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Phase-III Clinical Trial of Fluorine-18 Flurpiridaz Positron Emission Tomography for Evaluation of Coronary Artery Disease.
Maddahi, J, Lazewatsky, J, Udelson, JE, Berman, DS, Beanlands, RSB, Heller, GV, Bateman, TM, Knuuti, J, Orlandi, C
Journal of the American College of Cardiology. 2020;(4):391-401
Abstract
BACKGROUND Fluorine-18 flurpiridaz is a novel positron emission tomography (PET) myocardial perfusion imaging tracer. OBJECTIVES This study sought to assess the diagnostic efficacy of flurpiridaz PET versus technetium-99m-labeled single photon emission computed tomography SPECT for the detection and evaluation of coronary artery disease (CAD), defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). Flurpiridaz safety was also evaluated. METHODS In this phase III prospective multicenter clinical study, 795 patients with known or suspected CAD from 72 clinical sites in the United States, Canada, and Finland were enrolled. A total of 755 patients were evaluable, and the mean age was 62.3 ± 9.5 years, 31% were women, 55% had body mass index ≥30 kg/m2, and 71% had pharmacological stress. Patients underwent 1-day rest-stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m-labeled SPECT and ICA. Images were read by 3 experts blinded to clinical and ICA data. RESULTS Sensitivity of flurpiridaz PET (for detection of ≥50% stenosis by ICA) was 71.9% (95% confidence interval [CI]: 67.0% to 76.3%), significantly (p < 0.001) higher than SPECT (53.7% [95% CI: 48.5% to 58.8%]), while specificity did not meet the prespecified noninferiority criterion (76.2% [95% CI: 71.8% to 80.1%] vs. 86.6% [95% CI: 83.2% to 89.8%]; p = NS). Receiver-operating characteristic curve analysis demonstrated superior discrimination of CAD by flurpiridaz PET versus SPECT in the overall population, in women, obese patients, and patients undergoing pharmacological stress testing (p < 0.001 for all). Flurpiridaz PET was superior to SPECT for defect size (p < 0.001), image quality (p < 0.001), diagnostic certainty (p < 0.001), and radiation exposure (6.1 ± 0.4 mSv vs. 13.4 ± 3.2 mSv; p < 0.001). Flurpiridaz PET was safe and well tolerated. CONCLUSIONS Flurpiridaz PET myocardial perfusion imaging shows promise as a new tracer for CAD detection and assessment of women, obese patients, and patients undergoing pharmacological stress testing. A second phase III Food and Drug Administration trial is ongoing. (A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients with CAD; NCT01347710).
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Comprehensive Cardiac CT With Myocardial Perfusion Imaging Versus Functional Testing in Suspected Coronary Artery Disease: The Multicenter, Randomized CRESCENT-II Trial.
