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Coppola S, Chiumello D, Adnan A, Pozzi T, Forni LG, Gattinoni L. Diuretics in critically ill patients: a narrative review of their mechanisms and applications. Br J Anaesth 2025; 134:1638-1647. [PMID: 40221314 DOI: 10.1016/j.bja.2025.02.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 01/30/2025] [Accepted: 02/27/2025] [Indexed: 04/14/2025] Open
Abstract
Diuretics remain the cornerstone therapy of critically ill patients with volume overload as a result of cardiac failure, acute kidney injury or aggressive fluid resuscitation. This review summarises the principles of applied renal physiology, describing the mechanisms of action, the clinical applications, and the adverse effects of commonly used diuretics during critical illness. Loop diuretics, and in particular furosemide, remain the most popular, despite evidence of any effect on mortality or, indeed, on the need for renal replacement therapy. The efficacy of loop diuretics after administration depends on three factors. Firstly, the tubular concentration of the diuretic: continuous infusion of furosemide seems to provide a higher and more stable tubular concentration of furosemide with respect to bolus injection. Secondly, the interaction with albumin both in the plasma and in the renal tubule: despite a strong physiological rationale supporting this approach, albumin supplementation in hypoalbuminaemic patients does not seem to result in a higher diuretic efficacy. Thirdly, diuretic resistance, which can be addressed by optimising loop diuretic dose and by using combination therapy with other agents, including thiazides or thiazide-like diuretics or carbonic anhydrase inhibitors. These drugs constitute a useful adjunct to overcome loop diuretic resistance. Other agents such as distal potassium-sparing diuretics and osmotic diuretics can also be considered. The latter have been used successfully in hypokalaemia, rhabdomyolysis-associated acute kidney injury or to prevent ischaemia-reperfusion injury in kidney transplantation. Finally, this review provides the basic concepts of the interplay between acid-base equilibrium and diuretic therapy.
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Affiliation(s)
- Silvia Coppola
- Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital, Milan, Italy
| | - Davide Chiumello
- Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital, Milan, Italy; Department of Health Sciences, University of Milan, Milan, Italy; Coordinated Research Center on Respiratory Failure, University of Milan, Milan, Italy.
| | - Afiqah Adnan
- Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
| | - Tommaso Pozzi
- Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital, Milan, Italy; Department of Health Sciences, University of Milan, Milan, Italy
| | - Lui G Forni
- Royal Surrey Hospital NHS Foundation Trust, Guildford, UK; School of Medicine, University of Surrey, Kate Granger Building, Guildford, UK
| | - Luciano Gattinoni
- Department of Anaesthesiology, University Medical Center Göttingen, Göttingen, Germany
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Veasaw K, Mahmood U, Fishkin T, Frishman WH, Aronow WS. Treatment of Acute Heart Failure with Acetazolamide. Cardiol Rev 2025; 33:269-271. [PMID: 37754779 DOI: 10.1097/crd.0000000000000615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Abstract
The primary treatment for acute heart failure includes the use of intravenous loop diuretics to reduce congestion. Successful decongestion at the time of hospital discharge improves mortality and prevents rehospitalization in these patients. Loop diuretic therapy alone may not be enough for adequate decongestion, especially as diuretic resistance becomes more common. Other therapies include the addition of thiazide diuretics, though increasing evidence might suggest a better alternative to add-on therapy. In this review, we will discuss the new evidence for the use of the diuretic acetazolamide in acute heart failure.
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Affiliation(s)
| | - Uzair Mahmood
- Department of Cardiology, Westchester Medical Center, New York Medical College, Valhalla, NY
| | | | | | - Wilbert S Aronow
- From the Department of Medicine
- Department of Cardiology, Westchester Medical Center, New York Medical College, Valhalla, NY
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3
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Cuthbert JJ, Luo E, Ahmed ASM, Ajith M, Butt H, Pinhol H, Baffour Korsah F, Bulemfu J, Ford S, Constable G, Cox L, Rigby AS, Clark AL. Rationale and design of the acetazolamide as a chloride sparing diuretic in patients admitted with heart failure (ADA-HF) trial. EUROPEAN HEART JOURNAL OPEN 2025; 5:oeaf019. [PMID: 40134849 PMCID: PMC11934269 DOI: 10.1093/ehjopen/oeaf019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 08/15/2024] [Accepted: 02/13/2025] [Indexed: 03/27/2025]
Abstract
Aims The Acetazolamide as a chloride-sparing Diuretic in patients Admitted with Heart Failure (ADA-HF) trial will assess the safety and diuretic effect of oral ACZ given alongside a high-dose IV loop diuretic in patients admitted to the hospital with heart failure (HF) and severe fluid retention. Hypochloraemia is common in patients with HF and is associated with worse outcomes, but there are few treatment options available: we will also assess whether ACZ reduces urine chloride loss. Methods and results The ADA-HF trial is a single centre, open-label, randomized-controlled trial of ACZ 250 mg twice daily plus standard care vs. standard care alone. The trial duration is 4 days. We will recruit 50 patients with severe peripheral oedema due to HF requiring standard care (240 mg of IV furosemide per day given via continuous infusion at 10 mg per hour). The co-primary endpoints are (1) the difference in net fluid loss daily, and over 4 days; and (2) difference in serum chloride concentrations between baseline and day 4. The trial has 80% power to detect a difference in fluid balance of 500-1000 mL per day; and a difference in serum chloride concentration of 1 mmol/L per day. Secondary endpoints include but are not limited to: time to recruit per patient; rate of adverse events; rate of recruitment; and cause-specific rate of drop-out of the study. Conclusion ACZ may be a useful adjunct to diuretic therapy, but the safety and diuretic efficacy of oral ACZ when used alongside high-dose loop diuretics is unknown. ADA-HF will complement the ADVOR trial and may clarify what role ACZ may have for patients with severe congestion. Trial registration ISRCTN registry. ISRCTN13060336. Registered on 09/02/2023. URL: https://doi.org/10.1186/ISRCTN13060336.
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Affiliation(s)
- Joseph J Cuthbert
- Clinical Sciences Centre, Hull York Medical School, University of Hull, Cottingham Road, Kingston-Upon-Hull HU6 7RX, UK
- Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Elton Luo
- Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Aia S M Ahmed
- Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Meenakshy Ajith
- Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Hafiz Butt
- Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Henrietta Pinhol
- Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Felix Baffour Korsah
- Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Jeanne Bulemfu
- Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Sarah Ford
- Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Grant Constable
- Research and Development, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Leanne Cox
- Research and Development, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
| | - Alan S Rigby
- Hull York Medical School, University of Hull, Cottingham Road, Kingston-Upon-Hull HU6 7RX, UK
| | - Andrew L Clark
- Department of Cardiology, Hull University Teaching Hospital NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull HU16 5JQ, UK
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4
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Eda S, Kaur M, Rehman MM, Sompalli S, Blair K, Chaudhari SS, Wei CR, Allahwala D. Effectiveness of Acetazolamide in Patients With Heart Failure: A Systematic Review and Meta-Analysis. Cureus 2024; 16:e75778. [PMID: 39816299 PMCID: PMC11733630 DOI: 10.7759/cureus.75778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2024] [Indexed: 01/18/2025] Open
Abstract
This systematic review and meta-analysis evaluated the efficacy and safety of acetazolamide as an adjunctive diuretic therapy in acute heart failure (AHF) patients. A comprehensive literature search was conducted across multiple electronic databases, including PubMed, Embase, Cochrane Library, and Scopus, identifying seven studies (five randomized controlled trials and two observational studies) that met the eligibility criteria. The analysis revealed that acetazolamide significantly enhanced mean natriuresis (mean differences (MD) 52.72 mmol, 95% confidence interval (CI: 15.52 to 89.92) and mean diuresis (MD 432.88 mmol, 95% CI: 205.82 to 659.93) compared to control groups. However, no significant difference was observed in all-cause mortality between patients receiving acetazolamide and those who did not (relative risks (RR): 1.23, 95% CI: 0.86 to 1.76, p-value: 0.25). While high heterogeneity was reported in natriuresis outcomes (I2: 90%), diuresis results showed no heterogeneity (I2: 0%). These findings suggest that acetazolamide effectively enhances fluid removal when used in combination with standard loop diuretics, supporting its role as adjunctive therapy in AHF management. However, limitations, including the small number of studies and inclusion of both RCTs and observational studies, indicate the need for further large-scale trials to better understand acetazolamide's impact on long-term outcomes and identify specific patient populations who may benefit most from this therapy.
