{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:22:03Z","timestamp":1787163723160,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T00:00:00Z","timestamp":1631836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Advanced heart failure (HF) is a condition often requiring elevated doses of loop diuretics. Therefore, these patients often experience poor diuretic response. Both conditions have a detrimental impact on prognosis and hospitalization. Aims: This retrospective, multicenter study evaluates the effect of the addition of oral metolazone on diuretic response (DR), clinical congestion, NTproBNP values, and renal function over hospitalization phase. Follow-up analysis for a 6-month follow-up period was performed. Methods: We enrolled 132 patients with acute decompensated heart failure (ADHF) in advanced NYHA class with reduced ejection fraction (EF &lt; 40%) taking a mean furosemide amount of 250 \u00b1 120 mg\/day. Sixty-five patients received traditional loop diuretic treatment plus metolazone (Group M). The mean dose ranged from 7.5 to 15 mg for one week. Sixty-seven patients continued the furosemide (Group F). Congestion score was evaluated according to the ESC recommendations. DR was assessed by the formula diuresis\/40 mg of furosemide. Results: Patients in Group M and patients in Group F showed a similar prevalence of baseline clinical congestion (3.1 \u00b1 0.7 in Group F vs. 3 \u00b1 0.8 in Group M) and chronic kidney disease (CKD) (51% in Group M vs. 57% in Group F; p = 0.38). Patients in Group M experienced a better congestion score at discharge compared to patients in Group F (C score: 1 \u00b1 1 in Group M vs. 3 \u00b1 1 in Group F p &gt; 0.05). Clinical congestion resolution was also associated with weight reduction (\u22126 \u00b1 2 in Group M vs. \u22123 \u00b1 1 kg in Group F, p &lt; 0.05). Better DR response was observed in Group M compared to F (940 \u00b1 149 mL\/40 mgFUROSEMIDE\/die vs. 541 \u00b1 314 mL\/40 mgFUROSEMIDE\/die; p &lt; 0.01), whereas median \u0394NTproBNP remained similar between the two groups (\u22124819 \u00b1 8718 in Group M vs. \u22123954 \u00b1 5560 pg\/mL in Group F NS). These data were associated with better daily diuresis during hospitalization in Group M (2820 \u00b1 900 vs. 2050 \u00b1 1120 mL p &lt; 0.05). No differences were found in terms of WRF development and electrolyte unbalance at discharge, although Group M had a significant saline solution administration during hospitalization. Follow-up analysis did not differ between the group but a reduced trend for recurrent hospitalization was observed in the M group (26% vs. 38%). Conclusions: Metolazone administration could be helpful in patients taking an elevated loop diuretics dose. Use of thiazide therapy is associated with better decongestion and DR. Current findings could suggest positive insights due to the reduced amount of loop diuretics in patients with advanced HF.<\/jats:p>","DOI":"10.3390\/jcm10184207","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T21:23:29Z","timestamp":1631913809000},"page":"4207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Effects of Metolazone Administration on Congestion, Diuretic Response and Renal Function in Patients with Advanced Heart Failure"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6235-984X","authenticated-orcid":false,"given":"Alberto","family":"Palazzuoli","sequence":"first","affiliation":[{"name":"Cardiovascular Diseases Unit, Department of Medical Sciences, Le Scotte Hospital, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Ruocco","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Riuniti of Valdichiana Hospital, USL SUD-EST Toscana, Montepulciano, 53045 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6211-4482","authenticated-orcid":false,"given":"Paolo","family":"Severino","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal Anesthesiology and Cardiovascular Sciences, University La Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Gennari","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases Unit, Department of Medical Sciences, Le Scotte Hospital, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Pirrotta","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases Unit, Department of Medical Sciences, Le Scotte Hospital, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Stefanini","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases Unit, Department of Medical Sciences, Le Scotte Hospital, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9296-0281","authenticated-orcid":false,"given":"Francesco","family":"Tramonte","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases Unit, Department of Medical Sciences, Le Scotte Hospital, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Feola","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Regina Montis Regalis Hospital, 12084 Mondov\u00ec, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Mancone","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal Anesthesiology and Cardiovascular Sciences, University La Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fedele","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal Anesthesiology and Cardiovascular Sciences, University La Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,17]]},"reference":[{"key":"ref_1","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":"ref_2","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1093\/eurheartj\/ehab082","article-title":"The conceptual basis for a universal definition of heart failure: Congestion due to cardiac dysfunction","volume":"42","author":"Cleland","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s13054-015-1017-3","article-title":"Loop diuretics in acute heart failure: Beyond the decongestive relief for the kidney","volume":"19","author":"Palazzuoli","year":"2015","journal-title":"Crit. Care."