Lubbers, M, Coenen, A, Kofflard, M, Bruning, T, Kietselaer, B, Galema, T, Kock, M, Niezen, A, Das, M, van Gent, M, et al
JACC. Cardiovascular imaging. 2018;(11):1625-1636
Abstract
OBJECTIVES This study sought to assess the effectiveness, efficiency, and safety of a tiered, comprehensive cardiac computed tomography (CT) protocol in comparison with functional testing. BACKGROUND Although CT angiography accurately rules out coronary artery disease (CAD), incorporation of CT myocardial perfusion imaging as part of a tiered diagnostic approach could improve the clinical value and efficiency of cardiac CT in the diagnostic work-up of patients with angina pectoris. METHODS Between July 2013 and November 2015, 268 patients (mean age 58 years; 49% female) with stable angina (mean pre-test probability 54%) were prospectively randomized between cardiac CT and standard guideline-directed functional testing (95% exercise electrocardiography). The tiered cardiac CT protocol included a calcium scan, followed by CT angiography if calcium was detected. Patients with ≥50% stenosis on CT angiography underwent CT myocardial perfusion imaging. RESULTS By 6 months, the primary endpoint, the rate of invasive coronary angiograms without a European Society of Cardiology class I indication for revascularization, was lower in the CT group than in the functional testing group (2 of 130 [1.5%] vs. 10 of 138 [7.2%]; p = 0.035), whereas the proportion of invasive angiograms with a revascularization indication was higher (88% vs. 50%; p = 0.017). The median duration until the final diagnosis was 0 (0 of 0) days in the CT group and 0 (0 of 17) in the functional testing group (p < 0.001). Overall, 13% of patients randomized to CT required further testing, compared with 37% in the functional testing group (p < 0.001). The adverse event rate was similar (3% vs. 3%; p = 1.000), although the median cumulative radiation dose was higher for the CT group (3.1 mSv [interquartile range: 1.6 to 7.8] vs. 0 mSv [interquartile range: 0.0 to 7.1]; p < 0.001). CONCLUSIONS In patients with suspected stable CAD, a tiered cardiac CT protocol with dynamic perfusion imaging offers a fast and efficient alternative to functional testing. (Comprehensive Cardiac CT Versus Exercise Testing in Suspected Coronary Artery Disease 2 [CRESCENT2]; NCT02291484).
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Comparison of coronary computed tomography angiography image quality with high- and low-concentration contrast agents (CONCENTRATE): study protocol for a randomized controlled trial.
Im, DJ, Kim, YH, Choo, KS, Kang, JW, Jung, JI, Won, Y, Kim, HR, Chung, MH, Han, K, Choi, BW
Trials. 2016;(1):315
Abstract
BACKGROUND With the development of computed tomography (CT) technology, coronary CT angiography can be acquired with low doses of radiation and contrast agent without a loss of diagnostic performance. The primary objective of the CONCENTRATE study is to prove the noninferiority of the enhancement effect of low-concentration contrast agents compared to a high-concentration contrast agent of the coronary artery and myocardium with coronary CT angiography. METHODS/DESIGN The CONCENTRATE study is a prospective, multicenter, noninferiority, randomized trial evaluating the enhancement effect of low-concentration contrast agents (270 and 320 mg iodine/ml) compared with a high-concentration contrast agent (370 mg iodine/ml) in the coronary artery and myocardium of coronary artery CT angiography. The primary efficacy measurement is the enhancement of coronary arteries as measured in Hounsfield units. The target population comprises 318 patients with suspected coronary artery disease who have been referred for clinically indicated nonemergent coronary CT angiography. Eligible participants are randomized for three different concentrations of the contrast agent in a 1:1:1 allocation ratio to one of three arms. The CONCENTRATE trial is a double-blind study, where the subjects and the outcome assessor are blinded to the concentration of the contrast agent used for coronary the CT angiography. Eight clinical sites in Korea are participating in this trial. DISCUSSION The CONCENTRATE study will determine whether low-concentration contrast agents are able to provide diagnostic image quality in coronary CT angiography. TRIAL REGISTRATION NCT02549794 . Registered on 14 September 2015.
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Incremental diagnostic accuracy of computed tomography myocardial perfusion imaging over coronary angiography stratified by pre-test probability of coronary artery disease and severity of coronary artery calcification: The CORE320 study.
