Salt repletion and diuretic response: The role of serum chloride. A post-hoc analysis of the SALT-HF trial on furosemide and hypertonic saline solution administration in ambulatory patients with worsening heart failure
Corresponding Author
Julio Núñez
Cardiology Department, Hospital Clínico Universitario de Valencia (INCLIVA), University of Valencia, Valencia, Spain
These authors contributed equally.
Corresponding authors. Julio Núñez, Cardiology Department, Hospital Clínico Universitario de Valencia (INCLIVA), University of Valencia, Valencia, Spain. Email: [email protected]
Marta Cobo Marcos, Cardiology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain. Email: [email protected]
Search for more papers by this authorGema Miñana
Cardiology Department, Hospital Clínico Universitario de Valencia (INCLIVA), University of Valencia, Valencia, Spain
These authors contributed equally.
Search for more papers by this authorRafael de la Espriella
Cardiology Department, Hospital Clínico Universitario de Valencia (INCLIVA), University of Valencia, Valencia, Spain
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Search for more papers by this authorIsabel Zegrí-Reiriz
Cardiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Search for more papers by this authorJosep Comín-Colet
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Cardiology Department, Hospital Universitario de Bellvitge, IDIBELL, Barcelona, Spain
Search for more papers by this authorJorge Rubio Gracia
Internal Medicine Department, Hospital Universitario Lozano Blesa, University of Zaragoza, Aragon Health Research Institute (IIS Aragon), Zaragoza, Spain
Search for more papers by this authorJose Luis Morales-Rull
Internal Medicine Department, Hospital Universitario Arnau de Vilanova, Heart Failure Unit, Lleida Health Region, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain
Search for more papers by this authorPau Llàcer
Internal Medicine Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, and Department of Medicine and Medical Specialties, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Madrid, Spain
Search for more papers by this authorPablo Diez-Villanueva
Cardiology Department, Hospital Universitario de la Princesa, Madrid, Spain
Search for more papers by this authorJavier de Juan Bagudá
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Cardiology Department, University Hospital 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Madrid, and Department of Medicine, Faculty of Biomedical and Health Science, Universidad Europea de Madrid, Madrid, Spain
Search for more papers by this authorCarolina Ortiz Cortés
Cardiology Department, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain
Search for more papers by this authorJosebe Goirigolzarri-Artaza
Cardiology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain
Search for more papers by this authorJose Manuel García-Pinilla
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Cardiology Department, Hospital Universitario Virgen de la Victoria, Málaga; Instituto de Investigación Biomédica-Plataforma BIONAND, Málaga, and Departamento de Medicina y Dermatología, Universidad de Málaga, Málaga, Spain
Search for more papers by this authorElvira Barrios
Cardiology Department, Hospital Universitario Rey Juan Carlos Móstoles, Madrid, Spain
Search for more papers by this authorSusana del Prado Díaz
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Cardiology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Search for more papers by this authorSantiago Jiménez-Marrero
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Cardiology Department, Hospital Universitario de Bellvitge, IDIBELL, Barcelona, Spain
Search for more papers by this authorMaria Alejandra Restrepo-Córdoba
Cardiology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain
Search for more papers by this authorJeffrey Testani
Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA
Search for more papers by this authorCorresponding Author
Marta Cobo Marcos
Cardiology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain
Corresponding authors. Julio Núñez, Cardiology Department, Hospital Clínico Universitario de Valencia (INCLIVA), University of Valencia, Valencia, Spain. Email: [email protected]
Marta Cobo Marcos, Cardiology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain. Email: [email protected]
Search for more papers by this authorCorresponding Author
Julio Núñez
Cardiology Department, Hospital Clínico Universitario de Valencia (INCLIVA), University of Valencia, Valencia, Spain
These authors contributed equally.
Corresponding authors. Julio Núñez, Cardiology Department, Hospital Clínico Universitario de Valencia (INCLIVA), University of Valencia, Valencia, Spain. Email: [email protected]
Marta Cobo Marcos, Cardiology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain. Email: [email protected]
Search for more papers by this authorGema Miñana
Cardiology Department, Hospital Clínico Universitario de Valencia (INCLIVA), University of Valencia, Valencia, Spain
These authors contributed equally.
