Coronary Obstruction Detection by Molecular Personalized Gene Expression (Corus CAD or ASGES)

This prospective, multicenter study obtained peripheral blood samples for gene expression
score (GES) before MPI in 537 consecutive patients Patients with abnormal MPI usually
underwent invasive coronary angiography; all others had research coronary computed
tomographic angiography, with core laboratories defining coronary anatomy A total of 431
patients completed GES, coronary imaging (invasive coronary angiography or computed
tomographic angiography), and MPI Mean age was 56±10 years (48% women) The prespecified
primary end point was GES receiver-operating characteristics analysis to discriminate ≥50%
stenosis (15% prevalence by core laboratory analysis) Area under the receiver-operating
characteristics curve for GES was 0 79 (95% confidence interval, 0 73-0 84; P<0 001), with
sensitivity, specificity, and negative predictive value of 89%, 52%, and 96%, respectively,
at a prespecified threshold of ≤15 with 46% of patients below this score The GES outperformed
clinical factors by receiver-operating characteristics and reclassification analysis and
showed significant correlation with maximum percent stenosis. Six-month follow-up on 97% of
patients showed that 27 of 28 patients with adverse cardiovascular events or
revascularization had GES >15 Site and core-laboratory MPI had areas under the curve of 0 59
and 0 63, respectively, significantly less than GES.

Inclusion Criteria:

- Ages 45-90 for women; 35-90 for men.

- Stable chest pain syndrome (typical or atypical) or anginal equivalent in the judgment
of the investigator (e.g., pain in the neck, jaw, arm or shoulder or dyspnea possibly
due to cardiac ischemia).

- Referred for a stress test using MPI.

- The patient has signed the appropriate Institutional Review Board approved Informed
Consent Form.

Exclusion Criteria:

- History of known MI or significant CAD.

- Current MI or acute coronary syndrome.

- Current New York Heart Association (NYHA) class III or IV congestive heart failure
symptoms.

- Severe regurgitant or stenotic cardiac valvular lesion.

- Severe left ventricular systolic dysfunction (LVEF ≤ 35 % documented in the last
year); if no assessment was performed or documented in the year preceding enrollment,
presume normal LVEF.

- Active systemic infection (diagnosed by a combination of clinical symptoms and
laboratory testing, including but not limited to fever, leukocytosis, positive blood
cultures, pneumonia, urinary tract infection, or abscess in the preceding 2 months) or
chronic infection (e.g., HIV, Hepatitis B or C, Tuberculosis).

- Protocol-specified rheumatologic, autoimmune or hematologic conditions (e.g.,
rheumatoid arthritis, systemic lupus erythematosis, polymyalgia rheumatica, or
systemic sarcoidosis).

- Known or suspected diabetes mellitus or documented Hemoglobin A1c (HbA1c) ≥ 6.5;
presume normal HbA1c if none documented.

- Total WBC ≥ 11,000 cells/ul and platelet count ≤ 75,000 cells/ul from a CBC with
differential drawn within 7 days prior to enrollment [WBC ≥ 11,000 cells/ul and
platelet count ≤ 75,000 cells/ul from a CBC drawn > 7 days prior need to be re-drawn
at enrollment].

- Recipient of any organ transplant.

- Immunosuppressive or immunomodulatory therapy including any dose of systemic
corticosteroids in the preceding 2 months.

- Chemotherapy in the preceding year.

- Major surgery in the preceding 2 months.

- Blood or blood product transfusion in the preceding 2 months.

- Subjects for whom all forms (stress or pharmacologic) of MPI are contraindicated.

- Subjects for whom invasive coronary angiography or coronary CT angiography is
contraindicated, including IV beta-blocker.

- Subjects who planned to decline research CCTA or invasive coronary angiography,
regardless of MPI result.

- Subjects with history of atrial fibrillation/flutter or frequent irregular or rapid
heart rhythms.

- Known history of renal insufficiency (serum creatinine ≥ 2.0 mg/dL), or severe allergy
to iodinated contrast.