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Vagus Nerve Stimulation Promising In POTS


Stimulating the vagus nerve reduced orthostatic tachycardia in patients with postural tachycardia syndrome (POTS), possibly through decreased antiadrenergic autoantibodies and inflammatory cytokines, and improved cardiac autonomic function, in a small proof-of-concept study.


  • The double-blind study included 25 female patients with POTS, a syndrome of orthostatic intolerance (mean age 31 years and 81% Caucasian), who were randomly assigned to transcutaneous vagus nerve stimulation (tVNS) to the right tragus or sham stimulation to the earlobe, a site devoid of vagal innervation.

  • After training, patients delivered the tVNS themselves at a frequency of 20 Hz and pulse width of 200 ms during 1-hour daily sessions over 2 months.

  • At baseline and 2 months, patients underwent a tilt test to determine postural tachycardia; they remained supine for 25 minutes, followed by 10 minutes of standing, as tolerated.

  • Researchers used electrocardiogram data to examine heart rate and blood samples to assess serum cytokines and antiautonomic autoantibodies.

  • The primary outcome was a comparison of orthostatic tachycardia (standing – supine) between the two arms at 2 months.


  • At 2 months, postural tachycardia was significantly less in the active vs sham arm (mean postural increase in heart rate 17.6 beats/min vs 31.7 beats/min; P = .01).

  • There was a significant decrease in β1-adrenergic receptor (β1-AR; P = .01) and α1-AR (P = .04) autoantibody activity in the active vs sham group, which may account at least in part for the reduced orthostatic tachycardia, although the exact mechanisms for this effect have not been clearly defined, the authors said.

  • Serum tumor necrosis factor-α (TNF-α) levels were significantly decreased in the active group relative to the sham group (8.3 pg/mL vs 13.9 pg/mL; P = .01).

  • As for heart rate variability, change in low frequency (LF) and high frequency (HF) from supine to standing was significantly decreased, and postural change in LF/HF ratio, a surrogate for sympathovagal balance, was significantly lower in the active group compared with the sham group.


“Collectively, these data suggest that tVNS, a low-cost, low-risk intervention, applied for a short period of time in selected patients with POTS, may result in a significant amelioration of their disease,” the authors conclude.


The study was led by Stavros Stavrakis, MD, PhD, University of Oklahoma Health Sciences Center, Oklahoma City. It was published online November 22, 2023, in JACC: Clinical Electrophysiology.


The study had a small sample size, included only females, and extended only up to 2 months. As there was no improvement on the overall score from the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire, researchers can’t conclude tVNS improved patient reported outcomes. The study used 1 hour of daily stimulation but the optimal duration and ideal timing of tVNS is yet to be determined.


The study was supported by the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute, NIH/National Institute of General Medical Sciences, and individual donations from Francie Fitzgerald and family through the OU Foundation Fund. The authors have no relevant conflicts of interest.

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