Detecting Heart Disease Using First Pass Imaging With Gated SPECT Perfusion

In this clinical trial, patients with suspected or previously diagnosed coronary artery
disease who are clinically referred for either a treadmill exercise stress/rest SPECT study
or a vasodilatation stress/rest SPECT study will be considered for this protocol. The
vasodilation study may be either adenosine or regadenosin. In addition to the stress study,
a stress/rest echocardiography study and first pass image will also be obtained. The reason
to include echocardiography is to provide an independent measurement of the ejection
fraction during pharmacological stress for comparison to the ejection fraction from the
first pass study and from the ECG-gated SPECT study performed at rest. This will evaluate
the added value of calculation of stress left ventricular ejection fraction (LVEF) over
gated SPECT resting EF. This information will also assist in evaluating LV dysfunction
following induction of pharmacological stress Nuclear imaging compared with
echocardiographic stress EF, established imaging modalities for assessment of coronary heart
disease.

The study will include two ECHO imaging sessions and two SPECT imaging sessions.

Patients will undergo a resting first pass image during the administration
99mTc-tetrofosmin; and a resting ECHO study at an appropriate imaging time. The resting ECHO
will also be used to assess patient imaging window quality and to optimize equipment
settings for subsequent stress images. A rest gated-SPECT image will be acquired at the
appropriate imaging time.

The patient will then undergo a standard vasodilation stress infusion. A first pass image
will be obtained during the administration of 99mTc-tetrofosmin. An ECHO will be obtained
prior to the completion of the infusion. A gated-SPECT study will then be performed at the
appropriate imaging time.

Tetrofosmin ECG-gated SPECT Imaging:

One hundred patients will be enrolled in the vasodilation stress/rest ECG-gated SPECT
myocardial perfusion imaging group. Imaging time for each session will vary from one and a
half to three hours. A one or two day imaging protocol can be utilized. Depending on what
imaging session is done first (rest or stress), a "one-day" protocol consists of having the
first dose of 99mTc-Tetrofosmin as a low dose of 10-15mCi. The second dose will be the high
dose of 20-40mCi depending on the patient's weight. In the "two-day" protocol, patients will
receive a high dose of 99mTc-Tetrofosmin for both imaging sessions. The dose given will
depend on the patient's weight.

Rest Imaging:

If venous access is not already established, the standard universal precautions and 18-20
gauge catheter equipped with a 3-way stopcock will be inserted preferably in the antecubital
vein. The patient will be injected with the appropriate amount of 99mTc-Tetrofosmin. The
first pass image will be acquired during the injection (see first pass protocol). An Early
resting gated-SPECT imaging and an ECHO will be done at 15 minutes and then repeated at 60
minutes (see ECHO protocol).

Adenosine Imaging:

If venous access is not already established, the standard universal precautions and 18-20
gauge catheter equipped with a 3-way stopcock will be inserted preferably in the antecubital
vein. Patients will receive an infusion of adenosine at a rate of 140ug/kg/min. After 1.5
minutes of adenosine infusion, the appropriate dose of 99mTc-Tetrofosmin will be injected
and adenosine infusion will continue for 4.5 additional minutes, in compliance with the
standard 6-minute infusion protocol and current ASNC guidelines. The first pass image will
be acquired during the injection (see first pass protocol). Blood pressure and heart rate
will be documented every minute. 12 lead ECG will be obtained at baseline and printed once a
minute. There will be continuous monitoring of ECG and symptoms throughout the infusion.
The ECHO will be acquired at 2.5 min of adenosine infusion (see ECHO protocol). An Early
resting gated-SPECT imaging and an ECHO will be done at 15 minutes post infusion and then
repeated at 60 minutes.

Test Termination End Points (standard criteria)

- Symptomatic hypotension, bradycardia or high degree AV Block

- Severe shortness of breath or wheezing

- Completion of protocol

- ST Segment depression >2mm (horizontal or downsloping)

- Angina

- Life threatening arrhythmia

- Subject requests to stop

Regadenoson Imaging:

If venous access is not already established, the standard universal precautions and 18-20
gauge catheter equipped with a 3-way stopcock will be inserted preferably in the antecubital
vein.

Patients will receive an infusion of Regadenoson (0.4 mg regadenoson) by rapid intravenous
injection; followed immediately by 5 ml saline flush. 20-40 seconds after the saline flush
Tetrofosmin is injected and a first pass image is done.

Patients will receive an infusion of Regadenoson at a rate of (0.4 mg regadenoson). After
1.5 minutes of Regadenoson infusion, the appropriate dose of 99mTc-Tetrofosmin will be
injected and Regadenoson infusion will continue for 4.5 additional minutes, in compliance
with the standard 6-minute infusion protocol and current ASNC guidelines. The first pass
image will be acquired during the injection (see first pass protocol). Blood pressure and
heart rate will be documented every minute. 12 lead ECG will be obtained at baseline and
printed once a minute. There will be continuous monitoring of ECG and symptoms throughout
the infusion. The ECHO will be acquired at 2.5 min of Regadenoson infusion (see ECHO
protocol). An Early resting gated-SPECT imaging and an ECHO will be done at 15 minutes post
infusion and then repeated at 60 minutes.

