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Corrected Coronary Opacification Decrease from Coronary Computed ORIGINAL ARTICLE Corrected coronary opacification decrease from coronary computed tomography angiography: Validation with quantitative 13N-ammonia positron emission tomography Dominik C. Benz, MD,a Christoph Gra¨ni, MD,a Paola Ferro, MD,a Luis Neumeier,a Michael Messerli, MD,a Mathias Possner, MD,a Olivier F. Clerc, MD,a Catherine Gebhard, MD,a Oliver Gaemperli, MD,a Aju P. Pazhenkottil, MD,a Philipp A. Kaufmann, MD,a and Ronny R. Buechel, MDa a Department of Nuclear Medicine, Cardiac Imaging, University Hospital Zurich, Zurich, Switzerland Received Mar 25, 2017; accepted Jun 7, 2017 doi:10.1007/s12350-017-0980-2 Background. To assess the functional relevance of a coronary artery stenosis, corrected coronary opacification (CCO) decrease derived from coronary computed tomography angiography (CCTA) has been proposed. The present study aims at validating CCO decrease with quantitative 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI). Methods and Results. This retrospective study consists of 39 patients who underwent hybrid CCTA/PET-MPI. From CCTA, attenuation in the coronary lumen was measured before and after a stenosis and corrected to the aorta to calculate CCO and its decrease. Relative flow reserve (RFR) was calculated by dividing the stress myocardial blood flow (MBF) of a vessel territory subtended by a stenotic coronary by the stress MBF of the reference territories without stenoses. RFR was abnormal in 11 vessel territories (27%). CCO decrease yielded a sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for prediction of an abnormal RFR of 73%, 70%, 88%, 47%, and 70%, respectively. Conclusions. CCTA-derived CCO decrease has moderate diagnostic accuracy to predict an abnormal RFR in PET-MPI. However, its high negative predictive value to rule out functional relevance of a given lesion may confer clinical implications in the diagnostic work-up of patients with a coronary stenosis. (J Nucl Cardiol 2019;26:561–8.) Key Words: Corrected coronary opacification Æ quantitative PET myocardial perfusion imaging Æ relative flow reserve See related editorial, pp. 569–573 Electronic supplementary material The online version of this Dominik C. Benz and Christoph Gra¨ni share first authorship; Philipp article (doi:10.1007/s12350-017-0980-2) contains supplementary A. Kaufmann and Ronny R. Buechel share last authorship material, which is available to authorized users. Reprint requests: Ronny R. Buechel, MD, Department of Nuclear The authors of this article have provided a PowerPoint file, available Medicine, Cardiac Imaging, University Hospital Zurich, Ramistrasse for download at SpringerLink, which summarizes the contents of the 100, 8091 Zurich, Switzerland; [email protected] paper and is free for re-use at meetings and presentations. Search for 1071-3581/$34.00 the article DOI on SpringerLink.com. Copyright Ó 2017 American Society of Nuclear Cardiology. 561 562 Benz et al. Journal of Nuclear CardiologyÒ Validation of CCO decrease with quantitative PET March/April 2019 Abbreviations considered the gold standard for myocardial perfusion CCO Corrected coronary opacification assessment.19–21 Moreover, the calculation of relative CCTA Coronary computed tomography flow reserve (RFR) from PET-MPI has not only served angiography as the standard of reference for the validation of invasive SPECT Single photon emission computed FFR,22 but has also been shown in some patient tomography populations to yield significantly higher diagnostic PET Positron emission tomography accuracy than stress myocardial blood flow (MBF) or RFR Relative flow reserve coronary flow reserve (CFR).23 The aim of the present MBF Myocardial blood flow study was to validate CCO decrease with stress MBF in CFR Coronary flow reserve PET-MPI and to assess the accuracy of CCO decrease to TAC Time-activity curves predict an abnormal RFR as derived from the gold ICA Invasive coronary angiography standard PET-MPI. PCI Percutaneous coronary intervention METHODS Study Population INTRODUCTION We retrospectively identified 67 patients who underwent hybrid CCTA/PET-MPI at our institution due to known or Low-dose coronary computed tomography angiog- suspected CAD. Exclusion criteria were history of coronary raphy (CCTA) is a valuable non-invasive tool to assess artery bypass surgery and patients who suffered any events coronary artery disease (CAD) with high negative between the CCTA and the PET scan. The study protocol predictive value1 and to guide subsequent treatment was approved by the institutional review board (cantonal strategies.2,3 A limitation of CCTA is its moderate ethics committee, BASEC-Nr. 2016-00177) and informed performance in assessing the functional relevance of a consent was waived for