Empagliflozin improves cardiac function in heart failure with reduced ejection fraction independent of loading conditions
Identifieur interne : 000096 ( Pmc/Corpus ); précédent : 000095; suivant : 000097Empagliflozin improves cardiac function in heart failure with reduced ejection fraction independent of loading conditions
Auteurs : Bo Liang ; Yu-Xiu Zhao ; Ning GuSource :
- Cardiovascular Diabetology [ 1475-2840 ] ; 2020.
Abstract
The study regarding load-independent effects of empagliflozin contribute to improved cardiac function in experimental heart failure with reduced ejection fraction is very interesting. But there are a few things we need to pay attention to.
Url:
DOI: 10.1186/s12933-020-01004-9
PubMed: 32156272
PubMed Central: 7063753
Links to Exploration step
PMC:7063753Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Empagliflozin improves cardiac function in heart failure with reduced ejection fraction independent of loading conditions</title><author><name sortKey="Liang, Bo" sort="Liang, Bo" uniqKey="Liang B" first="Bo" last="Liang">Bo Liang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.410745.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1765 1045</institution-id><institution>Nanjing University of Chinese Medicine,</institution></institution-wrap>Nanjing, China</nlm:aff></affiliation></author><author><name sortKey="Zhao, Yu Xiu" sort="Zhao, Yu Xiu" uniqKey="Zhao Y" first="Yu-Xiu" last="Zhao">Yu-Xiu Zhao</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.410578.f</institution-id><institution>Hospital (T.C.M.) Affiliated to Southwest Medical University,</institution></institution-wrap>Luzhou, China</nlm:aff></affiliation></author><author><name sortKey="Gu, Ning" sort="Gu, Ning" uniqKey="Gu N" first="Ning" last="Gu">Ning Gu</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.410745.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1765 1045</institution-id><institution>Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,</institution></institution-wrap>Nanjing, China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32156272</idno><idno type="pmc">7063753</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063753</idno><idno type="RBID">PMC:7063753</idno><idno type="doi">10.1186/s12933-020-01004-9</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000096</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000096</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Empagliflozin improves cardiac function in heart failure with reduced ejection fraction independent of loading conditions</title><author><name sortKey="Liang, Bo" sort="Liang, Bo" uniqKey="Liang B" first="Bo" last="Liang">Bo Liang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.410745.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1765 1045</institution-id><institution>Nanjing University of Chinese Medicine,</institution></institution-wrap>Nanjing, China</nlm:aff></affiliation></author><author><name sortKey="Zhao, Yu Xiu" sort="Zhao, Yu Xiu" uniqKey="Zhao Y" first="Yu-Xiu" last="Zhao">Yu-Xiu Zhao</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.410578.f</institution-id><institution>Hospital (T.C.M.) Affiliated to Southwest Medical University,</institution></institution-wrap>Luzhou, China</nlm:aff></affiliation></author><author><name sortKey="Gu, Ning" sort="Gu, Ning" uniqKey="Gu N" first="Ning" last="Gu">Ning Gu</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.410745.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1765 1045</institution-id><institution>Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,</institution></institution-wrap>Nanjing, China</nlm:aff></affiliation></author></analytic><series><title level="j">Cardiovascular Diabetology</title><idno type="eISSN">1475-2840</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">The study regarding load-independent effects of empagliflozin contribute to improved cardiac function in experimental heart failure with reduced ejection fraction is very interesting. But there are a few things we need to pay attention to.