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Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload
AIMS: Sacubitril/valsartan (sac/val) has shown superior effect compared with blockade of the renin–angiotensin–aldosterone system in heart failure with reduced ejection fraction. We aimed to investigate effects of sac/val compared with valsartan in a pressure overload model of heart failure with pre...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006657/ https://www.ncbi.nlm.nih.gov/pubmed/33497525 http://dx.doi.org/10.1002/ehf2.13177 |
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author | Nordén, Einar Sjaastad Bendiksen, Bård Andre Andresen, Henriette Bergo, Kaja Knudsen Espe, Emil Knut Hasic, Almira Hauge‐Iversen, Ida Marie Veras, Ioanni Hussain, Rizwan I. Sjaastad, Ivar Christensen, Geir Cataliotti, Alessandro |
author_facet | Nordén, Einar Sjaastad Bendiksen, Bård Andre Andresen, Henriette Bergo, Kaja Knudsen Espe, Emil Knut Hasic, Almira Hauge‐Iversen, Ida Marie Veras, Ioanni Hussain, Rizwan I. Sjaastad, Ivar Christensen, Geir Cataliotti, Alessandro |
author_sort | Nordén, Einar Sjaastad |
collection | PubMed |
description | AIMS: Sacubitril/valsartan (sac/val) has shown superior effect compared with blockade of the renin–angiotensin–aldosterone system in heart failure with reduced ejection fraction. We aimed to investigate effects of sac/val compared with valsartan in a pressure overload model of heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Sprague–Dawley rats underwent aortic banding or sham (n = 16) surgery and were randomized to sac/val (n = 28), valsartan (n = 29), or vehicle (n = 26) treatment for 8 weeks. Sac/val reduced left ventricular weight by 11% compared with vehicle (P = 0.01) and 9% compared with valsartan alone (P = 0.04). Only valsartan reduced blood pressure compared with sham (P = 0.02). Longitudinal early diastolic strain rate was preserved in sac/val compared with sham, while it was reduced by 23% in vehicle (P = 0.03) and 24% in valsartan (P = 0.02). Diastolic dysfunction, measured by E/e'SR, increased by 68% in vehicle (P < 0.01) and 80% in valsartan alone (P < 0.001), while sac/val showed no increase. Neither sac/val nor valsartan prevented interstitial fibrosis. Although ejection fraction was preserved, we observed mild systolic dysfunction, with vehicle showing a 28% decrease in longitudinal strain (P < 0.01). Neither sac/val nor valsartan treatment improved this dysfunction. CONCLUSIONS: In a model of HFpEF induced by cardiac pressure overload, sac/val reduced hypertrophy compared with valsartan alone and ameliorated diastolic dysfunction. These effects were independent of blood pressure. Early systolic dysfunction was not affected, supporting the notion that sac/val has the largest potential in conditions characterized by reduced ejection fraction. Observed anti‐hypertrophic effects in preserved ejection fraction implicate potential benefit of sac/val in the clinical setting of hypertrophic remodelling and impaired diastolic function. |
format | Online Article Text |
id | pubmed-8006657 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80066572021-04-01 Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload Nordén, Einar Sjaastad Bendiksen, Bård Andre Andresen, Henriette Bergo, Kaja Knudsen Espe, Emil Knut Hasic, Almira Hauge‐Iversen, Ida Marie Veras, Ioanni Hussain, Rizwan I. Sjaastad, Ivar Christensen, Geir Cataliotti, Alessandro ESC Heart Fail Original Research Articles AIMS: Sacubitril/valsartan (sac/val) has shown superior effect compared with blockade of the renin–angiotensin–aldosterone system in heart failure with reduced ejection fraction. We aimed to investigate effects of sac/val compared with valsartan in a pressure overload model of heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Sprague–Dawley rats underwent aortic banding or sham (n = 16) surgery and were randomized to sac/val (n = 28), valsartan (n = 29), or vehicle (n = 26) treatment for 8 weeks. Sac/val reduced left ventricular weight by 11% compared with vehicle (P = 0.01) and 9% compared with valsartan alone (P = 0.04). Only valsartan reduced blood pressure compared with sham (P = 0.02). Longitudinal early diastolic strain rate was preserved in sac/val compared with sham, while it was reduced by 23% in vehicle (P = 0.03) and 24% in valsartan (P = 0.02). Diastolic dysfunction, measured by E/e'SR, increased by 68% in vehicle (P < 0.01) and 80% in valsartan alone (P < 0.001), while sac/val showed no increase. Neither sac/val nor valsartan prevented interstitial fibrosis. Although ejection fraction was preserved, we observed mild systolic dysfunction, with vehicle showing a 28% decrease in longitudinal strain (P < 0.01). Neither sac/val nor valsartan treatment improved this dysfunction. CONCLUSIONS: In a model of HFpEF induced by cardiac pressure overload, sac/val reduced hypertrophy compared with valsartan alone and ameliorated diastolic dysfunction. These effects were independent of blood pressure. Early systolic dysfunction was not affected, supporting the notion that sac/val has the largest potential in conditions characterized by reduced ejection fraction. Observed anti‐hypertrophic effects in preserved ejection fraction implicate potential benefit of sac/val in the clinical setting of hypertrophic remodelling and impaired diastolic function. John Wiley and Sons Inc. 2021-01-26 /pmc/articles/PMC8006657/ /pubmed/33497525 http://dx.doi.org/10.1002/ehf2.13177 Text en © 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Research Articles Nordén, Einar Sjaastad Bendiksen, Bård Andre Andresen, Henriette Bergo, Kaja Knudsen Espe, Emil Knut Hasic, Almira Hauge‐Iversen, Ida Marie Veras, Ioanni Hussain, Rizwan I. Sjaastad, Ivar Christensen, Geir Cataliotti, Alessandro Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload |
title | Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload |
title_full | Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload |
title_fullStr | Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload |
title_full_unstemmed | Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload |
title_short | Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload |
title_sort | sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload |
topic | Original Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006657/ https://www.ncbi.nlm.nih.gov/pubmed/33497525 http://dx.doi.org/10.1002/ehf2.13177 |
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