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Implications of Serum Chloride Homeostasis in Acute Heart Failure (from ROSE-AHF).

ABSTRACT: Lower serum chloride (Cl) levels are strongly associated with increased long-term mortality after admission for acute heart failure (AHF). However, the therapeutic implications of serum Cl levels during AHF are unknown. We sought to determine the short-term clinical response and postdischarge outcomes associated with serum Cl levels in AHF. Serum Cl was measured at randomization (n = 358) and during hospitalization from patients with AHF in the Renal Optimization Strategies Evaluation in Acute Heart Failure trial. Outcomes included diuretic response and renal function at 72 hours and death and rehospitalization at 60 and 180 days. Baseline Cl tertiles were 84 to 98; 99 to 102; and 103 to 117 meq/l. Baseline Cl level was associated with diuretic efficiency (p <0.001) but not change in cystatin C (p = 0.30) at 72 hours and was associated with 60-day death (hazard ratio [HR] 0.86, p = 0.029), 60-day death and rehospitalization (HR 0.90, p = 0.01), and 180-day death (HR 0.91, p = 0.049). These associations were attenuated with additional adjustment for loop diuretic dose (p >0.05). Chloride change correlated with weight change (? 0.18, p = 0.001), cystatin C change (? -0.35, p <0.001), and cumulative sodium excretion (? -0.21, p <0.001) but was not associated with any clinical outcomes (p >0.05 for all). In conclusion, serum Cl levels in AHF were inversely associated with loop diuretic response and were prognostic. However, changes in Cl levels were associated with parameters of decongestion but not with clinical outcomes.

SUBMITTER: Grodin JL

PROVIDER: S-EPMC5161696 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Implications of Serum Chloride Homeostasis in Acute Heart Failure (from ROSE-AHF).

Grodin Justin L JL Sun Jie-Lena JL Anstrom Kevin J KJ Chen Horng H HH Starling Randall C RC Testani Jeffrey M JM Tang W H Wilson WH

The American journal of cardiology 20160930 1

Lower serum chloride (Cl) levels are strongly associated with increased long-term mortality after admission for acute heart failure (AHF). However, the therapeutic implications of serum Cl levels during AHF are unknown. We sought to determine the short-term clinical response and postdischarge outcomes associated with serum Cl levels in AHF. Serum Cl was measured at randomization (n = 358) and during hospitalization from patients with AHF in the Renal Optimization Strategies Evaluation in Acute H ...[more]

PMID: 27816115

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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.

Project description:IMPORTANCE:Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. OBJECTIVE:To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 ?g/kg/min) or low-dose nesiritide (0.005 ?g/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. DESIGN, SETTING, AND PARTICIPANTS:Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. INTERVENTIONS:Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n?=?122) and nesiritide (n?=?119) groups were independently compared with the pooled placebo group (n?=?119). MAIN OUTCOMES AND MEASURES:Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). RESULTS:Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P?=?.59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P?=?.72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296 mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, -618 to 1176 mL; P?=?.49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, -0.04; 95% CI, -0.13 to 0.05; P?=?.36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes. CONCLUSION AND RELEVANCE:In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01132846.

Dataset Information

Implications of Serum Chloride Homeostasis in Acute Heart Failure (from ROSE-AHF).

Publications

Implications of Serum Chloride Homeostasis in Acute Heart Failure (from ROSE-AHF).

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