{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:38Z","timestamp":1792785878240,"version":"4.5.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100019353","name":"Belgian Health Care Knowledge Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019353","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001491","name":"Belgian American Educational Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001491","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Frans Van de Werf Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Acetazolamide inhibits proximal tubular sodium and bicarbonate re-absorption and improved decongestive response in acute heart failure in the ADVOR trial. It is unknown whether bicarbonate levels alter the decongestive response to acetazolamide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This is a sub-analysis of the randomized, double-blind, placebo-controlled ADVOR trial that randomized 519 patients with acute heart failure and volume overload in a 1:1 ratio to intravenous acetazolamide (500 mg\/day) or matching placebo on top of standardized intravenous loop diuretics (dose equivalent of twice oral maintenance dose). The primary endpoint was complete decongestion after 3 days of treatment (morning of day 4). Impact of baseline HCO3 levels on the treatment effect of acetazolamide was assessed. : Of the 519 enrolled patients, 516 (99.4%) had a baseline HCO3 measurement. Continuous HCO3 modelling illustrated a higher proportional treatment effect for acetazolamide if baseline HCO3 \u2265 27 mmol\/l. A total of 234 (45%) had a baseline HCO3 \u2265 27 mmol\/l. Randomization towards acetazolamide improved decongestive response over the entire range of baseline HCO3\u2212 levels (P = 0.004); however, patients with elevated baseline HCO3 exhibited a significant higher response to acetazolamide [primary endpoint: no vs. elevated HCO3; OR 1.37 (0.79\u20132.37) vs. OR 2.39 (1.35\u20134.22), P-interaction = 0.065), with higher proportional diuretic and natriuretic response (both P-interaction &amp;lt; 0.001), greater reduction in congestion score on consecutive days (treatment \u00d7 time by HCO3-interaction &amp;lt;0.001) and length of stay (P-interaction = 0.019). The larger proportional treatment effect was mainly explained by the development of diminished decongestive response in the placebo arm (loop diuretics only), both with regard to reaching the primary endpoint of decongestion as well as reduction in congestion score. Development of elevated HCO3 further worsened decongestive response in the placebo arm (P-interaction = 0.041). A loop diuretic only strategy was associated with an increase in the HCO3 during the treatment phase which was prevented by acetazolamide (day 3: placebo 74.8% vs. acetazolamide 41.3%, P &amp;lt; 0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Acetazolamide improves decongestive response over the entire range of HCO3\u2212 levels; however, the treatment response is magnified in patients with baseline or loop diuretic-induced elevated HCO3 (marker of proximal nephron NaHCO3 retention) by specifically counteracting this component of diuretic resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehad236","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:06:36Z","timestamp":1683158796000},"page":"1995-2005","source":"Crossref","is-referenced-by-count":53,"title":["Pre-treatment bicarbonate levels and decongestion by acetazolamide: the ADVOR trial"],"prefix":"10.1093","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6036-2113","authenticated-orcid":false,"given":"Pieter","family":"Martens","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic , Cleveland, OH , USA"},{"name":"Department of Cardiology, Ziekenhuis Oost-Limburg A.V. , Schiepse bos 6, 3600 Genk , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik H","family":"Verbrugge","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Diseases, University Hospital Brussels , Jette , Belgium"},{"name":"Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel , Jette , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Dauw","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ziekenhuis Oost-Limburg A.V. , Schiepse bos 6, 3600 Genk , Belgium"},{"name":"Faculty of Medicine and Life Science, Hasselt University , Martelarenlaan 42, 3500 Hasselt , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7325-7734","authenticated-orcid":false,"given":"Petra","family":"Nijst","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ziekenhuis Oost-Limburg A.V. , Schiepse bos 6, 3600 Genk , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Meekers","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ziekenhuis Oost-Limburg A.V. , Schiepse bos 6, 3600 Genk , Belgium"},{"name":"Centre for Cardiovascular Diseases, University Hospital Brussels , Jette , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Silvio Nunes","family":"Augusto","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic , Cleveland, OH , 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 , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4595-0195","authenticated-orcid":false,"given":"Line","family":"Heylen","sequence":"additional","affiliation":[{"name":"Department of Nefrology, Ziekenhuis Oost-Limburg A.V. , Genk , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0190-2228","authenticated-orcid":false,"given":"Kevin","family":"Damman","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Mebazaa","sequence":"additional","affiliation":[{"name":"Department of Medicine, Universit\u00e9 Paris Cit\u00e9, Inserm MASCOT, APHP , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5640-0332","authenticated-orcid":false,"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, National and Kapodistrian University of Athens, Athens University Hospital Attikon , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Ruschitzka","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart Center, University Hospital Zurich and University of Zurich , Zurich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Hong 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