{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:56:23Z","timestamp":1790085383021,"version":"4.0.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,1,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Oral treatment with the exogenous ketone body 3\u2010hydroxybutyrate improves cardiac function in patients with heart failure with reduced ejection fraction, but ketosis is limited to 3 to 4\u2009hours. Treatment with (R)\u20101,3\u2010butanediol (BD) provides prolonged ketosis in healthy controls, but the hemodynamic and metabolic profile is unexplored in patients with heart failure with reduced ejection fraction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              This was a randomized, single\u2010blind, placebo\u2010controlled, crossover study. Transthoracic echocardiography and venous blood samples were performed at baseline and hourly for 6\u2009hours after an oral dose of BD (0.5\u2009g\/kg) or taste\u2010matched placebo. The primary end point was the average between\u2010treatment difference in cardiac output during the 6\u2010hour period after intake. Secondary end points were stroke volume, heart rate, left ventricular ejection fraction, circulating 3\u2010hydroxybutyrate, and free fatty acids. Twelve patients with heart failure with reduced ejection fraction were included. BD treatment provided significant increase in circulating 3\u2010hydroxybutyrate by 1400\u2009\u03bcmol\/L (95% CI, 1262\u20131538\u2009\u03bcmol\/L,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and increased cardiac output by 0.9\u2009L\/min (95% CI, 0.7\u20131.1\u2009L\/min,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) compared with placebo. Stroke volume increased by 15\u2009mL (95% CI, 11\u201319\u2009mL,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), and heart rate remained similar between treatments (\n              <jats:italic>P<\/jats:italic>\n              =0.150). Left ventricular ejection fraction increased by 3 percentage points (95% CI, 1\u20134 percentage points,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Global longitudinal strain improved (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Left ventricular contractility estimates increased after BD intake, and parameters of afterload were reduced. Finally, free fatty acids and glucose levels decreased.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Oral dosing of BD led to prolonged ketosis and cardiovascular and metabolic benefits in patients with heart failure with reduced ejection fraction. Treatment with BD is an attractive option to achieve beneficial effects from sustained therapeutic ketosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\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: NCT05768100.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.038461","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T03:59:11Z","timestamp":1735099151000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Cardiovascular and Metabolic Effects of Modulating Circulating Ketone Bodies With 1,3\u2010Butanediol in Patients With Heart Failure 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Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian Hylleberg","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1009-3768","authenticated-orcid":false,"given":"Oskar Kj\u00e6rgaard","family":"H\u00f8rsdal","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9228-3869","authenticated-orcid":false,"given":"Roni","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital 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