Italian multicenter, prospective study to evaluate the negative predictive value of 16- and 64-slice MDCT imaging in patients scheduled for coronary angiography (NIMISCAD-Non Invasive Multicenter Italian Study for Coronary Artery Disease)

Abstract This was a prospective, multicenter study designed to evaluate the utility of MDCT in the diagnosis of coronary artery disease (CAD) in patients scheduled for elective coro- nary angiography (CA) using different MDCT systems from different manu- facturers. Twenty national sites pro- spectively enrolled 367 patients between July 2004 and June 2006. Computed tomography (CT) was performed using a standardized/ optimized scan protocol for each type Coronary angiography (CA) represents the standard of reference to assess epicardial vessels and establish the presence of significant coronary artery disease (CAD). CA is a bi-dimensional diagnostic technique that allows evalua- tion of the vessel lumen [1] at high spatial (50 lps/cm) and temporal (<20 ms) resolution. However, CA has its limitations: it is an invasive technique, involves high costs, requires hospitalization, and has low patient compliance. The risks associated with CA are related to its invasiveness and result in a morbidity rate of 1.5% and a mortality rate of 0.15% [2]. In addition, a considerable proportion of patients undergoing CA are subsequently found not to have clinically significant disease [3, 4]. These limitations may justify the increasing clinical use of alternative non-invasive imaging techniques for the evaluation and exclusion of clinically significant CAD. Many centers have reported their experiences in using different multidetector computed tomography (MDCT) technologies, all of which have been characterized by high diagnostic accuracy in the assessment of patients scheduled for CA. Whether the reported diagnostic accuracy can be replicated in clinical practice needs to be established at different centers with varying expertise, in non-selected patient populations and with different MDCT systems before extensive clinical application of MDCT for CAD assessment. The primary aim of this study was to assess the negative predective value (NPV) of MDCT in a multicenter study using different MDCT machines/manufacturers to deter- mine if the technique could replace an invasive procedure to exclude the presence of significant CAD. Secondary objectives were to investigate whether MDCT performance is affected by patient characteristics such as pre-test CAD risk, body mass index (BMI), and coronary artery calcium score (CACS). Safety was also investigated. Materials and methods This was a national, multicenter, prospective trial sponsored by the Italian Society of Medical Radiology (SIRM). Adult patients previously scheduled for an elective CA evaluation for a diagnostic workup at each of the participating centers were consecutively evaluated for inclusion in the study. Exclusion criteria included preg- nancy or lactation, contraindication to intravenous admin- istration of iodinated contrast media, heart rate >70 beats per minute (bpm) despite beta-blocker treatment, absence of sinus rhythm, New York Heart Association (NYHA) class III–IV, previous coronary artery bypass graft surgery (CABG) or stenting, and creatinine value >2 mg/dl. The Institutional Review Boards of all centers approved the study protocol, and written informed consent was obtained from all patients before study inclusion in accordance with the national legislation and the Declaration of Helsinki. Patient preparation Patients with heart rates >70 bpm were given an oral dose of metoprolol tartrate 45–60 min before MDCT imaging or an intravenous beta-receptor blocker just before the scan. Heart rate, electrocardiogram (ECG), and blood pressure were monitored. MDCT protocol and image reconstructions Patients underwent 16- or 64-slice MDCT with a standardized and optimized protocol for each type of CT machine. Unenhanced prospective ECG-gated MDCT was performed for the assessment of calcium deposits by Agatston Score (AS). A bolus of 100– 120 ml of non-ionic iodinated contrast medium Ultra- vist® (Iopromide 370; Bayer Schering Pharma, Berlin, Germany) was intravenously injected, preferably through the right antecubital vein, at a flow rate of 3– 4 ml/s for the 16-slice MDCT system and 4–6 ml/s for the 64-slice MDCT system, and followed by a 40–50-ml saline chaser at the same flow rate. The main scan parameters have been given for each scanner type in Table 1, including the number of patients scanned on each CT system. ficity, and DA were 0.73 (95% CI 1115 of MDCT system (≥16 slices) and compared with quantitative CA per- formed within 2 weeks of MDCT. A total of 284 patients (81%) were studied by 16-slice MDCT systems, while 66 patients (19%) by 64-slice MDCT scanners. The primary analysis was on-site/off-site evaluation of the negative predictive value (NPV) on a per-patient basis. Secondary analyses included on-site evaluation on a per- artery and per-segment basis. On-site Introduction evaluation included 327 patients (CAD prevalence 58%). NPV, positive predictive value (PPV), sensitivity, specificity, and diagnostic accuracy (DA) were 0.91 (95% CI 0.85–0.95), 0.91 (95% CI 0.86–0.95), 0.94 (95% CI 0.89–0.97), 0.88 (95% CI 0.81– 0.93), and 0.91 (95% CI 0.88–0.94), respectively. Off-site analysis in- cluded 295 patients (CAD prevalence 56%). NPV, PPV, sensitivity, speci- 0.65–0.79), 0.93 (95% CI 0.87–0.97), 0.73 (95% CI 0.65–0.79), 0.93 (95% CI 0.87–0.97), and 0.82 (95% CI 0.77–0.86), respectively. The results of this study demonstrate the utility of MDCT in excluding significant CAD even when conducted by centers with varying degrees of expertise and using different MDCT machines.