{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T07:27:26Z","timestamp":1782458846591,"version":"3.54.5"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Patients with heart failure (HF) have a high burden of symptoms and physical limitations, regardless of ejection fraction (EF). Whether the benefits of SGLT2 (sodium-glucose cotransporter-2) inhibitors on these outcomes vary across the full range of EF remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Patient-level data were pooled from the DEFINE-HF trial (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction) of 263 participants with reduced EF (\u226440%), and PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure) of 324 participants with preserved EF (\u226545%). Both were randomized, double-blind 12-week trials of dapagliflozin versus placebo, recruiting participants with New York Heart Association class II or higher and elevated natriuretic peptides. The effect of dapagliflozin on the change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) at 12 weeks was tested with ANCOVA adjusted for sex, baseline KCCQ, EF, atrial fibrillation, estimated glomerular filtration rate, and type 2 diabetes. Interaction of dapagliflozin effects on KCCQ-CSS by EF was assessed using EF both categorically and continuously with restricted cubic spline. Responder analyses, examining proportions of patients with deterioration, and clinically meaningful improvements in KCCQ-CSS were conducted using logistic regression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Of 587 patients randomized (293 dapagliflozin, 294 placebo), EF was \u226440, &gt;40-\u226460, and &gt;60% in 262 (45%), 199 (34%), and 126 (21%), respectively. Dapagliflozin improved KCCQ-CSS at 12 weeks (placebo-adjusted difference 5.0 points [95% CI, 2.6\u20137.5];\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). This was consistent in participants with EF\u226440 (4.6 points [95% CI, 1.0\u20138.1];\n              <jats:italic>P<\/jats:italic>\n              =0.01), &gt;40 to \u226460 (4.9 points [95% CI, 0.8\u20139.0];\n              <jats:italic>P<\/jats:italic>\n              =0.02) and &gt;60% (6.8 points [95% CI, 1.5\u201312.1];\n              <jats:italic>P<\/jats:italic>\n              =0.01;\n              <jats:italic>P<\/jats:italic>\n              <jats:sub>interaction<\/jats:sub>\n              =0.79). Benefits of dapagliflozin on KCCQ-CSS were also consistent when analyzing EF continuously (\n              <jats:italic>P<\/jats:italic>\n              <jats:sub>interaction<\/jats:sub>\n              =0.94). In responder analyses, fewer dapagliflozin-treated patients had deterioration and more had small, moderate, and large KCCQ-CSS improvements versus placebo; these results were also consistent regardless of EF (all\n              <jats:italic>P<\/jats:italic>\n              <jats:sub>interaction<\/jats:sub>\n              values nonsignificant).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>In patients with HF, dapagliflozin significantly improves symptoms and physical limitations after 12 weeks of treatment, with consistent and clinically meaningful benefits across the full range of EF.<\/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 identifiers: NCT02653482 and NCT03030235.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.122.009837","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T09:00:42Z","timestamp":1684486842000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Dapagliflozin Improves Heart Failure Symptoms and Physical Limitations Across the Full Range of Ejection Fraction: Pooled Patient-Level Analysis From DEFINE-HF and PRESERVED-HF Trials"],"prefix":"10.1161","volume":"16","author":[{"given":"Michael E.","family":"Nassif","sequence":"first","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute, Kansas City, MO (M.E.N., S.L.W., K.G., B.A.A., T.K., M.N.K.)."},{"name":"University of Missouri-Kansas City (M.E.N., B.A.A., T.K., M.N.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0909-4309","authenticated-orcid":true,"given":"Sheryl L.","family":"Windsor","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute, Kansas City, MO (M.E.N., S.L.W., K.G., B.A.A., T.K., M.N.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2934-6913","authenticated-orcid":true,"given":"Kensey","family":"Gosch","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute, Kansas City, MO (M.E.N., S.L.W., K.G., B.A.A., T.K., M.N.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-0596","authenticated-orcid":true,"given":"Barry A.","family":"Borlaug","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute, Kansas City, MO (M.E.N., S.L.W., K.G., B.A.A., T.K., M.N.K.)."},{"name":"University of Missouri-Kansas City (M.E.N., B.A.A., T.K., M.N.K.)."},{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-6739","authenticated-orcid":true,"given":"Mansoor","family":"Husain","sequence":"additional","affiliation":[{"name":"Ted Rogers Centre for Heart Research, Peter Munk Cardiac Centre, University of Toronto, ON, Canada (M.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1254-6636","authenticated-orcid":true,"given":"Silvio E.","family":"Inzucchi","sequence":"additional","affiliation":[{"name":"Yale School of Medicine, New Haven, CT (S.E.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalane W.","family":"Kitzman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Sections on Cardiovascular Medicine and Geriatrics, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6412-7989","authenticated-orcid":true,"given":"Darren K.","family":"McGuire","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas (D.K.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"University of Michigan School of Medicine, Ann Arbor (B.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7093-7048","authenticated-orcid":true,"given":"Benjamin M.","family":"Scirica","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (B.M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5655-8201","authenticated-orcid":true,"given":"Sanjiv J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Umpierrez","sequence":"additional","affiliation":[{"name":"Emory University, Atlanta, GA (G.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0176-8471","authenticated-orcid":true,"given":"Bethany A.","family":"Austin","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute, Kansas City, MO (M.E.N., S.L.W., K.G., B.A.A., T.K., 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