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Congestive heart failure (CHF) remains a major cause of morbidity, rehospitalization, and mortality worldwide, particularly among elderly and polymorbid patients. Systemic congestion is its most characteristic clinical manifestation and the leading cause of hospitalization for acute heart failure. Standard treatment relies on loop diuretics, primarily furosemide, to reduce fluid overload and alleviate congestive symptoms. However, in clinical practice, many patients exhibit an inadequate diuretic response or resistance to furosemide, particularly in the context of cardiorenal syndrome (CRS), where cardiac and renal dysfunction mutually exacerbate each other. This profile, frequently observed in advanced stages of heart failure, significantly limits the effectiveness of guideline-directed medical therapies (GDMTs), particularly SGLT2 inhibitors, mineralocorticoid receptor antagonists, and angiotensin-converting enzyme (ACE) inhibitors, whose use is often restricted by hypotension, hyperkalemia, or impaired renal function.
Thus, in this subgroup of patients, conventional pharmacological approaches encounter a therapeutic barrier, necessitating the search for alternative or complementary strategies targeting sodium and water depletion without compromising renal perfusion. In this context, the combined administration of hypertonic saline (HS) and furosemide has been proposed as a pathophysiologically sound approach to break the vicious cycle of cardiorenal syndrome. Hypertonic saline solution (HSS) acts by restoring effective intravascular volume, improving renal perfusion, and promoting more efficient natriuresis through better furosemide delivery to the distal nephron. Pioneering studies by Paterna et al. showed that the concomitant administration of HSS (1.4-3% NaCl, 150-250 mL) and intravenous furosemide increased diuresis, improved the hemodynamic profile, and reduced the length of hospital stay and readmission rates without deterioration of renal function.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HSS group | Experimental |
|
|
| placebo group | Placebo Comparator |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hypertonic sodium chloride 10% | Drug | 50 mL of 10% hypertonic sodium chloride (NaCl) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants rehospitalized for heart failure | Description: Number of participants requiring rehospitalization for heart failure during follow-up. | 30 days and 60 days |
| All-cause mortality | Description: Number of deaths from any cause during follow-up. | 30 days and 60 days |
| Measure | Description | Time Frame |
|---|---|---|
| Serum creatinine level | Evaluation of serum creatinine levels. | 30 days 60 days |
| Blood urea level | Evaluation of blood urea levels. | 30 days 60 days |
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Inclusion Criteria:
Exclusion Criteria:
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PD will not be shared due to concerns related to patient confidentiality and data privacy
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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Participants will be randomized into two parallel groups. The HSS group will receive 50 mL of 10% hypertonic sodium chloride (NaCl) combined with 250 mg of furosemide administered as a slow intravenous infusion over 60 minutes, once weekly for 2 months. The placebo group will receive 50 mL of 0.9% sodium chloride (NaCl) combined with 250 mg of furosemide administered as a slow intravenous infusion over 60 minutes, once weekly for 2 months.
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| Sodium Chloride 0.9% |
| Drug |
50 mL of 0.9% sodium chloride (NaCl) |
|
| Furosemide intravenous solution | Drug | Furosemide 250 mg administered intravenously over 60 minutes once weekly for 2 months. |
|
| BNP or NT-proBNP concentration | Evaluation of BNP or NT-proBNP levels. | 30days 60 days |
| Quality of life and patient satisfaction score assessed using a Likert scale | Description: Assessment of quality of life and patient satisfaction using a 5-point Likert scale ranging from 1 to 5, where: 1 = very dissatisfied/very poor quality of life 5 = very satisfied/excellent quality of life Higher scores indicate better patient satisfaction and quality of life. | 30 days and 60 days |
| D014570 |
| Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017670 |
| Sodium Compounds |