A Multi-Center Study Combined Non-Invasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography

Preclinical Study
A preclinical study was performed in our laboratory to validate the accuracy of
multidetector computed tomography (MDCT) to measure differences in regional
myocardial perfusion during adenosine stress in a canine model (LAD, left
anterior descending artery stenosis), during first-pass contrast-enhanced
helical MDCT. The model was performed in eight dogs, contrast-enhanced MDCT
imaging was performed 5 minutes into the adenosine infusion. Images were
analyzed using a semi automated approach to define the regional signal density
ratio (myocardial signal density/left ventricular blood pool signal density) in
stenosed and remote territories and then compared with microsphere myocardial
blood flow measurements. The main findings of the study were first-pass,
contrast-enhanced helical MDCT imaging can detect a LAD territory flow deficit
during adenosine stress and MDCT signal density ratios of stenosed and remote
myocardial beds correlate well (R=0.98) with microsphere-derived absolute
microsphere myocardial blood flow measurements (J Am Coll Cardiol
2006;48:153-60).

Single Center Clinical Study
A clinical study was performed in our laboratory which included 43 patients
with suspected coronary artery disease using 64 row (n=24) and 256 row (n=19)
detector computed tomography to determine if adenosine stress MDCT perfusion
imaging in conjunction with MDCT angiography can detect atherosclerosis causing
territorial myocardial perfusion abnormalities when compared with single photon
emission computed tomography (SPECT) myocardial perfusion imaging. MDCT
angiograms were evaluated for stenosis >= 50% and MDCT perfusion images were
analyzed for transmural distribution of perfusion using the transmural
perfusion ratio (subendocardial attenuation density/subepicardial attenuation
density). SPECT myocardial perfusion images were evaluated for fixed and
reversible perfusion deficits using a 17-segment model. The main findings of
the study were: 1) adenosine stress MDCT perfusion imaging can detect
transmural differences in myocardial perfusion. 2) transmural differences in
the subendocardial and subepicardial attenuation densities can be quantified
using the transmural perfusion ratio and the transmural perfusion ratio is
inversely related to percent diameter stenosis, 3) MDCT perfusion imaging when
combined with MDCT angiography can accurately (multivessel disease adjusted
sensitivity 85.7%, specificity 94.9%, positive predictive value 90.0%, and
negative predictive value 92.5%) predict atherosclerosis causing territorial
perfusion deficits on SPECT myocardial perfusion imaging (Circulation Imaging
May 2009).

Multicenter Clinical Study (The CORE64 Trial)
The Coronary Artery Evaluation using 64-row Multidetector Computed Tomography
Angiography (CORE64) study was a prospective, multicenter diagnostic study
which was conducted at our institution using centralized blinded analysis to
determine the diagnostic accuracy of 64-detector 0.5mm slice thickness MDCT
angiography in comparison with conventional coronary angiography (CCA), in
patients with suspected CAD. The study was designed to determine whether
64-detector MDCT angiography can reliably define the presence or absence of
obstructive disease and also identify those patients who may require coronary
revascularization. Nine centers enrolled 291 patients who completed MDCT
angiography prior to CCA, and had calcium scores <=600. Diameter stenoses >=50%
were considered obstructive. The Core-64 trial showed that 64-detector MDCT
angiography has reliable accuracy for the diagnosis of obstructive coronary
disease. The area under the receiver operating characteristic curve of 0.93 is
consistent with robust diagnostic performance and indicates that 64-detector
MDCT angiography has powerful discriminative ability to identify patients with
and without coronary obstruction. Additionally, MDCT angiography compared well
with CCA in predicting clinically-driven revascularization and severity of
obstructive CAD which supports its clinical utility for identifying symptomatic
patients who may need coronary interventions (NEJM November 2008).

The primary objective of this study is to evaluate the diagnostic accuracy of
coronary artery luminal stenosis and corresponding myocardium perfusion defects
in patients with suspected coronary artery disease by use of volume computed
tomography.. The primary diagnostic parameter will be the area under the
receiver operating characteristic curve, sensitivity and specificity of
multi-detector computed tomography for identifying the combination of coronary
artery stenosis >= 50% and a corresponding myocardium perfusion defect in a
patient with suspected coronary artery disease, compared with conventional
coronary angiography and single phonton emission computed tomography myocardium
perfusion imaging.

