Hyponatremia in
congestive heart failure (CHF) is associated with increased morbidity and mortality, underlining the importance of adequate assessment and treatment of this
electrolyte imbalance in patients with CHF. Current treatment options for
hyponatremia in CHF include
hypertonic saline solution,
loop diuretics, fluid restriction, and other pharmacologic agents, such as
demeclocycline,
lithium carbonate, and
urea.
Hypertonic saline solution must be administered with extreme caution because excessively slow or rapid
sodium correction can lead to severe neurologic adverse effects.
Loop diuretics are useful for reducing the water retention caused by CHF. However, the potent diuresis induced by agents such as
furosemide results in loss of
sodium and other essential
electrolytes, which may exacerbate
hyponatremia. Fluid restriction is only moderately effective and often difficult to implement in the hospital setting. Agents such as
demeclocycline and
lithium have potentially serious renal and cardiovascular side effects. The
arginine vasopressin (AVP) receptor antagonists are a promising new class of aquaretic agents that increase free-water excretion while maintaining levels of
sodium and other essential
electrolytes.
Tolvaptan (OPC-41061),
lixivaptan (VPA-985), and
conivaptan (YM-087) are currently under development for the treatment of
hyponatremia. Although
tolvaptan and
lixivaptan are selective for the vasopressin-2 (V(2)) receptor responsible for the antidiuretic actions of AVP,
conivaptan demonstrates activity at both the V(2) receptor and the V(1a) receptor responsible for the vasoconstricting properties of AVP. This dual receptor activity may be particularly useful in patients with CHF. These patients may benefit from the increased cardiac output, reduced total peripheral resistance, and reduced mean arterial blood pressure that results from V(1a) receptor blockade as well as the reduced congestion, reduced cardiac preload, and increased
sodium concentrations induced by V(2) receptor antagonism.