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

A Blood-based Gene Expression Test (Corus CAD or ASGES) for Obstructive Coronary Artery Disease Tested in Symptomatic Nondiabetic Patients Referred for Myocardial Perfusion Imaging.

To validate the use of Corus CAD (Age/Sex/Gene Expression score - ASGES) blood assay in subjects who are referred for the work-up of coronary artery disease. The study will evaluate the clinical utility of a gene expression test Corus CAD (Age, Sex, Gene Expression Score - ASGES) in subjects referred for myocardial perfusion imaging (MPI) work-up for suspected obstructive atherosclerotic coronary artery disease (CAD). The Corus CAD (ASGES) is a gene expression test that quantify the expression of multiple genes from circulating peripheral blood cells to detect the presence of clinically significant obstructive CAD in patients with chest pain.

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.