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, andhigher 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).
Bibliographical noteFunding Information:
The DOSE-AHF and CARRESS-HF studies were funded by the National Heart, Lung, and Blood Institute , U.S. National Institutes of Health . Gambro/CHF Solutions provided research grant funding and equipment to Duke University in support of the CARRESS-HF trial. Dr. Goldsmith has received honoraria from CHF Solutions; and grant support, consulting, and speaker fees from Otsuka America Pharmaceuticals, not directly relevant to the present work. Dr. Mentz has received research support from Bristol-Meyers Squibb, GlaxoSmithKline, Novartis, Otsuka, ResMed, Amgen, AstraZeneca, Gilead, and Thoratec. Dr. DeVore has received research support from American Heart Association , Novartis , and Thoratec . Dr. O'Connor has consulted for Cardiorentis; and has received research funding from Roche Diagnostics . Dr. Hernandez has received research support from Amgen, Bristol-Meyers Squibb, Janssen, and Novartis. Dr. Braunwald has received research grant support from Duke University to NHLBI Heart Failure Network . All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John R. Teerlink, MD, has served as Guest Editor for this paper.
© 2015 American College of Cardiology Foundation.
- Acute heart failure
- Cardiorenal syndrome
- RAAS activation