Test Termination End Points (standard criteria)

- Symptomatic hypotension, bradycardia or high degree AV Block

- Severe shortness of breath or wheezing

- Completion of protocol

- ST Segment depression >2mm (horizontal or downsloping)

- Angina

- Life threatening arrhythmia

- Subject requests to stop

Treadmill Exercise (Stress) Imaging:

If venous access is not already established, the standard universal precautions and 18-20
gauge catheter equipped with a 3-way stopcock will be inserted preferably in the antecubital
vein. Patients will follow a preset treadmill protocol. ECG's will be continuously
monitored during exercise and are printed out for each stage of exercise. Patients will be
injected with the appropriate amount of 99mTc-Tetrofosmin. The first pass image will be
acquired during the injection (see first pass protocol). Due to logistical difficulties, the
ECHO will not be performed for this imaging session.

Test Termination End Points (standard criteria)

- Severe Fatigue

- ST segment depression or elevation >2mm (horizontal or downsloping)

- Severe Angina

- Severe Shortness of breath/ wheezing

- Significant drop (20mmHG) in blood pressure

- Significant elevation of blood pressure:

- Systolic :> 220mmHG

- Diastolic :> 120mmHG

- Severe lower extremity discomfort

- Signs of severe peripheral circulatory insufficiency: lightheadedness, nausea, pallor

- Onset of second or third degree AV Block

- Ventricular Tachycardia

- Symptomatic SVT

- Patient request to stop

- Completion of Protocol

- For a Nuclear Imaging Study, patient should reach 85% of age predicted maximum heart
rate prior to the injection of radioisotope (220-age). Once target is reached then the
isotope is injected and patient should exercise for 2 more minutes post injection

Echocardiography Imaging:

Instrument settings will be optimized to ensure the best delineation of the endocardial
borders of the left ventricle. Rest ECHO will be obtained in the standard protocol for both
imaging groups. Patients in the adenosine vasodilatation stress group will have an ECHO
during the infusion of adenosine in the standard views. Patients in the exercise stress
group will have an ECHO immediately after exercise in the standard views. Patients in both
groups will have an ECHO 15 minutes and 60 minutes after stress.

2D and 3D- Echocardiography Views

Primary views:

- Apical four chamber 2D view (2D and color tissue Doppler)

- Apical two chamber 2D view (2D and color tissue Doppler)

- Apical 3D view

Secondary 2D views:

- Parasternal short axis at base, mid and apex of LV (2D and color tissue Doppler)

- Parasternal long axis

First Pass Radionuclide Angiography:

Patients are prepped as outlined previously including IV placement. For the resting image,
patients are connected to the camera gate device for continuous registration of the ECG.
Patients will be placed against the face of the camera to begin isotope infusion. The camera
will detect the presence of the isotope within the SVC and initiate recording of the data;
real time acquisition progress will be displayed on the computer screen.

During the acquisition for the treadmill exercise image, patients will be connected to the
camera gate device for continuous registration of the ECG. Patients are placed against the
face of the camera. The height of the camera is set to the patient and "Treadmill tracking"
is set to the "ON" position. At peak exercise, the isotope is injected. The camera will
detect the presence of the isotope within the SVC and initiate recording of the data; real
time acquisition progress is displayed on the computer screen.

During acquisition for the adenosine vasodilatation image, patients are connected to the
camera gate device for continuous registration of the ECG. Patients are placed against the
face of the camera. The isotope is infused at 1.5 minutes of adenosine infusion. The camera
will detect the presence of the isotope within the SVC and initiate recording of the data;
real time acquisition progress is displayed on the computer screen.

The total image time for the first pass study is 30 seconds.

Inclusion criteria:

- Males and females age 18 through 80 years

- Female patients who are: surgically sterile (hysterectomy or bilateral tubule
libation), at least one year post-menopausal, or have a negative pregnancy test on
the day of treatment

- Written informed consent

Exclusion Criteria:

- Patient consumed food/beverage/medication containing caffeine/methylxanthines up to
12 hours prior to infusion

- Exacerbation of COPD, Asthma (actively wheezing)

- Sinus node dysfunction in absence of pacemaker

- Use of Aggrenox (ASA/Dipyridamole), Pentoxifylline (Trental) , or oral Dipyridamole
(Persantine)

- Atrial fibrillation

- Pregnant/breast feeding

- Non English speaking patients

- Subject is allergic or intolerant to aminophylline, regadenoson

- Subject has a history of known or suspected bronchospastic lung disease [e.g.,
asthma, wheezing, chronic obstructive pulmonary disease (COPD, etc.)]

- Patients with first degree or second degree AV block