Vagus Nerve Stimulation Reduces Orthostatic Tachycardia in Women With POTS

At 2 months, transcutaneous vagus nerve stimulation (tVNS) therapy improves autonomic, inflammatory, and immunologic markers in postural tachycardia syndrome (POTS), according to trial results published in the Journal of the American College of Cardiology: Clinical Electrophysiology.

POTS affects mainly young females. Orthostatic intolerance and related symptoms caused by POTS are related to lower quality of life. Few treatments have been shown to help consistently, and the pathophysiology of POTS is debated. One hypothesis is that co-occurring sympathetic autonomic dysfunction, release of inflammatory cytokines, and autoantibody activity against adrenergic receptors disrupt vasomotor activity.

In previous animal research, stimulation of the vagus nerve, applied to the tragus of the ear, improved autonomic tone and reduced inflammation. To see if they could replicate these findings on humans, researchers conducted a randomized, controlled, double-blind clinical trial, Autoimmune Basis for Postural Tachycardia Syndrome (ClinicalTrials.gov Identifier: NCT05043051), that would examine the effect of tVNS on POTS over a 2-month period compared with sham stimulation.

The researchers recruited a cohort of 25 female participants (mean age, 31; 81% White) from the University of Oklahoma Health Sciences Center’s arrhythmia clinic who were currently receiving medication for POTS. Of 25 patients who completed the study, 11 were randomly assigned to active tVNS treatment intervention; the other 14 were assigned to a sham tVNS group.

Participants self-administered stimulation using an ear clip attached to the tragus at home for 1 hour daily over 2 months. Stimulation wave frequency was 20 hertz; amplitude was individually set to 1 milliampere below each patient’s discomfort threshold.

At baseline and at 2-month follow-up, the researchers measured orthostatic response to a tilt test, blood levels of antiadrenergic autoantibodies and inflammatory cytokines, heart-rate variability via electrocardiogram, and questionnaire-reported autonomic symptoms.

At baseline, during the tilt test, the group who received tVNS therapy demonstrated a mean heart rate increase (ie, tachycardia) of 26.4 beats per minute (bpm; standard deviation [SD] = 11.3). At 2-month testing, the active treatment group showed a smaller heart rate increase of 17.6 bpm (SD = 9.9). No decrease in tachycardia occurred in the sham treatment group. The active treatment group also showed heart rate variability changes that may reflect improved autonomic balance, such as a smaller change in the ratio of low-frequency to high-frequency cardiac activity during postural transition in tilt testing.

Furthermore, at 2-month follow up, compared with control patients, those who received tVNS therapy demonstrated statistically significant decreases in blood levels of tumor necrosis factor-α, and α1 and β1 adrenergic receptor autoantibodies.

Also, after 2 months, only autonomic symptoms related to secretomotor function (eg, sweating) were lower in the active arm compared with the control arm (P =.001).

The researchers suggested that these results supported the hypothesis that inflammatory and vascular autoantibody dysfunction help drive the pathology of POTS.

The researchers were unable to compare results across POTS phenotypes due to the small participant pool. Another study limitation was the short duration of intervention and follow-up periods.

“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 researchers wrote.

They concluded, “While these results cannot be considered definitive, they nonetheless provide a proof of concept of a beneficial effect of tVNS in this patient population and form the basis for further human studies.”