all patients scanned before 2014. For coronary stenosis as is inherently true for any anatomic all patients scanned afterwards, written informed consent test.4 However, proof of functional relevance of a was obtained. No funding was obtained for performing this study. stenosis prior to any revascularization procedure is mandatory to improve outcome.5–7 Consequently, com- bining anatomic information on the coronary arteries CCTA Acquisition and Assessment of CCO derived from CCTA with functional information from Decrease single photon emission computed tomography (SPECT) or positron emission tomography (PET) myocardial Patients underwent contrast-enhanced CCTA on either a perfusion imaging (MPI) either side-by-side or fused as 64-slice scanner (n = 39; LightSpeed VCT or Discovery HD hybrid imaging was established and has been shown to 750, both GE Healthcare, Waukesha, WI, USA) or a 256-slice offer added clinical and prognostic value.8–10 Concur- scanner (n = 28; Revolution CT, GE Healthcare) using helical rently, there is growing interest in parameters derived (n = 4) or axial scanning with prospective ECG-triggering (n = 63) as previously described.24,25 Bolus tracking was directly from CCTA to assess the functional relevance performed and image acquisition was started 4 seconds after of a coronary lesion. Fractional flow reserve from CCTA the signal density reached a predefined (i.e. 120 Hounsfield (FFRCT) has been introduced recently and several units) or a visually detectable threshold in the ascending aorta. prospective trials have lent support to suggest a clinical In order to achieve a target heart rate \65 bpm, intravenous 11,12 role. Calculation of FFRCT, however, currently metoprolol (5-30 mg) was administered prior to scanning if remains a complex and cumbersome process with necessary. Furthermore, all patients received 2.5 mg sublingual limited availability, but easily and quickly derivable isosorbide dinitrate 2 minutes prior to the scan. parameters such as the transluminal attenuation gradient CCO decrease was measured for each coronary stenosis (TAG)13,14 and the decrease in corrected coronary (i.e. luminal diameter narrowing C50%) as previously 15 opacification (CCO)15–17 have emerged as promising described. In brief, a region of interest (ROI) with a diameter alternatives. While TAG may be more related to vessel of 1 mm was placed in the center of the coronary lumen and a ROI with a diameter of 10 mm was placed in the descending diameter than to stenosis severity,18 CCO decrease has aorta on the same axial slice. CCO was calculated as the ratio consistently yielded high diagnostic accuracy (79 to of mean attenuation in the coronary ROI over the aortic ROI. 89%) to predict functional relevance of a coronary CCO was measured twice as close as possible to the stenosis 15–17 stenosis. It has, nevertheless, not yet been investi- and due care was taken to avoid calcifications and streak gated in comparison to quantitative PET-MPI which is artifacts in the measurements and the lower values were used Journal of Nuclear CardiologyÒ Benz et al. 563 Volume 26, Number 2;561–8 Validation of CCO decrease with quantitative PET to calculate CCO decrease as the difference of proximal minus RESULTS distal value. Study Population PET Acquisition and RFR Calculation The baseline characteristics of the study population Patients underwent 13N-ammonia PET at rest and during (n = 67) are summarized in Table 1. Twenty-seven adenosine stress at a standard rate (0.14 mg/min/kg) over patients (40%) were referred for exclusion of CAD and 7 minutes with 700-900 MBq of 13N-ammonia administered 40 (60%) for evaluation of known CAD. Twenty-one intravenously into a peripheral vein after 3 minutes into stress. patients (53%) had a stent and 16 (40%) a history of Images were acquired either on a Discovery (LS/RX) PET/CT prior myocardial infarction. Figure 1 depicts screening, scanner or on an Advance PET scanner (both GE Healthcare), inclusion, and eligibility for analysis of the study 19 as previously reported in detail. population in a flow chart. Quantitative MBF and CFR were calculated using the com- mercially available PMOD software (version 3.7; PMOD Technologies Ltd., Zurich, Switzerland) developed and validated CCTA Findings at our institution.26 In brief, a volume of interest (VOI) encompass- ing the left ventricular myocardium was drawn and two more VOIs CCTA ruled out CAD in 26 patients (39%). In 41 were put into the blood pool of the left and right ventricle. patients (61%), 99 stenoses were documented in a total Myocardial and blood-pool time-activity curves (TAC) were of 73 vessels resulting in 18 patients with one-vessel, 14 obtained from dynamic frames corrected for radioisotope decay. patients with two-vessel, and 9 patients
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