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Background
Hyponatremia remains a challenge in the management of acute decompensated heart failure. A decrease in cardiac output and systemic blood pressure triggers the activation of RAAS, and renal conservation of sodium due to the perceived hypovolemia [1]. Hyponatremia is a well-established marker of poor prognosis in ADHF. In patients admitted for ADHF, hyponatremia, which is defined as a serum sodium level < 135 mEq/L, is associated with multiple adverse outcomes including worse short and long-term mortality, higher readmission rates, and longer length of hospital stay [2].
Acute heart failure causes millions of hospital admissions each year, with hyponatremia being a common finding in these patients [3]. Hospitalization and management of ADHF account for the largest proportion of the cost of care.
Fluid-overloaded heart failure patients are commonly treated with loop diuretics, unfortunately, due to a decrease in renal perfusion and the intense activation of the RAAS system, acutely decompensated heart failure patients tend to be less responsive to conventional oral doses of a loop diuretic [4]. This phenomenon is commonly referred to as “diuretic resistance” that is caused by multi-organ interplay between the renal and cardiovascular systems [5]. Diuretic resistance is defined as a failure to increase fluid and sodium output sufficiently to relieve volume overload, edema, or congestion despite a full dose of a loop diuretic, which can be further defined as a failure of oral furosemide (160 mg twice daily or equivalent) to increase sodium excretion of 90 mmol over 3 days [6].
The occurrence of diuretic resistance in patients with ADHF during hospitalization is associated with an increased mortality rate, increased length of stay, and consumption of more medical resources [7, 8–9].
Several studies have shown an association between hyponatremia and the increase in morbidity and mortality in patients who are admitted to the hospital due to heart failure. Hyponatremia is also associated with an increase in rehospitalization rates, increased length of stay, increased complications, and the cost of care while hospitalized [10]. The use of high-dose loop diuretics to overcome diuretic resistance in treating ADHF can precipitate several side effects including hypokalemia, metabolic alkalosis, hypovolemia, hypotension, and worsening renal function [11].
Vasopressin receptor antagonists are a new class of drugs that produce selective water diuresis without affecting sodium and potassium excretion [12]....