Abstract

OBJECTIVE: The objective was to study whether the temporal pattern of transient hyponatremia development in acute heart failure might provide insight into its pathophysiology and prognostic relevance. METHODS: A post hoc analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) and Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE AHF) studies was performed (n = 716). Patients were stratified according to the temporal pattern of hyponatremia development: (1) no hyponatremia, (2) persistent hyponatremia, (3) decompensation hyponatremia disappearing with decongestive treatment, and (4) treatment-induced hyponatremia. RESULTS: Transient decompensation versus no hyponatremia was associated with significantly elevated blood urea nitrogen/creatinine ratio (P < .001), plasma renin activity (P < .001), and plasma aldosterone levels (P < .001) at baseline. Disease severity characteristics of such patients were intermediate between no and persistent hyponatremia. In contrast, patients with treatment-induced versus no hyponatremia had similar baseline characteristics and comparable natriuretic peptide levels, and both groups had little neurohumoral activation at baseline. Diuretic efficacy, defined as net fluid balance (milliliters) per 40 mg furosemide-equivalent dose administered, was lower in patients with persistent or treatment-induced hyponatremia versus decompensation hyponatremia or no hyponatremia, respectively. The former versus latter groups also had more pronounced neurohumoral activation with decongestive treatment. The risk for all-cause mortality (hazard ratio, 2.50; 95% confidence interval, 1.50-4.19; P < .001) and death or heart failure readmission (hazard ratio, 2.18; 95% confidence interval, 1.60-2.97; P < .001) was significantly elevated in patients with persistent versus no hyponatremia, with the risk of decompensation and treatment hyponatremia situated in between. CONCLUSIONS: Transient hyponatremia is prognostically relevant, but it has a heterogeneous cause according to its temporal pattern of development.