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Affiliation(s)
- Sanjay Eda
- Medicine, MNR Medical College and Hospital, Sangareddy, IND
| | - Mandeep Kaur
- Hospital Medicine, Hospital Corporation of America (HCA) Capital Regional Medical Center, Tallahassee, USA
| | - Mian M Rehman
- Cardiology, Combined Military Hospital (CMH) Lahore Medical College and Institute of Dentistry, Lahore, PAK
| | | | - Keron Blair
- Medicine, American International School of Medicine, Georgetown, GUY
| | - Sandipkumar S Chaudhari
- Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, USA
- Family Medicine, University of North Dakota School of Medicine and Health Sciences, Fargo, USA
| | - Calvin R Wei
- Research and Development, Shing Huei Group, Taipei, TWN
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Milbradt TL, Sudo RYU, Gobbo MODS, Akinfenwa S, Moura B. Acetazolamide therapy in patients with acute heart failure: a systematic review and meta-analysis of randomized controlled trials. Heart Fail Rev 2024; 29:1039-1047. [PMID: 38985385 DOI: 10.1007/s10741-024-10417-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/03/2024] [Indexed: 07/11/2024]
Abstract
Acute heart failure (AHF) often leads to unfavorable outcomes due to fluid overload. While diuretics are the cornerstone treatment, acetazolamide may enhance diuretic efficiency by reducing sodium reabsorption. We performed a systematic review and meta-analysis on the effects of acetazolamide as an add-on therapy in patients with AHF compared to diuretic therapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCT). A random-effects model was employed to compute mean differences and risk ratios. Statistical analysis was performed using R software. The GRADE approach was used to rate the certainty of the evidence. We included 4 RCTs with 634 patients aged 68 to 81 years. Over a mean follow-up of 3 days to 34 months, acetazolamide significantly increased diuresis (MD 899.2 mL; 95% CI 249.5 to 1549; p < 0.01) and natriuresis (MD 72.44 mmol/L; 95% CI 39.4 to 105.4; p < 0.01) after 48 h of its administration. No association was found between acetazolamide use and WRF (RR 2.4; 95% CI 0.4 to 14.2; p = 0.3) or all-cause mortality (RR 1.2; 95% CI 0.8 to 1.9; p = 0.3). Clinical decongestion was significantly higher in the intervention group (RR 1.35; 95% CI 1.09 to 1.68; p = 0.01). Acetazolamide is an effective add-on therapy in patients with AHF, increasing diuresis, natriuresis, and clinical decongestion, but it was not associated with differences in mortality.
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Affiliation(s)
| | - Renan Yuji Ura Sudo
- Division of Medicine, Federal University of Grande Dourados, Dourados, Brazil
| | | | - Stephen Akinfenwa
- Division of Internal Medicine, University of Connecticut, Farmington, United States of America
| | - Brenda Moura
- Division of Cardiology, Porto Armed Forces Hospital, Porto, Portugal
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Llàcer P, Romero G, Trullàs JC, de la Espriella R, Cobo M, Quiroga B, Casado J, Slon-Roblero MF, Morales-Rull JL, Morgado JI, Ortiz A, Formiga F, Melendo-Viu M, de Sequera P, Recio A, Díez J, Manzano L, Núñez J. Consensus on the approach to hydrosaline overload in acute heart failure. SEMI/SEC/S.E.N. recommendations. REVISTA ESPANOLA DE CARDIOLOGIA (ENGLISH ED.) 2024; 77:556-565. [PMID: 38432324 DOI: 10.1016/j.rec.2024.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 01/09/2024] [Indexed: 03/05/2024]
Abstract
Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.).
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Affiliation(s)
- Pau Llàcer
- Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (Irycis), Madrid, Spain; Departamento de Medicina y Especialidades Médicas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
| | - Gregorio Romero
- Servicio de Nefrología, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain; Grupo de Trabajo de Medicina CardioRenal (CaReSEN), Sociedad Española de Nefrología (S.E.N.)
| | - Joan Carles Trullàs
- Servicio de Medicina Interna, Hospital d'Olot i Comarcal de la Garrotxa, Olot, Girona, Spain; Laboratori de Reparació i Regeneració Tissular (TRbLab), Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central (IrisCC), Barcelona, Spain
| | - Rafael de la Espriella
- Servicio de Cardiología, Hospital Clínico Universitario, Universitat de València, Instituto de Investigación Sanitaria del Hospital Clínico de Valencia (Incliva), Valencia, Spain; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
| | - Marta Cobo
- Servicio de Cardiología, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana (IDIPHISA), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
| | - Borja Quiroga
- Servicio de Nefrología, Hospital Universitario de La Princesa, Instituto de Investigación del Hospital de La Princesa (IIS-La Princesa), Madrid, Spain
| | - Jesús Casado
- Servicio de Medicina Interna, Hospital Universitario de Getafe, Getafe, Madrid, Spain
| | - María F Slon-Roblero
- Servicio de Nefrología, Hospital Universitario de Navarra, Pamplona, Navarra, Spain; Área de las Enfermedades Cardiovasculares y Renales, Instituto Navarro para la Investigación de la Salud (IdiSNA), Pamplona, Navarra, Spain
| | - José Luis Morales-Rull
- Servicio de Medicina Interna, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica (IRBLleida), Lleida, Spain
| | | | - Alberto Ortiz
- Servicio de Nefrología e Hipertensión, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (iiS-FJD), Universidad Autónoma de Madrid (UAM), Red de Investigación Cooperativa Orientada a Resultados en Salud b0d0 (RICORSb0d0), Madrid, Spain; Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Francesc Formiga
- Servicio de Medicina Interna, Hospital Universitari de Bellvitge, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
| | - María Melendo-Viu
- Servicio de Cardiología, Hospital Universitario Álvaro Cunqueiro, Vigo, Pontevedra, Spain
| | - Patricia de Sequera
- Servicio de Nefrología, Hospital Universitario Infanta Leonor, Universidad Complutense de Madrid, Madrid, Spain
| | - Alejandro Recio
- Servicio de Cardiología, Hospital Universitario Virgen Macarena, Sevilla, Spain
| | - Javier Díez
- Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Navarra, Spain
| | - Luis Manzano
- Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (Irycis), Madrid, Spain; Departamento de Medicina y Especialidades Médicas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
| | - Julio Núñez
- Servicio de Cardiología, Hospital Clínico Universitario, Universitat de València, Instituto de Investigación Sanitaria del Hospital Clínico de Valencia (Incliva), Valencia, Spain; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
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Sosa Mercado I, Putot S, Fertu E, Putot A. Acetazolamide Tolerance in Acute Decompensated Heart Failure: An Observational Study. J Clin Med 2024; 13:3421. [PMID: 38929950 PMCID: PMC11204894 DOI: 10.3390/jcm13123421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 06/03/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024] Open
Abstract
Objectives: This real-life study aimed to evaluate the safety of acetazolamide (ACZ), a carbonic anhydrase inhibitor with diuretic effects. ACZ has recently been proven to improve decongestion in the context of patients hospitalized for acute heart failure (HF). However, data in terms of safety are lacking. Methods: We conducted a monocentric observational prospective study from November 2023 to February 2024 in a 12-bed cardiology department, recording adverse events (hypotension, severe metabolic acidosis, severe hypokalemia and renal events) during in-hospital HF treatment. All patients hospitalized for acute HF during the study period treated with ACZ (500 mg IV daily for 3 days) on top of IV furosemide (n = 28, 48.3%) were compared with patients who have been treated with IV furosemide alone (n = 30, 51.7%). Results: The patients treated with ACZ were younger than those without (median age 78 (range 67-86) vs. 85 (79-90) years, respectively, p = 0.01) and had less frequent chronic kidney disease (median estimated glomerular fraction rate (60 (35-65) vs. 38 (26-63) mL/min, p = 0.02). As concerned adverse events during HF treatment, there were no differences in the occurrences of hypotension (three patients [10.7%] in the ACZ group vs. four [13.3%], p = 0.8), renal events (four patients [14.3%] in the ACZ group vs. five [16.7%], p = 1) and severe hypokalemia (two [7.1%] in the ACZ group vs. three [10%], p = 1). No severe metabolic acidosis occurred in either group. Conclusions: Although the clinical characteristics differed at baseline, with younger age and better renal function in patients receiving ACZ, the tolerance profile did not significantly differ from patients receiving furosemide alone. Additional observational data are needed to further assess the safety of ACZ-furosemide combination in the in-hospital management of HF, especially in older, frail populations.
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Affiliation(s)
- Ignacio Sosa Mercado
- Department of Cardiology and Vascular Diseases, Hôpitaux du Pays du Mont Blanc, 74700 Sallanches, France; (I.S.M.); (S.P.); (E.F.)
| | - Sophie Putot
- Department of Cardiology and Vascular Diseases, Hôpitaux du Pays du Mont Blanc, 74700 Sallanches, France; (I.S.M.); (S.P.); (E.F.)
| | - Elena Fertu
- Department of Cardiology and Vascular Diseases, Hôpitaux du Pays du Mont Blanc, 74700 Sallanches, France; (I.S.M.); (S.P.); (E.F.)
