Liberal Use of Sodium in Ambulatory Heart Failure

Study Overview
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Brief Summary
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This study investigates the effects of an increased sodium intake in heart failure patients with reduced ejection fraction and age-matched volunteers without heart failure.

Detailed Description
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At the start of the study, baseline investigations are performed including assessment of vital signs (blood pressure, heart rate, pulse oxygen saturation), weight, Everest congestion score (consisting of grading of dyspnea, orthopnea, jugular venous distention, rales, edema and fatigue), echocardiography, 24h urine collection, bio-impedance measurements and blood sample analysis with plasma renin and aldosterone Subsequently, a run-in phase of 2 weeks, without intervention, will start. After this run-in period, participants will be reassessed with the same baseline investigations. In addition, a skin biopsy will be performed as well as a blood volume measurement. In the next phase of the study, salt intake will be increased with 3 grams daily. The salt will be packed in capsules containing 1 g of sodium chloride (NaCl). Patients will be asked to take one capsule with their breakfast, lunch and dinner. Every 2 weeks a follow-up visit is planned. After 4 weeks of increased salt intake, a new skin biopsy will be taken and a blood volume measurement will be performed.

Official Title
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Liberal Use of Sodium in Ambulatory Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Dietary Supplement: Sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heart failure patients: Left ventricular ejection fraction ≤40% on echocardiogram obtained at inclusion Stable dose of guideline-recommended disease modifying drugs for at least 3 months. Maximum daily loop diuretic dose of 40 mg furosemide equivalents with a stable dose for the last month Healthy volunteers: Age > 60 y Normal ejection fraction (>50%) without heart failure No neurohormonal blockers for hypertension Normal NT-proBNP Exclusion Criteria: Heart failure hospitalization for congestion or myocardial infarction in past 3 months Permanent atrial fibrillation New York Heart Association (NYHA) class III-IV Estimated glomerular filtration rate (eGFR) < 30 mL/min Signs of congestion Severe right ventricular dysfunction Severe valvular disease Cardiothoracic anatomy not allowing satisfactory and reproducible recordings of echocardiogram Inability to fully comprehend and/or perform study procedures in the investigator's opinion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heart failure<br>After a run-in phase of 2 weeks, patients will add 3 g of sodium chloride to every meal, using a NaCl tablet of 1 g. They will continue the sodium tablet for 4 weeks with a study visit every 2 weeks. A skin biopsy will be performed before the start of the augmented salt intake and after 4 weeks. | Dietary Supplement: Sodium chloride<br>* 1 gram tid (with every meal)<br>|
| Active Comparator: Healthy volunteer<br>After a run-in phase of 2 weeks, volunteers will add 3 g of sodium chloride to every meal, using a NaCl tablet of 1 g. They will continue the sodium tablet for 4 weeks with a study visit every 2 weeks.A skin biopsy will be performed before the start of the augmented salt intake and after 4 weeks. | Dietary Supplement: Sodium chloride<br>* 1 gram tid (with every meal)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in skin glycosaminoglycan (GAG) content |  | 4 weeks | 
| Changes in skin sodium content |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in blood volume assessed by radiolabeled red blood cell technique |  | 4 weeks | 
| Changes in extracellular, intravascular volume and total body fluid volume (assessed with bioimpedance) |  | 6 weeks | 
| Changes in renal sodium handling |  | 6 weeks | 
| Changes in cardiac geometry assessed by echo |  | 6 weeks | 
| Changes in renal venous flow pattern |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sodium, Salt, Heart Failure