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Connelly, Ka" uniqKey="Connelly K">KA Connelly</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Desjardins, J F" uniqKey="Desjardins J">J-F Desjardins</name></author><author><name sortKey="Nghiem, L" uniqKey="Nghiem L">L Nghiem</name></author><author><name sortKey="Visram, A" uniqKey="Visram A">A Visram</name></author><author><name sortKey="Batchu, Sn" uniqKey="Batchu S">SN Batchu</name></author><author><name sortKey="Yerra, Vg" uniqKey="Yerra V">VG Yerra</name></author><author><name sortKey="Kabir, G" uniqKey="Kabir G">G Kabir</name></author><author><name sortKey="Thai, K" uniqKey="Thai K">K Thai</name></author><author><name sortKey="Advani, A" uniqKey="Advani A">A Advani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zinman, B" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cardiovasc Diabetol</journal-id><journal-id journal-id-type="iso-abbrev">Cardiovasc Diabetol</journal-id><journal-title-group><journal-title>Cardiovascular Diabetology</journal-title></journal-title-group><issn pub-type="epub">1475-2840</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32156272</article-id><article-id pub-id-type="pmc">7063753</article-id><article-id pub-id-type="publisher-id">1004</article-id><article-id pub-id-type="doi">10.1186/s12933-020-01004-9</article-id><article-categories><subj-group subj-group-type="heading"><subject>Commentary</subject></subj-group></article-categories><title-group><article-title>Empagliflozin improves cardiac function in heart failure with reduced ejection fraction independent of loading conditions</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-1749-6976</contrib-id><name><surname>Liang</surname><given-names>Bo</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Yu-Xiu</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-0704-6768</contrib-id><name><surname>Gu</surname><given-names>Ning</given-names></name><address><email>20193122@njucm.edu.cn</email></address><xref ref-type="aff" rid="Aff3">3</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="GRID">grid.410745.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1765 1045</institution-id><institution>Nanjing University of Chinese Medicine,</institution></institution-wrap>Nanjing, China</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="GRID">grid.410578.f</institution-id><institution>Hospital (T.C.M.) Affiliated to Southwest Medical University,</institution></institution-wrap>Luzhou, China</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="GRID">grid.410745.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1765 1045</institution-id><institution>Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,</institution></institution-wrap>Nanjing, China</aff></contrib-group><pub-date pub-type="epub"><day>10</day><month>3</month><year>2020</year></pub-date><pub-date pub-type="pmc-release"><day>10</day><month>3</month><year>2020</year></pub-date><pub-date pub-type="collection"><year>2020</year></pub-date><volume>19</volume><elocation-id>29</elocation-id><history><date date-type="received"><day>18</day><month>2</month><year>2020</year></date><date date-type="accepted"><day>23</day><month>2</month><year>2020</year></date></history><permissions><copyright-statement>© The Author(s) 2020</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated in a credit line to the data.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">The study regarding load-independent effects of empagliflozin contribute to improved cardiac function in experimental heart failure with reduced ejection fraction is very interesting. But there are a few things we need to pay attention to.</p></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>Empagliflozin</kwd><kwd>Heart failure with reduced ejection fraction</kwd><kwd>Sodium-glucose linked cotransporter-2 inhibitor</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100001809</institution-id><institution>National Natural Science Foundation of China</institution></institution-wrap></funding-source><award-id>81774229</award-id><principal-award-recipient><name><surname>Gu</surname><given-names>Ning</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2020</meta-value></custom-meta></custom-meta-group></article-meta></front><body><p id="Par3">The present Commentary refers to the recently published article by Connelly et al. [<xref ref-type="bibr" rid="CR1">1</xref>] describing that empagliflozin contributes to improving cardiac function in experimental heart failure with reduced ejection fraction (HFrEF). EMPA-REG OUTCOME demonstrated that patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care [<xref ref-type="bibr" rid="CR2">2</xref>]. The underlying mechanisms are also being explored. It has been shown that empagliflozin improves hemodynamics in a hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes [<xref ref-type="bibr" rid="CR3">3</xref>]. Glycaemic control with empagliflozin significantly ameliorated myocardial oxidative stress injury and cardiac fibrosis in diabetic mice [<xref ref-type="bibr" rid="CR4">4</xref>]. The drug also improves primary hemodynamic parameters and attenuates the progression of