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).

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Citation

Published Version (Please cite this version)

10.1016/j.jchf.2014.09.003

Publication Info

Mentz, Robert J, Susanna R Stevens, Adam D DeVore, Anuradha Lala, Justin M Vader, Omar F AbouEzzeddine, Prateeti Khazanie, Margaret M Redfield, et al. (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.

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Scholars@Duke

Mentz

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 focus on quality of life and patient preference.

I am the Editor in Chief of the Journal of Cardiac Failure - The official journal of the Heart Failure Society of America.

My research interests are focused on treating co-morbid diseases in heart failure patients and improving outcomes across the cardiovascular spectrum through clinical trials and outcomes research. Below, you will find my specific research interests:

  •     Cardiometabolic disease
  •     Co-morbidity characterization (diabetes, sleep apnea, renal failure) in heart failure
  •     Phenotypic characterization and risk prognostication of patients with heart failure
  •     Role of surrogate and nonfatal endpoints in clinical heart failure trials
  •     Biomarkers in heart failure
  •     Novel pharmacological and non-pharmacological approaches to heart failure
  •     Improving site-based heart failure research
DeVore

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 Duke Clinical Research Institute. He currently serves as the medical director of the Duke Heart Transplant program.

He attended medical school at the University of Chicago Pritzker School of Medicine and completed internal medicine residency at Brigham and Women’s Hospital. He then pursued cardiology training at Duke University and solidified his interests in clinical research and heart failure. He completed a research fellowship at the Duke Clinical Research Institute and a Masters of Health Sciences in Clinical Research before completing an advanced heart failure fellowship at Duke University.

The overarching goals of his research are to advance the current understanding of heart failure through clinical trials as well as develop an evidence base for implementation strategies that addresses the gap between heart failure trial results and clinical practice. For example, he has served on the Steering Committees for large clinical trials, including PIONEER-HF and SPIRRIT-HFpEF. Dr. DeVore also published the first clinical trial conducted within the American Heart Association’s Get With The Guidelines-Heart Failure program, a registry-based cluster randomized trial of quality improvement interventions. He was also the principal investigator for CONNECT-HF, a large-scale, pragmatic, cluster-randomized trial at 161 sites in the US evaluating heart failure quality improvement initiatives. Outside of his work on heart failure, Dr. DeVore is  married with 4 children and spends his time corralling them all and coaching youth baseball.

 

 

O'Connor

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.

Anstrom

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.

Felker

Gary Michael Felker

Professor of Medicine

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