REVEAL for Respiration Detection (REST)

Early recognition of changes in respiratory rate may be useful in monitoring a
patient*s disease status. Respiration rate has been shown to be an important
antecedent of patient deterioration (Hodgetts, Kenward, Vlachonikolis, Payne, &
Castle, 2002). Tachypnoea, the elevation of the respiratory rate, has been
suggested as the most important signal for interventions for the prevention of
cardiopulmonary arrests (Fieselmann, Hendryx, Helms, & Wakefield, 1993).

While automated techniques exist for measuring respiratory rate, they usually
require the use of equipment which might interfere with natural breathing, such
as spirometry (measuring the flow of air in and out during breathing) or might
be uncomfortable for the patient, such as inductance plethysmography.
Additionally these techniques require dedicated devices and do not allow for a
continuous monitoring of patients outside a hospital setting.

Measuring the respiratory rate from an ECG obtained from an implantable cardiac
monitor could overcome these limitations and has become more feasible with the
development of robust signal processing techniques (O'Brien & Heneghan, 2007)
(Orphanidou, Fleming, Shah, & Tarassenko, 2013).

The results from this study will help improve our understanding of the
feasibility of extracting the respiratory rate from the Reveal ECG signal and
provide data that can be used to design future studies. In the future,
monitoring respiratory rate could help indicate progression of cardiopulmonary
illnesses, including acute respiratory distress syndrome, pulmonary edema,
pulmonary embolism, pneumonia, COPD, and severe heart failure and be used to
improve the quality of care for patients by providing timely information to
help diagnosis and manage the patients.

This study is a prospective, non-randomized, single-center study evaluating the
correlation between the respiratory rate derived from the Reveal Insertable
Cardiac Monitor (ICM) electrocardiogram (ECG) with the respiratory rate
obtained from an external respiratory band in patients previously implanted
with a Reveal for unexplained syncope or suspected arrhythmia.

Subjects previously implanted with a Reveal for unexplained syncope or
suspected arrhythmia will be invited to participate and attend a single study
visit. The study visit is expected to take no more than 3 hours.

During the study visit the respiration band and Holter monitor will be placed
on the subject. Subjects will be studied in a quiet room, while in the supine
position. Subjects will be asked to perform a series of breathing exercises.
The breathing patterns will last up to 3 minutes each and will be separated by
a minimal amount of time to prepare for the next maneuver. Subjects will
breathe in the following patterns:

•Normal Breathing
Measurements will be taken to record normal breathing at the subject*s
spontaneous rate and tidal volume for 3 minutes.

•Periodic Breathing
A periodic breathing pattern will be recorded with consists of 20 seconds of
voluntary apnea followed by 30 seconds of spontaneous respiration. The pattern
will be repeated for up to 3 minutes. Subjects will be prompted when to
breathe and when to hold their breath.

•Controlled Breathing
Up to 3 minutes of metronome-set breathing at 12 breaths/min will be
collected.

•Posture Changes
3 minutes of normal breathing in each of the additional postures (supine, left
recumbent, right recumbent, sitting and standing) will be collected. If the
early respiratory maneuver were done in a sitting position, it can be eliminate
from this section of tests.

•Exercise
Subjects will perform a six minute walk to increase their respiratory rate,
after which an additional 3 minutes of breathing will be recorded. Walk
distance does not need to be recorded.

On completion of the respiratory maneuvers the Holter will be reviewed to
ensure the patient did not experience any arrhythmia while undergoing the
breathing exercises.

The potential risks to a subject participating in this study are believed to be
minimal. A subject may feel discomfort, dizziness or shortness of breath during
the maneuvers or experience skin reactions due to the application of the Holter
electrodes or MediByte device. There is also a possibility that during the
respiratory maneuvers study visit the patient may experience an arrhythmia
which would not be captured on the Reveal ICM.

There may be additional risks related to study participation that are unknown
at this time.