{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:56:54Z","timestamp":1787590614708,"version":"build-2736575974"},"reference-count":122,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A decline in mortality due to heart failure (HF) with reduced ejection fraction (HFrEF) has been attributed to effective guideline-directed medical therapies. But few effective therapies are available for HF with preserved ejection fraction (HFpEF), despite a high burden of HF events, or for HF with mildly reduced ejection fraction (HFmrEF). Novel therapies are needed for these HF subtypes.<\/jats:p>\n                  <jats:p>Clinical trials have demonstrated the efficacy of sodium\u2013glucose cotransporter 2 inhibitors for improving outcomes in HFpEF and HFmrEF. While renin\u2013angiotensin system inhibitors, angiotensin receptor\/neprilysin inhibitors, and steroidal mineralocorticoid receptor antagonists for HFpEF or HFmrEF have not demonstrated effects on primary trial outcomes, sub-analyses from large HF trials suggest they may reduce the risk of hospitalization for HF or mortality. Beta blockers may be beneficial for HFmrEF. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduced HF events and cardiovascular deaths in participants with HF and ejection fraction \u226540% in the FINEARTS-HF trial, and is under evaluation for HFpEF and HFmrEF in the REDEFINE-HF and CONFIRMATION-HF trials.<\/jats:p>\n                  <jats:p>As treatment for HFpEF and HFmrEF may be impacted by comorbidities, novel treatments could be tailored to specific phenotypes such as obesity and chronic kidney disease. Trials of glucagon-like peptide-1 receptor agonist (GLP-1 RA), semaglutide, and dual glucose-dependent insulinotropic polypeptide receptor agonist\/GLP-1 RA, tirzepatide, for HFpEF with obesity, observed an impact on HF hospitalization events and quality of life.<\/jats:p>\n                  <jats:p>Trials of selective mineralocorticoid modulator, balcinrenone, and aldosterone synthase inhibitor, vicadrostat, will address key evidence gaps and help improve outcomes for patients with HFpEF and HFmrEF.<\/jats:p>","DOI":"10.1093\/eschf\/xvag056","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:28:46Z","timestamp":1771331326000},"source":"Crossref","is-referenced-by-count":3,"title":["Established and emerging pharmacologic options and unmet needs in HFpEF and HFmrEF"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-2795","authenticated-orcid":false,"given":"Andrew J","family":"Sauer","sequence":"first","affiliation":[{"name":"Saint Luke's Mid America Heart Institute, 4401 Wornall Road, Kansas City, Missouri, MO 64111, USA School of Medicine, University of Missouri, Health Sciences Campus, 2411 Holmes Street, Kansas City, MO 64108 ,","place":["USA"]},{"name":"University of Missouri , Kansas City, MO ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozine M","family":"ter Maaten","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-0887","authenticated-orcid":false,"given":"Gianluigi","family":"Savarese","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"2026031412521112000_xvag056-B1","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1002\/ejhf.2115","article-title":"Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association","volume":"23","author":"Bozkurt","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"2026031412521112000_xvag056-B2","doi-asserted-by":"publisher","first-page":"e895","DOI":"10.1161\/CIR.0000000000001063","article-title":"2022 AHA\/ACC\/HFSA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"2026031412521112000_xvag056-B3","doi-asserted-by":"publisher","first-page":"3627","DOI":"10.1093\/eurheartj\/ehad195","article-title":"2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"44","author":"McDonagh","year":"2023","journal-title":"Eur Heart J"},{"key":"2026031412521112000_xvag056-B4","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur Heart J"},{"key":"2026031412521112000_xvag056-B5","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1253\/circj.CJ-25-0002","article-title":"JCS\/JHFS 2025 guideline on diagnosis and treatment of heart failure","volume":"89","author":"Kitai","year":"2025","journal-title":"Circ J"},{"key":"2026031412521112000_xvag056-B6","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.hlc.2021.09.019","article-title":"Characteristics and clinical outcomes in patients with heart failure with preserved ejection fraction compared to heart failure with reduced ejection fraction: insights from the VCOR heart failure snapshot","volume":"31","author":"Tan","year":"2022","journal-title":"Heart Lung Circ"},{"key":"2026031412521112000_xvag056-B7","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s41569-021-00605-5","article-title":"Heart failure with mid-range or mildly reduced ejection fraction","volume":"19","author":"Savarese","year":"2022","journal-title":"Nat Rev Cardiol"},{"key":"2026031412521112000_xvag056-B8","doi-asserted-by":"publisher","first-page":"676658","DOI":"10.3389\/fcvm.2021.676658","article-title":"Are HFpEF and HFmrEF so different? 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