Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by symptoms of chronic
orthostatic intolerance such as fatigue, lightheadedness, dizziness, palpitations and by
pronounced tachycardia without hypotension upon standing. In healthy volunteers,
transcutaneous vagal nerve stimulation (tVNS) may result in increased cardiac vagal activity
and reduced vascular sympathetic drive with minimal, if any, side effects. It is possible to
hypothesize that any therapeutic intervention aimed at increasing cardiac vagal modulation
might result in clinical improvement of the disease.
The aim of the study are to evaluate the medium-term effects of tVNS, performed every day for
a 14 days on cardiovascular autonomic profile and symptoms intensity in POTS patients.
Study and General Design
Phase 1- Enrollment:
23 POTS patients, older than 18 years of age, will be consecutively enrolled. Each POTS
patient will undergo complete medical evaluation at the time of enrollment, which will take
place seven days before baseline recordings (i.e. Control day, see below), in order to
individually optimize the tVNS amplitude and get patients familiarized with both the tVNS
procedure and the clinical laboratory environment. On the same day, 30-minute continuous tVNS
will be delivered to the patients under rigorous medical and hemodynamic supervision to
exclude any kind of short term adverse effects.
Transcutaneous vagal nerve stimulation (tVNS) will be performed using a noninvasive battery
powered Transcutaneous Electrical Nerve Stimulation device (Nemos ©; Cerbomed, Germany).
Electrical stimulation will be delivered by external electrodes through the skin surface at
the conca of right external ear. Electrical current will be applied continuously with a pulse
width of 200 μs and pulse frequency of 25 Hz, differently from previous protocols.
Stimulation amplitude will be adjusted between 0.1-6 milliampere (mA), to a maximal amplitude
level without causing patient discomfort.
Phase 2 Sham tVNS and Effective tVNS:
In every subject continuous ECG, beat by beat non-invasive arterial pressure (Nexfin device),
respiratory activity by thoracic piezoelectric belt will be recorded while supine and during
75° head-up tilt (rest-tilt protocol). After positioning the tVNS electrodes in the right ear
but without delivering tVNS (Sham tVNS), above mentioned signals will be recorded for 10
minutes while supine, for 15 minutes during 75° head-up tilt. The same protocol will be
repeated during stimulation amplitude will be adjusted to maximal tolerable level as assessed
in Phase 1 (effective acute tVNS).
The Composite Autonomic Symptom Scale (COMPASS 31) COMPASS 31 will be used to quantify the
following autonomic symptoms: orthostatic intolerance, vasomotor, secretomotor,
gastrointestinal, urinary and pupillomotor dysfunction symptoms .
Phase 3-Home daily stimulation:
Thereafter, every patient will be provided with a Nemos© device and electrodes for home daily
stimulation. Daily stimulation will consist of 4 hours of stimulation organized as 4 sessions
each lasting 1 hour, to be applied at the patient's convenience.
Phase 4- Post- 14-day tVNS. After 14 days of home daily tVNS, all the patients will undergo
the rest-tilt protocol described in Phase 2.
COMPASS 31 questionnaire will be administered while supine and during 75° head-up Tilt
