Cardiac and Sympathetic Baroreflex Sensitivity Is Not Affected by Transcutaneous Vagus Nerve Stimulation in Hyperadrenergic Postural Tachycardia Syndrome

Beatrice Cairo1, Vlasta Bari1, Beatrice De Maria2, Chiara Arduino3, Stefano Rigo4, Dana Shiffer4, Surat Kulapatana5, André Diedrich6, Italo Biaggioni5, Raffaello Furlan4, Alberto Porta1
1Department of Biomedical Sciences for Health, University of Milan, 2IRCCS Istituti Clinici Scientifici Maugeri, Milan, 3Department of Cardiothoracic, Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy, 4Humanitas Clinical and Research Center- IRCCS, 5Autonomic Dysfunction Center, Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, 6Department of Biomedical Engineering, Vanderbilt University

Abstract

Hyperadrenergic postural tachycardia syndrome (HyperPOTS) is characterized by sustained tachycardia upon standing, with symptoms compatible with a shift of the sympatho-vagal balance toward sympathetic predominance. Transcutaneous vagus nerve stimulation (tVNS) might be beneficial in HyperPOTS for the management of orthostatic intolerance symptoms. However, the acute effects of a single tVNS trial on baroreflex sensitivity (BRS) are still under investigation. We concomitantly evaluated BRS of the cardiac (cBRS) and sympathetic (sBRS) baroreflex arms in 19 HyperPOTS patients (39±11 yrs; 17 females) undergoing 75° head-up tilt test (HUT) during two randomized experimental sessions of electrical stimulation of the auricular branch of the transcutaneous vagus nerve delivered to the right auricular cymba concha. During the sham session the device was switched off (OFF), while during the active session the device was switched on (ON). Variability of heart period (HP), systolic and diastolic arterial pressure (SAP and DAP), and burst rate of muscle nerve sympathetic activity (MSNA) were extracted simultaneously from electrocardiogram, arterial pressure and MSNA signals. cBRS and sBRS were estimated as the transfer function gain (TFG) from SAP to HP and from DAP to MSNA burst rate respectively via a parametric approach based on bivariate autoregressive model. TFG was sampled at the peak of the squared coherence in the low frequency band (from 0.04 to 0.15 Hz). cBRS significantly decreased during HUT (OFF: 14.2±9.9 at REST vs 4.0±3.1 during HUT; ON: 8.6±4.1 at REST vs 4.6±2.5 during HUT), but did not vary across tVNS sessions. Conversely, both HUT and tVNS had no significant impact on sBRS. We conclude that the acute effects of single tVNS on the sensitivity of different arms of the baroreflex are negligible in HyperPOTS. Furthermore, HUT affects cBRS and does not seem to induce modifications of sBRS, potentially due to the baseline sympathetic overactivity of HyperPOTS.