Time course of markers of tissue repair after ablation of atrial fibrillation and their relation to left atrial structural changes and clinical ablation outcome.
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.
Richter
Bernhard
B
Department of Cardiology, Medical University of Vienna, Vienna, Austria. bernhard.richter@meduniwien.ac.at
Gwechenberger
Marianne
M
Socas
Ariel
A
Zorn
Gerlinde
G
Albinni
Sulaima
S
Marx
Manfred
M
Wolf
Florian
F
Bergler-Klein
Jutta
J
Loewe
Christian
C
Bieglmayer
Christian
C
Binder
Thomas
T
Wojta
Johann
J
Gössinger
Heinz D
HD
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
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D053773:Transforming Growth Factor beta1; C041876:procollagen Type III-N-terminal peptide; D020780:Matrix Metalloproteinase 9