Conventional
therapies for acute decongestion have yielded uniformly poor results in patients with acute
heart failure (AHF). The failure of current strategies may be due to advanced disease in hospitalized patients, incomplete
therapy, inherent limitations to existing
therapy, or some combination of all three factors.
Loop diuretics are the mainstay of current
therapy and are in theory not ideal since while producing immediate intravascular volume reduction and relief of symptoms they activate neurohormonal forces that are deleterious to both the heart and the kidney. Ultrafiltration is an alternative to
loop diuretics but has not proved advantageous in the setting of renal dysfunction, and if not carefully applied may also aggravate neurohormonal imbalance. In theory decongestive
therapy for AHF should remove large volumes of fluid quickly and safely and improve symptoms, particularly
dyspnea, without aggravating renal dysfunction or causing neurohormonal activation. Several studies have now suggested that the use of aquaretics such as antagonists to the
V2 receptor for
arginine vasopressin may be useful as adjunctive
therapy in AHF, particularly when renal dysfunction and/or
hyponatremia are present. These agents leverage osmotic forces to produce tissue decongestion while causing a water diuresis. They do not adversely affect renal function or neurohormonal balance. Building on the current base of knowledge about outcomes in AHF together with the only study of
vasopressin antagonists as short-term monotherapy in chronic
heart failure, it would be reasonable to design a trial in AHF in which the use of
loop diuretics was minimized in favor of these agents.