Low-Level EMF Stimulation for Paroxysmal Atrial Fibrillation

This is a prospective, randomized, sham-controlled trial. Patients will be enrolled upon
presentation to our electrophysiology (EP) lab for ablation of paroxysmal AF. After informed
consent is obtained, the patient will be randomized to one of two protocols that have been
pre-programmed into the magnetic field stimulator. As described below, one of the protocols
will be an active stimulation protocol, and one will be sham (i.e. no stimulation delivered).
These will be named "Stim 1" and "Stim 2" in the computer. Because the specifics of the
protocol are programmed into the stimulator by the device manufacturer, investigators will
not know which of these two protocols is active vs. sham. The patient will then be brought to
the EP lab for the procedure and will be placed on the lab table with their head positioned
in the magnetic coil. Vascular access will then be obtained and diagnostic catheters placed
as is standard practice for AF ablation.

Because the study is limited to patients with paroxysmal AF, patients will begin the study in
normal sinus rhythm (NSR). Before the experimental protocol is begun, baseline
electrophysiologic intervals will be recorded as is standard practice for all patients
presenting for EP study. This will include measurement of the atrio-ventricular nodal
effective refractory period (AVNERP) using programmed stimulation from the right atrial (RA)
appendage, atrio-his (AH) interval, and his-ventricular (HV) interval per standard practice.
Burst atrial pacing will then be utilized to induce AF. Measurements of the number of burst
pacing attempts required to induce AF, as well as the AF cycle length, and duration of
pacing-induced AF will be recorded. Attempts at AF induction will occur for 15 minutes. Prior
to induction of AF, 5ml of venous blood will be drawn from the central venous sheaths to
measure baseline levels of the inflammatory mediator (TNF)-α. These samples will be stored
for analysis.

After baseline measurements are obtained, the coil will be turned on and whichever protocol
the patient has been assigned to will be run. The system to be used contains a
signal-generator coupled to a Helmholtz coil capable of producing a magnetic field in
response to an electric current. The Helmholtz coil itself is has 9 inches of separation in
between the two coils that allows for placement of the coil around the participant's head and
upper neck. The choice of the head and neck as the site of stimulation is intended to target
the vagus nerve as it exits the jugular foramen to course caudally in the carotid sheath. The
system is designed to create a homogenous, isotropic magnetic field with a field strength
from 1 to 99 pico-Tesla (pT) with a frequency range of 0.01 Hz to 50 Hz.

Active Stimulation will involve application of a pulsed-EMF with the parameters 0.032
micro-gauss (µG) at 0.89 Hz for 60 minutes. In participants randomized to sham stimulation,
the coil will be positioned around the neck as previously described, but no current will be
applied to the stimulator.

During the 60 minute stimulation time, trans-septal puncture and mapping of the left atrium
will be performed as is standard practice for this procedure, but no ablation will be
performed. After the 60 minute protocol is complete, venous blood samples will again be drawn
(within 5 minutes of protocol completion), stored, and analyzed as previously described. If
the patient remains in AF after the end of the 60 minute session, they will be electrically
cardioverted to sinus rhythm. The same stimulation protocol as described previously will
again be employed, again noting number of attempts required to induce AF, duration of
pacing-induced AF, AF cycle length, and measurements of AVNERP, AH, HV intervals and levels
of TNF-α.

Inclusion Criteria:

- Adult patients aged 21-85 presenting for ablation of paroxysmal atrial fibrillation
(episodes of atrial fibrillation lasting < 7 days with or without prior cardioversion)

Exclusion Criteria:

- Left ventricular ejection fraction (LVEF) < 40%

- Stroke or myocardial infarction within the past 6 months

- Greater than moderate valvular stenosis or regurgitation as assessed by pre-procedure
transthoracic echocardiogram (TTE)

- Presence of a prosthetic heart valve.