{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T23:31:25Z","timestamp":1789255885776,"version":"build-2803163510"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":1689,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005357","name":"APVV","doi-asserted-by":"publisher","award":["15-0029"],"award-info":[{"award-number":["15-0029"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006109","name":"VEGA","doi-asserted-by":"publisher","award":["2\/0001\/17"],"award-info":[{"award-number":["2\/0001\/17"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["098436\/Z\/12\/B"],"award-info":[{"award-number":["098436\/Z\/12\/B"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["221805\/Z\/20\/Z"],"award-info":[{"award-number":["221805\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oxford National Institute for Health Research Biomedical Research Centre"},{"name":"Oxford British Heart Foundation Centre of Research Excellence"},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005357","name":"Agent\u00fara na Podporu V\u00fdskumu a V\u00fdvoja","doi-asserted-by":"publisher","award":["15\u20100029"],"award-info":[{"award-number":["15\u20100029"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006109","name":"Vedeck\u00e1 Grantov\u00e1 Agent\u00fara M\u0160VVa\u0160 SR a SAV","doi-asserted-by":"publisher","award":["2\/0001\/17"],"award-info":[{"award-number":["2\/0001\/17"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["098436\/Z\/12\/B"],"award-info":[{"award-number":["098436\/Z\/12\/B"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["221805\/Z\/20\/Z"],"award-info":[{"award-number":["221805\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Despite substantial improvements over the last three decades, heart failure (HF) remains associated with a poor prognosis. The sodium-glucose co-transporter-2 inhibitor empagliflozin demonstrated significant reductions of HF hospitalization in patients with HF independent of the presence or absence of type 2 diabetes mellitus in the EMPEROR-Reduced trial and cardiovascular mortality in the EMPA-REG OUTCOME trial. To further elucidate the mechanisms behind these positive outcomes, this study aims to determine the effects of empagliflozin treatment on cardiac energy metabolism and physiology using magnetic resonance spectroscopy (MRS) and cardiovascular magnetic resonance (CMR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The EMPA-VISION trial is a double-blind, randomized, placebo-controlled, mechanistic study. A maximum of 86 patients with HF with reduced ejection fraction (n = 43, Cohort A) or preserved ejection fraction (n = 43, Cohort B), with or without type 2 diabetes mellitus, will be enrolled. Participants will be randomized 1:1 to receive either 10 mg of empagliflozin or placebo for 12 weeks. Eligible patients will undergo cardiovascular magnetic resonance, resting and dobutamine stress MRS, echocardiograms, cardiopulmonary exercise tests, serum metabolomics, and quality of life questionnaires at baseline and after 12 weeks. The primary endpoint will be the change in resting phosphocreatine-to-adenosine triphosphate ratio, as measured by 31Phosphorus-MRS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EMPA-VISION is the first clinical trial assessing the effects of empagliflozin treatment on cardiac energy metabolism in human subjects in vivo. The results will shed light on the mechanistic action of empagliflozin in patients with HF and help to explain the results of the safety and efficacy outcome trials (EMPEROR-Reduced and EMPEROR-Preserved).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13406","type":"journal-article","created":{"date-parts":[[2021,5,8]],"date-time":"2021-05-08T11:48:28Z","timestamp":1620474508000},"page":"2580-2590","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Design and Rationale of the EMPA-VISION Trial: Investigating the Metabolic Effects of Empagliflozin in Patients with Heart Failure"],"prefix":"10.1093","volume":"8","author":[{"given":"Moritz J.","family":"Hundertmark","sequence":"first","affiliation":[{"name":"Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital , Headley Way, Oxford, OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olorunsola F.","family":"Agbaje","sequence":"additional","affiliation":[{"name":"Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Coleman","sequence":"additional","affiliation":[{"name":"Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyothis T.","family":"George","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmBH , Ingelheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Grempler","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach an der Riss ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rury R.","family":"Holman","sequence":"additional","affiliation":[{"name":"Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford , Oxford ,","place":["UK"]},{"name":"Oxford NIHR Biomedical Research Centre, Oxford University Hospitals , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan","family":"Lamlum","sequence":"additional","affiliation":[{"name":"Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital , Headley Way, Oxford, OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmBH , Ingelheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne E.","family":"Milton","sequence":"additional","affiliation":[{"name":"Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko G.","family":"Niessen","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach an der Riss ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Rider","sequence":"additional","affiliation":[{"name":"Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital , Headley