Sharma, RK, Arbab-Zadeh, A, Kishi, S, Chen, MY, Magalhães, TA, George, RT, Dewey, M, Rybicki, FJ, Kofoed, KF, de Roos, A, et al
International journal of cardiology. 2015;:570-7
Abstract
BACKGROUND Myocardial CT perfusion (CTP) has been validated as an incremental diagnostic predictor over coronary computed tomography angiography (CTA) in assessing hemodynamically significant stenosis. OBJECTIVES To assess the diagnostic performance of CTA and CTP alone versus combined CTA-CTP stratified by Morise's pre-test probability and coronary artery calcium (CAC, Agatston) score. METHODS 381 individuals (153 low/intermediate-risk for CAD, 83 high-risk, 145 known CAD) were further stratified based on CAC score cut-offs of 1-399 and ≥400. Area under the curve for receiver operating characteristics (AUC) was calculated to assess the diagnostic performance. Reference standards were QCA≥50% stenosis+corresponding SPECT summed stress score ≥1. RESULTS In both pre-test risk groups with an Agatston score of 1-399, AUCs of CTA-CTP were not significantly different than that from CTA alone. In the low/intermediate-risk group with CAC score 1-399, AUC for CTA-CTP (89) was higher than that for CTP (76, p=0.003) alone. In the same group with CAC score ≥400, AUCs were higher for CTA-CTP (97) than that for CTA (88, p=0.030) and CTP (83, p=0.033). In high risk/known CAD patients with CAC 1-399, diagnostic performance for CTA-CTP (77) was superior to CTP (71, p=0.037) alone. In the high risk/known CAD group with CAC score ≥400, AUCs for combined imaging were higher (86) than that for CTA (75, p<0.001) as well as CTP (78, p=0.020). CONCLUSIONS The incremental diagnostic accuracy of CTP over CTA persists in patients across severity spectra of pre-test probability of CAD and coronary artery calcification. In patients with severe coronary calcification (CAC score≥400), combined CTA-CTP has better diagnostic accuracy than CTA and CTP alone.
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Diagnostic Performance of Coronary CT Angiography and Myocardial Perfusion Imaging in Kidney Transplantation Candidates.
Winther, S, Svensson, M, Jørgensen, HS, Bouchelouche, K, Gormsen, LC, Pedersen, BB, Holm, NR, Bøtker, HE, Ivarsen, P, Bøttcher, M
JACC. Cardiovascular imaging. 2015;(5):553-562
Abstract
OBJECTIVES The goal of this study was to compare the diagnostic accuracy of the coronary artery calcium score (CACS), coronary computed tomography angiography (CTA), single-photon emission computed tomography (SPECT), and a combination of these tools in the diagnosis of obstructive coronary artery disease (CAD) in patients with chronic kidney disease referred for cardiac evaluation before kidney transplantation. BACKGROUND The optimal method for the detection of obstructive CAD in potential kidney transplant patients has not yet been identified. Previous studies have found that established noninvasive stress tests have low diagnostic accuracy, while the diagnostic performance of coronary CTA remains unknown. METHODS We prospectively studied 138 patients referred for pre-transplant cardiac evaluation (mean age 54 years; age range 22 to 72 years; 68% male; 43% treated with dialysis). All patients underwent CACS, coronary CTA, SPECT, and invasive coronary angiography. The results of the noninvasive tests were merged into integrated hybrid imaging results: Hybrid (CACS/SPECT) and Hybrid (coronary CTA/SPECT). RESULTS The overall prevalence of obstructive CAD (≥50% reduction in luminal diameter) according to quantitative invasive coronary angiography was 22%. Two-thirds of the patients with obstructive CAD had a stenosis located in a proximal coronary segment. In a patient-level model, the sensitivity and specificity, respectively, for diagnosing obstructive CAD were as follows: CACS (threshold of 400), 67% and 77%; coronary CTA, 93% and 63%; SPECT, 53% and 82%; Hybrid (CACS/SPECT), 33% and 97%; and Hybrid (coronary CTA/SPECT), 67% and 86%. The sensitivity for diagnosing obstructive CAD in a proximal segment was 70% for CACS (threshold 400), 100% for coronary CTA, 60% for SPECT, 40% for Hybrid (CACS/SPECT), and 75% for Hybrid (coronary CTA/SPECT). CONCLUSIONS Coronary CTA is a reliable test with high sensitivity and a high negative predictive value for diagnosing obstructive CAD before kidney transplantation. A noninvasive approach with use of either coronary CTA or a combination of coronary CTA and SPECT to rule out obstructive CAD seems recommendable in kidney transplant candidates. (ACToR-Study: Angiographic CT of Renal Transplantation Candidate-Study; NCT01344434).
