{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:35:20Z","timestamp":1784756120362,"version":"3.55.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":112,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Diuretic resistance is frequently observed in patients with acute decompensated heart failure (ADHF), specifically in those with chronic use of loop diuretics (LD). Natriuresis-guided therapy may be useful to overcome this, however it is unknown whether its effect is impacted by chronic LD use. The aim of this study was to evaluate the effect of outpatient LD use on natriuresis and clinical outcomes, and to determine whether natriuresis-guided therapy modifies these effects in patients hospitalized for ADHF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this prespecified sub-analysis of the PUSH-AHF trial, the association between outpatient LD use, predefined primary, secondary and safety outcomes as established in the PUSH-AHF protocol, and the effect of natriuresis-guided therapy as compared with standard of care was evaluated. Patients in both arms received the first in-hospital LD dose based on renal function and outpatient LD dose. Out of 310 randomized patients, 133 (43%) had no prior LD use, 65 (21%) used 0\u20131\u2009mg bumetanide and 112 (36%) used &amp;gt;1\u2009mg bumetanide (or equivalent). Patients with higher outpatient LD doses had a longer history of heart failure and worse renal function (p for trend &amp;lt;0.001). Higher outpatient LD doses were associated with lower 24-h natriuresis (340\u2009\u00b1\u2009194\u2009mmol vs. 420\u2009\u00b1\u2009200\u2009mmol in diuretic-na\u00efve patients, p for trend\u2009=\u20090.002). Natriuresis-guided therapy significantly increased 24-h natriuresis regardless of outpatient LD use (p for interaction\u2009=\u20090.420). No interaction between outpatient LD use, natriuresis-guided therapy and the effect on the combined endpoint of heart failure rehospitalization or all-cause mortality at 180\u2009days was observed (p for interaction\u2009=\u20090.881).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Outpatient LD use results in reduced natriuresis. However, the beneficial effects of natriuresis-guided diuretic therapy on 24-h natriuresis were consistent, regardless of previous LD use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.70080","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:29:36Z","timestamp":1761762576000},"page":"3111-3122","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Outpatient Loop Diuretic Use and the Effect of Natriuresis-Guided Diuretic Therapy: A Prespecified Sub-Analysis of the PUSH-AHF Study"],"prefix":"10.1093","volume":"27","author":[{"given":"Lara E.E.C.","family":"Zonneveld","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris E.","family":"Beldhuis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailun","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenifer E.","family":"Coster","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wybe","family":"Nieuwland","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan A.","family":"Krikken","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Damman","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,","place":["The Netherlands"]}],"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"}]}],"member":"286","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"2026021721524752700_ejhf70080-bib-0001","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.jacc.2013.11.053","article-title":"The global health and economic burden of hospitalizations 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