{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:45:47Z","timestamp":1790779547947,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T00:00:00Z","timestamp":1557360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T00:00:00Z","timestamp":1557360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Research Foundation \u2013 Flanders","award":["11L8214N"],"award-info":[{"award-number":["11L8214N"]}]},{"name":"Research Foundation \u2013 Flanders","award":["1127917\u2009N"],"award-info":[{"award-number":["1127917\u2009N"]}]},{"name":"Foundation Limburg Sterk Merk"},{"DOI":"10.13039\/501100009550","name":"Hasselt University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018216","name":"Ziekenhuis Oost-Limburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018216","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jessa Hospital"},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["11L8214N"],"award-info":[{"award-number":["11L8214N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1127917\u2009N"],"award-info":[{"award-number":["1127917\u2009N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009542","name":"Limburg Sterk Merk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009550","name":"Universiteit Hasselt","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009550","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To investigate the effects of acetazolamide on natriuresis, decongestion, kidney function and neurohumoral activation in acute heart failure (AHF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This prospective, two-centre study included 34 AHF patients on loop diuretics with volume overload. All had a serum sodium concentration &amp;lt;\u2009135\u2009mmol\/L and\/or serum urea\/creatinine ratio &amp;gt;\u200950 and\/or an admission serum creatinine increase of &amp;gt;\u20090.3 mg\/dL compared to baseline. Patients were randomised towards acetazolamide 250\u2013500\u2009mg daily plus bumetanide 1\u20132 mg bid vs. high-dose loop diuretics (bumetanide bid with daily dose twice the oral maintenance dose). The primary endpoint was natriuresis after 24\u2009h. Natriuresis after 24\u2009h was similar in the combinational treatment vs. loop diuretic only arm (264\u2009\u00b1\u2009126 vs. 234\u2009\u00b1\u2009133\u2009mmol; P\u2009=\u20090.515). Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide (84\u2009\u00b1\u200946 vs. 52\u2009\u00b1\u200942\u2009mmol\/mg bumetanide; P\u2009=\u20090.048). More patients in the combinational treatment arm had an increase in serum creatinine levels &amp;gt;\u20090.3 mg\/dL (P\u2009=\u20090.046). N-terminal pro-B-type natriuretic peptide reduction and peak neurohumoral activation within 72\u2009h were comparable among treatment arms. There was a non-significant trend towards lower all-cause mortality or heart failure readmissions in the group receiving acetazolamide with low-dose loop diuretics vs. high-dose loop diuretic monotherapy (P\u2009=\u20090.098).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Addition of acetazolamide increases the natriuretic response to loop diuretics compared to an increase in loop diuretic dose in AHF at high risk for diuretic resistance.<\/jats:p>\n                    <jats:p>Trial registration: ClinicalTrials.gov \u00a0NCT01973335.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1478","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T22:51:05Z","timestamp":1557442265000},"page":"1415-1422","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Acetazolamide to Increase Natriuresis in Congestive Heart Failure at High Risk for Diuretic Resistance"],"prefix":"10.1093","volume":"21","author":[{"given":"Frederik H.","family":"Verbrugge","sequence":"first","affiliation":[{"name":"Department of Cardiology, Ziekenhuis Oost-Limburg , Genk ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ziekenhuis Oost-Limburg , Genk ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Ameloot","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ziekenhuis Oost-Limburg , Genk ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Haemels","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, UZ Leuven , Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"Penders","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Ziekenhuis Oost-Limburg , Genk ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Dupont","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ziekenhuis Oost-Limburg , Genk ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Hong Wilson","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic , Cleveland, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Droogn\u00e9","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, UZ Leuven , Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Mullens","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ziekenhuis Oost-Limburg , Genk ,","place":["Belgium"]},{"name":"Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University , Diepenbeek ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,9]]},"reference":[{"key":"2026011721322403600_ejhf1478-bib-0001","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.amjmed.2006.09.011","article-title":"Congestion in acute heart failure syndromes: an essential target of evaluation and treatment","volume":"119","author":"Gheorghiade","year":"2006","journal-title":"Am J Med"},{"key":"2026011721322403600_ejhf1478-bib-0002","first-page":"379","article-title":"Diuretic resistance in acute heart failure","volume":"7","author":"Verbrugge","year":"2018","journal-title":"Eur Heart J Acute Cardiovasc Care"},{"key":"2026011721322403600_ejhf1478-bib-0003","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1056\/NEJMoa1005419","article-title":"Diuretic strategies in patients with acute decompensated heart failure","volume":"364","author":"Felker","year":"2011","journal-title":"N Engl J Med"},{"key":"2026011721322403600_ejhf1478-bib-0004","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1054\/jcaf.2002.125289","article-title":"The prognostic importance of different definitions of worsening renal function in congestive heart failure","volume":"8","author":"Gottlieb","year":"2002","journal-title":"J Card Fail"},{"key":"2026011721322403600_ejhf1478-bib-0005","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/eurheartj\/eht386","article-title":"Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis","volume":"35","author":"Damman","year":"2014","journal-title":"Eur Heart J"},{"key":"2026011721322403600_ejhf1478-bib-0006","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1161\/CIRCHEARTFAILURE.111.963413","article-title":"Is worsening renal function an ominous prognostic sign in patients with acute heart failure? The role of congestion and its interaction with renal function","volume":"5","author":"Metra","year":"2012","journal-title":"Circ Heart Fail"},{"key":"2026011721322403600_ejhf1478-bib-0007","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1161\/CIRCHEARTFAILURE.113.000895","article-title":"Loop diuretic efficiency: a metric of diuretic responsiveness with prognostic importance in acute decompensated heart failure","volume":"7","author":"Testani","year":"2014","journal-title":"Circ Heart Fail"},{"key":"2026011721322403600_ejhf1478-bib-0008","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cardfail.2015.07.007","article-title":"Intensification of medication therapy for cardiorenal syndrome in acute decompensated heart failure","volume":"22","author":"Grodin","year":"2016","journal-title":"J Card Fail"},{"key":"2026011721322403600_ejhf1478-bib-0009","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/0002-8703(55)90081-8","article-title":"Studies on the continuous use of a carbonic anhydrase inhibitor (diamox) in ambulatory patients","volume":"49","author":"Massumi","year":"1955","journal-title":"Am Heart J"},{"key":"2026011721322403600_ejhf1478-bib-0010","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/AC.70.3.3080630","article-title":"Determinants and impact of the natriuretic response to diuretic therapy in heart failure with reduced ejection fraction and volume overload","volume":"70","author":"Verbrugge","year":"2015","journal-title":"Acta Cardiol"},{"key":"2026011721322403600_ejhf1478-bib-0011","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0140-6736(56)90105-2","article-title":"Acetazolamide (diamox) in the treatment of congestive heart-failure","volume":"270","author":"Hanley","year":"1956","journal-title":"Lancet"},{"key":"2026011721322403600_ejhf1478-bib-0012","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1097\/00005344-199703000-00010","article-title":"Sequential nephron blockade breaks resistance to diuretics in edematous states","volume":"29","author":"Knauf","year":"1997","journal-title":"J Cardiovasc Pharmacol"},{"key":"2026011721322403600_ejhf1478-bib-0013","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s40261-017-0577-1","article-title":"Acetazolamide as add-on diuretic therapy in exacerbations of chronic heart failure: a pilot study","volume":"37","author":"Imiela","year":"2017","journal-title":"Clin Drug Investig"},{"key":"2026011721322403600_ejhf1478-bib-0014","first-page":"883","article-title":"Treatment of refractory congestive heart failure and normokalemic hypochloremic alkalosis with acetazolamide and spironolactone","volume":"123","author":"Khan","year":"1980","journal-title":"Can Med Assoc J"},{"key":"2026011721322403600_ejhf1478-bib-0015","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/ejhf.35","article-title":"The kidney in congestive heart failure: 'are natriuresis, sodium, and diuretics really the good, the bad and the ugly?'","volume":"16","author":"Verbrugge","year":"2014","journal-title":"Eur J Heart Fail"},{"key":"2026011721322403600_ejhf1478-bib-0016","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1159\/000354515","article-title":"Hypoxia-inducible factor-1alpha dependent pathways mediate the renoprotective role of acetazolamide against renal ischemia-reperfusion injury","volume":"32","author":"An","year":"2013","journal-title":"Cell Physiol