Author + information
- Received September 18, 2019
- Revision received November 13, 2019
- Accepted November 14, 2019
- Published online March 16, 2020.
- Stavros Stavrakis, MD, PhD∗ (, )
- Julie A. Stoner, PhD,
- Mary Beth Humphrey, MD, PhD,
- Lynsie Morris, MSc,
- Adrian Filiberti, PhD,
- Justin C. Reynolds, BS,
- Khaled Elkholey, MD,
- Isma Javed, MD,
- Nicholas Twidale, MD, PhD,
- Pavel Riha, MD,
- Subha Varahan, MD,
- Benjamin J. Scherlag, PhD,
- Warren M. Jackman, MD,
- Tarun W. Dasari, MD and
- Sunny S. Po, MD, PhD
- ↵∗Address for correspondence:
Dr. Stavros Stavrakis, University of Oklahoma Health Sciences Center, 800 Stanton L. Young Boulevard, Suite 5400, Oklahoma City, Oklahoma 73104.
Objectives This study was a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low level tragus stimulation (LLTS) in patients with paroxysmal AF.
Background Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve at the tragus (LLTS) acutely suppresses atrial fibrillation (AF) in humans, but the chronic effect remains unknown.
Methods LLTS (20 Hz, 1 mA below the discomfort threshold) was delivered using an ear clip attached to the tragus (active arm) (n = 26) or the ear lobe (sham control arm) (n = 27) for 1 h daily over 6 months. AF burden over 2-week periods was assessed by noninvasive continuous electrocardiogram monitoring at baseline, 3 months, and 6 months. Five-minute electrocardiography and serum were obtained at each visit to measure heart rate variability and inflammatory cytokines, respectively.
Results Baseline characteristics were balanced between the 2 groups. Adherence to the stimulation protocol (≤4 sessions lost per month) was 75% in the active arm and 83% in the control arm (p > 0.05). At 6 months, the median AF burden was 85% lower in the active arm compared with the control arm (ratio of medians: 0.15; 95% confidence interval: 0.03 to 0.65; p = 0.011). Tumor necrosis factor-alpha was significantly decreased by 23% in the active group relative to the control group (ratio of medians: 0.77; 95% confidence interval: 0.63 to 0.94; p = 0.0093). Frequency domain indices of heart rate variability were significantly altered with active versus control stimulation (p < 0.01). No device-related side effects were observed.
Conclusions Chronic, intermittent LLTS resulted in lower AF burden than did sham control stimulation, supporting its use to treat paroxysmal AF in selected patients. (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation [TREAT-AF]; NCT02548754)
This work was funded by National Institutes of Health/National Institute of General Medical Sciences grant #8P20GM103447 and American Heart Association grant #15MCPRP2579000 (to Dr. Stavrakis), with partial funding by National Institutes of Health/National Institute of General Medical Sciences grant #1U54GM10493. Dr. Jackman has served as a consultant for Biosense Webster and Spectrum Dynamics; has received lecture honoraria from Biosense Webster, Boston Scientific, Biotronik, and Abbott; and owns stock in Affera and APN Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received September 18, 2019.
- Revision received November 13, 2019.
- Accepted November 14, 2019.
- 2020 American College of Cardiology Foundation
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