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Natriuretic Response Is Highly Variable and Associated With 6-Month Survival: Insights From the ROSE-AHF Trial.

ABSTRACT: OBJECTIVES:This study sought to describe sodium excretion in acute decompensated heart failure (ADHF) clearly and to evaluate the prognostic ability of urinary sodium and fluid-based metrics. BACKGROUND:Sodium retention drives volume overload, with fluid retention largely a passive, secondary phenomenon. However, parameters (urine output, body weight) used to monitor therapy in ADHF measure fluid rather than sodium balance. Thus, the accuracy of fluid-based metrics hinges on the contested assumption that urinary sodium content is consistent. METHODS:Patients enrolled in the ROSE-AHF (Renal Optimization Strategies Evaluation-Acute Heart Failure) trial with 24-h sodium excretion available were studied (n = 316). Patients received protocol-driven high-dose loop diuretic therapy. RESULTS:Sodium excretion through the first 24 h was highly variable (range 0.12 to 19.8 g; median 3.63 g, interquartile range: 1.85 to 6.02 g) and was not correlated with diuretic agent dose (r = 0.06; p = 0.27). Greater sodium excretion was associated with reduced mortality in a univariate model (hazard ratio: 0.80 per doubling of sodium excretion; 95% confidence interval: 0.66 to 0.95; p = 0.01), whereas gross urine output (p = 0.43), net fluid balance (p = 0.87), and weight change (p = 0.11) were not. Sodium excretion of less than the prescribed dietary sodium intake (2 g), even in the setting of a negative net fluid balance, portended a worse prognosis (hazard ratio: 2.02; 95% confidence interval: 1.17 to 3.46; p = 0.01). CONCLUSIONS:In patients hospitalized with ADHF who were receiving high-dose loop diuretic agents, sodium concentration and excretion were highly variable. Sodium excretion was strongly associated with 6-month mortality, whereas traditional fluid-based metrics were not. Poor sodium excretion, even in the context of fluid loss, portends a worse prognosis.

SUBMITTER: Hodson DZ

PROVIDER: S-EPMC6501816 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Natriuretic Response Is Highly Variable and Associated With 6-Month Survival: Insights From the ROSE-AHF Trial.

Hodson Daniel Z DZ Griffin Matthew M Mahoney Devin D Raghavendra Parinita P Ahmad Tariq T Turner Jeffrey J Wilson F Perry FP Tang W H Wilson WHW Rao Veena S VS Collins Sean P SP Mullens Wilfried W Testani Jeffrey M JM

JACC. Heart failure 20190501 5

<h4>Objectives</h4>This study sought to describe sodium excretion in acute decompensated heart failure (ADHF) clearly and to evaluate the prognostic ability of urinary sodium and fluid-based metrics.<h4>Background</h4>Sodium retention drives volume overload, with fluid retention largely a passive, secondary phenomenon. However, parameters (urine output, body weight) used to monitor therapy in ADHF measure fluid rather than sodium balance. Thus, the accuracy of fluid-based metrics hinges on the c ...[more]

PMID: 31047017

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Project description:BACKGROUND:The ROSE AHF trial (Renal Optimization Strategies Evaluation in Acute Heart Failure) found that when compared with placebo, neither low-dose dopamine (2 µg/kg per minute) nor low-dose nesiritide (0.005 ?g/kg per minute without bolus) enhanced decongestion or preserved renal function in AHF patients with renal dysfunction. However, there may be differential responses to vasoactive agents in AHF patients with reduced versus preserved ejection fraction (EF). This post hoc analysis examined potential interaction between treatment effect and EF (EF ?40% versus >40%) on the ROSE AHF end points. METHODS AND RESULTS:ROSE AHF enrolled AHF patients (n=360; any EF) with renal dysfunction. The coprimary end points were cumulative urine volume and the change in serum cystatin-C in 72 hours. The effect of dopamine (interaction P=0.001) and nesiritide (interaction P=0.039) on urine volume varied by EF group. In heart failure with reduced EF, urine volume was higher with active treatment versus placebo, whereas in heart failure with preserved EF, urine volume was lower with active treatment. The effect of dopamine and nesiritide on weight change, sodium excretion, and incidence of AHF treatment failure also varied by EF group (interaction P<0.05 for all). There was no interaction between vasoactive treatment's effect and EF on change in cystatin-C. Compared with placebo, dopamine was associated with improved clinical outcomes in heart failure with reduced EF and worse clinical outcomes in heart failure with preserved EF. With nesiritide, there were no differences in clinical outcomes when compared with placebo in both heart failure with reduced EF and heart failure with preserved EF. CONCLUSIONS:In this post hoc analysis of ROSE AHF, the response to vasoactive therapies differed in patients with heart failure with reduced EF and heart failure with preserved EF. Investigations of AHF therapies should assess the potential for differential responses in AHF with preserved versus reduced EF. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01132846.

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Natriuretic Response Is Highly Variable and Associated With 6-Month Survival: Insights From the ROSE-AHF Trial.

Publications

Natriuretic Response Is Highly Variable and Associated With 6-Month Survival: Insights From the ROSE-AHF Trial.

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