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±1.7yrs, 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 180days 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 12months 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 90days. 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.

Keywords: Catheter ablation, Atrial fibrillation, Tissue repair, Matrix metalloproteinase-9, Transforming growth factor-β1, The aminoterminal propeptide of type III procollagen