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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

Feinberg School of Medicine Northwestern University, Chicago, Illinois 60611, USA.
Acute Cardiac Care 02/2007; 9(2):82-6. DOI: 10.1080/17482940701210179
Source: PubMed

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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    • "Hyponatremia can be caused by either dilution of the serum sodium by excess retained free water or by excessive sodium losses. Hyponatremia has been associated with poor survival in several nonmalignant diseases, such as congestive heart failure, liver cirrhosis, and infectious diseases (pneumonia, childhood meningitis, necrotizing soft-tissue infection) [6] [7] [8]. Serum sodium has been analyzed in mRCC patients treated with cytokines [9], and hyponatremia was found to be associated with a worse outcome. "
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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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    • "Discharge hyponatraemia was associated with a significantly increased risk for early mortality and rehospitalisation for recurrent heart failure events. In the Acute and Chronic Therapeutic Impact of Vasopressin Antagonist in Chronic Heart Failure Trial (ACTIV in CHF), hyponatraemia was observed in 22% of patients at the time of admission for AHF, and predicted mortality at 60 days after discharge [12]. In the Outcomes of Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure Study (OPTIME- CHF), patients in the lowest plasma sodium quartile had longer hospital stay and higher mortality compared to other plasma sodium quartiles [1]. "
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    ABSTRACT: Previous studies suggest that hyponatraemia is a marker of neurohormonal activation and increased mortality in patients with acute heart failure (AHF). Although diabetes is a common co-morbidity in heart failure, no prior study has considered the impact of serum glucose on this relationship. Over four consecutive months we prospectively registered all patients admitted due to AHF. Sodium and glucose levels were determined immediately upon admission. Patients were followed through admission and for the next 6 months. Of 342 patients enrolled, complete data were available for 331 patients. Hyponatraemia (sodium <135 mmol/L) was detected in 22% of patients. However, 47% of patients with hyponatraemia had concomitant hyperglycaemia (glucose level >11 mmol/L). Hyponatraemia was associated with increased 6-month mortality (21 vs. 8%, p=0.002). This association was restricted to patients who had hyponatraemia without concomitant hyperglycaemia. The 6-month mortality of patients with and without hyponatraemia was 11% versus 10% (p=0.87) when hyperglycaemia was present versus 29% and 7% (p<0.001) when hyperglycaemia was absent. In this preliminary study, hyperglycaemia-associated hyponatraemia was present in a significant proportion of patients admitted with AHF. In patients with hyperglycaemia, hyponatraemia had no prognostic significance, whereas in patients without hyperglycaemia, hyponatraemia remained a powerful predictor of mortality. These results need confirmation in a larger study.
    European Journal of Heart Failure 03/2008; 10(2):196-200. DOI:10.1016/j.ejheart.2008.01.008 · 6.58 Impact Factor
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    • "Of note, tolvaptan was not followed by hypotension, hypokalemia or renal function worsening, despite the higher weight loss. However, 60-day survival free of heart failure worsening was not improved, although a later data analysis showed that the improvement of serum sodium during hospitalization in the tolvaptan arm was associated with lower 60-day mortality [Rossi J. et al., 2007] "
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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.
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