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Accuracy of Computed Tomographic Angiography and Single-Photon Emission Computed Tomography-Acquired Myocardial Perfusion Imaging for the Diagnosis of Coronary Artery Disease.
Arbab-Zadeh, A, Di Carli, MF, Cerci, R, George, RT, Chen, MY, Dewey, M, Niinuma, H, Vavere, AL, Betoko, A, Plotkin, M, et al
Circulation. Cardiovascular imaging. 2015;(10):e003533
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Abstract
BACKGROUND Establishing the diagnosis of coronary artery disease (CAD) in symptomatic patients allows appropriately allocating preventative measures. Single-photon emission computed tomography (CT)-acquired myocardial perfusion imaging (SPECT-MPI) is frequently used for the evaluation of CAD, but coronary CT angiography (CTA) has emerged as a valid alternative. METHODS AND RESULTS We compared the accuracy of SPECT-MPI and CTA for the diagnosis of CAD in 391 symptomatic patients who were prospectively enrolled in a multicenter study after clinical referral for cardiac catheterization. The area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of CTA and SPECT-MPI for identifying patients with CAD defined as the presence of ≥1 coronary artery with ≥50% lumen stenosis by quantitative coronary angiography. Sensitivity to identify patients with CAD was greater for CTA than SPECT-MPI (0.92 versus 0.62, respectively; P<0.001), resulting in greater overall accuracy (area under the receiver operating characteristic curve, 0.91 [95% confidence interval, 0.88-0.94] versus 0.69 [0.64-0.74]; P<0.001). Results were similar in patients without previous history of CAD (area under the receiver operating characteristic curve, 0.92 [0.89-0.96] versus 0.67 [0.61-0.73]; P<0.001) and also for the secondary end points of ≥70% stenosis and multivessel disease, as well as subgroups, except for patients with a calcium score of ≥400 and those with high-risk anatomy in whom the overall accuracy was similar because CTA's superior sensitivity was offset by lower specificity in these settings. Radiation doses were 3.9 mSv for CTA and 9.8 for SPECT-MPI (P<0.001). CONCLUSIONS CTA is more accurate than SPECT-MPI for the diagnosis of CAD as defined by conventional angiography and may be underused for this purpose in symptomatic patients. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00934037.
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Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: rationale and design of a prospective, randomized, multicenter study.
Tejani, FH, Thompson, RC, Iskandrian, AE, McNutt, BE, Franks, B
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2011;(1):73-81
Abstract
BACKGROUND Caffeine attenuates the coronary hyperemic response to adenosine by competitive A₂(A) receptor blockade. This study aims to determine whether oral caffeine administration compromises diagnostic accuracy in patients undergoing vasodilator stress myocardial perfusion imaging (MPI) with regadenoson, a selective adenosine A(2A) agonist. METHODS This multicenter, randomized, double-blind, placebo-controlled, parallel-group study includes patients with suspected coronary artery disease who regularly consume caffeine. Each participant undergoes three SPECT MPI studies: a rest study on day 1 (MPI-1); a regadenoson stress study on day 3 (MPI-2), and a regadenoson stress study on day 5 with double-blind administration of oral caffeine 200 or 400 mg or placebo capsules (MPI-3; n = 90 per arm). Only participants with ≥ 1 reversible defect on the second MPI study undergo the subsequent stress MPI test. The primary endpoint is the difference in the number of reversible defects on the two stress tests using a 17-segment model. Pharmacokinetic/pharmacodynamic analyses will evaluate the effect of caffeine on the regadenoson exposure-response relationship. Safety will also be assessed. CONCLUSION The results of this study will show whether the consumption of caffeine equivalent to 2-4 cups of coffee prior to an MPI study with regadenoson affects the diagnostic validity of stress testing (ClinicalTrials.gov number, NCT00826280).