Decongestion strategies and renin-angiotensin-aldosterone system activation in acute heart failure.
Abstract
OBJECTIVES: The purpose of this study was to assess the relationship between biomarkers
of renin-angiotensin-aldosterone system (RAAS) activation and decongestion strategies,
worsening renal function, and clinical outcomes. BACKGROUND: High-dose diuretic therapy
in patients with acute heart failure (AHF) is thought to activate the RAAS; and alternative
decongestion strategies, such as ultrafiltration (UF), have been proposed to mitigate
this RAAS activation. METHODS: This study analyzed 427 AHF patients enrolled in the
DOSE-AHF (Diuretic Optimization Strategies in Acute Heart Failure) and CARRESS-HF
(Cardiorenal Rescue Study in Acute Decompensated Heart Failure) trials. We assessed
the relationship between 2 markers of RAAS activation (plasma renin activity [PRA]
and aldosterone) from baseline to 72 h and 96 h and decongestion strategy: high- versus
low-dose and continuous infusion versus bolus furosemide for DOSE-AHF and UF versus
stepped pharmacologic care for CARRESS-HF. We determined the relationships between
RAAS biomarkers and 60-day outcomes. RESULTS: Patients with greater RAAS activation
at baseline had lower blood pressures, lower serum sodium levels, and higher blood
urea nitrogen (BUN) concentration. Continuous infusion furosemide and UF were associated
with greater PRA increases (median: +1.66 vs. +0.66 ng/ml/h with continuous vs. bolus
infusion, respectively, p = 0.021; +4.05 vs. +0.56 ng/ml/h with UF vs. stepped care,
respectively, p = 0.014). There were no significant differences in RAAS biomarker
changes with high- versus low-dose diuretic therapy (both: p > 0.5). Neither baseline
log PRA nor log aldosterone was associated with increased death or HF hospitalization
(hazard ratio [HR] for a doubling of 1.05; 95% confidence interval [CI]: 0.98 to 1.13;
p = 0.18; and HR: 1.13; 95% CI: 0.99 to 1.28; p = 0.069, respectively). The change
in RAAS biomarkers from baseline to 72 and 96 h was not associated with outcomes (both:
p > 0.5). CONCLUSIONS: High-dose loop diuretic therapy did not result in RAAS activation
greater than that with low-dose diuretic therapy. UF resulted in greater PRA increase
than stepped pharmacologic care. Neither PRA nor aldosterone was significantly associated
with short-term outcomes in this cohort. (Determining Optimal Dose and Duration of
Diuretic Treatment in People With Acute Heart Failure [DOSE-AHF]; NCT00577135; Effectiveness
of Ultrafiltration in Treating People With Acute Decompensated Heart Failure and Cardiorenal
Syndrome [CARRESS]; NCT00608491).
Type
Journal articleSubject
RAAS activationacute heart failure
cardiorenal syndrome
decongestion
diuretics
outcomes
ultrafiltration
Aged
Aldosterone
Biomarkers
Blood Pressure
Blood Urea Nitrogen
Diuretics
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Furosemide
Heart Failure
Hemofiltration
Humans
Infusions, Intravenous
Injections, Intravenous
Male
Middle Aged
Renin
Renin-Angiotensin System
Sodium
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https://hdl.handle.net/10161/11075Published Version (Please cite this version)
10.1016/j.jchf.2014.09.003Publication Info
Mentz, Robert J; Stevens, Susanna R; DeVore, Adam D; Lala, Anuradha; Vader, Justin
M; AbouEzzeddine, Omar F; ... Felker, G Michael (2015). Decongestion strategies and renin-angiotensin-aldosterone system activation in acute
heart failure. JACC Heart Fail, 3(2). pp. 97-107. 10.1016/j.jchf.2014.09.003. Retrieved from https://hdl.handle.net/10161/11075.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Kevin J. Anstrom
Adjunct Professor in the Department of Biostatistics & Bioinformatics
My research interests include clinical trial design, causal inference, coordinating
centers, data monitoring, and pragmatic clinical research.
Adam David DeVore
Associate Professor of Medicine
Adam D. DeVore, MD, MHS
Dr. DeVore is a cardiologist and Associate Professor of Medicine in the Department
of Medicine, Division of Cardiology, at Duke University School of Medicine. His clinical
interests include caring for patients and families with heart failure, including those
with left ventricular assist devices and heart transplants. He is involved in and
leads multiple large studies of patients with heart failure at both Duke University
Medical Center and the
Gary Michael Felker
Professor of Medicine
Adrian Felipe Hernandez
Duke Health Cardiology Professor
Robert John Mentz
Associate Professor of Medicine
I am a cardiologist with a clinical and research interest in heart failure (going
from Failure to Function), including advanced therapies such as cardiac transplantation
and mechanical assist devices or “heart pumps." I serve our group as Chief of
the Heart Failure Section. I became a heart failure cardiologist in order to help
patients manage their chronic disease over many months and years. I consider myself
strongly committed to compassionate patient care with a
Christopher Michael O'Connor
Adjunct Professor in the Department of Medicine
Dr. O’Connor’s research interests include: acute heart failure; co-morbidities in
heart failure; clinical trials; biomarkers; and novel pharmacological and non-pharmacological
approaches for the treatment of heart failure.
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