| | - Alain Putot
- Department of Internal Medicine and Infectious Diseases, Hôpitaux du Pays du Mont Blanc, 74700 Sallanches, France
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Siddiqi AK, Maniya MT, Alam MT, Ambrosy AP, Fudim M, Greene SJ, Khan MS. Acetazolamide as an Adjunctive Diuretic Therapy for Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs 2024; 24:273-284. [PMID: 38416359 DOI: 10.1007/s40256-024-00633-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/29/2024] [Indexed: 02/29/2024]
Abstract
BACKGROUND Recent evidence suggests that acetazolamide may be beneficial as an adjunctive diuretic therapy in patients with acute decompensated heart failure (HF). We aim to pool all the studies conducted until now and provide updated evidence regarding the role of acetazolamide as adjunctive diuretic in patients with acute decompensated HF. METHODS PubMed/Medline, Cochrane Library, and Scopus were searched from inception until July 2023, for randomized and nonrandomized studies evaluating acetazolamide as add-on diuretic in patients with acute decompensated HF. Data about natriuresis, urine output, decongestion, and the clinical signs of congestion were extracted, pooled, and analyzed. Data were pooled using a random effects model. Results were presented as risk ratios (RRs), odds ratios (ORs), or weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Certainty of evidence was assessed using the grading of recommendation, assessment, development, and evaluation (GRADE) approach. A P value of < 0.05 was considered significant in all cases. RESULTS A total of 5 studies (n = 684 patients) were included with a median follow-up time of 3 months. Pooled analysis demonstrated significantly increased natriuresis (MD 55.07, 95% CI 35.1-77.04, P < 0.00001; I2 = 54%; moderate certainty), urine output (MD 1.04, 95% CI 0.10-1.97, P = 0.03; I2 = 79%; moderate certainty) and decongestion [odds ratio (OR) 1.62, 95% CI 1.14-2.31, P = 0.007; I2 = 0%; high certainty] in the acetazolamide group, as compared with controls. There was no significant difference in ascites (RR 0.56, 95% CI 0.23-1.36, P = 0.20; I2 = 0%; low certainty), edema (RR 1.02, 95% CI 0.52-2.0, P = 0.95; I2 = 45%; very low certainty), raised jugular venous pressure (JVP) (RR 0.86, 95% CI 0.63-1.17, P = 0.35; I2 = 0%; low certainty), and pulmonary rales (RR 0.82, 95% CI 0.44-1.51, P = 0.52; I2 = 25%; low certainty) between the two groups. CONCLUSIONS Acetazolamide as an adjunctive diuretic significantly improves global surrogate endpoints for decongestion therapy but not all individual signs and symptoms of volume overload. SYSTEMATIC REVIEW REGISTRATION This systematic review was prospectively registered on the PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ), registration number CRD498330.
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Affiliation(s)
| | | | | | - Andrew P Ambrosy
- Department of Cardiology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA
- Kaiser Permanente Northern California Division of Research, Oakland, CA, USA
| | - Marat Fudim
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
- Division of Cardiology, Duke University School of Medicine, Duke University Medical Center, 2301 Erwin Rd., Durham, NC, 27705, USA
| | - Stephen J Greene
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
- Division of Cardiology, Duke University School of Medicine, Duke University Medical Center, 2301 Erwin Rd., Durham, NC, 27705, USA
| | - Muhammad Shahzeb Khan
- Division of Cardiology, Duke University School of Medicine, Duke University Medical Center, 2301 Erwin Rd., Durham, NC, 27705, USA.
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9
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Wilson BJ, Bates D. Diuretic Strategies in Acute Decompensated Heart Failure: A Narrative Review. Can J Hosp Pharm 2024; 77:e3323. [PMID: 38204501 PMCID: PMC10754413 DOI: 10.4212/cjhp.3323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 06/15/2023] [Indexed: 01/12/2024]
Abstract
Background Heart failure is a common condition with considerable associated costs, morbidity, and mortality. Patients often present to hospital with dyspnea and edema. Inadequate inpatient decongestion is an important contributor to high readmission rates. There is little evidence concerning diuresis to guide clinicians in caring for patients with acute decompensated heart failure. Contemporary diuretic strategies have been defined by expert opinion and older landmark clinical trials. Objective To present a narrative review of contemporary recommendations, along with their underlying evidence and pharmacologic rationale, for diuretic strategies in inpatients with acute decompensated heart failure. Data Sources PubMed, OVID, and Embase databases were searched from inception to December 22, 2022, with the following search terms: heart failure, acute heart failure, decompensated heart failure, furosemide, bumetanide, ethacrynic acid, hydrochlorothiazide, indapamide, metolazone, chlorthalidone, spironolactone, eplerenone, and acetazolamide. Study Selection Randomized controlled trials and systematic reviews involving at least 100 adult patients (> 18 years) were included. Trials involving torsemide, chlorothiazide, and tolvaptan were excluded. Data Synthesis Early, aggressive administration of a loop diuretic has been associated with expedited symptom resolution, shorter length of stay, and possibly reduced mortality. Guidelines make recommendations about dose and frequency but do not recommend any particular loop diuretic over another; however, furosemide is most commonly used. Guidelines recommend that the initial furosemide dose (on admission) be 2-2.5 times the patient's home dose. A satisfactory diuretic response can be defined as spot urine sodium content greater than 50-70 mmol/L at 2 hours; urine output greater than 100-150 mL/h in the first 6 hours or 3-5 L in 24 hours; or a change in weight of 0.5-1.5 kg in 24 hours. If congestion persists after the maximization of loop diuretic therapy over the first 24-48 hours, an adjunctive diuretic such as thiazide or acetazolamide should be added. If decongestion targets are not met, continuous infusion of furosemide may be considered. Conclusions Heart failure with congestion can be managed with careful administration of high-dose loop diuretics, supported by thiazides and acetazolamide when necessary. Clinical trials are underway to further evaluate this strategy.
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Affiliation(s)
- Ben J Wilson
- , MD, FRCPC, is a Clinical Assistant Professor with the Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta
| | - Duane Bates
- , BScPharm, ACPR, is a Clinical Pharmacist with the Calgary Zone, Alberta Health Services, Calgary, Alberta
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Sabina M, Barakat Z, Feliciano A, Lamb A, Alsamman MM. Unlocking the Potential of Acetazolamide: A Literature Review of an Adjunctive Approach in Heart Failure Management. J Clin Med 2024; 13:288. [PMID: 38202295 PMCID: PMC10780103 DOI: 10.3390/jcm13010288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 12/28/2023] [Accepted: 01/01/2024] [Indexed: 01/12/2024] Open
Abstract
Background: Heart failure (HF) patients often experience persistent fluid overload despite standard diuretic therapy. The adjunctive use of acetazolamide, a carbonic anhydrase inhibitor, in combination with loop diuretics has shown promise in improving decongestion and diuretic efficacy. This literature review aims to analyze six studies evaluating the effectiveness of acetazolamide as an additive treatment for acute decompensated heart failure (ADHF) and its impact on various outcomes. Methods: We searched the PubMed database using the terms "acetazolamide heart failure". We refined our search with specific filters (as shown our PRISMA flow diagram) and exclusion criteria, narrowing down our results to five studies. We included an extra study via expert recommendation, ultimately including six studies for comprehensive analysis. Results: The review highlights the positive effects of acetazolamide on decongestion, natriuresis, and diuresis in HF patients. However, it also showcases the limitations of these trials. Discussion: While the reviewed studies demonstrate the potential benefits of acetazolamide in enhancing decongestion and diuretic efficiency, there are limitations to consider, including small sample sizes, lack of blinding, and limited external validity. Further research is needed to confirm these findings, compare acetazolamide with other diuretic combinations, and explore its effects in a broader population of heart failure patients, including those in the United States. The use of acetazolamide in HF management warrants continued investigation to optimize its role in improving decongestion and patient outcomes.
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Affiliation(s)
- Michael Sabina
- Lakeland Regional Health Medical Center, Lakeland 33805-4500, FL, USA; (Z.B.); (A.F.); (A.L.); (M.M.A.)
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Villaschi A, Pellegrino M, Condorelli G, Chiarito M. Diuretic Combination Therapy in Acute Heart Failure: An Updated Review. Curr Pharm Des 2024; 30:2597-2605. [PMID: 39005124 DOI: 10.2174/0113816128316596240625110337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 05/30/2024] [Indexed: 07/16/2024]
Abstract
Loop diuretics are the cornerstone of decongestive therapy in patients presenting with acute heart failure and have been extensively studied in randomized clinical trials. Therefore, in current guidelines, they are the only drug with a class I recommendation to treat signs and symptoms of congestion when present. However, the percentage of patients achieving successful decongestion is suboptimal, and diuretic resistance frequently develops. Patients with a poor response to loop diuretics and those discharged with residual signs of congestion are characterized by a worse prognosis over time. Recently, a renovated interest in different diuretic classes sprouted among heart failure researchers in order to improve decongestion strategies and ameliorate short- and long-term clinical outcomes. Randomized clinical trials investigating associations among diuretic classes and loop diuretics have been performed but yielded variable results. Therefore, despite initial evidence of a possible benefit from some of these compounds, a definite way to approach diuretic resistance via diuretic combination therapy is still missing. The aim of this review is to summarize current clinical evidence on the use of diuretic combination therapy in patients with acute heart failure and to suggest a possible approach to avoid or counteract diuretic resistance.