Search for more papers by this authorRafael de la Espriella
Cardiology Department, Hospital Clínico Universitario de Valencia (INCLIVA), University of Valencia, Valencia, Spain
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Search for more papers by this authorIsabel Zegrí-Reiriz
Cardiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Search for more papers by this authorJosep Comín-Colet
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Cardiology Department, Hospital Universitario de Bellvitge, IDIBELL, Barcelona, Spain
Search for more papers by this authorJorge Rubio Gracia
Internal Medicine Department, Hospital Universitario Lozano Blesa, University of Zaragoza, Aragon Health Research Institute (IIS Aragon), Zaragoza, Spain
Search for more papers by this authorJose Luis Morales-Rull
Internal Medicine Department, Hospital Universitario Arnau de Vilanova, Heart Failure Unit, Lleida Health Region, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain
Search for more papers by this authorPau Llàcer
Internal Medicine Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, and Department of Medicine and Medical Specialties, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Madrid, Spain
Search for more papers by this authorPablo Diez-Villanueva
Cardiology Department, Hospital Universitario de la Princesa, Madrid, Spain
Search for more papers by this authorJavier de Juan Bagudá
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Cardiology Department, University Hospital 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Madrid, and Department of Medicine, Faculty of Biomedical and Health Science, Universidad Europea de Madrid, Madrid, Spain
Search for more papers by this authorCarolina Ortiz Cortés
Cardiology Department, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain
Search for more papers by this authorJosebe Goirigolzarri-Artaza
Cardiology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain
Search for more papers by this authorJose Manuel García-Pinilla
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Cardiology Department, Hospital Universitario Virgen de la Victoria, Málaga; Instituto de Investigación Biomédica-Plataforma BIONAND, Málaga, and Departamento de Medicina y Dermatología, Universidad de Málaga, Málaga, Spain
Search for more papers by this authorElvira Barrios
Cardiology Department, Hospital Universitario Rey Juan Carlos Móstoles, Madrid, Spain
Search for more papers by this authorSusana del Prado Díaz
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Cardiology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Search for more papers by this authorSantiago Jiménez-Marrero
Centro de Investigación Biomédica en Red (CIBER) Cardiovascular, Madrid, Spain
Cardiology Department, Hospital Universitario de Bellvitge, IDIBELL, Barcelona, Spain
Search for more papers by this authorMaria Alejandra Restrepo-Córdoba
Cardiology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain
Search for more papers by this authorJeffrey Testani
Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA
Search for more papers by this authorCorresponding Author
Marta Cobo Marcos
Cardiology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain
Corresponding authors. Julio Núñez, Cardiology Department, Hospital Clínico Universitario de Valencia (INCLIVA), University of Valencia, Valencia, Spain. Email: [email protected]
Marta Cobo Marcos, Cardiology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain. Email: [email protected]
Search for more papers by this authorABSTRACT
Aims
The efficacy of combining hypertonic saline solution (HSS) with loop diuretics in worsening heart failure (WHF) remains uncertain. Hypochloraemia has been associated with reduced diuretic efficacy. Some authors propose that chloride repletion may enhance natriuretic and diuretic responses. This post-hoc analysis of the SALT-HF trial evaluated the effect of single-dose administration of HSS plus intravenous (IV) furosemide versus IV furosemide, stratified by baseline serum chloride.
Methods and results
The analysis included 148 ambulatory patients with WHF from the double-blind, randomized SALT-HF trial. Participants received either an IV single dose of HSS plus furosemide or IV furosemide. The endpoints were 3-h urinary sodium excretion and diuresis, 7-day congestion score, and 30-day adverse events according to chloride levels. Multivariable linear and logistic regression models assessed the relationship between the intervention and the endpoints. The mean baseline serum chloride level was 100 ± 4 mmol/L. Sixteen patients (10.8%) were identified as hypochloraemic (serum chloride <96 mmol/L), balanced between treatment groups. Patients with hypochloraemia showed a lower natriuretic response (p < 0.05). Interaction analysis revealed a between-treatment differential natriuretic effect based on the chloride levels (pinteraction = 0.008). HSS plus furosemide increased natriuresis compared to furosemide at lower chloride levels. No differential between-treatment effect was found for 3-h diuresis. Similar heterogeneous results were found for the 7-day clinical congestion score and 30-day heart failure events, with a benefit with HSS in patients with lower chloride levels.
Conclusion
In ambulatory patients with WHF and hypochloraemia, adding HSS to furosemide may improve short-term natriuretic response and outcomes. These findings suggest that chloride supplementation may help overcome diuretic resistance in these patients.
Supporting Information
| Filename | Description |
|---|---|
| ejhf3597-sup-0001-FileS1.docxWord 2007 document , 24.9 KB | DATA S1. Baseline characteristics across treatment arms. |
| ejhf3597-sup-0002-FileS2.docxWord 2007 document , 25.4 KB | DATA S2. Baseline characteristics across baseline quartiles of serum chloride. |
| ejhf3597-sup-0003-FileS3.tifTIFF image, 65.9 KB | DATA S3. Association between serum chloride levels and 3-h absolute urinary sodium excretion. |
| ejhf3597-sup-0004-FileS4.tifTIFF image, 31.6 KB | DATA S4. Association between serum chloride levels dichotomized at 96 mmol/L, and 3-h absolute urinary sodium excretion across the treatment arms. Estimates are presented as least square means. HSS, hypertonic saline solution. |
| ejhf3597-sup-0005-FileS5.tifTIFF image, 183.7 KB | DATA S5. Association between serum chloride levels and 3-h urinary chloride excretion across treatment arms. HSS: hypertonic saline solution. |
| ejhf3597-sup-0006-FileS6.tifTIFF image, 140.7 KB | DATA S6. Association between serum sodium levels and 3-h urinary sodium excretion across treatment arms. HSS, hypertonic saline solution. |
| ejhf3597-sup-0007-FileS7.tifTIFF image, 291.1 KB | DATA S7. Association between serum sodium levels and 3-h urinary output across treatment arms. HSS, hypertonic saline solution. |
| ejhf3597-sup-0008-FileS8.tifTIFF image, 272.2 KB | DATA S8. Association between serum sodium levels and 7-day clinical congestion score across treatment arms. HSS, hypertonic saline solution. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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