Impact of Sodium Chloride Supplementation for Natriuresis, Blood Pressure and Neurohormonal Activity in Chronic Heart Failure With Reduced Ejection Fraction and Low Serum Sodium Concentration - Double-blinded, Placebo-controlled, Prospective Trial

Heart failure (HF) is a complex clinical syndrome characterized by symptoms and signs resulting from structural and/or functional cardiac abnormalities that lead to elevated intracardiac pressure and/or reduced cardiac output at rest or during exertion. The pathophysiology of HF is strongly associated with neurohormonal activation, including increased activity of the renin-angiotensin-aldosterone system, vasopressin, endothelin, and natriuretic peptides. Pharmacological therapies targeting these pathways, collectively referred to as guideline-directed medical therapy (GDMT) in HF with reduced ejection fraction (HFrEF), significantly reduce mortality and unplanned hospitalizations when administered at recommended doses.

Despite advances in treatment, HF remains a progressive disease characterized by recurrent episodes of decompensation and poor long-term outcomes. Epidemiological data indicate that HF affects approximately 1-2% of the general population and is associated with high annual mortality and frequent hospital admissions. Neurohormonal disturbances contribute to sodium and water retention, leading to fluid accumulation and the need for diuretic therapy to restore euvolemia. Although diuretics effectively relieve congestion-related symptoms, they do not improve long-term outcomes and may contribute to electrolyte disturbances, particularly hyponatremia, which is itself associated with worse outcomes in advanced HF.

For many years, strict dietary sodium restriction was considered a cornerstone of HF management because excessive sodium intake was believed to promote fluid retention due to impaired renal autoregulation. However, recent evidence has challenged this paradigm. Studies conducted in the era of modern neurohormonal blockade have demonstrated that sodium restriction does not improve clinical outcomes in HF patients. The SODIUM-HF trial showed no clinical benefit from dietary sodium restriction, while other studies, including those by Dauw et al., demonstrated that oral sodium chloride supplementation of 3 g/day is safe in HF patients, does not increase fluid overload, and may improve natriuresis while reducing plasma renin activity.

At the same time, a major limitation of contemporary HF treatment remains the inability to achieve optimal GDMT dosing in many patients. Hypotension frequently prevents dose escalation or initiation of additional prognostically beneficial therapies, resulting in only approximately 40% of patients receiving all recommended medications at target doses. Therefore, strategies aimed at improving blood pressure stability and sodium balance may facilitate better optimization of HF therapy.

Based on these observations, the present study was designed to evaluate whether oral sodium chloride supplementation in patients with chronic HFrEF and low serum sodium levels may safely improve sodium handling, neurohormonal balance, blood pressure, and tolerance of GDMT. Additionally, the study aims to assess whether sodium supplementation may facilitate optimization of GDMT dosing in patients prone to hypotension.