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Affiliation(s)
- Alessandro Villaschi
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Marta Pellegrino
- Department of Cardiology, Ospedale Maggiore ASST Lodi, Lodi, Italy
| | - Gianluigi Condorelli
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Mauro Chiarito
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
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12
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Frățilă G, Sorohan BM, Achim C, Andronesi A, Obrișcă B, Lupușoru G, Zilișteanu D, Jurubiță R, Bobeică R, Bălănică S, Micu G, Mocanu V, Ismail G. Oral Furosemide and Hydrochlorothiazide/Amiloride versus Intravenous Furosemide for the Treatment of Resistant Nephrotic Syndrome. J Clin Med 2023; 12:6895. [PMID: 37959360 PMCID: PMC10648037 DOI: 10.3390/jcm12216895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 10/30/2023] [Accepted: 11/01/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Data on diuretic treatment in nephrotic syndrome (NS) are scarce. Our goal was to assess the non-inferiority of the combined oral diuretics (furosemide/hydrochlorothiazide/amiloride) compared to intravenous (i.v.) furosemide in patients with NS and resistant edema. METHODS We conducted a prospective randomized trial on 22 patients with resistant nephrotic edema (RNE), defined as hypervolemia and a FENa < 0.2%. Based on a computer-generated 1:1 randomization, we assigned patients to receive either intravenous furosemide (40 mg bolus and then continuous administration of 5 mg/h) or oral furosemide (40 mg/day) and hydrochlorothiazide/amiloride (50/5 mg/day) for a period of 5 days. Clinical and laboratory measurements were performed daily. Hydration status was assessed by bioimpedance on day 1 and at the end of day 5 after treatment initiation. The primary endpoint was weight change from baseline to day 5. Secondary endpoints were hydration status change measured by bioimpedance and safety outcomes (low blood pressure, severe electrolyte disturbances, acute kidney injury and worsening hypervolemia). RESULTS Primary endpoint analysis showed that after 5 days of treatment, there was a significant difference in weight change from baseline between groups [adjusted mean difference: -3.33 kg (95% CI: -6.34 to -0.31), p = 0.03], with a higher mean weight change in the oral diuretic treatment group [-7.10 kg (95% CI: -18.30 to -4.30) vs. -4.55 kg (95%CI: -6.73 to -2.36)]. Secondary endpoint analysis showed that there was no significant difference between groups regarding hydration status change [adjusted mean difference: -0.05 L (95% CI: -2.6 to 2.6), p = 0.96], with a mean hydration status change in the oral diuretic treatment group of -4.71 L (95% CI: -6.87 to -2.54) and -3.91 L (95% CI: -5.69 to -2.13) in the i.v. diuretic treatment group. We observed a significant decrease in adjusted mean serum sodium of -2.15 mmol/L [(95% CI: -4.25 to -0.05), p = 0.04]), favored by the combined oral diuretic treatment [-2.70 mmol/L (95% CI: -4.89 to -0.50) vs. -0.10 mmol/L (95%CI: -1.30 to 1.10)]. No statistically significant difference was observed between the two groups in terms of adverse events. CONCLUSIONS A combination of oral diuretics based on furosemide, amiloride and hydrochlorothiazide is non-inferior to i.v. furosemide in weight control of patients with RNE and a similar safety profile.
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Affiliation(s)
- Georgiana Frățilă
- Department of Nephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (G.F.); (C.A.); (A.A.); (B.O.); (G.L.); (D.Z.); (G.I.)
| | - Bogdan Marian Sorohan
- Department of Nephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (G.F.); (C.A.); (A.A.); (B.O.); (G.L.); (D.Z.); (G.I.)
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Camelia Achim
- Department of Nephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (G.F.); (C.A.); (A.A.); (B.O.); (G.L.); (D.Z.); (G.I.)
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
| | - Andreea Andronesi
- Department of Nephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (G.F.); (C.A.); (A.A.); (B.O.); (G.L.); (D.Z.); (G.I.)
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
| | - Bogdan Obrișcă
- Department of Nephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (G.F.); (C.A.); (A.A.); (B.O.); (G.L.); (D.Z.); (G.I.)
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
| | - Gabriela Lupușoru
- Department of Nephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (G.F.); (C.A.); (A.A.); (B.O.); (G.L.); (D.Z.); (G.I.)
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
| | - Diana Zilișteanu
- Department of Nephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (G.F.); (C.A.); (A.A.); (B.O.); (G.L.); (D.Z.); (G.I.)
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
| | - Roxana Jurubiță
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
| | - Raluca Bobeică
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
| | - Sonia Bălănică
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
| | - Georgia Micu
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
| | - Valentin Mocanu
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
| | - Gener Ismail
- Department of Nephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (G.F.); (C.A.); (A.A.); (B.O.); (G.L.); (D.Z.); (G.I.)
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; (R.J.); (R.B.); (S.B.); (G.M.); (V.M.)
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Tamargo J, Agewall S, Borghi C, Ceconi C, Cerbai E, Dan GA, Ferdinandy P, Grove EL, Rocca B, Sulzgruber P, Semb AG, Sossalla S, Niessner A, Kaski JC, Dobrev D. New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2023; 9:pvad034. [PMID: 37169875 PMCID: PMC10236523 DOI: 10.1093/ehjcvp/pvad034] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/10/2023] [Accepted: 05/10/2023] [Indexed: 05/13/2023]
Abstract
Cardiovascular diseases (CVD) remain the leading cause of death worldwide and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022 including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of "old" drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensin receptor blockers plus β-blockers), and secondary cardiovascular prevention (i.e. low-dose aspirin, ramipril and atorvastatin), thereby filling existing gaps in knowledge, and opening new avenues for the treatment of CVD. Clinical trials confirming the role of dapagliflozin in patients with HF and mildly reduced or preserved ejection fraction, long-term evolocumab to reduce the risk of cardiovascular events, vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation, antibiotic prophylaxis in patients at high risk for infective endocarditis before invasive dental procedures, and vutrisiran for the treatment of hereditary transthyretin-related amyloidosis with polyneuropathy were also reviewed. Finally, we briefly discuss recent clinical trials suggesting that FXIa inhibitors may have the potential to uncouple thrombosis from hemostasis and attenuate/prevent thromboembolic events with minimal disruption of hemostasis.
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Affiliation(s)
- Juan Tamargo
- Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón, Plaza de Ramón y Cajal s/n, Madrid 28040, Spain
| | - Stefan Agewall
- Department of Cardiology, Oslo University Hospital and Institute of Clinical Medicine, Oslo University, Oslo, Norvay
| | - Claudio Borghi
- Department of Cardiovascular Medicine, University of Bologna-IRCCS AOU S. Orsola, Bologna, Italy
| | - Claudio Ceconi
- Unit of Cardiologia, ASST Garda, Desenzano del Garda, Italy
| | - Elisabetta Cerbai
- Department Neurofarba, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy
| | - Gheorghe A Dan
- “Carol Davila” University of Medicine, Colentina University Hospital, Bucharest, Romania
| | - Péter Ferdinandy
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
- Pharmahungary Group, Szeged, Hungary
| | - Erik Lerkevang Grove
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark
| | - Bianca Rocca
- Section of Pharmacology, Catholic University School of Medicine, Rome, Italy
| | - Patrick Sulzgruber
- Department of Medicine, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Anne Grete Semb
- Preventive Cario-Rheuma Clinic, Division of Research and Innovation, REMEDY Centre, Diakonhjemmet Hospital, Oslo, Norway
| | - Samuel Sossalla
- Department of Internal Medicine II, University Regensburg, Regensburg, Germany
| | - Alexander Niessner
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Juan Carlos Kaski
- Molecular and Clinical Sciences Research Institute, St. George's, University of London, Cranmer Terrace, London SW17 0RE, UK
| | - Dobromir Dobrev
- Institute of Pharmacology, West-German Heart and Vascular Centre, University Duisburg-Essen, Essen, Germany
- Department of Medicine, Montreal Heart Institute and Université de Montréal, Montréal, Canada
- Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA
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Khan J, Graham FJ, Masini G, Iaconelli A, Friday JM, Lang CC, Pellicori P. Congestion and Use of Diuretics in Heart Failure and Cardiomyopathies: a Practical Guide. Curr Cardiol Rep 2023; 25:411-420. [PMID: 37074565 DOI: 10.1007/s11886-023-01865-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/19/2023] [Indexed: 04/20/2023]
Abstract
PURPOSE OF REVIEW Heart failure is a highly prevalent condition caused by many different aetiologies and characterised by cardiac dysfunction and congestion. Once developed, congestion leads to signs (peripheral oedema) and symptoms (breathlessness on exertion), adverse cardiac remodelling, and an increased risk of hospitalisation and premature death. This review summarises strategies that could enable early identification and a more objective management of congestion in patients with heart failure. RECENT FINDINGS For patients with suspected or diagnosed heart failure, combining an echocardiogram with assessment of great veins, lungs, and kidneys by ultrasound might facilitate recognition and quantification of congestion, the management of which is still difficult and highly subjective. Congestion is a one of the key drivers of morbidity and mortality in patients with heart failure and is often under-recognised. The use of ultrasound allows for a timely, simultaneous identification of cardiac dysfunction and multiorgan congestion; ongoing and future studies will clarify how to tailor diuretic treatments in those with or at risk of heart failure.
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Affiliation(s)
| | - Fraser J Graham
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
| | - Gabriele Masini
- Cardiothoracic and Vascular Department, University of Pisa, Pisa, Italy
- Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy
| | - Antonio Iaconelli
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
- Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy
| | - Jocelyn M Friday
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
| | - Chim C Lang
- NHS Tayside, Dundee, UK
- Department of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK
| | - Pierpaolo Pellicori
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
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15
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Malik BA, Nnodebe I, Fayaz A, Inayat H, Murtaza SF, Umer M, Zaidi SAT, Amin A. Effect of Acetazolamide as Add-On Diuretic Therapy in Patients With Heart Failure: A Meta-Analysis. Cureus 2023; 15:e37792. [PMID: 37213994 PMCID: PMC10198661 DOI: 10.7759/cureus.37792] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/18/2023] [Indexed: 05/23/2023] Open
Abstract
The aim of this meta-analysis was to assess the effectiveness of acetazolamide as an add-on diuretic therapy in patients with heart failure. This meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. A systematic literature search was independently performed by two authors using MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews to identify relevant studies assessing the use of acetazolamide in patients with heart failure. The search keywords included "acetazolamide" and "heart failure". The outcomes assessed in this meta-analysis included natriuresis (mmol/L), diuresis (Liters) and decongestion (absence of signs of volume overload) by 72 hours. Other outcomes assessed in this meta-analysis included hospitalization due to heart failure and all-cause mortality. A total of three studies included a total of 569 heart failure patients. The number of patients achieved decongestion was significantly higher in patients receiving acetazolamide compared to the patients randomized in the control group (RR: 1.34, 95% CI: 1.06-1.67). Compared to patients in the control group, mean natriuresis was significantly higher in acetazolamide patients (MD: 74.91, 95% CI: 39.85-109.97). Diuresis was significantly higher in patients receiving acetazolamide compared to the control group (MD: 0.44, 95% CI: 0.16-0.72). No significant difference was found between the two groups in terms of all-cause mortality and hospitalization due to heart failure. In conclusion, our meta-analysis suggests that acetazolamide may have beneficial impacts on heart failure patients by increasing the number of successful decongestions. Additionally, patients who were treated with acetazolamide had significantly higher natriuresis and diuresis compared to patients in the control group.
