{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:32:35Z","timestamp":1791513155168,"version":"4.3.4"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2023,5,30]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Sodium\u2013glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production. The authors aimed to investigate whether treatment with empagliflozin leads to changes in myocardial energetics, serum metabolomics, and cardiorespiratory fitness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>EMPA-VISION (Assessment of Cardiac Energy Metabolism, Function and Physiology in Patients With Heart Failure Taking Empagliflozin) is a prospective, randomized, double-blind, placebo-controlled, mechanistic trial that enrolled 72 symptomatic patients with chronic HF with reduced ejection fraction (HFrEF; n=36; left ventricular ejection fraction \u226440%; New York Heart Association class \u2265II; NT-proBNP [N-terminal pro-B-type natriuretic peptide] \u2265125 pg\/mL) and HF with preserved ejection fraction (HFpEF; n=36; left ventricular ejection fraction \u226550%; New York Heart Association class \u2265II; NT-proBNP \u2265125 pg\/mL). Patients were stratified into respective cohorts (HFrEF versus HFpEF) and randomly assigned to empagliflozin (10 mg; n=35: 17 HFrEF and 18 HFpEF) or placebo (n=37: 19 HFrEF and 18 HFpEF) once daily for 12 weeks. The primary end point was a change in the cardiac phosphocreatine:ATP ratio (PCr\/ATP) from baseline to week 12, determined by phosphorus magnetic resonance spectroscopy at rest and during peak dobutamine stress (65% of age-maximum heart rate). Mass spectrometry on a targeted set of 19 metabolites was performed at baseline and after treatment. Other exploratory end points were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Empagliflozin treatment did not change cardiac energetics (ie, PCr\/ATP) at rest in HFrEF (adjusted mean treatment difference [empagliflozin \u2013 placebo], \u20130.25 [95% CI, \u20130.58 to 0.09];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.14) or HFpEF (adjusted mean treatment difference, \u20130.16 [95% CI, \u20130.60 to 0.29];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.47]. Likewise, there were no changes in PCr\/ATP during dobutamine stress in HFrEF (adjusted mean treatment difference, \u20130.13 [95% CI, \u20130.35 to 0.09];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.23) or HFpEF (adjusted mean treatment difference, \u20130.22 [95% CI, \u20130.66 to 0.23];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.32). No changes in serum metabolomics or levels of circulating ketone bodies were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In patients with either HFrEF or HFpEF, treatment with 10 mg of empagliflozin once daily for 12 weeks did not improve cardiac energetics or change circulating serum metabolites associated with energy metabolism when compared with placebo. Based on our results, it is unlikely that enhancing cardiac energy metabolism mediates the beneficial effects of SGLT2i in HF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT03332212.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.122.062021","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T05:01:09Z","timestamp":1681794069000},"page":"1654-1669","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":121,"title":["Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin: The Randomized, Controlled EMPA-VISION Trial"],"prefix":"10.1161","volume":"147","clinical-trial-number":[{"clinical-trial-number":"nct03332212","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5475-7987","authenticated-orcid":true,"given":"Moritz J.","family":"Hundertmark","sequence":"first","affiliation":[{"name":"Oxford Centre for Clinical Magnetic Resonance Research (M.J.H., H.L., S.M., F.E.M., B.R., O.R., C.T.R., L.V., M.M., S.N.), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, UK."},{"name":"Department of Internal Medicine I, University Hospital Wuerzburg, Germany (M.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2797-3385","authenticated-orcid":true,"given":"Amanda","family":"Adler","sequence":"additional","affiliation":[{"name":"Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine (A.A., R.C., R.R.H., J.E.M.), University of Oxford, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6983-5423","authenticated-orcid":true,"given":"Charalambos","family":"Antoniades","sequence":"additional","affiliation":[{"name":"Acute Multidisciplinary Imaging and Interventional Centre (C.A., S.N.), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5194-8550","authenticated-orcid":true,"given":"Ruth","family":"Coleman","sequence":"additional","affiliation":[{"name":"Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine (A.A., R.C., R.R.H., J.E.M.), University of Oxford, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1336-7744","authenticated-orcid":true,"given":"Julian L.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH, Ingelheim, Germany (J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1256-874X","authenticated-orcid":true,"given":"Rury R.","family":"Holman","sequence":"additional","affiliation":[{"name":"Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine (A.A., R.C., R.R.H., J.E.M.), University of Oxford, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan","family":"Lamlum","sequence":"additional","affiliation":[{"name":"Oxford Centre for Clinical Magnetic Resonance Research (M.J.H., H.L., S.M., F.E.M., B.R., O.R., C.T.R., L.V., M.M., S.N.), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisoo","family":"Lee","sequence":"additional","affiliation":[{"name":"John Radcliffe Hospital, Oxford University Hospitals National Health Service Foundation Trust, UK (J.L., E.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Massey","sequence":"additional","affiliation":[{"name":"Elderbrook Solutions GmbH on behalf of Boehringer Ingelheim Pharma GmbH and Co. 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