Dual Energy CT for Ischemia Determination Compared to "Gold Standard" Non-Invasive and Invasive Techniques

Coronary artery disease is the leading cause of morbidity and mortality in the United States.
At present, professional guidelines endorse the use of an array of non-invasive tests for
patients with suspected coronary artery disease, which are limited to one of two approaches:
1) physiologic demonstration of ischemia by functional stress testing or 2) anatomic
visualization of stenosis by coronary computed tomographic angiography.

Stress test for physiologic assessment of coronary disease is performed most commonly with
the prognostic value unsurpassed by other non-invasive tests, with risk of cardiac events
escalating exponentially with increasing inducible hypoperfusion. However, despite its high
reported performance, the "real world" accuracy of stress test is less sanguine and
demonstrates generally poor discrimination of specific vessels that accommodate coronary
lesions that cause ischemia. These findings have encouraged the adoption of other stress
tests, such as positron emission tomography, which offers reliable attenuation correction,
increased count sensitivity, lower radiation dose and enhanced diagnostic performance.
Positron emission tomography also enables measures of absolute myocardial blood flow.

Coronary computed tomographic angiography is an alternative test that evaluates coronary
disease by direct anatomic visualization of stenoses in a manner similar to cardiac
catheterization. Similarly, when employing invasive fractional flow reserve to identify
ischemia, high-grade stenoses observed by computed tomography are causal of ischemia less
than half of the time.

Multicenter randomized trial data examining invasive methods have demonstrated that a
combined anatomic-physiologic approach by catheterization with fractional flow reserve
improves identification of patients who may benefit from revascularization, by restricting
revascularization to those with high-grade stenoses that specifically cause ischemia.
Nevertheless, the combination of catheterization with fractional flow reserve is invasive, is
not widely adopted in clinical practice, and is costly.

Computed tomography perfusion is a novel non-invasive technique that can evaluate the
physiologic significance of coronary disease, and is performed by adding a single image
acquisition to computed tomography in the same setting. The combination of computed
tomography perfusion to computed tomography may represent an ideal "one-stop shop" that may
allow for both anatomic and physiologic evaluation of coronary disease, serve as a more
effective gatekeeper to cardiac catheterization, and better identify patients that would
benefit from revascularization.

The emergence of dual energy computed tomography techniques enables potentially improved
perfusion assessment. In particular, projection-based dual energy computed tomography is a
novel computed tomography method that incorporates energy-dependent models for basis material
decomposition within tissue, and may allow for absolute quantification of myocardial blood
[iodine] volume with high accuracy and allows for single energy monochromatic imaging that
retains image stability while reducing common computed tomography artifacts. Both of these
measures by projection-based dual energy computed tomography enable quantitative assessment
of myocardial iodine uptake, but the diagnostic performance of dual energy computed
tomography as compared to nuclear stress testing has not been tested systematically to date.

To date, an integrated anatomic-physiologic approach by non-invasive methods has been
lacking, largely due to the lack of a test that is capable of providing both accurate
anatomic and physiologic data in a single setting.

The DECIDE-Gold trial will be a prospective multicenter study to evaluate the diagnostic
performance of the dual energy computed tomography perfusion for the detection and exclusion
of hemodynamically significant coronary artery disease, as defined by fractional flow
reserve, the reference standard. The targeted population is subjects with suspected coronary
artery disease who are referred for non-emergent clinically-indicated invasive coronary
angiography or rest-stress nuclear imaging. The study is considered non-significant risk as
investigators will be blinded to the dual energy computed tomography perfusion analyses will
in no part play a role in the subject's medical treatment or clinical course.

Inclusion Criteria:

- Age ≥ 18 years

- Patients provide written informed consent

- Patients scheduled to undergo clinically-indicated non-emergent invasive coronary
angiography

- suspected coronary artery disease

Exclusion Criteria:

- Suspicion of acute coronary syndrome (acute myocardial infarction and unstable angina)

- Recent prior myocardial infarction within 40 days of ICA

- Known complex congenital heart disease

- Significant arrhythmia or tachycardia

- Impaired chronic renal function (serum creatinine > 1.5 mg/dl or GFR < 30 ml/min)

- Patients with known anaphylactic allergy to iodinated contrast

- Pregnancy or unknown pregnancy status

- Contraindication to adenosine, including 2nd or 3rd degree heart block; sick sinus
syndrome; long QT syndrome; severe hypotension, severe asthma, severe COPD or
bronchodilator-dependent COPD

- Patient requires an emergent procedure

- Evidence of ongoing or active clinical instability, including acute chest pain (sudden
onset), cardiogenic shock, unstable blood pressure with systolic blood pressure <90
mmHg, and severe congestive heart failure (NYHA III or IV) or acute pulmonary edema