The CORE-320 trial will be a prospective multicenter, international study of
coronary multi-detector computed tomography using 320 detectors to determine
coronary artery atherosclerosis and corresponding myocardial ischemia. The
enrollment is expected to commence in the summer of 2009. This study consists
of 2 periods: Screening/Imaging and Follow-up. For each participant, it is
anticipated that the Screening evaluation periods will last less than 2 months
and will be followed by the Imaging period (less than 60 days). The Follow-up
period will last for approximately 2 years.

CT Scan
• CT images are made possible through the use of radiation. The amount of
radiation exposure you will receive from undergoing a heart CT scan is about
1.4 to 2.5 rems. Naturally occurring radiation (cosmic radiation, radon, etc.)
produces whole body radiation exposures of about 0.3 rems per year.
• Occupationally exposed individuals are permitted to receive whole body
exposures of 5 rems per year.
• To reduce the risk of getting too much radiation, you will not be allowed to
join this study if you have had an excessive amount of radiation in the past.
• There can be radiation exposure to the ovaries. Therefore, women who are
able to have children should receive the least possible amount of radiation, by
having a lead apron placed on the abdomen.
CT Contrast
• Reactions to the contrast agent are uncommon and occur in less than 1 in 1000
people
• These reactions can range from mild itching and hives, to serious reactions
including difficulty breathing and anaphylactic shock (low blood pressure and
severe problems with breathing). Anaphylactic shock can result in death.
• To minimize this risk, you will not be allowed to join this study if you have
a known allergy to CT contrast.
• In the event you have an allergic reaction to CT contrast, a physician will
be present to give you medical treatment
• There is also a small risk of kidney damage from the contrast agent. Such
damage is also rare and is usually, but not always, reversible. You will not be
allowed to have a CT with contrast if your kidney function is impaired.

SPECT Study
• SPECT images are made possible through the use of radiation. Subjects will
receive a single study: CARDIOLITE or MYOVIEW SPECT. The average total
radiation dose to the patients using conventional clinical doses (i.e., rest=8
mCi, stress=25 mCi) will be 13 mSv (a mSv is a unit of radiation dose). The
total radiation exposure is 24% of that allowed annually for a radiation
worker.
• SPECT imaging is a routine clinical diagnostic procedure. The major source of
discomfort is the need to lie still on a supine position for a relatively short
time (12-15 minutes for each rest and stress images).

Adenosine
• Adenosine is a very short acting drug and most of the side effects go away
within 1-2 minutes after the infusion is turned off. The side effects include
flushing (44%), chest discomfort (40%), urge to breathe deeply (28%), headache
(18%), throat, neck or jaw discomfort (15%), gastrointestinal discomfort (13%),
and lightheadedness or dizziness (12%). Less common side effects include arm
or hand discomfort (4%), temporary ECG abnormalities (3%), tingling of the
limbs, hands and feet (2%), low blood pressure (2%), and nervousness (2%).
Heart attacks, life-threatening abnormal heart rhythms and death have been
reported in very rare instances (<1%).

Beta-blocker
• Beta-blockers may cause low heart rates, low blood pressure, dizziness,
breathing problems, or an allergic reaction. You will be observed for any of
these effects. If you have any history of lung problems or asthma, please let
the study personnel know.

Intravenous (IV) Insertion
• The CTA staff or research coordinator will use a needle to insert two
intravenous catheters (one
each arm) in order to inject contrast and adenosine.
• There is a risk of pain at the site where the needle is placed. You are also
at risk for infection, bruising, swelling and bleeding at the site. When any IV
medicine is given, there is always a chance that needle inserted in a vein may
infiltrate (become blocked or puncture the wall of the vein) causing temporary
swelling, bruising, and or pain. Should this occur, the study nurse would
remove the IV and insert a new needle into another vein. In order to reduce
these risks, the CT staff or research coordinator will follow standard
procedures for the safe insertion of IV catheters.

Blood Sample
• A small needle will be used to draw about 3 tablespoon of blood from a vein
in your arm. The risks from blood sampling include the small risk of bleeding,
bruising, infection, getting dizzy or lightheaded. Standard hospital
techniques will be used to reduce these risks. Taking blood may cause pain,
bleeding or bruising where the needle is place. In rare cases, it may result in
fainting. There is small risk of infection.
Other Risks
• There may be side effects and discomforts that are not yet known.