{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:23:37Z","timestamp":1790000617355,"version":"4.0.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":344,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Sodium\u2013glucose cotransporter 2 inhibitors (SGLT2i) improve cardiac performance and clinical outcomes in patients with heart failure, yet mechanisms underlying these beneficial effects remain incompletely understood. We sought to determine whether SGLT2i-induced improvements in cardiac function are dependent on increased cardiac oxidation of ketone bodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We employed a mouse model with a cardiac-specific knock-out of the enzyme D-\u03b2-hydroxybutyrate dehydrogenase-1 (BDH1cko), rendering mice incapable of oxidizing the principal ketone body \u03b2-hydroxybutyrate in cardiomyocytes. Male BDH1cko and littermate controls underwent either permanent coronary artery ligation of the left anterior descending coronary artery to induce myocardial infarction (MI) or sham surgery. Two weeks after surgery, mice were randomized to 6\u2009weeks of empagliflozin or vehicle treatment. Cardiac function was assessed using transthoracic echocardiography before and after treatment, and histological and molecular analyses were performed after sacrifice. Empagliflozin treatment resulted in a twofold increase in circulating ketone bodies. Mean infarct size (36\u2009\u00b1\u20094% of the left ventricle) was comparable among MI groups. In control mice, empagliflozin treatment resulted in a significant increase in left ventricular ejection fraction (LVEF) whereas LVEF remained stable in the vehicle treated group (\u0394LVEF \u22121.1\u2009\u00b1\u20092.2% vs. 5.2\u2009\u00b1\u20091.5%, p\u2009&amp;lt;\u20090.05). Empagliflozin did not influence cardiac contractility in BDH1cko mice (\u0394LVEF \u22125.9\u2009\u00b1\u20092.1% vs. \u22121.5\u2009\u00b1\u20092.8%, p\u2009=\u20090.213). Other echocardiographic, histological and molecular signatures of adverse myocardial remodelling were not affected by empagliflozin treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The beneficial effects of empagliflozin on cardiac contractility in post-MI heart failure are attenuated in mice which are incapable of oxidizing the ketone body \u03b2-hydroxybutyrate in their hearts. These findings suggest that enhanced cardiac ketone body oxidation contributes to the cardioprotective effects of SGLT2i.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3633","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T02:34:25Z","timestamp":1741746865000},"page":"1353-1358","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Myocardial Ketone Body Oxidation Contributes to Empagliflozin-Induced Improvements in Cardiac Contractility in Murine Heart Failure"],"prefix":"10.1093","volume":"27","author":[{"given":"Suzanne Nathalie","family":"Voorrips","sequence":"first","affiliation":[{"name":"University Medical Center Groningen, Department of Cardiology, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6044-1299","authenticated-orcid":false,"given":"Constantin Laurent","family":"Palm","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Department of Cardiology, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huitzilihuitl","family":"Saucedo-Orozco","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Department of Cardiology, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belend","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Department of Cardiology, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth Marloes","family":"Schouten","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Department of Cardiology, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Feringa","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Department of Cardiology, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo I.","family":"Sanchez-Aguilera","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Department of Cardiology, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten T.","family":"Nijholt","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Department of Cardiology, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salva R.","family":"Yurista","sequence":"additional","affiliation":[{"name":"Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital \u2013 Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Meer","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Department of Cardiology, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman H.W.","family":"Sillj\u00e9","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Department of Cardiology, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1362-7019","authenticated-orcid":false,"given":"B. 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