In a previous study (Dalgleish et al., 2021), the investigators found that taVNS lengthens
the PQ-interval in healthy study participants with regular sinus rhythm. This finding
indicates that taVNS slows AV-conduction. Thus, it is reasonable to assume that taVNS may
lower ventricular rate in patients with persistent atrial fibrillation. This assumption is in
line with a recent study (Stavarakis et al., 2020) demonstrating reduced atrial fibrillation
burden in patients with paroxysmal atrial fibrillation in response to a 6-month taVNS
intervention.
The investigators hypothesize that taVNS reduces ventricular rate in patients with persistent
atrial fibrillation. This hypothesis is based on the finding that taVNS lengthens the
PQ-interval in healthy individuals with sinus rhythm (Dalgleish et al., 2021), demonstrating
that taVNS slows AV-nodal conduction. Thus, it is conceivable that taVNS reduces the number
of atrial excitations that are transmitted into the ventricles in patients with persistent
atrial fibrillation. This effect should result in a lower ventricular rate. Testing this
hypothesis is significant, because if the hypothesis would be verified, taVNS would have the
potential to elicit an additive effect to AV-nodal blocking agents, and thus, may allow to
reduce the dose of such drugs, effectively reducing potential adverse effects.
The study is designed as a two-week randomized cross-over study. Participants will start with
either taVNS or sham-taVNS (randomly assigned) during the first week and then switch to the
other intervention during the second week of the study. Throughout the two-week study,
ambulatory ECG will be recorded using an ECG patch that allows continuous ECG recording for
up to 14 days. Participants will self-apply taVNS or sham-taVNS for 30 min every day
throughout the 2-week study.
Participants will meet with the investigators 3 times throughout the 2-week study protocol:
On the first study day, participants will be instrumented with the ECG patch and instructed
in the use of the taVNS device. In addition, patients will be instructed to keep a diary to
record the time of the taVNS/sham-taVNS application, the stimulation parameters, and any
potential therapeutic or adverse effects. The second study visit will occur at the end of the
first study week. During this meeting, the function of the ECG patch and taVNS device will be
verified, the diary will be inspected to verify protocol adherence, and the intervention will
be switched to either taVNS or sham-taVNS application (depending on randomization). The final
study visit will occur at the end of the study (after 2 weeks). The ECG patch will be
retrieved, and the diary inspected for protocol adherence.
