Autonomic innervation and segmental muscular disconnections at the human pulmonary vein-atrial junction: implications for catheter ablation of atrial-pulmonary vein junction

Abstract

Objectives: This study sought to examine the muscle connections and autonomic nerve distributions at the human pulmonary vein (PV)-left atrium (LA) junction.

Background: One approach to catheter ablation of atrial fibrillation (AF) is to isolate PV muscle sleeves from the LA. Elimination of vagal response further improves success rates.

Methods: We performed immunohistochemical staining on 192 circumferential venoatrial segments (32 veins) harvested from 8 autopsied human hearts using antibodies to tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT).

Results: Muscular discontinuities of widths 0.1 to 5.5 mm (1.1 +/- 1.0 mm) and abrupt 90 degrees changes in fiber orientation were found in 70 of 192 (36%) and 36 of 192 (19%) of PV-LA junctions, respectively. Although these anisotropic features were more common in the anterosuperior junction (p < 0.01), they were also present around the entire PV-LA junction. Autonomic nerve density was highest in the anterosuperior segments of both superior veins (p < 0.05 versus posteroinferior) and inferior segments of both inferior veins (p < 0.05 vs. superior), highest in the LA within 5 mm of the PV-LA junction (p < 0.01), and higher in the epicardium than endocardium (p < 0.01). Adrenergic and cholinergic nerves were highly co-located at tissue and cellular levels. A significant proportion (30%) of ganglion cells expressed dual adrenocholinergic phenotypes.

Conclusions: Muscular discontinuities and abrupt fiber orientation changes are present in >50% of PV-LA segments, creating significant substrates for re-entry. Adrenergic and cholinergic nerves have highest densities within 5 mm of the PV-LA junction, but are highly co-located, indicating that it is impossible to selectively target either vagal or sympathetic nerves during ablation procedures.