Hyponatremia, Heart Failure, and the Role of Tolvaptan

Abstract

Hyponatremia–usually defined by serum sodium < 135 mEq/L–is common in heart failure (HF); it remains unclear whether it worsens HF or is merely a marker of more severe disease. Hyponatremia may develop from causes besides HF and symptoms may be mistakenly attributed to HF. Hyponatremia correction may be required for optimal HF management in some cases, and it can prevent neurologic complications. Symptoms, volume status, and onset timing determine treatment, which should correct serum sodium in a controlled manner. Arginine vasopressin is elevated in hypervolemic/euvolemic hyponatremia, favoring water reabsorption despite low serum osmolality. The oral selective V2-receptor antagonist tolvaptan blocks arginine vasopressin effects in the renal collecting ducts, promoting aquaresis without increasing sodium/potassium excretion. In clinical trials, tolvaptan significantly increased serum sodium in patients with euvolemic/hypervolemic hyponatremia, including HF. When added to conventional HF treatment, tolvaptan produced early symptomatic benefit, without long–term improvement in an HF population consisting primarily of normonatremic patients. Tolvaptan is approved for treatment of clinically significant hypervolemic/euvolemic hyponatremia (serum sodium < 125 mEq/L or less marked symptomatic hyponatremia that has resisted correction with fluid restriction), but not HF without hyponatremia.