title: Cardiac resynchronization therapy in patients with chronic heart failure is associated with anti-inflammatory and anti-remodeling effects.
abstract: OBJECTIVE
  Proinflammatory cytokines, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular (LV) structural remodeling. We aimed to investigate the effects of cardiac resynchronization therapy (CRT) on serum levels of amino-terminal prohormone B-type natriuretic peptide (NT-proBNP), some interleukins (IL-1β, IL-6, IL-8), MMP-2 and TIMP-2 in patients with chronic heart failure (CHF).
  
  
  METHODS
  We studied 27 patients (15 M/12 F) with CHF, III-IV NYHA class, implanted with a biventricular pacemaker/defibrillator and 40 healthy subjects (23 M/17 F). Blood samples were collected at baseline and 1 week, 3, 6, and 12 months after CRT device implantation. Cardiac function was assessed echocardiographically.
  
  
  RESULTS
  CRT induced significant improvement in the NYHA class (baseline 3.2±0.5 vs. 1.0 at 12 months, P=0.0002) and significant LV reverse remodeling, with a 41% (P=0.001) reduction in LV end-systolic volume (LVESV). This was associated with a significant reduction in serum NT-proBNP, IL-6 and IL-8. Positive extracellular matrix remodeling was illustrated by decreasing levels of MMP-2 and increasing TIMP-2. MMP-2/TIMP-2 ratio decreased with 55% (P=0.003) from baseline value at 12 months and the correlation with LVESV reduction was 0.41 (P=0.001).
  
  
  CONCLUSIONS
  Structural response to CRT is associated with reduced immune activation and positive extracellular matrix remodeling.
authors.affiliation: Institute of Oncology Bucharest, Department of Carcinogenesis and Molecular Biology, 252 Fundeni, 022338, Bucharest, Romania. adinaelenastanciu@yahoo.com
authors.forename: Adina Elena
authors.initials: AE
authors.lastname: Stanciu
authors.forename: Radu Gabriel
authors.initials: RG
authors.lastname: Vatasescu
authors.forename: Marcel Marian
authors.initials: MM
authors.lastname: Stanciu
authors.forename: Corneliu
authors.initials: C
authors.lastname: Iorgulescu
authors.forename: Alexandra Ioana
authors.initials: AI
authors.lastname: Vasile
authors.forename: Maria
authors.initials: M
authors.lastname: Dorobantu
mesh_terms: D000368:Aged; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D058409:Cardiac Resynchronization Therapy Devices; D016022:Case-Control Studies; D002908:Chronic Disease / Q000628:therapy; D004452:Echocardiography; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D006333:Heart Failure / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007249:Inflammation / Q000628:therapy; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D016896:Treatment Outcome; D020257:Ventricular Remodeling
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D010446:Peptide Fragments; C560823:TIMP2 protein, human; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2