Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial.
ABSTRACT Hyponatremia predicts poor outcome in patients with acute heart failure syndromes. This study evaluated the relationship between baseline serum sodium, change in serum sodium, and 60-day mortality in hospitalized heart failure patients.
A post-hoc analysis of the ACTIV in CHF trial was performed. ACTIV in CHF randomized 319 patients hospitalized for worsening heart failure to placebo or one of three tolvaptan doses. Cox proportional hazards regression-analysis was used to explore the relationship between baseline hyponatremia, sodium change during the hospitalization, and 60-day mortality.
Hyponatremia was observed in 69 patients (21.6%). After covariate adjustment, baseline hyponatremia was a statistically significant predictor of 60-day mortality (P = 0.0016). Follow-up serum sodium data were available in 68 patients. At hospital discharge, 45 of 68 (66.2%) hyponatremic patients had improvements in serum sodium levels (> or = 2 mmol/l). Hyponatremic patients with a serum sodium improvement had a mortality rate of 11.1% at 60 days post discharge, compared with a 21.7% mortality rate in those showing no improvement. After covariate adjustment, change in serum sodium was a statistically significant predictor of 60-day mortality (HR: 0.736, 95% CI: 0.569-0.952 for each 1-mmol/l increase in serum sodium from baseline).
Serum sodium improvements during hospitalization for heart failure were associated with improved survival at 60 days.
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ABSTRACT: Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients treated with immunotherapy. To investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium. Data on 1661 patients treated with first-line vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy for mRCC were available from 18 cancer centers to study the impact of hyponatremia (serum sodium level <135 mmol/l) on clinical outcomes. The primary objective was overall survival (OS) and secondary end points included time to treatment failure (TTF) and the disease control rate (DCR). The chi-square test was used to compare the DCR in patients with and without hyponatremia. OS and TTF were estimated with the Kaplan-Meier method and differences between groups were examined by the log-rank test. Multivariable logistic regression (for DCR) and Cox regression (for OS and TTF) were undertaken adjusted for prognostic risk factors. Median OS after treatment initiation was 18.5 mo (95% confidence interval [CI], 17.5-19.8 mo), with 552 (33.2%) of patients remaining alive on a median follow-up of 22.1 mo. Median baseline serum sodium was 138 mmol/l (range: 122-159 mmol/l), and hyponatremia was found in 14.6% of patients. On univariate analysis, hyponatremia was associated with shorter OS (7.0 vs 20.9 mo), shorter TTF (2.9 vs 7.4 mo), and lower DCR rate (54.9% vs 78.8%) (p<0.0001 for all comparisons). In multivariate analysis, these effects remain significant (hazard ratios: 1.51 [95% CI, 1.26-1.80] for OS, and 1.57 [95% CI, 1.34-1.83] for TTF; odds ratio: 0.50 [95% CI, 34-0.72] for DCR; adjusted p<0.001). Results were similar if sodium was analyzed as a continuous variable (adjusted p<0.0001 for OS, TTF, and DCR). This is the largest multi-institutional report to show that hyponatremia is independently associated with a worse outcome in mRCC patients treated with VEGF- and mTOR-targeted agents.European Urology 10/2013; 65(4). DOI:10.1016/j.eururo.2013.10.013 · 12.48 Impact Factor
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ABSTRACT: In this review the new approaches of medical treatment of heart failure are discussed. Hyponatremia represents one of pathogenetic pathways of heart failure symptoms progression and results from the relative excess of water compared to sodium. Arginine-vasopressin antagonists have a potency to prevent hyperntremia and suppress neurohumoral overactivity mechanisms. Results of several trials, which showed clinical benefit of these agents in patients with chronic heart failure, are discussed in this article.
Article: [Vasopressin antagonists].[Show abstract] [Hide abstract]
ABSTRACT: Vasopressin, like all the other neuro-hormonal systems, is activated in patients with cardiac insufficiency. Vasopressin attaches itself to two distinct specific receptors. It is through the intermediary of the renal V2 receptor, controlling the reabsorption of water by the collecting duct, that vasopressin finely regulates the blood osmolarity. The ubiquitous V1a receptor is essentially responsible for the vasoconstrictor effect of the hormone. Some specific antagonists for these two receptors have now been evaluated in various pathologies such as SIADH, cirrhosis or cardiac insufficiency. In this situation the mixed antagonists, anti-V1a-V2, seem more appropriate than the specific V1a or V2 receptor antagonists. The results of the first human studies are encouraging. The mixed antagonists reduce the pulmonary capillary pressure and increase diuresis and clearance of free water. But further studies are necessary to confirm these results and to demonstrate a reduction in morbidity and mortality before adding this class of medication to the therapeutic arsenal for our patients with cardiac insufficiency.Archives des maladies du coeur et des vaisseaux 03/2002; 95 Spec 4(5 Spec 4):59-61. · 0.40 Impact Factor