{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:42:15Z","timestamp":1784821335263,"version":"3.55.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Acute heart failure (AHF) requires immediate intervention, with diuretics central to managing volume overload. We conducted a prospective single-arm study to explore changes in diuretic and renal outcomes following initiation of combined angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 (SGLT2) inhibitors therapy in AHF patients. We enrolled 120 patients with left ventricular ejection fraction \u226440% and signs of fluid overload, initiation of combined ARNI and SGLT2 inhibitor therapy post-hemodynamic stabilization. Urine volume, renal function, and cardiovascular biomarkers were assessed over 9 days. Urine volume and diuretic response increased significantly on day 1, stabilizing above baseline levels. Cardiovascular biomarkers showed improvements, with decreased NT-proBNP and increased LVEF, without affecting eGFR. Increased diuresis and improved cardiac function parameters were observed during combination therapy. These hypothesis-generating findings support the need for randomized controlled trials to evaluate the clinical utility of this combination in AHF management. The short-term nature of the study and lack of a control group are limitations, which preclude definitive causal attribution of the observed effects. This study has been registered with the Chinese Clinical Trial Registry under registration number ChiCTR2600118845.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>Chinese Clinical Trial Registry (ChiCTR2600118845).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1815471","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:36:31Z","timestamp":1777613791000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Short-term renal and cardiac outcomes of combined ARNI and SGLT2 therapy in AHF patients: a prospective single-arm interventional study"],"prefix":"10.3389","volume":"13","author":[{"given":"MingLei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Quzhou KeCheng People\u2019s Hospital","place":["Quzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZiYing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Quzhou KeCheng People\u2019s Hospital","place":["Quzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ChenChen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Quzhou KeCheng People\u2019s Hospital","place":["Quzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YanDan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine and Science Education, Quzhou KeCheng People\u2019s Hospital","place":["Quzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1002\/ejhf.1492","article-title":"Acute heart failure congestion and perfusion status\u2014impact of the clinical classification on in-hospital and long-term outcomes; insights from the ESC-EORP-HFA heart failure long-term registry","volume":"21","author":"Chioncel","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.15420\/cfr.2016:25:2","article-title":"Global public health burden of heart failure","volume":"3","author":"Savarese","year":"2017","journal-title":"Card Fail Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1056\/NEJMoa1409077","article-title":"Angiotensin\u2013neprilysin inhibition versus enalapril in heart failure","volume":"371","author":"McMurray","year":"2014","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1056\/NEJMoa1812851","article-title":"Angiotensin\u2013neprilysin inhibition in acute decompensated heart failure","volume":"380","author":"Velazquez","year":"2019","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1111\/dom.12127","article-title":"Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes","volume":"15","author":"Lambers Heerspink","year":"2013","journal-title":"Diabetes Obes Metab"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1681\/ASN.2022020207","article-title":"Albuminuria-lowering effect of dapagliflozin, eplerenone, and their combination in patients with chronic kidney disease: a randomized crossover clinical trial","volume":"33","author":"Provenzano","year":"2022","journal-title":"JASN"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.1093\/eurheartj\/ehz240","article-title":"Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial","volume":"40","author":"Morrow","year":"2019","journal-title":"Eur Heart J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1053\/j.ajkd.2010.02.344","article-title":"Modification of the CKD epidemiology collaboration (CKD-EPI) equation for Japanese: accuracy and use for population estimates","volume":"56","author":"Horio","year":"2010","journal-title":"Am J Kidney Dis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/ki.1984.153","article-title":"Bumetanide and furosemide in heart failure","volume":"26","author":"Brater","year":"1984","journal-title":"Kidney Int"},{"key":"B10","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.cardfail.2018.07.462","article-title":"Calculated estimates of plasma volume in patients with chronic heart failure\u2014comparison with measured volumes","volume":"24","author":"Fudim","year":"2018","journal-title":"J Card Fail"},{"key":"B11","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.jchf.2024.09.017","article-title":"Diuretic potentiation strategies in acute heart failure","volume":"13","author":"Siddiqi","year":"2025","journal-title":"JACC Heart Fail"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e24303","DOI":"10.1002\/clc.24303","article-title":"Effect of sodium\u2212glucose co-transporter-2 inhibitor on estimated plasma volume in a patient with heart failure with reduced ejection fraction and a patient with heart failure with preserved ejection fraction","volume":"47","author":"Ta\u0165\u00e1na","year":"2024","journal-title":"Clin Cardiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s40360-019-0304-z","article-title":"Effects of neprilysin-renin inhibition in comparison with neprilysin-angiotensin inhibition on the neurohumoral changes in rats with heart