atherosclerosis by reducing hyperlipidemia and hyperglycemia [<xref ref-type="bibr" rid="CR5">5</xref>] and reduces the levels of CD36 and cardiotoxic lipids while improving autophagy in the hearts of Zucker diabetic fatty rats [<xref ref-type="bibr" rid="CR6">6</xref>]. Moreover, empagliflozin improves coronary microvascular function and contractile performance in prediabetic ob/ob<sup>−/−</sup> mice [<xref ref-type="bibr" rid="CR7">7</xref>] and attenuates ischemia and reperfusion injury through LKB1/AMPK signaling pathway [<xref ref-type="bibr" rid="CR8">8</xref>]. We believe that it is important and necessary to analyze and report the potential underlying mechanism of empagliflozin for the benefit of heart failure, especially HFrEF, both load-dependent and load-independent effects. This study identified experimental HFrEF model through ligation of the left anterior descending coronary artery to induce myocardial infarction of the left ventricle to suggest that empagliflozin had major beneficial effects on the principal load-independent measures of systolic function, preload recruitable stroke work relationship and end systolic pressure volume relationship, indicating its salutary effects were, at least in part, due to actions beyond a direct effect of reduced preload and afterload [<xref ref-type="bibr" rid="CR1">1</xref>]. But there are a few things we need to pay attention to. Firstly, this study established an experimental HFrEF model after myocardial infarction. Although this post myocardial infarction model develops structural hallmarks of HFrEF [<xref ref-type="bibr" rid="CR9">9</xref>], there are many causes of HFrEF, a more ideal model of heart failure is warranted. In addition, following confirmation of infarct size with echocardiography 1-week post myocardial infarction, animals were then further randomized to receive the vehicle, or the sodium-glucose linked cotransporter-2 inhibitor, empagliflozin (20 mg/kg/day by gavage), for 6 weeks [<xref ref-type="bibr" rid="CR1">1</xref>]. Prior to randomized administration, the authors applied echocardiography only to determine the infarct size but did not confirm the structure of the heart, ejection fraction value, and other typical features and phenotypes of HFrEF. Thirdly, 20 mg/kg/day of empagliflozin was administrated, this is really too much. Remember, the dose of empagliflozin is only 10 mg or 25 mg once daily in clinical trials [<xref ref-type="bibr" rid="CR2">2</xref>, <xref ref-type="bibr" rid="CR10">10</xref>], translating less than 3 mg/kg/day for rats. Finally, this is an experimental study, that is to say, a report from nonhuman study. We need evidence from clinical trials to further confirm this.</p></body><back><glossary><title>Abbreviation</title><def-list><def-item><term>HFrEF</term><def><p id="Par2">Heart failure with reduced ejection fraction</p></def></def-item></def-list></glossary><fn-group><fn><p><bold>Publisher's Note</bold></p><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p></fn></fn-group><ack><title>Acknowledgements</title><p>We thank all scientists and participants involved in HFrEF. We would like to extend our highest thanks and respect to public health professionals and medical professionals combating COVID-19!</p></ack><notes notes-type="author-contribution"><title>Authors’ contributions</title><p>BL, YXZ and NG analyzed and interpreted the data. BL was a major contributor in writing the manuscript. NG contributed to critical revision of the manuscript. All authors contributed to data acquisition, data analysis, or data interpretation. All authors read and approved the final manuscript.</p></notes><notes notes-type="funding-information"><title>Funding</title><p>This work was funded by National Natural Science Foundation of China (81774229), Jiangsu Leading Talent Project of Traditional Chinese Medicine (Jiangsu TCM 2018 No. 4), Jiangsu Science and Technology Department Project (BK20161115), Major Project of Nanjing Medical Science and Technology Development during 13th Five-year Plan (ZDX16013), and Jiangsu Universities Nursing Advantage Discipline Project (2019YSHL095).</p></notes><notes notes-type="data-availability"><title>Availability of data and materials</title><p>Not applicable.</p></notes><notes><title>Ethics approval and consent to participate</title><p id="Par4">Not applicable.</p></notes><notes><title>Consent for publication</title><p id="Par5">Not applicable.</p></notes><notes notes-type="COI-statement"><title>Competing interests</title><p id="Par6">The authors declare that they have no competing 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