Gene Expression Testing In The Evaluation Of Patients With Stable Ischemic Heart Disease

Expression levels of various genes in circulating white blood cells or whole blood samples have been reported to discriminate between cases of obstructive coronary artery disease and healthy controls. Multiplex gene expression testing has been combined with other risk factors to estimate the likelihood of obstructive coronary artery disease in patients who present with stable ischemic heart disease. These tests have the potential to improve the accuracy of predicting coronary artery disease. A commercially available test, Corus CAD, has been developed for this purpose without diabetes or inflammatory conditions. For individuals who have suspected stable ischemic heart disease without diabetes or inflammatory conditions who receive gene expression testing, the evidence includes retrospective case-control and prospective cohort studies. Relevant outcomes are overall survival, disease-specific survival, test validity, change in disease status, morbid events, and resource utilization. The diagnostic pathway for coronary artery disease includes information from medical history, along with age and sex, stress testing, and imaging. Newer noninvasive methods are being tested, such as gene expression testing. It is not clear how the Corus CAD gene expression test fits in the current diagnostic pathway and how results would be used to change current guideline-based risk stratification before and/or after other noninvasive testing. Results of 2 validation studies (Personalized Risk Evaluation and Diagnosis In the Coronary Tree [PREDICT], Coronary Obstruction Detection by Molecular Personalized Gene Expression [COMPASS]) have reported that the test may improve coronary artery disease prediction beyond the Diamond-Forrester prediction model. In the COMPASS study, the sensitivity and negative predictive value of the Corus CAD score in diagnosing obstructive coronary artery disease was superior to myocardial perfusion imaging in patients referred for myocardial perfusion imaging testing. However, in that study, the reported sensitivity of myocardial perfusion imaging was considerably lower than that generally reported in the literature. Neither PREDICT nor COMPASS used the guideline definition of obstructive coronary artery disease as the reference standard and had relatively few patients at intermediate risk based on clinical prediction rules. The sensitivity and negative predictive value of clinical models were not reported. An analysis of a cohort from the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial including patients with an intermediate pretest probability of obstructive coronary artery disease confirmed a high, negative predictive value for the Corus CAD score. The test also has been shown to have some predictive ability of future revascularization; too few major cardiac events have been observed during the limited duration of follow-up to assess predictive ability for that outcome. Evidence for the Corus CAD score has not directly demonstrated that the test is clinically useful and a chain of evidence cannot be constructed to support its utility. The evidence is insufficient to determine the effects of the technology on health outcomes.