{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T17:27:54Z","timestamp":1781803674919,"version":"3.54.5"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Acute decompensated heart failure (ADHF) is the leading cause of hospitalization in patients aged 65\u00a0years or older, and most of them present with congestion. The use of hydrochlorothiazide (HCTZ) may increase the response to loop diuretics. To evaluate the effect of adding HCTZ to furosemide on congestion and symptoms in patients with ADHF. This randomized clinical trial compared HCTZ 50\u00a0mg versus placebo for 3\u00a0days in patients with ADHF and signs of congestion. The primary outcome of the study was daily weight reduction. Secondary outcomes were change in creatinine, need for vasoactive drugs, change in natriuretic peptides, congestion score, dyspnea, thirst, and length of stay. Fifty-one patients were randomized\u201426 to the HCTZ group and 25 to the placebo group. There was an increment of 0.73\u00a0kg\/day towards additional weight reduction in the HCTZ group (HCTZ:\u2009\u2212\u20091.78\u2009\u00b1\u20091.08\u00a0kg\/day vs placebo:\u2009\u2212\u20091.05\u2009\u00b1\u20091.51\u00a0kg\/day;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.062). In post hoc analysis, the HCTZ group demonstrated significant weight reduction for every 40\u00a0mg of intravenous furosemide (HCTZ:\u2009\u2212\u20090.74\u2009\u00b1\u20090.47\u00a0kg\/40\u00a0mg vs placebo:\u2009\u2212\u20090.33\u2009\u00b1\u20090.80\u00a0kg\/40\u00a0mg;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.032). There was a trend to increase in creatinine in the HCTZ group (HCTZ: 0.50\u2009\u00b1\u20090.37 vs placebo: 0.27\u2009\u00b1\u20090.40;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.05) but no significant difference in onset of acute renal failure (HCTZ: 58% vs placebo: 41%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.38). No differences were found in the remaining outcomes. Adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure did not cause significant difference in daily body weight reduction compared to placebo. In analysis adjusted to the dose of intravenous furosemide, adding HCTZ 50\u00a0mg to furosemide resulted in a significant synergistic effect on weight loss.\n                  <\/jats:p>\n                  <jats:p>\n                    Trial registration: The Brazilian Clinical Trials Registry (ReBEC), a publically accessible primary register that participates in the World Health Organization International Clinical Trial Registry Platform; number RBR-5qkn8h. Registered in 23\/07\/2019 (retrospectively),\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.ensaiosclinicos.gov.br\/rg\/RBR-5qkn8h\/\">http:\/\/www.ensaiosclinicos.gov.br\/rg\/RBR-5qkn8h\/<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-96002-6","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T06:03:06Z","timestamp":1628834586000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Effect of adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure: a randomized clinical trial"],"prefix":"10.1038","volume":"11","author":[{"given":"Diogo Silva","family":"Piardi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maur\u00edcio","family":"Butzke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina Martins","family":"Mazzuca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Sessim","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia Giusti","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Jaskulski","family":"Kotzian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduarda Chiesa","family":"Ghisleni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Giaretta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila","family":"Bellaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle Aguiar","family":"Varaschin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur Pereira","family":"Garbin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5702-210X","authenticated-orcid":false,"given":"Lu\u00eds","family":"Beck-da-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"issue":"6","key":"96002_CR1","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.cardfail.2010.04.004","volume":"16","author":"Heart Failure Society of America","year":"2010","unstructured":"Heart Failure Society of America. HFSA 2010 comprehensive heart failure practice guideline. J. Card. Fail. 16(6), e1\u2013e2 (2010).","journal-title":"J. Card. Fail."