{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:37:11Z","timestamp":1791221831347,"version":"4.1.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00689"],"award-info":[{"award-number":["PI20\/00689"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012513","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Cardiovasculares","doi-asserted-by":"publisher","award":["16\/11\/00420"],"award-info":[{"award-number":["16\/11\/00420"]}],"id":[{"id":"10.13039\/501100012513","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00689"],"award-info":[{"award-number":["PI20\/00689"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012513","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Cardiovasculares","doi-asserted-by":"publisher","award":["16\/11\/00420"],"award-info":[{"award-number":["16\/11\/00420"]}],"id":[{"id":"10.13039\/501100012513","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The efficacy of combining hypertonic saline solution (HSS) with loop diuretics in worsening heart failure (WHF) remains uncertain. Hypochloraemia has been associated with reduced diuretic efficacy. Some authors propose that chloride repletion may enhance natriuretic and diuretic responses. This post-hoc analysis of the SALT-HF trial evaluated the effect of single-dose administration of HSS plus intravenous (IV) furosemide versus IV furosemide, stratified by baseline serum chloride.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The analysis included 148 ambulatory patients with WHF from the double-blind, randomized SALT-HF trial. Participants received either an IV single dose of HSS plus furosemide or IV furosemide. The endpoints were 3-h urinary sodium excretion and diuresis, 7-day congestion score, and 30-day adverse events according to chloride levels. Multivariable linear and logistic regression models assessed the relationship between the intervention and the endpoints. The mean baseline serum chloride level was 100\u2009\u00b1\u20094\u2009mmol\/L. Sixteen patients (10.8%) were identified as hypochloraemic (serum chloride &amp;lt;96\u2009mmol\/L), balanced between treatment groups. Patients with hypochloraemia showed a lower natriuretic response (p\u2009&amp;lt;\u20090.05). Interaction analysis revealed a between-treatment differential natriuretic effect based on the chloride levels (pinteraction\u2009=\u20090.008). HSS plus furosemide increased natriuresis compared to furosemide at lower chloride levels. No differential between-treatment effect was found for 3-h diuresis. Similar heterogeneous results were found for the 7-day clinical congestion score and 30-day heart failure events, with a benefit with HSS in patients with lower chloride levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In ambulatory patients with WHF and hypochloraemia, adding HSS to furosemide may improve short-term natriuretic response and outcomes. These findings suggest that chloride supplementation may help overcome diuretic resistance in these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3597","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T21:00:41Z","timestamp":1739307641000},"page":"960-971","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Salt Repletion and Diuretic Response: The Role of Serum Chloride. A Post-hoc Analysis of the SALT-HF Trial on Furosemide and Hypertonic Saline Solution Administration in Ambulatory Patients with Worsening Heart Failure"],"prefix":"10.1093","volume":"27","author":[{"given":"Julio","family":"N\u00fa\u00f1ez","sequence":"first","affiliation":[{"name":"Cardiology Department, Hospital Cl\u00ednico Universitario de Valencia (INCLIVA), University of Valencia , Valencia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Mi\u00f1ana","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Cl\u00ednico Universitario de Valencia (INCLIVA), University of Valencia , Valencia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"de la Espriella","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Cl\u00ednico Universitario de Valencia (INCLIVA), University of Valencia , Valencia ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Cardiovascular , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Zegr\u00ed-Reiriz","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital de la Santa Creu i Sant Pau , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Com\u00edn-Colet","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Cardiovascular , Madrid ,","place":["Spain"]},{"name":"Cardiology Department, Hospital Universitario de Bellvitge, IDIBELL , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Rubio Gracia","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Lozano Blesa, University of Zaragoza, Aragon Health Research Institute (IIS Aragon) , Zaragoza ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Morales-Rull","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Arnau de Vilanova, Heart Failure Unit, Lleida Health Region, Institut de Recerca Biom\u00e8dica de Lleida (IRBLleida) , Lleida ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pau","family":"Ll\u00e0cer","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, Madrid, and Department of Medicine and Medical Specialties, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcal\u00e1 , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Diez-Villanueva","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitario de la Princesa , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"de Juan Bagud\u00e1","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Cardiovascular , Madrid ,","place":["Spain"]},{"name":"Cardiology Department, University Hospital 12 de Octubre, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (Imas12), Madrid, and Department of Medicine, Faculty of Biomedical and Health Science, Universidad Europea de Madrid , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Ortiz Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitario San Pedro de Alc\u00e1ntara , C\u00e1ceres ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josebe","family":"Goirigolzarri-Artaza","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitario Cl\u00ednico San Carlos , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Manuel","family":"Garc\u00eda-Pinilla","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Cardiovascular , Madrid ,","place":["Spain"]},{"name":"Cardiology Department, Hospital Universitario Virgen de la Victoria, M\u00e1laga; Instituto de Investigaci\u00f3n Biom\u00e9dica-Plataforma BIONAND, M\u00e1laga, and Departamento de Medicina y Dermatolog\u00eda, Universidad de M\u00e1laga , M\u00e1laga ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Barrios","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitario Rey Juan Carlos M\u00f3stoles , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"del Prado D\u00edaz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Cardiovascular , Madrid ,","place":["Spain"]},{"name":"Cardiology Department, Hospital Universitario Ram\u00f3n y Cajal , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Jim\u00e9nez-Marrero","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Cardiovascular , Madrid ,","place":["Spain"]},{"name":"Cardiology Department, Hospital Universitario de Bellvitge, IDIBELL , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alejandra","family":"Restrepo-C\u00f3rdoba","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitario Cl\u00ednico San Carlos , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Testani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Cobo Marcos","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Universitario Puerta de Hierro , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"2026021721475140900_ejhf3597-bib-0001","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.jacc.2019.12.059","article-title":"Diuretic therapy for patients with heart failure: JACC state-of-the-art review","volume":"75","author":"Felker","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"2026021721475140900_ejhf3597-bib-0002","first-page":"47","article-title":"Assessment of filling pressures and fluid overload in heart failure: An updated perspective","volume":"76","author":"Espriella","year":"2023","journal-title":"Rev Esp Cardiol (Engl Ed)"},{"key":"2026021721475140900_ejhf3597-bib-0003","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.recesp.2024.01.003","article-title":"Consensus on the approach to hydrosaline overload in acute heart failure. 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