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Affiliation(s)
- Bilal Aziz Malik
- Internal Medicine, CMH Lahore Medical College and Institute of Dentistry, Lahore, PAK
| | - Ijeoma Nnodebe
- Medicine, Basingstoke and North Hampshire Hospital, Basingstoke, GBR
| | - Azrung Fayaz
- Medicine, Khyber Teaching Hospital, Peshawar, PAK
| | - Habiba Inayat
- Internal Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | | | - Muhammed Umer
- Internal Medicine, Dow University of Health Sciences, Civil Hospital Karachi, Karachi, PAK
| | | | - Adil Amin
- Cardiology, Pakistan Navy Station (PNS) Shifa, Karachi, PAK
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Persistent Hypochloremia Is Associated with Adverse Prognosis in Patients Repeatedly Hospitalized for Heart Failure. J Clin Med 2023; 12:jcm12041257. [PMID: 36835793 PMCID: PMC9962161 DOI: 10.3390/jcm12041257] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 01/30/2023] [Accepted: 02/03/2023] [Indexed: 02/09/2023] Open
Abstract
BACKGROUND Hypochloremia reflects neuro-hormonal activation in patients with heart failure (HF). However, the prognostic impact of persistent hypochloremia in those patients remains unclear. METHODS We collected the data of patients who were hospitalized for HF at least twice between 2010 and 2021 (n = 348). Dialysis patients (n = 26) were excluded. The patients were divided into four groups based on the absence/presence of hypochloremia (<98 mmol/L) at discharge from their first and second hospitalizations: Group A (patients without hypochloremia at their first and second hospitalizations, n = 243); Group B (those with hypochloremia at their first hospitalization and without hypochloremia at their second hospitalization, n = 29); Group C (those without hypochloremia at their first hospitalization and with hypochloremia at their second hospitalization, n = 34); and Group D (those with hypochloremia at their first and second hospitalizations, n = 16). RESULTS a Kaplan-Meier analysis revealed that all-cause mortality and cardiac mortality were the highest in Group D compared to the other groups. A multivariable Cox proportional hazard analysis revealed that persistent hypochloremia was independently associated with both all-cause death (hazard ratio 3.490, p < 0.001) and cardiac death (hazard ratio 3.919, p < 0.001). CONCLUSIONS In patients with HF, prolonged hypochloremia over two hospitalizations is associated with an adverse prognosis.
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Côté JM, Goulamhoussen N, McMahon BA, Murray PT. Diuretic combinations in critically ill patients with respiratory failure: A systematic review and meta-analysis. World J Crit Care Med 2022; 11:178-191. [PMID: 36331969 PMCID: PMC9136719 DOI: 10.5492/wjccm.v11.i3.178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/11/2022] [Accepted: 04/24/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In patients with respiratory failure, loop diuretics remain the cornerstone of the treatment to maintain fluid balance, but resistance is common.
AIM To determine the efficacy and safety of common diuretic combinations in critically ill patients with respiratory failure.
METHODS We searched MEDLINE, Embase, Cochrane Library and PROSPERO for studies reporting the effects of a combination of a loop diuretic with another class of diuretic. A meta-analysis using mean differences (MD) with 95% confidence interval (CI) was performed for the 24-h fluid balance (primary outcome) and the 24-h urine output, while descriptive statistics were used for safety events.
RESULTS Nine studies totalling 440 patients from a total of 6510 citations were included. When compared to loop diuretics alone, the addition of a second diuretic is associated with an improved negative fluid balance at 24 h [MD: -1.06 L (95%CI: -1.46; -0.65)], driven by the combination of a thiazide plus furosemide [MD: -1.25 L (95%CI: -1.68; -0.82)], while no difference was observed with the combination of a loop-diuretic plus acetazolamide [MD: -0.40 L (95%CI: -0.96; 0.16)] or spironolactone [MD: -0.65 L (95%CI: -1.66; 0.36)]. Heterogeneity was high and the report of clinical and safety endpoints varied across studies.
CONCLUSION Based on limited evidence, the addition of a second diuretic to a loop diuretic may promote diuresis and negative fluid balance in patients with respiratory failure, but only when using a thiazide. Further larger trials to evaluate the safety and efficacy of such interventions in patients with respiratory failure are required.
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Affiliation(s)
- Jean Maxime Côté
- Division of Nephrology, Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal H2X0C1, Québec, Canada
| | - Nadir Goulamhoussen
- Division of Nephrology, Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal H2X0C1, Québec, Canada
| | - Blaithin A McMahon
- Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Patrick T Murray
- Department of Medicine, School of Medicine, University College Dublin, Dublin D078NN, Ireland
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18
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de la Espriella R, Santas E, Zegri Reiriz I, Górriz JL, Cobo Marcos M, Núñez J. Quantification and treatment of congestion in heart failure: A clinical and pathophysiological overview. Nefrologia 2022; 42:145-162. [PMID: 36153911 DOI: 10.1016/j.nefroe.2021.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 04/06/2021] [Indexed: 06/16/2023] Open
Abstract
Renal sodium and water retention with resulting extracellular volume expansion and redistribution are hallmark features of heart failure syndromes. However, congestion assessment, monitoring, and treatment represent a real challenge in daily clinical practice. This document reviewed historical and contemporary evidence of available methods for determining volume status and discuss pharmacological aspects and pathophysiological principles that underlie diuretic use.
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Affiliation(s)
- Rafael de la Espriella
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, Spain; Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, Spain
| | - Enrique Santas
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, Spain; Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, Spain
| | - Isabel Zegri Reiriz
- Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, Spain; Servicio de Cardiología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Jose Luis Górriz
- Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, Spain; Servicio de Nefrología, Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, Spain; Departamento de Medicina, Universidad de Valencia, Spain
| | - Marta Cobo Marcos
- Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, Spain; Servicio de Cardiología, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain; CIBER Cardiovascular, Spain
| | - Julio Núñez
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, Spain; CIBER Cardiovascular, Spain.
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19
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Tellor KB, Armbruster AL. Key Points for Pharmacists From the ACC Expert Consensus Decision Pathway for Patients Hospitalized With Heart Failure. J Pharm Pract 2022; 36:662-667. [PMID: 35038280 DOI: 10.1177/08971900211064709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Heart failure (HF) is a complex condition, and its clinical course often includes periods of decompensation that represent a deterioration in clinical status. During these periods, patients may experience worsening HF symptoms requiring hospitalization. Heart failure that necessitates hospitalization increases the risk of mortality and rehospitalization. In order to help facilitate appropriate care of patients hospitalized with HF, the American College Cardiology (ACC) published an expert consensus decision pathway (ECDP) that focuses on a multidisciplinary approach. The ECDP is divided into multiple nodes and pharmacists play integral roles in each one. There are many opportunities for pharmacists to optimize medical therapy, reinforce adherence, and provide medication and disease state education throughout hospitalization. This review article will highlight inpatient medication management of HF for hospital pharmacists.
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Affiliation(s)
| | - Anastasia L Armbruster
- St. Louis College of Pharmacy at University of Health Sciences and Pharmacy, St. Louis, MO, USA
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20
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Inpatient Diuretic Management of Acute Heart Failure: A Practical Review. Am J Cardiovasc Drugs 2021; 21:595-608. [PMID: 33709346 DOI: 10.1007/s40256-020-00463-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/10/2020] [Indexed: 02/08/2023]
Abstract
The inpatient treatment of acute heart failure (AHF) is aimed at achieving euvolemia, relieving symptoms, and reducing rehospitalization. Adequate treatment of AHF is rooted in understanding the pharmacokinetics and pharmacodynamics of select diuretic agents used to achieve decongestion. While loop diuretics remain the primary treatment of AHF, the dosing strategies of loop diuretics and the use of adjunct diuretic classes to augment clinical response can be complex. This review examines the latest strategies for diuretic management in patients with AHF, including dosing and monitoring strategies, interaction of diuretics with other medication classes, use adjunctive therapies, and assessing endpoints for diuretic. The goal of the review is to guide the reader through commonly encountered clinical scenarios and pitfalls in the diuretic management of patients with AHF.
