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Vasopressin Antagonism in Heart Failure

Steven R. Goldsmith, MD^_*,_* and Mihai Gheorghiade, MD

^_* Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota
Northwestern University Feinberg School of Medicine, Chicago, Illinois

View larger version (13K): [in a new window]   Figure 1 Vasopressin could aggravate the progression of heart failure by adversely affecting ventricular remodeling, worsening clinical congestion, and contributing to hyponatremia. V1a effects would be predominantly those causing arterial vasoconstriction, increasing afterload, and adversely affecting ventricular structure and function. Direct myocardial V1a effects could also be present. V2 effects could lead to excessive circulatory congestion, adversely affecting myocardial structure and function via increasing preload. V2 effects would also lead to hyponatremia. AVP = arginine vasopressin; LV = left ventricular.

View larger version (34K): [in a new window]   Figure 2 Hemodynamic effects of infused arginine vasopressin (AVP) in patients with chronic heart failure. CO = cardiac output; HR = heart rate; MAP = mean arterial pressure; PCWP = pulmonary capillary wedge pressure; SV = stroke volume; SVR = systemic vascular resistance. *p < 0.01; p < 0.05. Adapted from Goldsmith SR, et al. J Am Coll Cardiol 1986;8:779–83.

View larger version (22K): [in a new window]   Figure 3 Effects of tolvaptan relative to placebo on body weight at 24 h (the primary end point of the study) and at discharge in the Acute and Chronic Therapeutic Impact of a Vasopressin (ACTIV) trial. *p < 0.05 vs. placebo. Adapted from reference 55. White bars = placebo; black bars = tolvaptan 0 mg; dotted bars = tolvaptan 60 mg; grey bars = tolvaptan 90 mg.

View larger version (27K): [in a new window]   Figure 4 Effect of tolvaptan on serum sodium in those patients presenting with initial sodium under 135 mEq/ in the Acute and Chronic Therapeutic Impact of a Vasopressin (ACTIV) trial. Adapted from reference 55. White bars = placebo; black bars = 30 mg; dotted bars = 60 mg; grey bars = 90 mg.