Conivaptan and its role in the treatment of hyponatremia

Hyponatremia is the most common electrolyte abnormality in hospitalized patients and is associated with increased morbidity and mortality. The recognition of the central role that arginin vasopressin plays in the pathogenesis of hyponatremia and the discovery that its actions are mediated by stimulation of V1A and V2 receptors have led to the development of a new class of drugs, the arginin vasopressin antagonists. Conivaptan is a nonselective V1A and V2 receptors antagonist that was the first of this class to be approved by the FDA for the management of euvolemic and hypervolemic hyponatremia. Its short-term safety and efficacy for the correction of hyponatremia have been established by multiple double-blind, randomized, controlled studies. Blocking the effects of arginin vasopressin on V2 receptors produces aquaresis – the electrolyte-sparing excretion of water – an ideal approach to correct hypervolemic hyponatremia. The nonselectivity of conivaptan offers a theoretical advantage for its use in heart failure that may merit further exploration

Comparative neurohormonal responses in patients with preserved and impaired left ventricular ejection fraction: Results of the studies of left ventricular dysfunctions (SOLVD) registry

AbstractObjectives. The aim of this study was to determine the differences in neurohumoral responses between patients with pulmonary congestion with and without impaired left ventricular ejection fraction.Background. Previous studies have established the presence of neurohumoral activation in patients with congestive heart failure. It is not known whether the activation of these neurohumoral mechanisms is related to the impairment in systolic contractility.Methods. The 898 patients recruited into the Studies of Left Ventricular Dysfunction (SOLVD) Registry substudy were examined to identify those patients with pulmonary congestion on chest X-ray film who had either unpaired (<- 45%, group I) or preserved (> 45%, group II) left ventricular ejection fraction. Plasma norepinephrine, plasma renin activity, arginine vasopressin and atrial natriuretic peptide levels were measured in these two groups of patients and compared with values in matched control subjects,Results. Distribution of the New York Heart Association symptom classification was the same in the two groups of patients. Compared with control subjects, patients in group II with pulmonary congestion and preserved ejection fraction had no activation of the neurohumoral mechanisms, except for a small but statistically significant increase in arginine vasopressin and plasma renin activity. Compared with patients in group II, those in group I with pulmonary congestion and unpaired ejection fraction had significant increases in plasma norepinephrine (p < 0.002), plasma renin activity (p < 0.02) and atrial natriuretic peptide levels (p < 0.0007). When we controlled for baseline differences between groups I and II, the between-group differences in plasma norepinephrine (p < 0.02) and atrial natriuretic peptide (p < 0.002) remained significant. However, plasma renin activity was not significantly different between groups I and II. When the effects of diuretic agents and angiotensinconverting enzyme inhibitors were adjusted, patients with lower ejection fraction were found to have significantly higher plasma norepinephrine and atrial natriuretic peptide levels.Conclusions. The results point to the importance of the decrease in left ventricular ejection fraction as one of the mechanisms for activation of neurohormones in patients with heart failure

Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure

Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association