title: Decongestion strategies and renin-angiotensin-aldosterone system activation in acute heart failure.
abstract: OBJECTIVE
  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).
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina. Electronic address: robert.mentz@duke.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mentz
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Adam D
authors.initials: AD
authors.lastname: DeVore
authors.affiliation: Department of Medicine, Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts; Department of Medicine, Division of Cardiology, New York University Langone Medical Center, New York University School of Medicine, New York, New York.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Lala
authors.affiliation: Department of Medicine, Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Vader
authors.affiliation: Department of Medicine, Division of Cardiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Omar F
authors.initials: OF
authors.lastname: AbouEzzeddine
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Prateeti
authors.initials: P
authors.lastname: Khazanie
authors.affiliation: Department of Medicine, Division of Cardiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.affiliation: Department of Medicine, Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Lynne W
authors.initials: LW
authors.lastname: Stevenson
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: Department of Medicine, Division of Cardiology, Hennepin County Medical Center, Minneapolis, Minnesota.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldsmith
authors.affiliation: Department of Medicine, Division of Cardiology, Hennepin County Medical Center, Minneapolis, Minnesota.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Bart
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: Department of Medicine, Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D001806:Blood Urea Nitrogen; D004232:Diuretics / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005665:Furosemide / Q000008:administration & dosage; D006333:Heart Failure / Q000628:therapy*; D006440:Hemofiltration; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System; D012964:Sodium / Q000097:blood
chemical_list: D015415:Biomarkers; D004232:Diuretics; D000450:Aldosterone; D005665:Furosemide; D012964:Sodium; D012083:Renin
keywords: RAAS activation; acute heart failure; cardiorenal syndrome; decongestion; diuretics; outcomes; ultrafiltration