Right to Left Cardiac Shunt Detection

The purpose of this study is to evaluate the sensitivity and specificity of the Cardiox Flow
Detection System (FDS) in identifying an intracardiac right-to-left shunt (RLS) compared to
the results of transesophageal echocardiography (TEE).

RLS intracardiac shunts are associated with a number of clinically important syndromes
including paradoxical thromboembolism (causing stroke or other systemic infarct), migraine
headaches (particularly with aura), desaturation with obstructive sleep apnea, and
decompression illness. From a research perspective, the detection of shunts in subjects with
these types of syndromes is critical in helping to define the role of RLS in these disease
processes. From a clinical perspective, shunt detection will be increasingly important in an
era where interventional procedures for repairing cardiac defects are available for subjects
determined to be at risk.

The currently accepted reference standard for detection of an intra-cardiac patent foramen
ovale/atrial septal defect (PFO/ASD) RLS is a transesophageal echocardiography (TEE), a
procedure that is invasive, uncomfortable, and requires conscious sedation.

Alternative options include transthoracic echocardiography (TTE) with injection of agitated
saline (with and without Valsalva strain), a procedure that is far less sensitive than TEE
due to the echocardiography imaging limitations seen in many adults.

Finally, transcranial Doppler (TCD) with injection of agitated saline (with and without
Valsalva strain) is a newer entrant into this arena that does not require sedation or any
invasive instrumentation.

The Cardiox Model 100 FDS utilizes an optical sensor positioned on the surface of the
subject's skin at the scaphoid fossa of the ear. Next, a predetermined dose of an indicator
dye, indocyanine green (ICG), is injected at a predetermined rate into a peripheral
antecubital vein of the subject while the subject performs a breathing maneuver called a
Valsalva maneuver. The exhalation by the subject into a mouthpiece connected to a pressure
transducer via a flexible tubing extension, or its equivalent (ie, performing the Valsalva
maneuver), is an essential step for all existing RLS detection methods. The Valsalva
maneuver by the subject creates a pressure differential between the right and left sides of
the heart. This Valsalva maneuver results in blood flow from the right side of the heart to
the left side of the heart through an ASD, and/or causes a PFO, if present, to open, also
allowing blood to flow directly from the right side to the left side of the heart without
passing through the lungs (pulmonary vasculature) for oxygenation.

The Earpads, including their fluorescence sensor arrays (FSA), are used to measure the
relative concentration (ie, fluorescence signal level) of ICG dye in the bloodstream as a
function of time. If a premature inflection or peak occurs in the ICG dye concentration
level at a time point prior to the rise and fall of the concentration associated with the
main bolus of indicator, then a RLS is present in the heart. The amplitude of this premature
ICG dye-dilution curve (referred to as "RLS-indicator dilution curve") is used to
subsequently quantify the magnitude of the right-to-left shunt by ratiometrically comparing
the amplitude of this RLS indicator dilution curve to the amplitude of the main indicator
dilution curve associated with that portion of the injected ICG dye that follows the normal
pathway from the right side of the heart, through the lungs, and into the left side of the
heart (referred to as "normal indicator dilution curve").