Way, Oxford, OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher T.","family":"Rodgers","sequence":"additional","affiliation":[{"name":"Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital , Headley Way, Oxford, OX3 9DU ,","place":["UK"]},{"name":"Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, Cambridge Biomedical Campus , Cambridge ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladislav","family":"Valkovi\u010d","sequence":"additional","affiliation":[{"name":"Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital , Headley Way, Oxford, OX3 9DU ,","place":["UK"]},{"name":"Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences , Bratislava ,","place":["Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Wicks","sequence":"additional","affiliation":[{"name":"John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masliza","family":"Mahmod","sequence":"additional","affiliation":[{"name":"Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital , Headley Way, Oxford, OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Neubauer","sequence":"additional","affiliation":[{"name":"Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital , Headley Way, Oxford, OX3 9DU ,","place":["UK"]},{"name":"Oxford NIHR Biomedical Research Centre, Oxford University Hospitals , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"2026012114210172400_ehf213406-bib-0001","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.jacc.2017.04.025","article-title":"2017 ACC\/AHA\/HFSA focused update of the 2013 ACCF\/AHA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America","volume":"70","author":"Yancy","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0002","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur Heart J"},{"key":"2026012114210172400_ehf213406-bib-0003","doi-asserted-by":"crossref","first-page":"7","DOI":"10.15420\/cfr.2016:25:2","article-title":"Global public health burden of heart failure","volume":"3","author":"Savarese","year":"2017","journal-title":"Card Fail Rev"},{"key":"2026012114210172400_ehf213406-bib-0004","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.ijcard.2013.12.028","article-title":"The annual global economic burden of heart failure","volume":"171","author":"Cook","year":"2014","journal-title":"Int J Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0005","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1001\/jama.296.18.2209","article-title":"Systolic and diastolic heart failure in the community","volume":"296","author":"Bursi","year":"2006","journal-title":"JAMA"},{"key":"2026012114210172400_ehf213406-bib-0006","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1093\/eurheartj\/eht066","article-title":"Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND","volume":"34","author":"Brouwers","year":"2013","journal-title":"Eur Heart J"},{"key":"2026012114210172400_ehf213406-bib-0007","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart Disease and Stroke Statistics\u20142019 update: a report from the American Heart Association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0008","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1161\/CIRCULATIONAHA.111.080770","article-title":"Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes","volume":"126","author":"Steinberg","year":"2012","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0009","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1136\/hrt.2008.156646","article-title":"Elevated glycated haemoglobin is a strong predictor of mortality in patients with left ventricular systolic dysfunction who are not receiving treatment for diabetes mellitus","volume":"95","author":"Goode","year":"2009","journal-title":"Heart"},{"key":"2026012114210172400_ehf213406-bib-0010","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.hfc.2012.06.005","article-title":"Insulin resistance and heart failure: molecular mechanisms","volume":"8","author":"Aroor","year":"2012","journal-title":"Heart Fail Clin"},{"key":"2026012114210172400_ehf213406-bib-0011","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1463-1326.2011.01517.x","article-title":"Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors","volume":"14","author":"Grempler","year":"2012","journal-title":"Diabetes Obes Metab"},{"key":"2026012114210172400_ehf213406-bib-0012","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N Engl J Med"},{"key":"2026012114210172400_ehf213406-bib-0013","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1056\/NEJMoa2022190","article-title":"Cardiovascular and renal outcomes with empagliflozin in heart failure","volume":"383","author":"Packer","year":"2020","journal-title":"N Engl J Med"},{"key":"2026012114210172400_ehf213406-bib-0014","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa1911303","article-title":"Dapagliflozin in patients with heart failure and reduced ejection fraction","volume":"381","author":"McMurray","year":"2019","journal-title":"N Engl J Med"},{"key":"2026012114210172400_ehf213406-bib-0015","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa2030183","article-title":"Sotagliflozin in patients with diabetes and recent worsening heart failure","volume":"384","author":"Bhatt","year":"2021","journal-title":"N Engl J Med"},{"key":"2026012114210172400_ehf213406-bib-0016","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1161\/CIRCULATIONAHA.118.034222","article-title":"Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS Program (Canagliflozin Cardiovascular Assessment Study)","volume":"138","author":"Radholm","year":"2018","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0017","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1161\/CIRCULATIONAHA.120.050255","article-title":"Efficacy of ertugliflozin on