Biochem"},{"key":"2026011721322403600_ejhf1478-bib-0017","doi-asserted-by":"crossref","first-page":"e79327","DOI":"10.1371\/journal.pone.0079327","article-title":"Potentiation of the effect of thiazide derivatives by carbonic anhydrase inhibitors: molecular mechanisms and potential clinical implications","volume":"8","author":"Zahedi","year":"2013","journal-title":"PLoS One"},{"key":"2026011721322403600_ejhf1478-bib-0018","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1080\/00015385.2018.1455947","article-title":"Spironolactone to increase natriuresis in congestive heart failure with cardiorenal syndrome","volume":"74","author":"Verbrugge","year":"2019","journal-title":"Acta Cardiol"},{"key":"2026011721322403600_ejhf1478-bib-0019","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1136\/hrt.32.3.399","article-title":"Assessment of proximal tubular sodium reabsorption during water diuresis in patients with heart disease","volume":"32","author":"Gibson","year":"1970","journal-title":"Br Heart J"},{"key":"2026011721322403600_ejhf1478-bib-0020","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s11897-017-0345-9","article-title":"SGLT-2 inhibitors in heart failure: implications for the kidneys","volume":"14","author":"Verbrugge","year":"2017","journal-title":"Curr Heart Fail Rep"},{"key":"2026011721322403600_ejhf1478-bib-0021","doi-asserted-by":"crossref","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":"2026011721322403600_ejhf1478-bib-0022","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jchf.2014.02.007","article-title":"Understanding the heterogeneity in volume overload and fluid distribution in decompensated heart failure is key to optimal volume management: role for blood volume quantitation","volume":"2","author":"Miller","year":"2014","journal-title":"JACC Heart Fail"},{"key":"2026011721322403600_ejhf1478-bib-0023","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1007\/s00246-005-1132-z","article-title":"Acetazolamide for prevention of contrast-induced nephropathy: a new use for an old drug","volume":"27","author":"Assadi","year":"2006","journal-title":"Pediatr Cardiol"},{"key":"2026011721322403600_ejhf1478-bib-0024","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1093\/eurjhf\/hft110","article-title":"Haemoconcentration, renal function, and post-discharge outcomes among patients hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial","volume":"15","author":"Greene","year":"2013","journal-title":"Eur J Heart Fail"},{"key":"2026011721322403600_ejhf1478-bib-0025","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.cardfail.2014.08.002","article-title":"Prognostic value of glomerular filtration changes versus natriuretic response in decompensated heart failure with reduced ejection","volume":"20","author":"Verbrugge","year":"2014","journal-title":"J Card Fail"},{"key":"2026011721322403600_ejhf1478-bib-0026","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1161\/CIRCULATIONAHA.113.005081","article-title":"Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus","volume":"129","author":"Cherney","year":"2014","journal-title":"Circulation"},{"key":"2026011721322403600_ejhf1478-bib-0027","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1056\/NEJMoa1515920","article-title":"Empagliflozin and progression of kidney disease in type 2 diabetes","volume":"375","author":"Wanner","year":"2016","journal-title":"N Engl J Med"},{"key":"2026011721322403600_ejhf1478-bib-0028","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and cardiovascular and renal events in type 2 diabetes","volume":"377","author":"Neal","year":"2017","journal-title":"N Engl J Med"},{"key":"2026011721322403600_ejhf1478-bib-0029","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/ejhf.1307","article-title":"Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial","volume":"20","author":"Mullens","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"2026011721322403600_ejhf1478-bib-0030","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1056\/NEJMoa1210357","article-title":"Ultrafiltration in decompensated heart failure with cardiorenal syndrome","volume":"367","author":"Bart","year":"2012","journal-title":"N Engl J Med"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejhf.1478","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.1478","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.1478","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/21\/11\/1415\/66192252\/eurjhf_21_11_1415.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/21\/11\/1415\/66192252\/eurjhf_21_11_1415.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:32:57Z","timestamp":1768703577000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/21\/11\/1415\/8407169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,9]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,5,9]]},"published-print":{"date-parts":[[2019,11,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.1478","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,11]]},"published":{"date-parts":[[2019,5,9]]},"assertion":[{"value":"2018-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}