Comprehensive Evaluation of Patients With Chest Pain Using Cardiac Computed Tomography: Value of Adding Regadenoson Stress Perfusion Imaging to Noninvasive Coronary Angiography

Background. In the United States, more than 8 million patients require emergency department evaluation for acute chest pain every year. The estimated cost for these evaluations is > $10 billion and the loss of economic productivity is likely far greater. Multidetector computed tomography (MDCT) is a popular alternative to diagnostic invasive coronary angiography (ICA) (Deetjen, et al. 2007, Schroeder, et al. 2008, de Roos 2010) and is gaining wide clinical acceptance for its ability to rule out significant coronary artery disease (CAD) (Hulten, Bittencourt, Ghoshhajra and Blankstein 2012). However, in patients with acute chest pain, abnormal CT coronary angiography (CTCA) findings frequently result in additional nuclear myocardial perfusion imaging (MPI) to determine the hemodynamic significance of coronary stenosis (Garcia, Lessick and Hoffmann 2006, Deetjen, et al. 2007, Miller, et al. 2008, Schroeder, et al. 2008, de Roos 2010). This is because the presence and extent of myocardial ischemia is more important than the severity of a coronary stenosis for identifying patients who would benefit from coronary revascularization. Accordingly, with the growing interest in simultaneous evaluation of coronary anatomy and the hemodynamic significance of CAD in a single test, studies have focused on the potential of MDCT to assess myocardial perfusion (Techasith and Cury 2011). One hurdle this approach needs to overcome is that it relies on visual assessment of manually selected 2D slices, rather than 3D analysis of the entire myocardium, and requires manual adjustment of contrast windows, both carrying the risk of missing subendocardial perfusion defects.

Prior data and hypothesis. To overcome these limitations, we recently developed a technique for quantitative 3D analysis of myocardial perfusion, which uses the distribution of x-ray attenuation to calculate for each myocardial segment an index of severity and extent of perfusion abnormality (Kachenoura, et al. 2010). Having confirmed the ability of this analysis to detect regadenoson-induced perfusion abnormalities in consecutive patients referred for CTCA (Mor-Avi, et al. 2012), we propose a new study aimed at determining the value of this methodology in patients presenting in the emergency department with acute chest pain. We selected this cohort to further validate CT perfusion analysis and to determine whether it provides additive utility over CTCA alone, because these patients are increasingly referred by emergency departments for CTCA in large numbers, instead of nuclear vasodilator stress testing, thus losing valuable physiologic information. Because our perfusion index was specifically designed to take into account the fact that stress-induced perfusion defects are subendocardial, we hypothesize that our quantitative 3D analysis can accurately identify patients presenting at the emergency department with acute chest pain due to underlying hemodynamically significant coronary stenosis, aid in the identification of individuals most likely to benefit from revascularization, and thus improve the ability to predict patient outcomes. Indeed, our previous study showed that with regadenoson, our perfusion index is 2-3 times higher in myocardial segments supplied by arteries with significant stenosis (Patel, et al. 2011), and thus improves the diagnosis of hemodynamically significant CAD.

Aims. This study was designed to achieve the following goals: (1) to test the above hypothesis by comparing stress MDCT perfusion data with invasive fractional flow reserve (FFR) data in patients with significant stenosis who undergo ICA; and (2) to determine the added value of MDCT perfusion as an adjunct to CTCA for predicting patient outcomes.

Study design. In this study, MDCT imaging will be performed during regadenoson stress in approximately 150 consecutive patients with chest pain referred for CTCA, who agree to undergo additional MDCT imaging during vasodilator stress. Patients with contraindications to CTCA, including known allergies to iodine, renal dysfunction (creatinine >1.6 mg/dL), inability to perform a 10 sec breath-hold, and contraindications to beta-blockers or regadenoson, such as chronic obstructive pulmonary disease, advanced heart block or systolic blood pressure <90 mmHg, will be excluded from the study. In addition, patients with a history of cardiothoracic surgery or pacemaker or coronary stent implantation will be excluded. Myocardial perfusion will be assessed using quantitative volumetric analysis, but will not be reported to the referring physician in order to avoid referral bias. In each patient, we will collect the following information at the time of enrollment: age, gender, height, weight, blood pressure, tobacco use, history of heart disease, hypertension, stroke and diabetes. In addition, a blood sample will be obtained to allow analysis of lipids and cardiac enzymes. In a subgroup of patients who also undergo ICA, MDCT perfusion will be compared with the ICA findings, including the degree of stenosis and FFR. Enrollment will be stopped when 30 patients with ICA data are enrolled (based on power analysis). All study patients will be followed up to determine the predictive value of MDCT perfusion for major cardiovascular events at 1 moth and 1 year after presentation.

MDCT imaging protocol. Beta-blocker metoprolol will be given orally (50 mg, 1 hr prior to imaging) and/or intravenously (5 to 15 mg immediately prior to imaging), as necessary to achieve a target heart rate of <70 bpm. Images will be acquired during suspended respiration (256-channel iCT scanner, Philips). Initially, CTCA will be performed at rest according to the standard clinical protocol. Then, regadenoson (Lexiscan, Astellas) will be administered (0.4mg, i.v. bolus) at least 15 minutes later to ensure contrast clearance. An additional set of images will be acquired 1 minute after the administration of regadenoson to ensure imaging during peak vasodilator effect. Stress images will be acquired following injection of 50 ml of iodinated contrast at a rate of 4 ml/sec, using prospective gating, in order to minimize radiation exposure, resulting in an average of 2 mSv for the additional stress scan.