{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:09:51Z","timestamp":1785416991936,"version":"3.56.0"},"reference-count":122,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"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>Congestion is the main therapeutic target of acute heart failure (HF) treatment, and loop diuretics (LDs) are widely used drugs for this purpose. Despite their extensive use, these agents remain largely understudied in terms of modality administration, treatment duration, and escalation dose for subjects responding poorly to therapy. LDs were initially investigated in several edematous statuses such as cirrhosis, nephrotic syndrome, and congestive HF and initially approved for the treatment of cardiogenic congestion in 1966. Despite the long history and the undoubted role in congestion management, the use of LDs in the acute phase is mostly based on the physician\u2019s experience, the oral amount chronically administered, and clinical decongestion response. Recent literature suggests monitoring diuretic activity by the evaluation of daily diuresis, weight loss, and sample urinary sodium assessment after early intravenous LD administration. More recently, the measurement of urinary sodium integrated with urinary and blood creatinine values and fluid status has been suggested as optimal marker to predict whole diuretic efficiency and to target the optimal dose. However, this method is not easily available in the chronic setting or in patients with recurrent hospitalization taking a high loop diuretic amount. Since high loop diuretic dose is related to diuretic resistance (DR) and poorer outcome, additional diuretics acting in different nephron sites are often required. Current sequential nephron blockade can stimulate diuresis by synergic mechanisms. This strategy is attempted in patients with poor response, revealing good results in the early period, but the effects of neuro-endocrine stimulation and electrolyte balance across long-term follow-up are still questioned. This paper reviews the historical course of loop diuretics and highlights the need for a universal approach based on clinical conditions, cardio\u2013renal interactions, and HF phenotypes.<\/jats:p>","DOI":"10.3390\/jcm13061674","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T04:47:05Z","timestamp":1710478025000},"page":"1674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Changing Role of Loop Diuretics in Heart Failure Management across the Last Century"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6235-984X","authenticated-orcid":false,"given":"Alberto","family":"Palazzuoli","sequence":"first","affiliation":[{"name":"Cardiovascular Diseases Unit Cardio Thoracic and Vascular Department, Le Scotte Hospital, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4683-4639","authenticated-orcid":false,"given":"Pietro","family":"Mazzeo","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Azienda Ospedaliera Regionale \u201cSan Carlo\u201d, 85100 Potenza, Italy"},{"name":"Cardiology Division, San Pio Da Pietrelcina Hospital, Azienda Ospedaliera Regionale \u201cSan Carlo\u201d, 66054 Marsicovetere, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martino","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Clinical Cardiology, AOU San Giovanni di Dio e Ruggi D\u2019Aragona, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2823-1797","authenticated-orcid":false,"given":"Christian","family":"Cadeddu Dessalvi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Mariano","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Policlinico Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2352-2103","authenticated-orcid":false,"given":"Andrea","family":"Salzano","sequence":"additional","affiliation":[{"name":"Cardiac Unit, AORN A Cardarelli, 80131 Naples, Italy"},{"name":"Cardiac Unit, University Hospital of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Severino","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University Policlinico Umberto I, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fedele","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University Policlinico Umberto I, 00161 Rome, Italy"},{"name":"Istituto Nazionale Ricerche Cardiovascolari (INRC), 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/ejhf.1502","article-title":"Clinical phenotypes of acute heart failure based on signs and symptoms of perfusion and congestion at emergency department presentation and their relationship with patient management and outcomes","volume":"21","author":"Javaloyes","year":"2019","journal-title":"Eur. 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