PROspective Multicenter Imaging Study for Evaluation of Chest Pain

Pragmatic randomized trial of clinical effectiveness of diagnostic testing strategies for
coronary artery disease (CAD), to be performed in outpatient settings including acute and
primary care and cardiology offices. Qualifying patients presenting with new or worsening
symptoms suspicious for clinically significant CAD who require diagnostic testing and have
not been previously evaluated will be randomized to an initial strategy of either anatomic
or functional testing. All subsequent decisions regarding additional testing, medications
and/or procedures will be at the discretion of the responsible clinical care team Within the
functional testing arm, the subject's care team will select the specific test to be
performed (exercise electrocardiogram (ECG), stress nuclear, or stress echocardiogram
(echo)) consistent with 'usual care' in that practice setting. The subject's care team will
be provided with 'Information sheets' summarizing current standards for test interpretation
and preventive care, but specific medical treatment will not be mandated by the trial.

Inclusion Criteria:

- new or worsening chest pain suspicious for clinically significant coronary artery
disease (CAD)

- no prior evaluation for this episode of symptoms

- planned non-invasive testing for diagnosis

- men age ≥55 years

- men age ≥45 years with increased probability of coronary artery disease (CAD) due to
either (A. Diabetes Mellitus (DM) requiring medical treatment OR Peripheral Arterial
Disease (PAD) defined as documented >50% peripheral arterial stenosis treated
medically or invasively OR cerebrovascular disease (stroke, documented > 50% carotid
stenosis treated medically or invasively) OR B. At least one of the following
cardiovascular risk factors: 1-Ongoing tobacco use, 2-Hypertension, 3-Abnormal ankle
brachial index (ABI) defined as less than <0.9, 4-Dyslipidemia

- women age ≥65 years

- women age ≥50 years with increased probability of coronary artery disease (CAD) due
to either (A. Diabetes Mellitus (DM) requiring medical treatment OR Peripheral
Arterial Disease (PAD) defined as documented >50% peripheral arterial stenosis
treated medically or invasively OR cerebrovascular disease (stroke, documented > 50%
carotid stenosis treated medically or invasively) OR B. At least one of the following
cardiovascular risk factors: 1-Ongoing tobacco use, 2-Hypertension, 3-Abnormal ankle
brachial index (ABI) defined as less than <0.9, 4-Dyslipidemia

- Serum creatinine ≤ 1.5 mg/dL within the past 90 days

- Negative urine/serum pregnancy test for female subjects of child-bearing potential

Exclusion Criteria:

- Diagnosed or suspected acute coronary syndrome (ACS) requiring hospitalization or
urgent or emergent testing; Elevated troponin or creatine kinase-myocardial band
(CK-MB)

- Hemodynamically or clinically unstable condition systolic blood pressure (BP) < 90
mmHg, atrial or ventricular arrhythmias, or persistent resting chest pain felt to be
ischemic despite adequate therapy)

- Known coronary artery disease (CAD) with prior Myocardial infarction (MI),
percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or any
angiographic evidence of coronary artery disease (CAD) ≥50% lesion in a major
epicardial vessel

- Any invasive coronary angiography or non-invasive anatomic or functional
cardiovascular (CV) test for detection of coronary artery disease (CAD), including
coronary tomographic angiography (CTA) and exercise electrocardiogram (ECG), within
the previous twelve (12) months

- Known significant congenital, valvular (> moderate) or cardiomyopathic process
(hypertrophic cardiomyopathy or reduced systolic left ventricular function (LVEF) ≤
40%)) which could explain cardiac symptoms

- Contraindication to undergoing a coronary tomographic angiography (CTA), including
but not limited to: a. Allergy to iodinated contrast agent, b. Unable to receive beta
blockers unless heart rate < 65 beats per minute, c. Pregnancy

- Life expectancy < 2 years

- Unable to provide written informed consent or participate in long-term follow-up