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/clc.20771","article-title":"Loop Diuretic Therapy in Heart Failure: The Need for Solid Evidence on a Fluid Issue","volume":"33","author":"Chiong","year":"2010","journal-title":"Clin. Cardiol."},{"key":"ref_5","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":"ref_6","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ejhf.1369","article-title":"The use of diuretics in heart failure with congestion\u2014A position statement from the Heart Failure Association of the European Society of Cardiology","volume":"21","author":"Mullens","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ahj.2010.05.032","article-title":"Diuretic dose and long-term outcomes in elderly patients with heart failure after hospitalization","volume":"160","author":"Tu","year":"2010","journal-title":"Am. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.ahj.2012.08.019","article-title":"Effect of admission oral diuretic dose on response to continuous versus bolus intravenous diuretics in acute heart failure: An analysis from diuretic optimization strategies in acute heart failure","volume":"164","author":"Shah","year":"2012","journal-title":"Am. Heart J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1161\/CIRCHEARTFAILURE.108.821785","article-title":"Loop diuretics in acute decompensated heart failure: Necessary? Evil? A necessary evil?","volume":"2","author":"Felker","year":"2009","journal-title":"Circ. Heart Fail."},{"key":"ref_10","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":"ref_11","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1002\/ejhf.2145","article-title":"Diuretic response and effects of diuretic omission in ambulatory heart failure patients on chronic low-dose loop diuretic therapy","volume":"23","author":"Dauw","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ahj.2015.05.003","article-title":"Diuretic response in acute heart failure-an analysis from ASCEND-HF","volume":"170","author":"Dunning","year":"2015","journal-title":"Am. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1093\/eurheartj\/ehu065","article-title":"Diuretic response in acute heart failure: Clinical characteristics and prognostic significance","volume":"35","author":"Valente","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.jacc.2010.06.034","article-title":"Combination of loop diuretics with thiazide-type diuretics in heart failure","volume":"56","author":"Jentzer","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1002\/ejhf.1236","article-title":"Advanced heart failure: A position statement of the Heart Failure Association of the European Society of Cardiology","volume":"20","author":"Metra","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/ehf2.12226","article-title":"Rationale and study design of intravenous loop diuretic administration in acute heart failure: DIUR-AHF","volume":"4","author":"Palazzuoli","year":"2017","journal-title":"ESC Heart Fail."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1093\/eurjhf\/hfq045","article-title":"Assessing and grading congestion in acute heart failure: A scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine","volume":"12","author":"Gheorghiade","year":"2010","journal-title":"Eur. J. Heart Fail."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1093\/eurheartj\/ehu320","article-title":"Terminology and definition of changes renal function in heart failure","volume":"35","author":"Damman","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nrcardio.2014.215","article-title":"Diuretic response in acute heart failure-pathophysiology, evaluation, and therapy","volume":"12","author":"Valente","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7326\/0003-4819-103-1-1","article-title":"Acute vasoconstriction response to intravenous furosemide in patients with chronic congestive heart failure. Activation of neurohormonal axis","volume":"103","author":"Francis","year":"1985","journal-title":"Ann. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.ejheart.2007.07.011","article-title":"Relation between dose of loop diuretics and outcomes in heart failure population: Results of the ESCAPE trial","volume":"9","author":"Hasselblad","year":"2007","journal-title":"Eur. J. Heart Fail."