Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia. In previous experimental
studies, the investigators found that low-level vagus nerve (VN) stimulation (LLVNS), at
voltages substantially below that which slowed the sinus rate, significantly suppressed AF
inducibility and decreased AF duration. The investigators subsequently developed a
non-invasive neuromodulatory therapy, in which LLVNS was delivered to the auricular branch of
the VN located at the tragus, the anterior protuberance of the outer canine ear (low level
tragus stimulation; LLTS). The anti-arrhythmic effects of LLTS were similar to those of LLVNS
delivered to the cervical VN trunk. More recently, in a proof-of-concept study in humans, the
investigators showed that in patients with drug-refractory AF undergoing AF ablation, LLTS
for just one hour significantly shortened the AF duration and decreased inflammatory
cytokines.

The overall objective of this proposal is to translate in ambulatory patients with paroxysmal
AF the results of previous studies showing acute suppression of AF and inflammation in
anesthetized canines as well as humans, in order to examine the long-term therapeutic effects
of this approach. The investigators hypothesize that intermittent (1 hour daily) LLTS for 6
months may result in long-term decrease of AF burden and suppression inflammatory cytokines
in patients with paroxysmal AF. Patients will be randomized to either active or sham LLTS.
LLTS will be delivered through a transcutaneous electrical nerve stimulation (TENS) device
for 1 hour daily over a 6-month period. AF burden will be defined as the percent of time
spent in AF over a 2-week period, assessed by noninvasive continuous ECG monitoring at
baseline and at 6 months. In addition, blood samples will be collected from patients at
baseline, and at 3 and 6 months, for cytokine measurement. These investigations will
establish the first evidence of the long-term effects of LLTS on AF suppression in patients
with paroxysmal AF and may provide the basis for a potential expansion of the therapeutic
targets of this treatment modality beyond AF.