Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Ventricular Premature Complexes (TREAT-PVC): A Randomized Clinical Trial.

BACKGROUND

Low-level tragus stimulation (LLTS) of the auricular branch of the vagus nerve at the tragus reduces atrial fibrillation burden. Its efficacy on premature ventricular complexes (PVCs) is unknown, however.

OBJECTIVES

The goal of this study was to evaluate the efficacy of daily LLTS on PVC burden in patients with idiopathic PVC.

METHODS

TREAT-PVC (LLTS to Treat Premature Ventricular Contractions) is a sham-controlled, double-blind, randomized trial. Eligible patients with >10% PVC burden were randomized 1:1 to receive LLTS vs sham stimulation to the earlobe (20 Hz, 1 mA below the discomfort threshold; 1 hour daily). The primary outcome was reduction of PVC burden at 6 months assessed by using 10-day ambulatory electrocardiographic monitoring.

RESULTS

Among 100 randomized patients, 96 were included into final analysis (N = 48 for each group) with no significant adverse effects. Baseline characteristics were balanced between groups (PVC burden: LLTS = 18.7%; sham = 16.7%). Adherence to the study protocol was similar between the 2 groups (LLTS = 85.4%; sham = 89.6%). At 6 months, both groups showed reduced PVC burden assessed by 10-day monitoring (LLTS median value: 18.7% to 11.1% [P < 0.01]; sham median value: 16.7% to 12.6% [P < 0.01]), although with no differences between the 2 groups. Skin sympathetic nerve activity and inflammatory markers (tumor necrosis factor-α, interleukin-1, and interleukin-6) remained unchanged in both groups. Heart rate variability parameters showed similar significant changes in each group (higher low-frequency, high-frequency, and very-low-frequency power; and a lower low-frequency/high-frequency ratio), suggesting that autonomic balance shifted toward parasympathetic dominance. However, there were no differences between the 2 groups (P > 0.05 for all parameters).

CONCLUSIONS

LLTS and sham stimulation produced parallel results, indicating the presence of significant placebo effects. Future transcutaneous neuromodulation studies should include placebo effects into sample size calculation. (LLTS to Treat Premature Ventricular Contractions [TREAT-PVC]; NCT04909528).