heart failure-related events in patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease: results of the VERTIS CV trial","volume":"142","author":"Cosentino","year":"2020","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0018","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s12933-019-0938-6","article-title":"Lessons learned from the DAPA-HF trial concerning the mechanisms of benefit of SGLT2 inhibitors on heart failure events in the context of other large-scale trials nearing completion","volume":"18","author":"Packer","year":"2019","journal-title":"Cardiovasc Diabetol"},{"key":"2026012114210172400_ehf213406-bib-0019","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0140-6736(20)31824-9","article-title":"SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials","volume":"396","author":"Zannad","year":"2020","journal-title":"Lancet"},{"key":"2026012114210172400_ehf213406-bib-0020","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1161\/CIRCULATIONAHA.120.052186","article-title":"Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF)","volume":"143","author":"Lee","year":"2021","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0021","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jacc.2020.11.008","article-title":"Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction","volume":"77","author":"Santos-Gallego","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0022","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1161\/CIRCULATIONAHA.107.702795","article-title":"Metabolic mechanisms in heart failure","volume":"116","author":"Ashrafian","year":"2007","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0023","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1056\/NEJMra063052","article-title":"The failing heart\u2014an engine out of fuel","volume":"356","author":"Neubauer","year":"2007","journal-title":"N Engl J Med"},{"key":"2026012114210172400_ehf213406-bib-0024","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s11906-006-0023-x","article-title":"On the hypothesis that the failing heart is energy starved: lessons learned from the metabolism of ATP and creatine","volume":"8","author":"Ingwall","year":"2006","journal-title":"Curr Hypertens Rep"},{"key":"2026012114210172400_ehf213406-bib-0025","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1161\/CIR.0b013e31829b5b44","article-title":"Exercise standards for testing and training: a scientific statement from the American Heart Association","volume":"128","author":"Fletcher","year":"2013","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0026","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1093\/eurheartj\/ehv442","article-title":"Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus","volume":"37","author":"Levelt","year":"2016","journal-title":"Eur Heart J"},{"key":"2026012114210172400_ehf213406-bib-0027","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jchf.2014.09.009","article-title":"Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy","volume":"3","author":"Beadle","year":"2015","journal-title":"JACC Heart Fail"},{"key":"2026012114210172400_ehf213406-bib-0028","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1093\/eurheartj\/ehi816","article-title":"Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine\/adenosine triphosphate ratio in patients with heart failure","volume":"27","author":"Fragasso","year":"2006","journal-title":"Eur Heart J"},{"key":"2026012114210172400_ehf213406-bib-0029","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and cardiovascular and renal events in type 2 diabetes","volume":"377","author":"Neal","year":"2017","journal-title":"N Engl J Med"},{"key":"2026012114210172400_ehf213406-bib-0030","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1056\/NEJMoa1812389","article-title":"Dapagliflozin and cardiovascular outcomes in type 2 diabetes","volume":"380","author":"Wiviott","year":"2019","journal-title":"N Engl J Med"},{"key":"2026012114210172400_ehf213406-bib-0031","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.jacc.2015.03.016","article-title":"Cardiovascular drug development: is it dead or just hibernating?","volume":"65","author":"Fordyce","year":"2015","journal-title":"J Am Coll Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0032","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1016\/j.jacc.2020.10.026","article-title":"Understanding the mechanistic benefit of heart failure drugs matters","volume":"76","author":"Januzzi","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0033","doi-asserted-by":"crossref","DOI":"10.1001\/jamacardio.2020.7585","article-title":"Time to clinical benefit of dapagliflozin and significance of prior heart failure hospitalization in patients with heart failure with reduced ejection fraction","author":"Berg","year":"2021","journal-title":"JAMA Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0034","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jacbts.2016.11.009","article-title":"Metabolic origins of heart failure","volume":"2","author":"Wende","year":"2017","journal-title":"JACC Basic Transl Sci"},{"key":"2026012114210172400_ehf213406-bib-0035","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1161\/01.CIR.96.7.2190","article-title":"Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy","volume":"96","author":"Neubauer","year":"1997","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0036","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1161\/01.CIR.94.8.1894","article-title":"Creatine kinase system in failing and nonfailing human