Effects of Inflammatory Cell Death Caused by Catheter Ablation on Atrial Fibrillation

Abstract

Atrial fibrillation (AF) poses a serious healthcare burden on society due to its high morbidity and the resulting serious complications such as thrombosis and heart failure. The principle of catheter ablation is to achieve electrical isolation by linear destruction of cardiac tissue, which makes AF a curable disease. Currently, catheter ablation does not have a high long-term success rate. The current academic consensus is that inflammation and fibrosis are central mechanisms in the progression of AF. However, artificially caused inflammatory cell death by catheter ablation may have a significant impact on structural and electrical remodeling, which may affect the long-term prognosis. This review first focused on the inflammatory response induced by apoptosis, necrosis, necroptosis, pyroptosis, ferroptosis and their interaction with arrhythmia. Then, we compared the differences in cell death induced by radiofrequency ablation, cryoballoon ablation and pulsed-field ablation. Finally, we discussed the structural and electrical remodeling caused by inflammation and the association between inflammation and the recurrence of AF after catheter ablation. Collectively, pulsed-field ablation will be a revolutionary innovation with faster, safer, better tissue selectivity and less inflammatory response induced by apoptosis-dominated cell death.

Keywords: atrial fibrillation; cryoballoon ablation; electroporation; inflammatory cell death; radiofrequency ablation.

Figure 1

The association between inflammatory cell death and AF. This figure briefly recapitulates the association between inflammatory cell death and AF induce inflammatory cell death. Inflammatory cell death caused by artificial therapeutic regimens releases inflammatory factors that lead to structural and electrical remodeling, thereby contributing to the permanent progression of the arrhythmia. The cross-link between AF and inflammatory cell death creates a vicious loop.

Figure 2

Overview of the inflammatory pathways induced by inflammatory cell death. Release of inflammatory factors, mainly DAMPs, following cardiomyocytes death promotes polarization and chemotaxis of inflammatory cells. In turn, inflammatory cells secrete inflammatory factors which alter the structure and electrical conduction activity of the local microenvironment.

Figure 3

Comparison of cell death patterns due to RFA and PFA. RFA causes damage by localized cell necrosis, whereas PFA causes damage by apoptotic cell death. By comparing the schematic diagrams, RFA causes widespread necrosis, and the area of necrosis may contain patterns of death including necrosis, necroptosis, pyroptosis, and ferroptosis. A large accumulation of inflammatory cells such as neutrophils, monocytes and lymphocytes are chemotactic to the migrated area, which in turn induces a strong inflammatory response. Whereas the necrosis by PFA is limited to the area close to the catheter, the wider damage is predominantly apoptotic. There is also relatively little infiltration of inflammatory cells in the migratory zone.