Heterogeneous atrial denervation creates substrate for sustained atrial fibrillation

Area of Science:

• Cardiovascular Electrophysiology
• Autonomic Nervous System
• Atrial Fibrillation Pathophysiology

Background:

• Heterogeneous electrophysiological properties, influenced by autonomic innervation, are crucial for maintaining atrial fibrillation (AF).
• Autonomic dysfunction, particularly sympathetic innervation, plays a role in AF development and persistence.

Purpose of the Study:

• To investigate if heterogeneous sympathetic denervation using phenol could induce a state conducive to sustained AF.
• To explore the electrophysiological effects of targeted sympathetic denervation on atrial refractoriness and AF cycle length.

Main Methods:

• 15 dogs underwent atrial epicardial phenol application, while 11 received a sham procedure.
• AF inducibility, effective refractory period (ERP), and AF cycle lengths were assessed post-procedure.
• Positron Emission Tomography (PET) imaging with sympathetic ([11C]hydroxyephedrine, HED) and parasympathetic (5-[11C]methoxybenzovesamicol, MOBV) tracers evaluated nerve integrity.

Main Results:

• 14 of 15 phenol-treated dogs developed sustained AF, compared to none in the sham group.
• Phenol application significantly shortened ERP and increased dispersion of refractoriness and AF cycle length.
• PET imaging revealed HED uptake defects at phenol application sites, indicating sympathetic denervation, with no MOBV uptake defects.

Conclusions:

• Heterogeneous sympathetic atrial denervation with phenol effectively facilitates sustained AF.
• Targeted disruption of sympathetic innervation alters atrial electrophysiology, promoting AF maintenance.