},{"key":"96002_CR2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000757","author":"SS Virani","year":"2020","unstructured":"Virani, S. S. et al. Heart disease and stroke statistics\u20142020 update: A report from the American Heart Association. Circulation https:\/\/doi.org\/10.1161\/CIR.0000000000000757 (2020).","journal-title":"Circulation"},{"issue":"6","key":"96002_CR3","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.cardfail.2013.04.002","volume":"19","author":"MM Givertz","year":"2013","unstructured":"Givertz, M. M. et al. Acute decompensated heart failure: Update on new and emerging evidence and directions for future research. J. Card. Fail. 19(6), 371\u2013389 (2013).","journal-title":"J. Card. Fail."},{"issue":"6","key":"96002_CR4","first-page":"433","volume":"104","author":"DC de Albuquerque","year":"2015","unstructured":"de Albuquerque, D. C. et al. I Brazilian registry of heart failure\u2014Clinical aspects, care quality and hospitalization outcomes. Arq. Bras. Cardiol. 104(6), 433\u2013442 (2015).","journal-title":"Arq. Bras. Cardiol."},{"issue":"1","key":"96002_CR5","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.ijcard.2004.04.006","volume":"102","author":"LE Rohde","year":"2005","unstructured":"Rohde, L. E. et al. Health outcomes in decompensated congestive heart failure: A comparison of tertiary hospitals in Brazil and United States. Int. J. Cardiol. 102(1), 71\u201377 (2005).","journal-title":"Int. J. Cardiol."},{"issue":"10","key":"96002_CR6","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1016\/S0735-1097(03)00309-7","volume":"41","author":"A Nohria","year":"2003","unstructured":"Nohria, A. et al. Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure. J. Am. Coll. Cardiol. 41(10), 1797\u20131804 (2003).","journal-title":"J. Am. Coll. Cardiol."},{"issue":"4","key":"96002_CR7","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1111\/j.1527-5299.2004.03317.x","volume":"10","author":"L Beck-da-Silva","year":"2004","unstructured":"Beck-da-Silva, L. et al. Persistent orthopnea and the prognosis of patients in the heart failure clinic. Congest. Heart Fail. 10(4), 177\u2013180 (2004).","journal-title":"Congest. Heart Fail."},{"issue":"6","key":"96002_CR8","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.jacc.2013.04.070","volume":"62","author":"FH Verbrugge","year":"2013","unstructured":"Verbrugge, F. H. et al. Abdominal contributions to cardiorenal dysfunction in congestive heart failure. J. Am. Coll. Cardiol. 62(6), 485\u2013495 (2013).","journal-title":"J. Am. Coll. Cardiol."},{"issue":"6","key":"96002_CR9","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1007\/s11936-011-0148-3","volume":"13","author":"S Dandamudi","year":"2011","unstructured":"Dandamudi, S. & Chen, H. H. Evolving treatment strategies for management of cardiorenal syndrome. Curr. Treat. Options Cardiovasc. Med. 13(6), 556\u2013569 (2011).","journal-title":"Curr. Treat. Options Cardiovasc. Med."},{"issue":"20","key":"96002_CR10","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1056\/NEJMra1703100","volume":"377","author":"DH Ellison","year":"2017","unstructured":"Ellison, D. H. & Felker, G. M. Diuretic treatment in heart failure. N. Engl. J. Med. 377(20), 1964\u20131975 (2017).","journal-title":"N. Engl. J. Med."},{"issue":"6","key":"96002_CR11","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s11897-015-0273-5","volume":"12","author":"P Martens","year":"2015","unstructured":"Martens, P., Nijst, P. & Mullens, W. Current approach to decongestive therapy in acute heart failure. Curr. Heart Fail. Rep. 12(6), 367\u2013378 (2015).","journal-title":"Curr. Heart Fail. Rep."},{"issue":"2","key":"96002_CR12","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/ejhf.1369","volume":"21","author":"W Mullens","year":"2019","unstructured":"Mullens, W. et al. The use of diuretics in heart failure with congestion\u2014A position statement from the Heart Failure Association of the European Society of Cardiology: Diuretics in heart failure. Eur. J. Heart Fail. 21(2), 137\u2013155 (2019).","journal-title":"Eur. J. Heart Fail."},{"issue":"5","key":"96002_CR13","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1002\/ejhf.74","volume":"16","author":"RJ Mentz","year":"2014","unstructured":"Mentz, R. J. et al. Decongestion in acute heart failure: Decongestion in heart failure. Eur. J. Heart Fail. 16(5), 471\u2013482 (2014).","journal-title":"Eur. J. Heart Fail."},{"issue":"9","key":"96002_CR14","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1056\/NEJMoa1005419","volume":"364","author":"GM Felker","year":"2011","unstructured":"Felker, G. M. et al. Diuretic strategies in patients with acute decompensated heart failure. N. Engl. J. Med. 364(9), 797\u2013805 (2011).","journal-title":"N. Engl. J. Med."