Christopher T
Neubauer, Stefan
Rider, Oliver J
Obesity modifies the energetic phenotype of dilated cardiomyopathy
title Obesity modifies the energetic phenotype of dilated cardiomyopathy
title_full Obesity modifies the energetic phenotype of dilated cardiomyopathy
title_fullStr Obesity modifies the energetic phenotype of dilated cardiomyopathy
title_full_unstemmed Obesity modifies the energetic phenotype of dilated cardiomyopathy
title_short Obesity modifies the energetic phenotype of dilated cardiomyopathy
title_sort obesity modifies the energetic phenotype of dilated cardiomyopathy
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885325/
https://www.ncbi.nlm.nih.gov/pubmed/34542592
http://dx.doi.org/10.1093/eurheartj/ehab663
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