Background: Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve at the tragus (LLTS) is a promising treatment for atrial fibrillation (AF), however, the role of adrenergic remodeling in AF, and the impact of LLTS on adrenergic signaling are poorly understood.
Objective: To examine the relationship between the adrenergic co-transmitter neuropeptide Y (NPY) and 1) AF progression, and 2) LLTS.
Methods: We randomized patients with paroxysmal AF (pAF) to LLTS (20Hz, 1mA < pain threshold) using an ear clip attached to the tragus (LLTS, n=26) or ear lobe (sham, n=27) for an hour daily for 6 months. NPY levels were measured by immunosorbent assay at baseline, and at 3- and 6-month periods. The primary outcome was AF burden over 6 months.
Results: The study cohort included 54 patients with pAF (55% females, median AF duration 24 months) and structurally normal hearts (mean LV EF 60±9%). On univariate analysis, baseline (BL) NPY levels were positively correlated with age (r = 0.32, p=0.029); BMI (r=0.38, p=0.01); heart rate (r=0.38, p=0.026); and diastolic function E/e’ (r=0.43, p=0.027). In the sham group, NPY levels significantly increased at 6 months vs. BL (63.2±5.9 vs. 42.7±4.7 pg/mL, respectively, p=0.01); however, in the LLTS group, 6-month NPY levels were comparable to BL (37.1±4.8 vs. 39.3±4.6 pg/mL, respectively, p=0.64). At 6 months, NPY levels in the LLTS group were significantly lower than sham (37.1±4.8 vs. 63.2±5.9, respectively, p=0.008). Interestingly, in the LLTS group, NPY levels negatively correlated with the degree of change in AF burden during follow up (r=-0.48, p=0.036). During follow up, heart rate during AF was 14.4 bpm lower in LLTS group vs. sham (95% CI 2.9 - 25.9 bpm, p=0.014). Episodes of rapid ventricular response during AF were less frequent in the LLTS group vs. sham (OR=0.36, 95% CI 0.18 - 0.72, p=0.004).
Conclusion: In this pilot study, the adrenergic co-transmitter NPY was associated with AF progression, and may identify patients likely to benefit from LLTS. Larger prospective studies are needed to validate these findings.