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21
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de la Espriella R, Santas E, Zegri Reiriz I, Górriz JL, Cobo Marcos M, Núñez J. Quantification and Treatment of Congestion in Heart Failure: A Clinical and Pathophysiological Overview. Nefrologia 2021; 42:S0211-6995(21)00114-4. [PMID: 34289940 DOI: 10.1016/j.nefro.2021.04.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/27/2021] [Accepted: 04/06/2021] [Indexed: 01/12/2023] Open
Abstract
Renal sodium and water retention with resulting extracellular volume expansion and redistribution are hallmark features of heart failure syndromes. However, congestion assessment, monitoring, and treatment represent a real challenge in daily clinical practice. This document reviewed historical and contemporary evidence of available methods for determining volume status and discuss pharmacological aspects and pathophysiological principles that underlie diuretic use.
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Affiliation(s)
- Rafael de la Espriella
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, España; Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, España
| | - Enrique Santas
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, España; Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, España
| | - Isabel Zegri Reiriz
- Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, España; Servicio de Cardiología, Hospital de la Santa Creu i Sant Pau, Barcelona, España
| | - José Luis Górriz
- Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, España; Servicio de Nefrología, Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, España; Departamento de Medicina, Universidad de Valencia, España
| | - Marta Cobo Marcos
- Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, España; Servicio de Cardiología, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, España; CIBER Cardiovascular, España
| | - Julio Núñez
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, España; Grupo de Trabajo Cardiorrenal, Asociación de Insuficiencia Cardiaca, Sociedad Española de Cardiología, España; Departamento de Medicina, Universidad de Valencia, España; CIBER Cardiovascular, España.
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22
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Chrysant SG, Chrysant GS. The pathophysiology and management of diuretic resistance in patients with heart failure. Hosp Pract (1995) 2021; 50:93-101. [PMID: 33596757 DOI: 10.1080/21548331.2021.1893065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVES The objectives of the study are to investigate the causes of diuretic resistance in patients with advanced congestive heart failure (CHF), since diuretics are the cornerstone of treatment of these patients. Several studies have shown that diuretic resistance in patients with advanced CHF is common, ranging from 25% to 50% in hospitalized patients. METHODS In order to get a current perspective as to the magnitude of diuretic resistance in such patients, a focused Medline search of the English language literature was conducted between 2015 and 2020 using the search terms, CHF, diuretics, treatment, resistance, frequency, and 30 papers with pertinent information were selected. RESULTS The analysis of data from the selected papers demonstrated that diuretic resistance is common in hospitalized patients with advanced CHF and frequently associated with renal failure, which is secondary to CHF. CONCLUSIONS Diuretic resistance appears to be common in patients with advanced CHF and it is mostly due to decreased cardiac output, low blood pressure, decreased glomerular filtration rate, decreased filtration of sodium, and increased tubular reabsorption of sodium. Diuretic resistance in such patients can be overcome with the combination of loop diuretics with thiazide and thiazide-like diuretics, aldosterone antagonists, as well as other agents. The data from these studies in combination with collateral literature will be discussed in this review.
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Affiliation(s)
- Steven G Chrysant
- Department of cardiology, University of Oklahoma Health Sciences Center, Oklahoma, United States.,Department of cardiology, INTEGRIS Baptist Medical Center, Oklahoma, United States
| | - George S Chrysant
- Department of cardiology, University of Oklahoma Health Sciences Center, Oklahoma, United States.,Department of cardiology, INTEGRIS Baptist Medical Center, Oklahoma, United States
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23
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Narasimhan B, Aravinthkumar R, Correa A, Aronow WS. Pharmacotherapeutic principles of fluid management in heart failure. Expert Opin Pharmacother 2021; 22:595-610. [PMID: 33560159 DOI: 10.1080/14656566.2020.1850694] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Introduction: Heart failure is a major public health concern that is expected to increase over the decades to come. Despite significant advances, fluid overload and congestion remain a major therapeutic challenge. Vascular congestion and neurohormonal activation are intricately linked and the goal of therapy fundamentally aims to reduce both.Areas covered: The authors briefly review a number of core concepts that elucidate the link between fluid overload and neuro-hormonal activation. This is followed by a review of heart-kidney interactions and the impact of diuresis in this setting. Following an in-depth review of currently available pharmacological agents, the rationale and evidence behind their use, the authors end with a brief note on novel agents/approaches to aid volume management in HF.Expert opinion: A number of non-pharmacological advances in the management of volume overload in heart failure, though promising - are associated with a number of shortcomings. Pharmacological therapy remains the cornerstone of volume management. A number of novel approaches, utilizing existing therapies as well as the emergence of new agents over the past decade bode well for the vulnerable HF population.
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Affiliation(s)
- Bharat Narasimhan
- Department of Medicine, Mount Sinai Morningside, Mount Sinai West, New York, NY
| | | | - Ashish Correa
- Department of Cardiology, Mount Sinai Morningside, Mount Sinai West, Icahn School of Medicine at Mount Sinai
| | - Wilbert S Aronow
- Department of Cardiology, Westchester Medical center/New York Medical College, Valhalla, NY
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24
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Kataoka H. Proposal for New Classification and Practical Use of Diuretics According to Their Effects on the Serum Chloride Concentration: Rationale Based on the "Chloride Theory". Cardiol Ther 2020; 9:227-244. [PMID: 32378135 PMCID: PMC7584720 DOI: 10.1007/s40119-020-00172-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Indexed: 02/06/2023] Open
Abstract
Currently, diuretic therapy for heart failure (HF) pathophysiology is primarily focused on the sodium and water balance. Over the last several years, however, chloride (Cl) has been recognized to have an important role in HF pathophysiology, as both a prognostic marker and a possible central factor regulating the body fluid status. I recently proposed a unifying hypothesis for HF pathophysiology, called the "chloride theory", during HF worsening and recovery, as follows. Chloride is the key electrolyte for regulating both reabsorption of tubular electrolytes and water in the kidney through the renin-angiotensin-aldosterone system and distributing body fluid in each compartment of the body. As changes between the serum Cl concentration and plasma volume are intimately associated with worsening HF and its recovery after decongestive therapy, modulation of the serum Cl concentration by careful selection and combination of various diuretics and their doses could become an attractive therapeutic option for HF. In this review, I will propose a new classification and practical use of diuretics according to their effects on the serum Cl concentration. Diuretic use according to this classification is expected to be a useful strategy for the treatment of patients with HF.
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26
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Abstract
Recent studies have shown impressive cardiovascular health benefits in individuals treated with SGLT2 inhibitors (SGLT2i) regardless of diabetic status. The underlying mechanisms driving these benefits are not well understood. Recently in Circulation, Griffin et al. (2020) reported the first human study investigating the diuretic effect of empagliflozin.
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Affiliation(s)
- Ashish Verma
- Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
| | - Ankit B Patel
- Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Sushrut S Waikar
- Section of Nephrology, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA
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27
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Congestion in heart failure: a contemporary look at physiology, diagnosis and treatment. Nat Rev Cardiol 2020; 17:641-655. [DOI: 10.1038/s41569-020-0379-7] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/02/2020] [Indexed: 12/14/2022]
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28
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Zymliński R, Stepinska J. Looking for Medications to Support the Treatment of Acute Decompensated Heart Failure. Cardiology 2020; 145:224-226. [DOI: 10.1159/000505902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 01/13/2020] [Indexed: 11/19/2022]
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29
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Kataoka H. Comparison of Changes in Plasma Volume and Renal Function between Acetazolamide and Conventional Diuretics: Understanding the Mechanical Differences according to the "Chloride Theory". Cardiology 2019; 145:215-223. [PMID: 31865322 DOI: 10.1159/000504533] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Accepted: 11/04/2019] [Indexed: 11/19/2022]
Abstract
OBJECTIVE We compared the effects of the chloride-regaining diuretic acetazolamide with those of conventional diuretics on plasma volume, serum electrolytes, and renal function in acutely decompensated heart failure (HF) patients. METHODS A retrospective analysis was performed on the data of 13 patients treated with acetazolamide (Group A) and 13 patients with conventional diuretics (Group B) matched based on diuresis-induced weight reduction (≥1 kg) during resolution of worsening HF. Changes in plasma volume (Strauss formula), renal function, and serum electrolytes under treatment were determined by peripheral blood tests. RESULTS Clinical characteristics at baseline were not different between groups A and B. After diuretic therapy, body weight reduction (-2.23 ± 1.11 vs. -2.22 ± 1.06 kg, p = 0.97) and the number of residual HF-related signs (0.31 ± 0.48 vs. 0.23 ± 0.44, p = 0.67) was not different between groups. After each treatment, the serum chloride concen-tration increased in Group A, but decreased in Group B (+5.31 ± 4.91 vs. - 4.54 ± 4.68 mEq/L, p < 0.0001). Plasma volume (0.63 ± 13.1 vs. -12.1 ± 10.5%, p < 0.01) and renal function determined by changes in serum creatinine concentration (0.048 ± 0.12 vs. 0.21 ± 0.24 mg/dL, p < 0.047) were preserved in Group A compared with Group B. CONCLUSIONS While both groups exhibited equivalent body weight reduction and resolution of HF-related signs after each diuretic treatment, acetazolamide treatment preserved plasma volume and renal function compared to conventional diuretics.
