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-beta 1 (TGF-beta 1), 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 6 h, 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-beta 1: 2.4 +/- 0.4-fold, PIIINP: 1.3 +/- 0.1-fold). MMP-9 was significantly up-regulated until day 90, TGF-beta 1 only on day 2. PIIINP increased from day 2 to 7. The area under the curve (AUC) of MMP-9 and TGF-beta 1 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-beta 1 is associated with a greater reduction of LA size. High PIIINP levels after ablation predict a poor ablation outcome. (C) 2010 Elsevier Ireland Ltd. All rights reserved..