Significance of hyponatremia in heart failure.

Heart failure is one of the most common, costly, disabling and growing diseases (McMurray and Pfeffer in Lancet 365(9474):1877-1889, 2005). Hyponatremia, conventionally defined as a serum-sodium concentration equal or less than 135 mmol/l (American Heart Association in Heart disease and stroke statistics--2007 update. American Heart Association, Dallas, 2007; Stewart et al. in Eur J Heart Fail 4:361-371, 2002), is a common phenomenon in patients with heart failure, with an incidence of 20-25% (Krumholz et al. in Arch Intern Med 157:e99-e104, 1997; Rosamond et al. in Circulation 117(4):e25-e146, 2008; Adrogue and Madias in N Engl J Med 342:1581-1589, 2000) and seems to be of prognostic importance in patients with heart failure (Luca et al. in Am J Cardiol 96:19L-23L, 2005; Gheorghiade et al. in Eur Heart J 28:980-988, 2007; Gheorghiade et al. in Arch Intern Med 167:1998-2005, 2007). So far treatment strategies have been limited and burdened by side effects. The development of hyponatremia in the setting of heart failure is related to the arginine vasopressin (AVP) dysregulation. Thus, AVP receptor antagonists are a promising approach to treatment. However, several questions remain: whether there is a cause-and-effect mechanism, if the correction of hyponatremia improves outcomes, and defining the specific cut-off level of serum-sodium that should be used to define hyponatremia. In this review, we aim to summarize the literature on hyponatremia in patients with heart failure within several aspects: incidence in clinical trials and registries, prognostic value, underlying mechanisms, therapeutic options, and possible future perspectives.