Liberal Use of Sodium in Ambulatory Heart Failure (LUSA-HF)

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.

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.

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.

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.

Changes in extracellular, intravascular volume and total body fluid volume (assessed with bioimpedance)

The Everest score assesses congestion, based on a point scale with a range from 0 (no congestion) to 18 (worst congestion)

NT-proBNP will be measured using Roche diagnostics assay (Mannhein, Germany) and expresed as picogram per liter

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.