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30
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Hollenberg SM, Warner Stevenson L, Ahmad T, Amin VJ, Bozkurt B, Butler J, Davis LL, Drazner MH, Kirkpatrick JN, Peterson PN, Reed BN, Roy CL, Storrow AB. 2019 ACC Expert Consensus Decision Pathway on Risk Assessment, Management, and Clinical Trajectory of Patients Hospitalized With Heart Failure: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2019; 74:1966-2011. [PMID: 31526538 DOI: 10.1016/j.jacc.2019.08.001] [Citation(s) in RCA: 233] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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31
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Verbrugge FH, Martens P, Ameloot K, Haemels V, Penders J, Dupont M, Tang WHW, Droogné W, Mullens W. Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance. Eur J Heart Fail 2019; 21:1415-1422. [PMID: 31074184 DOI: 10.1002/ejhf.1478] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 03/06/2019] [Accepted: 04/08/2019] [Indexed: 01/24/2023] Open
Abstract
AIMS To investigate the effects of acetazolamide on natriuresis, decongestion, kidney function and neurohumoral activation in acute heart failure (AHF). METHODS AND RESULTS This prospective, two-centre study included 34 AHF patients on loop diuretics with volume overload. All had a serum sodium concentration < 135 mmol/L and/or serum urea/creatinine ratio > 50 and/or an admission serum creatinine increase of > 0.3 mg/dL compared to baseline. Patients were randomised towards acetazolamide 250-500 mg daily plus bumetanide 1-2 mg bid vs. high-dose loop diuretics (bumetanide bid with daily dose twice the oral maintenance dose). The primary endpoint was natriuresis after 24 h. Natriuresis after 24 h was similar in the combinational treatment vs. loop diuretic only arm (264 ± 126 vs. 234 ± 133 mmol; P = 0.515). Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide (84 ± 46 vs. 52 ± 42 mmol/mg bumetanide; P = 0.048). More patients in the combinational treatment arm had an increase in serum creatinine levels > 0.3 mg/dL (P = 0.046). N-terminal pro-B-type natriuretic peptide reduction and peak neurohumoral activation within 72 h 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 = 0.098). CONCLUSION 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. TRIAL REGISTRATION ClinicalTrials.gov NCT01973335.
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Affiliation(s)
| | - Pieter Martens
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Koen Ameloot
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Veerle Haemels
- Department of Cardiovascular Medicine, UZ Leuven, Leuven, Belgium
| | - Joris Penders
- Department of Laboratory Medicine, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Matthias Dupont
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Wai Hong Wilson Tang
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Walter Droogné
- Department of Cardiovascular Medicine, UZ Leuven, Leuven, Belgium
| | - Wilfried Mullens
- Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium.,Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
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32
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Wongboonsin J, Thongprayoon C, Bathini T, Ungprasert P, Aeddula NR, Mao MA, Cheungpasitporn W. Acetazolamide Therapy in Patients with Heart Failure: A Meta-Analysis. J Clin Med 2019; 8:jcm8030349. [PMID: 30871038 PMCID: PMC6463174 DOI: 10.3390/jcm8030349] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 03/04/2019] [Accepted: 03/08/2019] [Indexed: 02/07/2023] Open
Abstract
Background and objectives: Fluid overload and central sleep apnea are highly prevalent in patients with heart failure (HF). We performed this meta-analysis to assess the effects of acetazolamide therapy on acid/base balance and apnea indexes. Methods: A literature search was conducted using EMBASE, MEDLINE, and Cochrane Database from inception through 18 November 2017 to identify studies evaluating the use of acetazolamide in HF. Study results were analyzed using a random effects model. The protocol for this systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017065401). Results: Nine studies (three randomized controlled trials and six cohort studies) with a total of 229 HF patients were enrolled. After acetazolamide treatment, there were significant decreases in serum pH (mean difference (MD) of −0.04 (95% CI, −0.06 to −0.02)), pCO2 (MD of −2.06 mmHg (95% CI, −3.60 to −0.53 mmHg)), and serum bicarbonate levels (MD of −6.42 mmol/L (95% CI, −10.05 to −2.79 mmol/L)). When compared to a placebo, acetazolamide significantly increased natriuresis (standardized mean difference (SMD) of 0.67 (95% CI, 0.08 to 1.27)), and decreased the apnea-hypopnea index (AHI) (SMD of −1.06 (95% CI, −1.75 to −0.36)) and central apnea index (CAI) (SMD of −1.10 (95% CI, −1.80 to −0.40)). Egger’s regression asymmetry tests revealed no publication bias with p = 0.20, 0.75 and 0.59 for analysis of the changes in pH, pCO2, and serum bicarbonate levels with use of acetazolamide in HF patients. Conclusion: Our study demonstrates significant reduction in serum pH, increase in natriuresis, and improvements in apnea indexes with use of acetazolamide among HF patients.
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Affiliation(s)
- Janewit Wongboonsin
- Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
| | - Tarun Bathini
- Department of Internal Medicine, University of Arizona, Tucson, AZ 85721, USA.
| | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
| | - Narothama Reddy Aeddula
- Division of Nephrology, Department of Medicine, Deaconess Health System, Evansville, IN 47747, USA.
| | - Michael A Mao
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
| | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
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Yang X, Zhu H, Yang X, Li N, Huang H, Liu T, Guo X, Xu X, Xia L, Deng C, Tian X, Yang Z. Targeting CAIX with [ 64Cu]XYIMSR-06 Small Molecular Radiotracer Enables Noninvasive PET Imaging of Malignant Glioma in U87 MG Tumor Cell Xenograft Mice. Mol Pharm 2019; 16:1532-1540. [PMID: 30803240 DOI: 10.1021/acs.molpharmaceut.8b01210] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Carbonic anhydrase IX (CAIX) plays an important role in glioma cell proliferation, invasion, metastasis, and resistance to radiotherapy and chemotherapy. An effective and noninvasive PET molecular imaging agent targeting CAIX would help its diagnosis and treatment but is not currently available. Recently, a low-molecular-weight (LMW) CAIX targeting agent, [64Cu]XYIMSR-06, was reported to have significantly improved properties for targeting clear cell renal cell carcinoma (ccRCC). We are encouraged to investigate the feasibility of adapting this agent for the diagnosis and treatment of CAIX-overexpressing malignant glioma. In vitro cell uptake and binding affinity assays were used to verify the binding capacity of [64Cu]XYIMSR-06 to U87 MG tumor cells in which CAIX overexpression was confirmed. The U87 MG tumor-bearing mouse (in situ and subcutaneous) model was built, and mice were injected with the radiotracer and/or coinjected with acetazolamide (0.2 g/kg) as a blocking agent for noninvasive micro-PET imaging. Micro-PET imaging was performed at 2, 4, and 8 h postinjection. ROI (region of interest)-based semiquantification was performed in an orthotopic glioma tumor model. Biodistribution throughout each organ was performed at 2, 4, 4 h block, 8, and 24 h postinjection. Hematoxylin and eosin (HE) staining and immunofluorescence or immunohistochemistry (IF/IHC) staining were implemented postimaging to assess the expression of CAIX in tumor organs. In vitro, [64Cu]XYIMSR-06 exhibits greater uptake in glioma cells (high CAIX expression) than in HCT116 cells (low CAIX expression). The binding affinity of [64Cu]XYIMSR-06 to U87 MG cell lines reaches up to 4.22 nM. Both orthotopic and subcutaneous tumors were clearly visualized at 2-8 h postinjection. Biodistribution studies demonstrated a maximum tumor uptake of 3.13% ID/g at 4 h postinjection, and the tumor to brain ratio (T/brain) was 6.51 at 8 h postinjection. The ROI-based T/brain values were 7.03 and 5.46 at 2 and 8 h postinjection, respectively. Histopathological analysis confirmed the overexpression of CAIX in gliomas, and the area of CAIX-positive IF staining is extremely consistent with the morphology on micro-PET imaging. In this study, [64Cu]XYIMSR-06 demonstrated specific accumulation in CAIX-expressing U87 MG glioma tumors, indicating that the radiotracer has the potential for noninvasively monitoring and guiding personalized treatment of malignant glioma and other tumors overexpressing CAIX.
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Affiliation(s)
- Xianteng Yang
- Guizhou University School of Medicine , Guiyang , Guizhou 550025 , China.,Department of Orthopaedics , People's Hospital of Guizhou Province , Guiyang , Guizhou 550002 , China
| | - Hua Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine , Peking University Cancer Hospital & Institute , Beijing 100142 , China
| | - Xing Yang
- Department of Nuclear Medicine , Peking University First Hospital , Beijing 100034 , China
| | - Nan Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine , Peking University Cancer Hospital & Institute , Beijing 100142 , China
| | - Haifeng Huang
- Guizhou University School of Medicine , Guiyang , Guizhou 550025 , China.,Department of Orthopaedics , People's Hospital of Guizhou Province , Guiyang , Guizhou 550002 , China
| | - Teli Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine , Peking University Cancer Hospital & Institute , Beijing 100142 , China
| | - Xiaoyi Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine , Peking University Cancer Hospital & Institute , Beijing 100142 , China
| | - Xiaoxia Xu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine , Peking University Cancer Hospital & Institute , Beijing 100142 , China
| | - Lei Xia
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine , Peking University Cancer Hospital & Institute , Beijing 100142 , China
| | - Chaoyong Deng
- Guizhou University School of Medicine , Guiyang , Guizhou 550025 , China
| | - Xiaobin Tian
- Guizhou Medical University , Guiyang , Guizhou 550004 , China
| | - Zhi Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine , Peking University Cancer Hospital & Institute , Beijing 100142 , China
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Hwang S, Kang JY, Kim MJ, Shin DM, Hong JH. Carbonic anhydrase 12 mutation modulates membrane stability and volume regulation of aquaporin 5. J Enzyme Inhib Med Chem 2018; 34:179-188. [PMID: 30451023 PMCID: PMC6249555 DOI: 10.1080/14756366.2018.1540475] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Patients carrying the carbonic anhydrase12 E143K mutation showed the dry mouth phenotype. The mechanism underlying the modulation of aquaporin 5 and function in the salivary glands by carbonic anhydrase12 remains unknown. In this study, we identified the mislocalised aquaporin 5 in the salivary glands carrying the E143K. The intracellular pH of E143K cells was more acidic than that of the cells carrying wild type. To evaluate the role of carbonic anhydrase12 on the volume regulation of aquaporin 5, the submandibular gland cells were subjected to hypotonic stimuli. E143K enhanced the extent of swelling of cells on hypotonicity. Aquaporin 5 modulates water influx through ion transporters to prevent osmotic imbalance. These results suggest that the carbonic anhydrase12 E143K, including acidification or inflammation, mediates volume dysregulation by the loss of aquaporin 5. Thus, carbonic anhydrase12 may determine sensible effects on the cellular osmotic regulation by modulating aquaporin 5.
