title: Chronic subcutaneous brain natriuretic peptide therapy in asymptomatic systolic heart failure.
abstract: We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy.
  
  
  
  We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice-daily SQ BNP 10 µg/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (-39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P < 0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo.
  
  
  
  Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF.
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKie
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Schirger
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Benike
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Lynn K
authors.initials: LK
authors.lastname: Harstad
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Slusser
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: David O
authors.initials: DO
authors.lastname: Hodge
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Horng H
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D005440:Fluid Therapy; D005919:Glomerular Filtration Rate; D054143:Heart Failure, Systolic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D055104:Infusions, Subcutaneous; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D045283:Natriuretic Agents / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000627:therapeutic use*; D012964:Sodium / Q000652:urine*
chemical_list: D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D012964:Sodium; D006152:Cyclic GMP
keywords: Asymptomatic; Heart failure; Natriuretic peptides; Renal