myocardium","volume":"94","author":"Nascimben","year":"1996","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0037","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12933-018-0717-9","article-title":"Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes","volume":"17","author":"Matsutani","year":"2018","journal-title":"Cardiovasc Diabetol"},{"key":"2026012114210172400_ehf213406-bib-0038","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s12933-018-0775-z","article-title":"Impact of dapagliflozin on left ventricular diastolic function of patients with type 2 diabetic mellitus with chronic heart failure","volume":"17","author":"Soga","year":"2018","journal-title":"Cardiovasc Diabetol"},{"key":"2026012114210172400_ehf213406-bib-0039","doi-asserted-by":"crossref","first-page":"e212","DOI":"10.2337\/dc16-1312","article-title":"Effect of empagliflozin on left ventricular mass and diastolic function in individuals with diabetes: an important clue to the EMPA-REG OUTCOME trial?","volume":"39","author":"Verma","year":"2016","journal-title":"Diabetes Care"},{"key":"2026012114210172400_ehf213406-bib-0040","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1161\/CIRCULATIONAHA.119.040057","article-title":"Effects of canagliflozin on heart failure outcomes associated with preserved and reduced ejection fraction in type 2 diabetes mellitus","volume":"139","author":"Figtree","year":"2019","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0041","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1161\/CIRCULATIONAHA.119.040130","article-title":"Effect of dapagliflozin on heart failure and mortality in type 2 diabetes mellitus","volume":"139","author":"Kato","year":"2019","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0042","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1161\/01.CIR.99.17.2261","article-title":"Diastolic dysfunction in hypertensive heart disease is associated with altered myocardial metabolism","volume":"99","author":"Lamb","year":"1999","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0043","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.jacc.2009.05.012","article-title":"Heart failure with preserved ejection fraction is characterized by dynamic impairment of active relaxation and contraction of the left ventricle on exercise and associated with myocardial energy deficiency","volume":"54","author":"Phan","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0044","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1161\/01.CIR.86.6.1810","article-title":"31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure","volume":"86","author":"Neubauer","year":"1992","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0045","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/j.1472-8206.2012.01029.x","article-title":"Beneficial effects of beta-blockers on left ventricular function and cellular energy reserve in patients with heart failure","volume":"27","author":"Spoladore","year":"2013","journal-title":"Fundam Clin Pharmacol"},{"key":"2026012114210172400_ehf213406-bib-0046","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.jacc.2006.03.060","article-title":"A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure","volume":"48","author":"Fragasso","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0047","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1042\/cs0990027","article-title":"First clinical trial with etomoxir in patients with chronic congestive heart failure","volume":"99","author":"Schmidt-Schweda","year":"2000","journal-title":"Clin Sci (Lond)"},{"key":"2026012114210172400_ehf213406-bib-0048","first-page":"1843","article-title":"Single dose of empagliflozin increases in vivo cardiac energy status in diabetic db\/db mice","volume":"114","author":"Abdurrachim","year":"2018","journal-title":"Cardiovasc Res"},{"key":"2026012114210172400_ehf213406-bib-0049","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.2337\/dc16-0330","article-title":"CV protection in the EMPA-REG OUTCOME trial: a \u201cthrifty substrate\u201d hypothesis","volume":"39","author":"Ferrannini","year":"2016","journal-title":"Diabetes Care"},{"key":"2026012114210172400_ehf213406-bib-0050","first-page":"149","article-title":"Ketoacids? Good medicine?","volume":"114","author":"Cahill","year":"2003","journal-title":"Trans Am Clin Climatol Assoc"},{"key":"2026012114210172400_ehf213406-bib-0051","doi-asserted-by":"crossref","DOI":"10.1093\/eurheartj\/ehy563.P3193","article-title":"The ketone body 3-hydroxybutyrate increases cardiac output without affecting myocardial external efficiency","volume":"39","author":"Nielsen","year":"2018","journal-title":"Eur Heart J"},{"key":"2026012114210172400_ehf213406-bib-0052","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/S0735-1097(18)31215-4","article-title":"Empagliflozin induces a myocardial metabolic shift from glucose consumption to ketone metabolism that mitigates adverse cardiac remodeling and improves myocardial contractility","volume":"71","author":"Santos-Gallego","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0053","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.cmet.2016.07.018","article-title":"Empagliflozin's fuel hypothesis: not so soon","volume":"24","author":"Lopaschuk","year":"2016","journal-title":"Cell Metab"},{"key":"2026012114210172400_ehf213406-bib-0054","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1007\/BF01908203","article-title":"Ketone bodies maintain normal cardiac function and myocardial high energy phosphates during insulin-induced hypoglycemia in vivo","volume":"84","author":"Bruer","year":"1989","journal-title":"Basic Res Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0055","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1161\/CIRCRESAHA.116.310078","article-title":"Evolving concepts of myocardial energy metabolism: more than just fats and