Document Detail


Novel protein therapeutics for systolic heart failure: chronic subcutaneous B-type natriuretic peptide.
MedLine Citation:
PMID:  23122795     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The purpose of the present study was to translate our laboratory investigations to establish safety and efficacy of 8 weeks of chronic SC B-type natriuretic peptide (BNP) administration in human Stage C heart failure (HF).
BACKGROUND: B-Type natriuretic peptide is a cardiac hormone with vasodilating, natriuretic, renin-angiotensin inhibiting, and lusitropic properties. We have previously demonstrated that chronic cardiac hormone replacement with subcutaneous (SC) administration of BNP in experimental HF resulted in improved cardiovascular function.
METHODS: We performed a randomized double-blind placebo-controlled proof of concept study comparing 8 weeks of SC BNP (10 μg/kg bid) (n = 20) with placebo (n = 20) in patients with ejection fraction <35% and New York Heart Association functional class II to III HF. Primary outcomes were left ventricular (LV) volumes and LV mass determined by cardiac magnetic resonance imaging. Secondary outcomes include LV filling pressure by Doppler echo, humoral function, and renal function.
RESULTS: Eight weeks of chronic SC BNP resulted in a greater reduction of LV systolic and diastolic volume index and LV mass index as compared with placebo. There was a significantly greater improvement of Minnesota Living with Heart Failure score, LV filling pressure as demonstrated by the reductions of E/e' ratio, and decrease in left atrial volume index as compared with placebo. Glomerular filtration rate was preserved with SC BNP, as was the ability to activate plasma 3',5'-cyclic guanosine monophosphate (p < 0.05 vs. placebo).
CONCLUSIONS: In this pilot proof of concept study, chronic protein therapy with SC BNP improved LV remodeling, LV filling pressure, and Minnesota Living with Heart Failure score in patients with stable systolic HF on optimal therapy. Renin-angiotensin was suppressed, and glomerular filtration rate was preserved. Subcutaneous BNP represents a novel, safe, and efficacious protein therapeutic strategy in human HF. Further studies are warranted to determine whether these physiologic observations can be translated into improved clinical outcomes and ultimately delay the progression of HF. (Cardiac Hormone Replacement With BNP in Heart Failure: A Novel Therapeutic Strategy; NCT00252187).
Authors:
Horng H Chen; James F Glockner; John A Schirger; Alessandro Cataliotti; Margaret M Redfield; John C Burnett
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-01
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  60     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-30     Completed Date:  2013-01-30     Revised Date:  2013-12-11    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2305-12     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00252187
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MeSH Terms
Descriptor/Qualifier:
Double-Blind Method
Drug Administration Schedule
Female
Heart Failure, Systolic / blood,  drug therapy*,  physiopathology
Humans
Injections, Subcutaneous
Male
Natriuretic Peptide, Brain / administration & dosage*,  therapeutic use
Pilot Projects
Ventricular Remodeling / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
P01 HL 76611/HL/NHLBI NIH HHS; P01 HL076611/HL/NHLBI NIH HHS; R01 HL 36634/HL/NHLBI NIH HHS; R01 HL 84155/HL/NHLBI NIH HHS; R01 HL084155/HL/NHLBI NIH HHS; UL1 RR024150/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
114471-18-0/Natriuretic Peptide, Brain
Comments/Corrections
Comment In:
J Am Coll Cardiol. 2012 Dec 4;60(22):2313-5   [PMID:  23122792 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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