Effect of Oral Appliance Therapy on Atrial Fibrillation

Atrial fibrillation (AF) is highly prevalent in the U.S. and possesses a greater risk in
patients with sleep disordered breathing (SDB) versus patients without SDB. AF recurrence
after catheter ablation is associated with 25% increased risk in patients with obstructive
sleep apnea (OSA). One hypothesis suggests that the repeated hypoxic episodes time-linked to
OSA and central sleep apnea may act as chemo-reflex triggers that enhances brainstem
sympathetic activity in conjunction with responses to OSA-event hypoxia. This hypothesis is
believed to induce tachycardia and cardiovascular stress. In an animal model, episodes of
hypoxia were shown to induce pulmonary vein burst firing and reduction of the negative
tracheal pressure promptly restored normal sinus rhythm. The Trigeminocardiac reflex
hypothesis implicates chemo- and mechanoreceptors in the oronasal cavity that provides
signaling to the reticular formation via the mesencephalic nucleus of the trigeminal nerve
and serves to control breathing, cardiac function, blood pH, amongst other body functions.

The sympathetic system in patients with OSA syndrome is considered to be chronically
hypersensitized. A hyperarousal state suggests AF patients with OSA would tend to have AF
occur more frequently in conjunction with apnea hypopnea events. An increase in autonomic
sympathetic cardiac dominance with a withdrawal of cardiac parasympathetic control could
easily be driven by mechanoreceptors in the oropharynx upon airway narrowing and present as
decreased heart rate variability. Considering that the upper airway is often the site of
greatest airflow restriction (i.e. snoring), a potential sudden rise in autonomic sympathetic
nerve activity in sensory afferent fibers from the oropharynx should be the first to
communicate the airflow reduction to brainstem. This theory is supported by our own
preliminary data and those in other reports. Oral appliance (OA) therapy that prevents
snoring in conjunction with a mouth shield should simultaneously facilitate an open airway
and prevent mouth breathing. The combination effect is expected to decrease vagus nerve motor
efferent activity to the esophagus, facilitate nasal breathing, reduce sympathetic tone,
promote stable sleep and increase HRV. In patients with AF, the MyTAP + MS intervention is
likely to also facilitate putatively effective medical therapies, reduce noxious AF triggers,
and maintain normal oral bacterial flora levels and cardiac functioning.

Inclusion Criteria:

- Pre-qualified for ablation AF intervention

- AF > 1 documented episode in a 24-hour electrocardiogram (ECG) Holter examination or
implanted AF monitor in the previous 1 month prior to study enrollment; [AF episode
defined as at least 12 hours duration]

- At least 8 teeth per arch to support OA device

- Use of CPAP and willingness to switch to OA use

- Willing and able to provide verbal and written informed consent

- Ability to understand how to apply and utilize the sleep recorder and the OA device

Exclusion Criteria:

- Patients with implantable cardiac rhythm device [pacemakers or internal cardiac device
(ICDs)] or cardiopulmonary disease [heart failure, COPD, ventricular dysrhythmia]

- Unable or unwilling to complete the study demands and schedule

- Comorbidities of other sleep disorders other than OSA

- No active TMD or jaw muscle pain, morphological airway abnormalities

- Pre-existing difficulty swallowing; throat or neck related health issues; endocrine
dysfunction; severe psychiatric and neurological disorders; intellectually disabled;
handicaps limiting sleep position

- Previous OA therapy or restrictions in jaw opening

- Prior ablation of AF, MI, stroke or decompensation of heart failure within the last
six months, untreated overt hyper- or hypothyroidism

- Commencement of new anti-arrhythmic drug since last monitor check

- Pharmacological dependency

- Concomitant use of hypnotic agents or other sleep aids, nicotine or alcohol intake

- Mallampati score > III

- Palatine tonsils - grade > 2

- History of Uvulopalatopharyngoplasty (UPPP) surgery