title: Time course of markers of tissue repair after ablation of atrial fibrillation and their relation to left atrial structural changes and clinical ablation outcome.
abstract: BACKGROUND
  Radiofrequency ablation of atrial fibrillation (AF) creates left atrial (LA) tissue damage with a subsequent healing process. We sought to prospectively assess the time course of biomarkers of tissue repair after ablation and to evaluate their association with clinical variables.
  
  
  METHODS
  30 consecutive patients (57.9 ± 1.7 yrs, 63% males) with paroxysmal AF underwent a CARTO-guided LA circumferential ablation, Lasso-guided segmental pulmonary vein isolation and ablation of complex fractionated atrial electrograms. Matrix metalloproteinase-9 (MMP-9) and transforming growth factor-β1 (TGF-β1), both key regulators of tissue repair, and the aminoterminal propeptide of type III procollagen (PIIINP), reflecting collagen synthesis, were determined in blood samples before and 6h, 1, 2, 7, 30, 90 and 180 days post-ablation.
  
  
  RESULTS
  All markers showed a significant ablation-induced up-regulation (MMP-9: 1.8 ± 0.1-fold, TGF-β1: 2.4 ± 0.4-fold, PIIINP: 1.3 ± 0.1-fold). MMP-9 was significantly up-regulated until day 90, TGF-β1 only on day 2. PIIINP increased from day 2 to 7. The area under the curve (AUC) of MMP-9 and TGF-β1 correlated with the ablation-induced reduction of LA volume (both p<0.05). The AUC of MMP-9 was additionally associated with the amount of radiofrequency energy delivered during ablation (p < 0.05). At 12 months of follow-up 57% of patients were free of AF off antiarrhythmic drugs. The AUC of PIIINP independently predicted recurrent AF (p < 0.05).
  
  
  CONCLUSIONS
  Markers of healing showed a significant up-regulation after AF ablation detectable for up to 90 days. A more pronounced up-regulation of MMP-9 or TGF-β1 is associated with a greater reduction of LA size. High PIIINP levels after ablation predict a poor ablation outcome.
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria. bernhard.richter@meduniwien.ac.at
authors.forename: Bernhard
authors.initials: B
authors.lastname: Richter
authors.forename: Marianne
authors.initials: M
authors.lastname: Gwechenberger
authors.forename: Ariel
authors.initials: A
authors.lastname: Socas
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Zorn
authors.forename: Sulaima
authors.initials: S
authors.lastname: Albinni
authors.forename: Manfred
authors.initials: M
authors.lastname: Marx
authors.forename: Florian
authors.initials: F
authors.lastname: Wolf
authors.forename: Jutta
authors.initials: J
authors.lastname: Bergler-Klein
authors.forename: Christian
authors.initials: C
authors.lastname: Loewe
authors.forename: Christian
authors.initials: C
authors.lastname: Bieglmayer
authors.forename: Thomas
authors.initials: T
authors.lastname: Binder
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Heinz D
authors.initials: HD
authors.lastname: Gössinger
mesh_terms: D000367:Age Factors; D001281:Atrial Fibrillation / Q000601:surgery*; D015415:Biomarkers / Q000097:blood; D017115:Catheter Ablation; D005260:Female; D006325:Heart Atria / Q000000981:diagnostic imaging / Q000601:surgery*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011446:Prospective Studies; D011667:Pulmonary Veins / Q000601:surgery; D012008:Recurrence; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D014463:Ultrasonography; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D053773:Transforming Growth Factor beta1; C041876:procollagen Type III-N-terminal peptide; D020780:Matrix Metalloproteinase 9