{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:20Z","timestamp":1787028920423,"version":"build-2736575974"},"reference-count":16,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:00:00Z","timestamp":1779580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background: SGLT2 inhibitors improve outcomes in heart failure with reduced ejection fraction (HFrEF), but whether early recovery patterns after initiation differ according to HF etiology in real-world practice remains uncertain. Objective: To evaluate whether ischemic versus non-ischemic etiology is associated with different 6-month cardiac, renal, biomarker, and exploratory metabolic trajectories after early in-hospital SGLT2 inhibitor initiation in HFrEF. Materials and Methods: In this prospective single-center observational cohort (2022\u20132025), consecutive adults hospitalized with first-presentation acute HFrEF who initiated empagliflozin or dapagliflozin within 48 h of admission were enrolled. Patients were classified as having ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM). The primary analytic cohort included patients with paired baseline and 6-month echocardiography. The primary outcome was change in left ventricular ejection fraction (LVEF); eGFR and NT-proBNP were secondary outcomes. Exploratory metabolic\/laboratory variables were summarized descriptively using paired available-case follow-up. The study was approved by the institutional ethics committee and registered in ClinicalTrials.gov under the CaRD registry framework (NCT06090591). Results: The paired 6-month echocardiographic analytic cohort comprised 241 patients who survived to reassessment (ICM n = 90; NICM n = 151). NICM showed greater improvement in LVEF than ICM (\u0394LVEF +10% [IQR 0\u201318] vs. +5% [IQR 0\u201312]; p = 0.049) and a more favorable eGFR trajectory (\u0394eGFR 0.30 [IQR \u22125.90 to 6.60] vs. \u22122.70 [IQR \u221212.60 to 3.40] mL\/min\/1.73 m2; p = 0.038). NT-proBNP declined substantially in both groups, with no between-group difference in change magnitude (p = 0.845), although 6-month values remained higher in ICM (p = 0.034). However, after multivariable adjustment, ischemic etiology was no longer independently associated with 6-month LVEF or eGFR outcomes. Exploratory metabolic findings varied descriptively by etiology but should be interpreted cautiously because follow-up completeness and background treatment intensity varied across variables. Conclusions: In this real-world cohort of patients with HFrEF who initiated SGLT2 inhibitors during hospitalization, HF etiology was associated with different short-term cardiorenal recovery patterns, whereas NT-proBNP reduction was similar across groups. These findings characterize etiology-related recovery within a treated cohort rather than differential SGLT2 inhibitor efficacy and should therefore be considered as hypothesis-generating.<\/jats:p>","DOI":"10.3390\/medicina62061017","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:30:33Z","timestamp":1779669033000},"page":"1017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Heart Failure Etiology and 6-Month Cardiorenal Recovery Patterns After Early In-Hospital SGLT2 Inhibitor Initiation in HFrEF: A Prospective Real-World Cohort"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2317-6300","authenticated-orcid":false,"given":"Marija","family":"Radi\u0107","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Diseases, University hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-9691","authenticated-orcid":false,"given":"Ivana","family":"Jurin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran","family":"Rode","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2848-6041","authenticated-orcid":false,"given":"Luka","family":"\u0160imunovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School of Dental Medicine, University of Zagreb, Gunduli\u0107eva 5, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Kolund\u017ei\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3768-9134","authenticated-orcid":false,"given":"Irzal","family":"Had\u017eibegovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University hospital Dubrava, 10000 Zagreb, Croatia"},{"name":"Faculty of Dental Medicine and Health Care, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9526-3393","authenticated-orcid":false,"given":"\u0160ime","family":"Manola","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University hospital Dubrava, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Vitlov","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanja","family":"Ivanovi\u0107 Mihajlovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijela","family":"Grizelj","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-683X","authenticated-orcid":false,"given":"Hrvoje","family":"Falak","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Udovi\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University hospital Dubrava, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomislav","family":"Letilovi\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Cardiology, University Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1161\/01.CIR.0000078641.19365.4C","article-title":"Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance","volume":"108","author":"McCrohon","year":"2003","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1001\/jama.2013.1363","article-title":"Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy","volume":"309","author":"Gulati","year":"2013","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.jchf.2020.12.015","article-title":"Global differences in burden and treatment of ischemic heart disease in acute heart failure: REPORT-HF","volume":"9","author":"Tromp","year":"2021","journal-title":"JACC Heart Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/ejhf.2333","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"24","author":"McDonagh","year":"2022","journal-title":"Eur. J. Heart Fail."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1001\/jama.2013.1954","article-title":"Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: The ASTRONAUT randomized trial","volume":"309","author":"Gheorghiade","year":"2013","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1056\/NEJMoa1812851","article-title":"Angiotensin-neprilysin inhibition in acute decompensated heart failure","volume":"380","author":"Velazquez","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/s41591-021-01659-1","article-title":"The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: A multinational randomized trial","volume":"28","author":"Voors","year":"2022","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/dom.15696","article-title":"Key results from observational studies and real-world evidence of sodium-glucose cotransporter-2 inhibitor effectiveness and safety in reducing cardio-renal risk","volume":"26","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Prosperi, S., D\u2019Amato, A., Labbro Francia, A., Monosilio, S., Cesti\u00e8, C., Iannucci, S.M., Netti, L., Angotti, D., Filomena, D., and Mariani, M.V. (2024). Sodium-glucose cotransporter 2 inhibitor therapy in different scenarios of heart failure: An overview of the current literature. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111458"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1056\/NEJM197112232852601","article-title":"The natural history of congestive heart failure: The Framingham study","volume":"285","author":"McKee","year":"1971","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0140-6736(20)31824-9","article-title":"SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: A meta-analysis of the EMPEROR-Reduced and DAPA-HF trials","volume":"396","author":"Zannad","year":"2020","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1161\/CIRCULATIONAHA.120.051685","article-title":"Cardiac and kidney benefits of empagliflozin in heart failure across the spectrum of kidney function: Insights from EMPEROR-Reduced","volume":"143","author":"Zannad","year":"2021","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1161\/CIRCULATIONAHA.120.050391","article-title":"Efficacy of dapagliflozin on renal function and outcomes in patients with heart failure with reduced ejection fraction","volume":"143","author":"Jhund","year":"2021","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1002\/ehf2.15223","article-title":"SGLT2i Reduce Arrhythmic Events in Heart Failure Patients with Cardiac Implantable Electronic Devices","volume":"12","author":"Mariani","year":"2025","journal-title":"ESC Heart Fail."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1016\/j.jacc.2016.09.931","article-title":"Prognostic implications of changes in N-terminal pro-B-type natriuretic peptide in patients with heart failure","volume":"68","author":"Zile","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1097\/MOL.0000000000000751","article-title":"Lipid effects of sodium-glucose cotransporter 2 inhibitors","volume":"32","author":"Lazarte","year":"2021","journal-title":"Curr. Opin. Lipidol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/6\/1017\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:01:22Z","timestamp":1779670882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/6\/1017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,24]]},"references-count":16,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["medicina62061017"],"URL":"https:\/\/doi.org\/10.3390\/medicina62061017","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,24]]}}}