failure","volume":"20","author":"Dizaye","year":"2019","journal-title":"BMC Pharmacol Toxicol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s00392-022-02049-4","article-title":"Body fluid regulation via chronic inhibition of sodium\u2013glucose cotransporter-2 in patients with heart failure: a post hoc analysis of the CANDLE trial","volume":"112","author":"Fujiki","year":"2023","journal-title":"Clin Res Cardiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3792","DOI":"10.1002\/ehf2.12965","article-title":"Renal function dynamics following co-administration of sacubitril\/valsartan and empagliflozin in patients with heart failure and type 2 diabetes","volume":"7","author":"De La Espriella","year":"2020","journal-title":"ESC Heart Fail"},{"key":"B16","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.nefro.2017.05.015","article-title":"La disminuci\u00f3n de triyodotironina se asocia con la elevaci\u00f3n del p\u00e9ptido natriur\u00e9tico cerebral N-terminal y con la mortalidad en pacientes en di\u00e1lisis","volume":"37","author":"Prado-Uribe","year":"2017","journal-title":"Nefrolog\u00eda"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1161\/CIRCULATIONAHA.119.042929","article-title":"Dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction: the DEFINE-HF trial","volume":"140","author":"Nassif","year":"2019","journal-title":"Circulation"},{"key":"B18","doi-asserted-by":"publisher","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":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-025-10572-5","article-title":"Dapagliflozin in acute heart failure: lessons from the DAPA ACT HF-TIMI 68 trial","volume":"31","author":"Skowronski","year":"2025","journal-title":"Heart Fail Rev"},{"key":"B20","doi-asserted-by":"publisher","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":"B21","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41440-022-01085-x","article-title":"Canagliflozin independently reduced plasma volume from conventional diuretics in patients with type 2 diabetes and chronic heart failure: a subanalysis of the CANDLE trial","volume":"46","author":"Shiina","year":"2023","journal-title":"Hypertens Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1007\/s10157-018-1603-1","article-title":"Comparison of the effects of tolvaptan and furosemide on renal water and sodium excretion in patients with heart failure and advanced chronic kidney disease: a subanalysis of the K-STAR study","volume":"22","author":"Tominaga","year":"2018","journal-title":"Clin Exp Nephrol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.kint.2020.11.021","article-title":"Early eGFR decline after SGLT2i initiation: knowns and unknowns","volume":"99","author":"Gregg","year":"2021","journal-title":"Kidney Int"},{"key":"B24","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.jchf.2018.02.004","article-title":"Renal effects and associated outcomes during angiotensin-neprilysin inhibition in heart failure","volume":"6","author":"Damman","year":"2018","journal-title":"JACC Heart Fail"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e010111","DOI":"10.1161\/CIRCHEARTFAILURE.122.010111","article-title":"Urinary cGMP (cyclic guanosine monophosphate)\/BNP (B-type natriuretic peptide) ratio, sacubitril\/valsartan, and outcomes in heart failure with reduced ejection fraction: an analysis of the PARADIGM-HF trial","volume":"16","author":"Butt","year":"2023","journal-title":"Circ Heart Fail"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1002\/ejhf.2968","article-title":"Similarities and distinctions between acetazolamide and sodium\u2013glucose cotransporter 2 inhibitors in patients with acute heart failure: key insights into ADVOR and EMPULSE","volume":"25","author":"Packer","year":"2023","journal-title":"Eur J Heart Fail"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e018689","DOI":"10.1161\/JAHA.120.018689","article-title":"Obesity and serial NT-proBNP levels in guided medical therapy for heart failure with reduced ejection fraction: insights from the GUIDE-IT trial","volume":"10","author":"Parcha","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"B28","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1177\/2048872615585521","article-title":"The use of discharge haemoglobin and NT-proBNP to improve short and long-term outcome prediction in patients with acute heart failure","volume":"6","author":"Stojcevski","year":"2017","journal-title":"Eur Heart J Acute Cardiovasc Care"},{"key":"B29","doi-asserted-by":"publisher","first-page":"22342","DOI":"10.1038\/s41598-021-01759-5","article-title":"Combined effects of ARNI and SGLT2 inhibitors in diabetic patients with heart failure with reduced ejection fraction","volume":"11","author":"Kim","year":"2021","journal-title":"Sci Rep"},{"key":"B30","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.cardfail.2019.04.002","article-title":"Prognostic implications of changes in amino-terminal pro\u2013B-type natriuretic peptide in acute decompensated heart failure: insights from ASCEND-HF","volume":"25","author":"Grodin","year":"2019","journal-title":"J Card Fail"},{"key":"B31","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1080\/00015385.2024.2406683","article-title":"Prognostic value of sst2 in long-term mortality in acute heart failure","volume":"79","author":"Matyar","year":"2024","journal-title":"Acta Cardiol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1001\/jamacardio.2023.1101","article-title":"Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in heart failure\u2014does the story begin and End with the kidney?","volume":"8","author":"Patel","year":"2023","journal-title":"JAMA Cardiol"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1815471\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:36:31Z","timestamp":1777613791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1815471\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":32,"alternative-id":["10.3389\/fcvm.2026.1815471"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1815471","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]},"article-number":"1815471"}}