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Randomized Controlled Trial
. 2015 Mar 10;65(9):867-75.
doi: 10.1016/j.jacc.2014.12.026.

Low-level transcutaneous electrical vagus nerve stimulation suppresses atrial fibrillation

Stavros Stavrakis  1 , Mary Beth Humphrey  2 , Benjamin J Scherlag  1 , Yanqing Hu  2 , Warren M Jackman  1 , Hiroshi Nakagawa  1 , Deborah Lockwood  1 , Ralph Lazzara  1 , Sunny S Po  3
Affiliations
Randomized Controlled Trial

Low-level transcutaneous electrical vagus nerve stimulation suppresses atrial fibrillation

Stavros Stavrakis et al. J Am Coll Cardiol. .

Abstract

Background: Transcutaneous low-level tragus electrical stimulation (LLTS) suppresses atrial fibrillation (AF) in canines.

Objectives: This study examined the antiarrhythmic and anti-inflammatory effects of LLTS in humans.

Methods: Patients with paroxysmal AF who presented for AF ablation were randomized to either 1 h of LLTS (n = 20) or sham control (n = 20). Attaching a flat metal clip onto the tragus produced LLTS (20 Hz) in the right ear (50% lower than the voltage slowing the sinus rate). Under general anesthesia, AF was induced by burst atrial pacing at baseline and after 1 h of LLTS or sham treatment. Blood samples from the coronary sinus and the femoral vein were collected at those time points and then analyzed for inflammatory cytokines, including tumor necrosis factor alpha and C-reactive protein, using a multiplex immunoassay.

Results: There were no differences in baseline characteristics between the 2 groups. Pacing-induced AF duration decreased significantly by 6.3 ± 1.9 min compared with baseline in the LLTS group, but not in the control subjects (p = 0.002 for comparison between groups). AF cycle length increased significantly from baseline by 28.8 ± 6.5 ms in the LLTS group, but not in control subjects (p = 0.0002 for comparison between groups). Systemic (femoral vein) but not coronary sinus tumor necrosis factor (TNF)-alpha and C-reactive protein levels decreased significantly only in the LLTS group.

Conclusions: LLTS suppresses AF and decreases inflammatory cytokines in patients with paroxysmal AF. Our results support the emerging paradigm of neuromodulation to treat AF.

Keywords: atrial fibrillation; autonomic nervous system; inflammation; neuromodulation.

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Figures

FIGURE 1
FIGURE 1. Study Protocol
(A) Following the first induction of atrial fibrillation (AF) the groups underwent low-level electrical stimulation of the auricular branch of the right vagus nerve at the tragus (LLTS) or a sham procedure for 1 hour, followed by a second round of AF induction (B) To achieve electrical stimulation, a flat metal clip was attached to the right tragus (dashed circle), which served as the cathode. Another clip on the ear lobe served as the anode.
FIGURE 2
FIGURE 2. Voltage Threshold for Heart Rate Slowing
(A) Before stimulation, sinus cycle length is 900 ms. (B) During stimulation at 20 V (note stimulation artifact), there is an increase in the sinus cycle length to 930 ms.
FIGURE 3
FIGURE 3. Effect of LLTS on Cycle Length
There was a significant increase in AF cycle length compared to baseline in the LLTS group, but not in the control group. Abbreviations as in Figure 1.
FIGURE 4
FIGURE 4. Effect of LLTS on AERP
Both the right atrial (RA) and coronary sinus (CS) atrial effective refractory period (AERP) increased in the LLTS group and decreased in the control group. Other abbreviations as in Figure 1.
FIGURE 5
FIGURE 5. Effect of LLTS on Systemic CRP Levels
There was a significant decrease in systemic C-reactive protein (CRP) levels compared to baseline in the LLTS group, but not in the control group. Other abbreviations as in Figure 1.
Figure
Figure. CENTRAL ILLUSTRATION Neuromodulation Suppresses Inflammation and AF
This study examined the antiarrhythmic and anti-inflammatory effects of low-level electrical stimulation of the auricular branch of the right vagus nerve at the tragus (LLTS) in patients referred for atrial fibrillation (AF) ablation. We demonstrated for the first time in humans that LLTS compared to control (A) decreased AF duration and (B) suppressed inflammatory cytokines. TNF-α = tumor necrosis factor-alpha.
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