},{"issue":"19","key":"96002_CR15","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1016\/j.jacc.2010.06.034","volume":"56","author":"JC Jentzer","year":"2010","unstructured":"Jentzer, J. C., DeWald, T. A. & Hernandez, A. F. Combination of loop diuretics with thiazide-type diuretics in heart failure. J. Am. Coll. Cardiol. 56(19), 1527\u20131534 (2010).","journal-title":"J. Am. Coll. Cardiol."},{"issue":"7","key":"96002_CR16","first-page":"697","volume":"20","author":"LE Rohde","year":"2004","unstructured":"Rohde, L. E. et al. Reliability and prognostic value of traditional signs and symptoms in outpatients with congestive heart failure. Can. J. Cardiol. 20(7), 697\u2013702 (2004).","journal-title":"Can. J. Cardiol."},{"issue":"12","key":"96002_CR17","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1093\/oxfordjournals.eurheartj.a014805","volume":"17","author":"TPJ Dormans","year":"1996","unstructured":"Dormans, T. P. J. & Gerlag, P. G. G. Combination of high-dose furosemide and hydrochlorothiazide in the treatment of refractory congestive heart failure. Eur. Heart J. 17(12), 1867\u20131874 (1996).","journal-title":"Eur. Heart J."},{"issue":"19","key":"96002_CR18","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1093\/eurheartj\/ehu065","volume":"35","author":"MAE Valente","year":"2014","unstructured":"Valente, M. A. E. et al. Diuretic response in acute heart failure: Clinical characteristics and prognostic significance. Eur. Heart J. 35(19), 1284\u20131293 (2014).","journal-title":"Eur. Heart J."},{"issue":"1","key":"96002_CR19","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ejim.2013.08.711","volume":"25","author":"JP Ferreira","year":"2014","unstructured":"Ferreira, J. P. et al. Mineralocorticoid receptor antagonism in acutely decompensated chronic heart failure. Eur. J. Intern. Med. 25(1), 67\u201372 (2014).","journal-title":"Eur. J. Intern. Med."},{"issue":"9","key":"96002_CR20","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1001\/jamacardio.2017.2198","volume":"2","author":"J Butler","year":"2017","unstructured":"Butler, J. et al. Efficacy and safety of spironolactone in acute heart failure: The ATHENA-HF randomized clinical trial. JAMA Cardiol. 2(9), 950\u2013958 (2017).","journal-title":"JAMA Cardiol."},{"issue":"1","key":"96002_CR21","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1161\/CIRCHEARTFAILURE.111.963413","volume":"5","author":"M Metra","year":"2012","unstructured":"Metra, M. et al. Is worsening renal function an ominous prognostic sign in patients with acute heart failure?: The role of congestion and its interaction with renal function. Circ. Heart Fail. 5(1), 54\u201362 (2012).","journal-title":"Circ. Heart Fail."},{"issue":"12","key":"96002_CR22","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1001\/jamainternmed.2013.552","volume":"173","author":"GB Aliti","year":"2013","unstructured":"Aliti, G. B. et al. Aggressive fluid and sodium restriction in acute decompensated heart failure: A randomized clinical trial. JAMA Intern. Med. 173(12), 1058 (2013).","journal-title":"JAMA Intern. Med."},{"key":"96002_CR23","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.nut.2018.02.007","volume":"54","author":"KS Machado d'Almeida","year":"2018","unstructured":"Machado d\u2019Almeida, K. S. et al. Aggressive fluid and sodium restriction in decompensated heart failure with preserved ejection fraction: Results from a randomized clinical trial. Nutrition 54, 111\u2013117 (2018).","journal-title":"Nutrition"}],"updated-by":[{"DOI":"10.1038\/s41598-021-96943-y","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-96002-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-96002-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-96002-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T07:28:47Z","timestamp":1670052527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-96002-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,13]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["96002"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-96002-6","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-150836\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,13]]},"assertion":[{"value":"19 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2021","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-021-96943-y","URL":"https:\/\/doi.org\/10.1038\/s41598-021-96943-y","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16474"}}