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Affiliation(s)
- Soyoung Hwang
- a Department of Physiology , College of Medicine, Gachon University , Incheon , Republic of Korea
| | - Jung Yun Kang
- b Department of Oral Biology , BK21 PLUS Project, College of Dentistry, Yonsei University , Seoul , Republic of Korea
| | - Min Jae Kim
- b Department of Oral Biology , BK21 PLUS Project, College of Dentistry, Yonsei University , Seoul , Republic of Korea
| | - Dong Min Shin
- b Department of Oral Biology , BK21 PLUS Project, College of Dentistry, Yonsei University , Seoul , Republic of Korea
| | - Jeong Hee Hong
- a Department of Physiology , College of Medicine, Gachon University , Incheon , Republic of Korea.,c Department of Health Sciences and Technology, GAIHST, Gachon University , Incheon , Republic of Korea
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Núñez J, Heredia R, Payá A, Sanchis I, Prado S, Miñana G, Santas E, Espriella R, Núñez E, Sanchis J, Bayés‐Genís A. Use of acetazolamide in the treatment of patients with refractory congestive heart failure. Cardiovasc Ther 2018; 36:e12465. [DOI: 10.1111/1755-5922.12465] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 08/25/2018] [Accepted: 09/03/2018] [Indexed: 11/28/2022] Open
Affiliation(s)
- Julio Núñez
- Cardiology Department Hospital Clínico Universitario de Valencia INCLIVA Departamento de Medicina Universitat de València Valencia Spain
- CIBER in Cardiovascular Diseases (CIBERCV) Madrid Spain
| | - Raquel Heredia
- Cardiology Department Hospital Clínico Universitario de Valencia INCLIVA Departamento de Medicina Universitat de València Valencia Spain
| | - Ana Payá
- Cardiology Department Hospital Clínico Universitario de Valencia INCLIVA Departamento de Medicina Universitat de València Valencia Spain
| | - Ignacio Sanchis
- Cardiology Department Hospital Clínico Universitario de Valencia INCLIVA Departamento de Medicina Universitat de València Valencia Spain
| | - Susana Prado
- Cardiology Department Hospital Universitario Ramón y Cajal Madrid Spain
| | - Gema Miñana
- Cardiology Department Hospital Clínico Universitario de Valencia INCLIVA Departamento de Medicina Universitat de València Valencia Spain
| | - Enrique Santas
- Cardiology Department Hospital Clínico Universitario de Valencia INCLIVA Departamento de Medicina Universitat de València Valencia Spain
| | - Rafael Espriella
- Cardiology Department Hospital Clínico Universitario de Valencia INCLIVA Departamento de Medicina Universitat de València Valencia Spain
| | - Eduardo Núñez
- Cardiology Department Hospital Clínico Universitario de Valencia INCLIVA Departamento de Medicina Universitat de València Valencia Spain
| | - Juan Sanchis
- Cardiology Department Hospital Clínico Universitario de Valencia INCLIVA Departamento de Medicina Universitat de València Valencia Spain
- CIBER in Cardiovascular Diseases (CIBERCV) Madrid Spain
| | - Antoni Bayés‐Genís
- CIBER in Cardiovascular Diseases (CIBERCV) Madrid Spain
- Heart Institute Hospital Universitari Germans Trias i Pujol Badalona Spain
- Department of Medicine Universitat Autonoma de Barcelona Barcelona Spain
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Mullens W, Verbrugge FH, Nijst P, Martens P, Tartaglia K, Theunissen E, Bruckers L, Droogne W, Troisfontaines P, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M. Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial. Eur J Heart Fail 2018; 20:1591-1600. [DOI: 10.1002/ejhf.1307] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Revised: 07/11/2018] [Accepted: 08/02/2018] [Indexed: 12/20/2022] Open
Affiliation(s)
- Wilfried Mullens
- Ziekenhuis Oost-Limburg; Genk Belgium
- Hasselt University, Diepenbeek/Hasselt; Belgium
| | | | | | | | | | | | | | | | | | - Kevin Damman
- University Medical Center Groningen; Groningen The Netherlands
| | - Johan Lassus
- Helsinki University Central Hospital; Helsinki Finland
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Kataoka H. Vasopressin antagonist-like effect of acetazolamide in a heart failure patient: a case report. EUROPEAN HEART JOURNAL-CASE REPORTS 2018; 2:yty076. [PMID: 31020154 PMCID: PMC6177024 DOI: 10.1093/ehjcr/yty076] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 06/08/2018] [Indexed: 02/05/2023]
Abstract
Background Hyponatraemia is easily corrected by treatment with an oral vasopressin antagonist, but these medications are costly and their use at outpatient clinics is restricted by government-managed insurance in Japan. Acetazolamide could be an alternative diuretic to a vasopressin antagonist. Case Summary An 83-year-old dyspnoeic male patient was emergently admitted to the hospital due to decompensated heart failure (HF), hypotension, and hyperkalaemia-associated sinus arrest with a junctional escape rhythm. Urgent treatment with a noradrenaline drip infusion and a beta stimulant adhesive skin patch promptly restored sinus rhythm with conducted normal QRS complex, which resolved the hypotension. Blood tests on admission revealed moderately elevated b-type natriuretic peptide (BNP, 576 pg/mL), hyponatraemia (128 mEq/L), hypochloraemia (95 mEq/L), hyperkalaemia (5.7 mEq/L), and preserved renal function (creatinine, 1.0 mg/dL) under no cardiovascular medications. Immediately after admission, low-dose oral acetazolamide (500 mg/day) and polystyrene sulfonate-Ca jelly (Argamate, 25 g/day for 3 days) were prescribed to correct the decompensated HF status and electrolyte disturbance. Three days later, both the serum sodium and chloride concentrations had recovered to normal levels (136 mEq/L and 104 mEq/L, respectively), and the serum potassium concentration had decreased to 4.5 mEq/L. Two weeks later, the patient’s HF status became stable and the serum BNP concentration returned to normal (55 pg/mL). Discussion The present case indicates that the classic diuretic of acetazolamide would have a vasopressin blockade-like effect and could be an alternative diuretic to vasopressin antagonists for some proportion of HF patients with hyponatraemia.
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Affiliation(s)
- Hajime Kataoka
- Division of Internal Medicine, Nishida Hospital, Tsuruoka-Nishi-Machi 2-266, Saiki-City, Oita, Japan
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Affiliation(s)
- Nevio Cimolai
- Department of Pathology and Laboratory Medicine, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
- Department of Pathology and Laboratory Medicine, Children's and Women's Health, Centre of British Columbia, 4480 Oak Street, Vancouver, BC, V6H3V4, Canada.
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Liu T, Chen X, Xing J, Ge Z. Effects of acetazolamide on the conformations and activities of digestive enzymes: pepsin and trypsin. Med Chem Res 2018. [DOI: 10.1007/s00044-018-2172-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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The Art and Science of Using Diuretics in the Treatment of Heart Failure in Diverse Clinical Settings. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018. [PMID: 29500794 DOI: 10.1007/5584_2018_182] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/28/2024]
Abstract
It is important to understand the rationale for appropriate use of different diuretics, alone or in combination, in different heart failure patients, under diverse clinical settings. Clinicians and nurses engaged in heart failure care, must be familiar with different diuretics, their appropriate doses, methods of administration, monitoring of the responses, and the side-effects. Inappropriate use of diuretics, both under-treatment and overtreatment, and poor follow-up can lead to failures, and adverse outcomes. Adequate treatment of congestion, with rather aggressive use of diuretics, is necessary, even if that may worsen renal function temporarily in some patients. Diuretic treatment should later be titrated down, by early recognition of the euvolemic sate, which can be assessed by clinical examination, measurement of the natriuretic peptides, and when possible, echocardiographic estimation of the left ventricular filling pressure. You need to treat patients, who are truly resistant to the loop diuretics, by administering the diuretics as intravenous bolus injection followed by continuous infusion, and/or by sequential nephron blockade by adding the thiazide diuretics. You need to use the diuretics based on a sound understanding of the pathophysiology of the disease process, the pharmacokinetics and pharmacodynamics of the diuretics, even when strong evidences for your choices might be lacking. Some patients may benefit from injection of loop diuretics together with hypertonic saline, and others from injection of loop diuretics with albumin. Patient education, and regular follow up of the treatment of heart failure patients, in out-patient settings are important for reducing the rates of complications, and for reducing the needs for urgent hospitalizations.
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