Short and long term effects of a two-week transcutaneous vagus nerve stimulation in hyperadrenergic postural orthostatic tachycardia syndrome: a proof-of-concept trial

Hyperadrenergic POTS (Hyper-POTS) is characterized by excessive central sympathetic activity and impaired cardiovagal modulation. A single transcutaneous vagus nerve stimulation (tVNS) rebalanced cardiovascular autonomic control in previous studies. Repetitive tVNS may similarly restore autonomic balance and improve symptoms in Hyper-POTS. Twenty-two Hyper-POTS were studied at baseline (Pre-tVNS), after 14 days of tVNS (tVNS), and within 24 months post-discontinuation (Post-tVNS). The modified Vanderbilt Orthostatic Symptoms Score (mVOSS) quantified symptoms. ECG, arterial pressure, respiratory activity, and muscle sympathetic nerve activity (MSNA) were continuously recorded while supine and during 75° head-up tilt (HUT). Cardiac vagal modulation (high frequency power,HF), sinoatrial node sympatho-vagal interaction (low-to high-frequency ratio,LF/HF), sympathetic vasomotor control (LF) and arterial baroreflex sensitivity (α) were assessed by spectral analysis. Baroreflex sensitivity was also evaluated by spontaneous sequences (BRS) technique. At tVNS, MSNA decreased in both positions. tVNS increased HF and decreased LF/HF in supine. During HUT, αLF increased, HF increased and HR decreased compared to Pre-tVNS. Total symptom score declined in both positions, with improvements in multiple mVOSS domains during tilt. At Post-tVNS, HF and BRS increased in both positions. During HUT, αLF increased, HR and LF decreased. MSNA returned to Pre-tVNS in both positions. Total symptom score showed sustained improvement. Fourteen-day tVNS enhanced cardiovagal modulation, reduced sympathetic activity, and improved orthostatic symptoms in Hyper-POTS patients. Additionally, some benefits persisted beyond the stimulation period. Thus, tVNS could potentially be used as an additional therapeutic tool in Hyper-POTS.