carbohydrates","volume":"119","author":"Lopaschuk","year":"2016","journal-title":"Circ Res"},{"key":"2026012114210172400_ehf213406-bib-0056","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1161\/CIRCULATIONAHA.117.029166","article-title":"Effect of empagliflozin on the metabolic signature of patients with type 2 diabetes mellitus and cardiovascular disease","volume":"136","author":"Kappel","year":"2017","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0057","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/cvr\/cvq240","article-title":"Mitochondria in heart failure","volume":"88","author":"Rosca","year":"2010","journal-title":"Cardiovasc Res"},{"key":"2026012114210172400_ehf213406-bib-0058","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1007\/s00125-017-4509-7","article-title":"Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+\/H+ exchanger, lowering of cytosolic Na+ and vasodilation","volume":"61","author":"Uthman","year":"2018","journal-title":"Diabetologia"},{"key":"2026012114210172400_ehf213406-bib-0059","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.jchf.2017.07.009","article-title":"Targeted metabolomic profiling of plasma and survival in heart failure patients","volume":"5","author":"Lanfear","year":"2017","journal-title":"JACC Heart Fail"},{"key":"2026012114210172400_ehf213406-bib-0060","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0124844","article-title":"Metabolomic fingerprint of heart failure with preserved ejection fraction","volume":"10","author":"Zordoky","year":"2015","journal-title":"PLoS ONE"},{"key":"2026012114210172400_ehf213406-bib-0061","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1093\/eurheartj\/ehaa270","article-title":"Omics phenotyping in heart failure: the next frontier","volume":"41","author":"Bayes-Genis","year":"2020","journal-title":"Eur Heart J"},{"key":"2026012114210172400_ehf213406-bib-0062","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1161\/01.CIR.99.9.1173","article-title":"Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical outcome","volume":"99","author":"Belardinelli","year":"1999","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0063","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1161\/CIRCULATIONAHA.109.934059","article-title":"Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy","volume":"122","author":"Abozguia","year":"2010","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0064","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1093\/eurheartj\/ehaa943","article-title":"Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes","volume":"42","author":"Abraham","year":"2021","journal-title":"Eur Heart J"},{"key":"2026012114210172400_ehf213406-bib-0065","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1161\/CIRCULATIONAHA.119.042929","article-title":"Dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction: the DEFINE-HF trial","volume":"140","author":"Nassif","year":"2019","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0066","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1093\/eurheartj\/ehaa1007","article-title":"Empagliflozin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: the EMPEROR-Reduced trial","volume":"42","author":"Butler","year":"2021","journal-title":"Eur Heart J"},{"key":"2026012114210172400_ehf213406-bib-0067","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1161\/CIRCULATIONAHA.119.044138","article-title":"Effects of dapagliflozin on symptoms, function, and quality of life in patients with heart failure and reduced ejection fraction: results from the DAPA-HF trial","volume":"141","author":"Kosiborod","year":"2020","journal-title":"Circulation"},{"key":"2026012114210172400_ehf213406-bib-0068","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ahj.2011.09.027","article-title":"Relationships between changes in patient-reported health status and functional capacity in outpatients with heart failure","volume":"163","author":"Flynn","year":"2012","journal-title":"Am Heart J"},{"key":"2026012114210172400_ehf213406-bib-0069","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0218153","article-title":"Metabolic modulation predicts heart failure tests performance","volume":"14","author":"Contaifer","year":"2019","journal-title":"PLoS ONE"},{"key":"2026012114210172400_ehf213406-bib-0070","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/clc.22899","article-title":"Early effects of empagliflozin on exercise tolerance in patients with heart failure: a pilot study","volume":"41","author":"Nunez","year":"2018","journal-title":"Clin Cardiol"},{"key":"2026012114210172400_ehf213406-bib-0071","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1002\/ejhf.1596","article-title":"Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial","volume":"21","author":"Anker","year":"2019","journal-title":"Eur J Heart Fail"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ehf2.13406","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ehf2.13406","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/8\/4\/2580\/65569470\/eschf_8_4_2580.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/8\/4\/2580\/65569470\/eschf_8_4_2580.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T19:25:43Z","timestamp":1769023543000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/8\/4\/2580\/8344352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,6]]},"references-count":71,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,5,6]]},"published-print":{"date-parts":[[2021,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.13406","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,8]]},"published":{"date-parts":[[2021,5,6]]},"assertion":[{"value":"2020-10-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}