title: Chronic Peptide Therapy With B-Type Natriuretic Peptide in Patients With Pre-Clinical Diastolic Dysfunction (Stage B Heart Failure).
abstract: This study determined whether there is development of tachyphylaxis to enhancement of cardiorenal response to acute volume loading (AVL) with B-type natriuretic peptide (BNP) after 12-week, twice-daily subcutaneous BNP administration in patients with preclinical diastolic dysfunction (PDD).
  
  
  
  PDD is characterized by normal systolic function and moderate or severe diastolic dysfunction but no symptoms of heart failure (HF). Impairment in cardiorenal endocrine response to stress by AVL exists in PDD and is corrected by acute administration of subcutaneous BNP.
  
  
  
  A double-blinded, placebo-controlled proof-of-concept study was conducted to compare 12 weeks of twice daily subcutaneous BNP, 10 μg/kg (n = 24), versus placebo (n = 12) in PDD. Subjects underwent 2 study visits, at baseline and after 12 weeks. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular AVL.
  
  
  
  Among those with PDD, there was a statistically significant improvement in diastolic function after 12 weeks of BNP, as measured by a decrease in the Doppler E/e' ratio (where E is early mitral inflow velocity and e' is mitral annulus early diastolic motion) (p = 0.004) and improvement of diastolic dysfunction grade (p = 0.008). After 12 weeks, there was statistically significantly greater sodium excretion, urine flow, and urinary cyclic guanosine monophosphate excretion to AVL (all p < 0.001), as well as a trend toward greater glomerular filtration rate (p = 0.050) in the BNP group as compared to the placebo group.
  
  
  
  In subjects with PDD, chronic BNP administration resulted in sustained improvement in diastolic function without development of tachyphylaxis to the enhancement of cardiorenal response to volume expansion with BNP. (Human Brain Natriuretic Peptide [BNP] [or Nesiritide] to Help Heart, Kidney and Humoral Function; NCT00405548).
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota; Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Siu-Hin
authors.initials: SH
authors.lastname: Wan
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota; Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKie
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota; Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: John A
authors.initials: JA
authors.lastname: Schirger
authors.affiliation: Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Slusser
authors.affiliation: Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: David O
authors.initials: DO
authors.lastname: Hodge
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota; Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota; Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota; Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota. Electronic address: chen.horng@mayo.edu.
authors.forename: Horng H
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058070:Asymptomatic Diseases; D001783:Blood Flow Velocity; D006152:Cyclic GMP / Q000652:urine; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D054144:Heart Failure, Diastolic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve; D045283:Natriuretic Agents / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000627:therapeutic use*; D000075082:Proof of Concept Study; D012964:Sodium / Q000652:urine; D013618:Tachyphylaxis; D016896:Treatment Outcome
chemical_list: D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain; D012964:Sodium; D006152:Cyclic GMP
keywords: B-type natriuretic peptide; cardiorenal syndrome; diastolic dysfunction; heart failure with preserved ejection fraction