title: Effect of cardiac resynchronization therapy on broad neurohormone biomarkers in heart failure.
abstract: BACKGROUND
  Neurohormonal dysregulation contributes to heart failure (HF) progression. We sought to determine the effect of cardiac resynchronization therapy (CRT) on nerve growth factor (NGF), a biomarker that promotes the maturation and survival of sympathetic nerve endings, and amino-terminal propeptide of type III procollagen (PIIINP), a marker of type III collagen synthesis.
  
  
  METHODS
  This prospective study consisted of 45 consecutive patients who received cardiac resynchronization therapy defibrillator for advanced HF and 20 healthy age-matched controls. New York Heart Association class, distance of 6-min walk, echocardiography and plasma concentrations of NGF, PIIINP, b-type natriuretic peptide (BNP), norepinephrine, and epinephrine were measured before and 6 months after CRT. Response to CRT was defined as 15% or greater reduction in left ventricular end-systolic volume index at 6-month follow-up.
  
  
  RESULTS
  The baseline BNP (2.61 ± 0.51 vs. 1.53 ± 0.44 ug/L, P < 0.01) and PIIINP (0.88 ± 0.21 vs. 0.71 ± 0.14 μg/L, P = 0.01), but not other biomarkers, were elevated in HF compared to controls. Twenty-two of 45 patients (49%) responded to CRT. The responder group demonstrated significant decrease only in BNP level from 2.61 ± 0.51 to 2.31 ± 0.41 μg/L (P = 0.04) at 6-month follow-up, paralleling the clinical improvements. The baseline PIIINP, rather than the other biomarkers, was lower in CRT responders than non-responders (0.80 ± 0.20 vs. 0.96 ± 0.19 μg/L, P = 0.03). Univariate and multivariate analysis showed that less elevated plasma PIIINP level in HF might be an independent biomarker predicting better response to CRT (odds ratio = 0.20, 95% CI = 0.03-1.17, P = 0.07).
  
  
  CONCLUSIONS
  The less elevated PIIINP level in HF, which is suggestive of a lesser amount of cardiac fibrosis, has a trend in association with a favorable response to CRT. Contrary to previous reports, NGF levels are not reduced during HF with optimal medical therapy, and there is no NGF rebound in CRT responders.
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Ying-Xue
authors.initials: YX
authors.lastname: Dong
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.forename: Horng H
authors.initials: HH
authors.lastname: Chen
authors.forename: Sharon
authors.initials: S
authors.lastname: Sandberg
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Yang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Cha
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D058406:Cardiac Resynchronization Therapy; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018450:Disease Progression; D004452:Echocardiography; D004562:Electrocardiography; D004837:Epinephrine / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D016015:Logistic Models; D008297:Male; D020932:Nerve Growth Factor / Q000097:blood*; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D020932:Nerve Growth Factor; D009638:Norepinephrine; D004837:Epinephrine