Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography

Patients with acute chest pain and normal or non-diagnostic electrocardiograms (ECGs)
represent a cohort whose management is notably inefficient and diagnostically challenging.
Because in less than 30% of EDs diagnostic testing (e.g. nuclear imaging, echocardiography,
and exercise treadmill ECG) that would allow physicians to rule out the occurrence of
myocardial ischemia is performed as part of the initial evaluation, most of these patients
are hospitalized for 24 to 36 hours to exclude the presence of acute coronary syndrome
(ACS). Of the six million acute chest pain patients admitted each year in the U.S. under
these conditions, less than 10% of them ultimately receive a diagnosis of ACS at discharge.
Moreover, inpatient care for negative evaluations imparts an economic burden in excess of $8
billion annually.

Since acute myocardial ischemia and necrosis are rare in the absence of coronary artery
disease, a technology that reliably identifies CAD may allow physicians to discharge chest
pain patients directly from the ED. Cardiac CT is a safe, high-speed, noninvasive imaging
technique that accurately detects coronary atherosclerotic plaque and stenosis, and also
allows physicians to assess global and regional LV function.

Observational studies have demonstrated that approximately 40% of acute chest pain patients
have no evidence of atherosclerosis on cardiac CT, and that an additional 30% have no
evidence of hemodynamically significant (>50%) coronary artery stenosis. Both of these
criteria are powerful predictors of the absence of both ACS and major adverse cardiovascular
events (negative predictive value [NPV] of 98%). The specificity of cardiac CT is further
increased when global and regional LV function is normal. Several studies have demonstrated
that cardiac CT, with its high NPV, can be effectively used to rule out ACS, but little is
known about the willingness ability of ED physicians to use this information to augment
patient management.

We therefore propose to perform a trial that will mobilize seven clinical sites and
randomize 1000 patients with acute chest pain and normal or non-diagnostic ECGs, to receive
either standard ED evaluation (no intervention) or a cardiac CT (experimental) in the
evaluation of acute chest pain in the emergency room. (Rule Out Myocardial Infarction using
Computer Assisted Computed Tomography [ROMICAT II]).

Inclusion Criteria:

1. Participant must have at least five minutes of chest pain or equivalent (chest
tightness; pain radiating to left, right, or both arms or shoulders, back, neck,
epigastrium, jaw/throat; or unexplained shortness of breath, syncope/presyncope,
generalized weakness, nausea, or vomiting thought to be of cardiac origin) at rest or
during exercise within 24 hours of ED presentation, warranting further risk
stratification, as determined by an ED attending.

2. Participant must have 2 or more cardiac risk factors (diabetes, hypertension,
hyperlipidemia, current smoker and family history of coronary artery disease).

3. Participant must be able to provide a written informed consent.

4. Participants must be <75 years of age, but >40 years of age.

5. Participant must be able to hold breath for at least 10 seconds.

6. Patient must be in sinus rhythm.

Exclusion Criteria:

1. New diagnostic ischemic ECG changes (ST-segment elevation or depression > 1 mm or
T-wave inversion > 4 mm) in more than two anatomically adjacent leads or left bundle
branch block

2. Documented or self-reported history of CAD (MI, percutaneous coronary interventions
[PCIs], coronary artery bypass graft [CABG], known significant coronary stenosis
[>50%])

3. Greater than 6 hours since presentation to ED.

4. BMI >40 kg/m2

5. Impaired renal function as defined by serum creatinine >1.5 mg/dL*

6. Elevated troponin-T (> 0.09 ng/ml)

7. Hemodynamically or clinically unstable condition (BP systolic < 80 mm Hg, atrial or
ventricular arrhythmias, persistent chest pain despite adequate therapy)

8. Known allergy to iodinated contrast agent

9. Currently symptomatic asthma

10. Documented or self-reported cocaine use within the past 48 hours (acute)

11. On Metformin therapy and unable or unwilling to discontinue for 48 hours after the CT
scan

12. Contraindication to beta blockers (taking daily antiasthmatic medication): This
exclusion only applies to patients with a heart rate >65 bpm at sites using a
non-dual source CT scanner

13. Participant with no telephone or cell phone numbers or no address (preventing
follow-up)

14. Participant with positive pregnancy test. Women of childbearing potential, defined as
<2 years of menopause in the absence of hysterectomy or tube ligation, must have a
pregnancy test performed within 24 hours before the CT scan.

15. Participant unwilling to provide a written informed consent.