The neural basis of atrial fibrillation

This review addresses recent basic and clinical studies which suggest that targeting autonomic nerves and ganglia on the heart can result in suppression of atrial fibrillation (AF) with less damage to myocardium than the presently employed procedure which involves extensive pulmonary vein (PV) isolation from the rest of the left atrium.

Clinical electrophysiologists in 1998 discovered that the majority of patients with paroxysmal form of AF, resistant to drugs and cardioversion, had focal, ectopic firing arising from the myocardial sleeves covering the PVs. They developed a strategy which called for inducing radiofrequency lesions which would supposedly isolate the PVs from the atria thereby curing this form of AF. To date this strategy has had limited success (70-85%). A new approach relies on targeting the ganglionated plexi (GP) at the entrances of the PVs. Several clinical reports provide evidence that this new approach can increase the success rate for radiofrequency ablation of paroxysmal AF (91-99%).

Experimental investigations in animal studies, both in vivo and in vitro, have accumulated evidence for a mechanistic basis for the ablation of GP to terminate paroxysmal AF. Specifically, release of the neurotransmitter, acetylcholine, from these GP causes shortening of atrial and PV sleeve refractoriness. In addition, the concomitant release of adrenergic neurotransmitters mobilizes excess calcium intracellularly leading to early afterdepolarizations and triggered firing particularly in PV cells. We conclude that hyperactivity of these local cardiac GP play a critical role in initiating the paroxysmal form of AF resistant to drugs and cardioversion. Targeting the GP for ablation can substantially increase the success rate for terminating AF in these patients.