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jchf.2014.09.007","article-title":"Intravenous fluids in acute decompensated heart failure","volume":"3","author":"Bikdeli","year":"2015","journal-title":"JACC Heart Fail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jchf.2019.10.012","article-title":"Real World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure: A US. Center\u2019s Experience","volume":"8","author":"Griffin","year":"2020","journal-title":"JACC Heart Fail."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ijcard.2014.03.020","article-title":"Hypertonic saline with furosemide for the treatment of acute congestive heart failure: A systematic review and meta-analysis","volume":"173","author":"Gandhi","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jchf.2019.11.010","article-title":"Hypertonic Saline: The Genesis of the Exodus of Fluid in Heart Failure?","volume":"8","author":"Costanzo","year":"2020","journal-title":"JACC Heart Fail."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1093\/eurjhf\/hfr121","article-title":"Impact of diuretic dosing on mortality in acute heart failure using a propensity matched study","volume":"13","author":"Yilmaz","year":"2011","journal-title":"Eur. J. Heart Fail."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ijcard.2016.09.005","article-title":"Different diuretic dose and response in acute decompensated heart failure: Clinical characteristics and prognostic significance","volume":"224","author":"Palazzuoli","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s10557-016-6697-7","article-title":"Cardiac Dysfunction, Congestion and Loop Diuretics: Their Relationship to Prognosis in Heart Failure","volume":"30","author":"Pellicori","year":"2016","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ijcard.2017.03.114","article-title":"An exploratory analysis of the competing effects of aggressive decongestion and high-dose loop diuretic therapy in the DOSE trial","volume":"241","author":"Hanberg","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10741-019-09851-9","article-title":"Loop diuretic resistance complicating acute heart failure","volume":"25","author":"Cox","year":"2020","journal-title":"Heart Fail. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/s41569-020-0379-7","article-title":"Congestion in heart failure: A contemporary look at physiology, diagnosis and treatment","volume":"17","author":"Boorsma","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1093\/eurheartj\/ehr042","article-title":"Early dyspnoea relief in acute heart failure: Prevalence, association with mortality, and effect of rolofylline in the P.RO.TE.CT Study","volume":"32","author":"Metra","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ijcard.2018.01.067","article-title":"Prevalence, predictors and clinical outcome of residual congestion in acute decompensated heart failure","volume":"258","author":"Demissei","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1161\/CIRCHEARTFAILURE.114.001957","article-title":"Relief and Recurrence of Congestion During and After Hospitalization for Acute Heart Failure: Insights from Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARESS-HF)","volume":"8","author":"Lala","year":"2015","journal-title":"Circ. Heart Fail."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/ejhf.74","article-title":"Decongestion in acute heart failure","volume":"16","author":"Mentz","year":"2014","journal-title":"Eur. J. Heart Fail."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1093\/eurheartj\/ehn048","article-title":"measurement in clinical trial of acute heart failure syndromes: The need for an uniform approach","volume":"29","author":"Pang","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/ejhf.872","article-title":"Organ dysfunction, injury and failure in acute heart failure: From pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (E.SC)","volume":"19","author":"Harjola","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e009149","DOI":"10.1161\/JAHA.118.009149","article-title":"Outcomes Associated with a Strategy of Adjuvant Metolazone or High-Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis","volume":"7","author":"Houser","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1002\/phar.1798","article-title":"Efficacy and Safety of Intravenous Chlorothiazide versus Oral Metolazone in Patients with Acute Decompensated Heart Failure and Loop Diuretic Resistance","volume":"36","author":"Shulenberger","year":"2016","journal-title":"Pharmacotherapy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jchf.2019.09.012","article-title":"Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure: The 3T Trial","volume":"8","author":"Cox","year":"2020","journal-title":"JACC Heart Fail."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/18\/4207\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:01:06Z","timestamp":1760166066000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/18\/4207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,17]]},"references-count":40,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["jcm10184207"],"URL":"https:\/\/doi.org\/10.3390\/jcm10184207","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,17]]}}}