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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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Low-dose dual-isotope procedure planed for myocardial perfusion CZT-SPECT and assessed through a head-to-head comparison with a conventional single-isotope protocol.
Imbert, L, Roch, V, Merlin, C, Djaballah, W, Cachin, F, Perrin, M, Claudin, M, Verger, A, Boutley, H, Karcher, G, et al
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2018;(6):2016-2023
Abstract
PURPOSE OF THE REPORT This study aimed at assessing an original low-dose dual-isotope procedure in which the abnormal stress Tc-99m Sestamibi SPECT is followed by rest Tl-201 SPECT, along with a head-to-head comparison with a single-isotope procedure. METHODS AND RESULTS One hundred two patients, referred for a low-dose stress-SPECT with Sestamibi (123 ± 20 MBq) on a CZT camera and for whom a rest Sestamibi SPECT was warranted, had an additional Tl-201 rest-SPECT (52 ± 5 MBq) between stress and rest Sestamibi SPECT recordings. Tl-201 images were processed for spill-over and scatter corrections, and uptake differences with stress Sestamibi SPECT were analyzed: (1) for rest acquisitions from Tl-201 (dual-isotope procedure) and from Sestamibi (single-isotope procedure) and (2) in segments for which a diagnosis of ischemia, infarct, or normal perfusion was achieved. Mean effective dose was 8.3 mSv for dual-isotope but would decrease to 5.7 mSv for an expected rate of 37% of patients for whom rest-SPECT is not warranted. After a further background correction of Tl-201 images, the rest-stress difference in myocardial uptake was equivalent between dual- and single-procedures for identifying ischemic segments (respective areas-under-curves: 0.83 ± 0.03 and 0.81 ± 0.03). CONCLUSION This original dual-isotope procedure provides acceptable radiation doses and consistent results, as compared with conventional single-isotope.
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Prognostic Value of Risk Factors, Calcium Score, Coronary CTA, Myocardial Perfusion Imaging, and Invasive Coronary Angiography in Kidney Transplantation Candidates.
Winther, S, Svensson, M, Jørgensen, HS, Rasmussen, LD, Holm, NR, Gormsen, LC, Bouchelouche, K, Bøtker, HE, Ivarsen, P, Bøttcher, M
JACC. Cardiovascular imaging. 2018;(6):842-854
Abstract
OBJECTIVES This study sought to perform a prospective head-to-head comparison of the predictive value of clinical risk factors and a variety of cardiac imaging modalities including coronary artery calcium score (CACS), coronary computed tomography angiography (CTA), single-photon emission computed tomography (SPECT), and invasive coronary angiography (ICA) on major adverse cardiac events (MACE) and all-cause mortality in kidney transplantation candidates. BACKGROUND Current guidelines recommend screening for coronary artery disease in kidney transplantation candidates. Furthermore, noninvasive stress imaging is recommended in current guidelines, despite its low diagnostic accuracy and uncertain prognostic value. METHODS The study prospectively evaluated 154 patients referred for kidney transplantation. All patients underwent CACS, coronary CTA, SPECT, and ICA testing. The clinical endpoints were extracted from patients' interviews, patients' records, and registries. RESULTS The mean follow-up time was 3.7 years. In total, 27 (17.5%) patients experienced MACE, and 31 (20.1%) patients died during follow-up. In a time-to-event analysis, both risk factors and CACS significantly predicted death, but only CACS predicted MACE. Combining risk factors with CACS identified a very-low-risk cohort with a MACE event rate of 2.1%, and a 1.0% mortality rate per year. Of the diagnostic modalities, coronary CTA and ICA significantly predicted MACE, but only coronary CTA predicted death. In contrast, SPECT predicted neither MACE nor death. CONCLUSIONS Compared with traditional risk factors and other cardiac imaging modalities, CACS and coronary CTA seem superior for risk stratification in kidney transplant candidates. Applying a combination of risk factors and CACS and subsequently coronary CTA seems to be the most appropriate strategy. (Angiographic CT of Renal Transplantation Candidate Study [ACToR]; NCT01344434).
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Computed tomography myocardial perfusion vs 15O-water positron emission tomography and fractional flow reserve.
Williams, MC, Mirsadraee, S, Dweck, MR, Weir, NW, Fletcher, A, Lucatelli, C, MacGillivray, T, Golay, SK, Cruden, NL, Henriksen, PA, et al
European radiology. 2017;(3):1114-1124
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Abstract
OBJECTIVES Computed tomography (CT) can perform comprehensive cardiac imaging. We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with 15O-water positron emission tomography (PET) and invasive coronary angiography (ICA) with fractional flow reserve (FFR). METHODS 51 patients (63 (61-65) years, 80 % male) with known/suspected coronary artery disease (CAD) underwent 320-multidetector CTCA followed by "snapshot" adenosine stress CTP. Of these 22 underwent PET and 47 ICA/FFR. Obstructive CAD was defined as CTCA stenosis >50 % and CTP hypoperfusion, ICA stenosis >70 % or FFR <0.80. RESULTS PET hyperaemic myocardial blood flow (MBF) was lower in obstructive than non-obstructive territories defined by ICA/FFR (1.76 (1.32-2.20) vs 3.11 (2.44-3.79) mL/(g/min), P < 0.001) and CTCA/CTP (1.76 (1.32-2.20) vs 3.12 (2.44-3.79) mL/(g/min), P < 0.001). Baseline and hyperaemic CT attenuation density was lower in obstructive than non-obstructive territories (73 (71-76) vs 86 (84-88) HU, P < 0.001 and 101 (96-106) vs 111 (107-114) HU, P 0.001). PET hyperaemic MBF corrected for rate pressure product correlated with CT attenuation density (r = 0.579, P < 0.001). There was excellent per-patient sensitivity (96 %), specificity (85 %), negative predictive value (90 %) and positive predictive value (94 %) for CTCA/CTP vs ICA/FFR. CONCLUSION CT myocardial attenuation density correlates with 15O-water PET MBF. CTCA and CTP can accurately identify obstructive CAD. KEY POINTS •CT myocardial perfusion can aid the assessment of suspected coronary artery disease. • CT attenuation density from "snapshot" imaging is a marker of myocardial perfusion. • CT myocardial attenuation density correlates with 15 O-water PET myocardial blood flow. • CT attenuation density is lower in obstructive territories defined by invasive angiography. • Diagnostic accuracy of CTCA+CTP is comparable to invasive angiography + fractional flow reserve.
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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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Comparative Impact of Hypoglycemic Agents on Severity and Extent of Myocardial Ischemia in Patients With Type 2 Diabetes Mellitus Undergoing Myocardial Perfusion Scintigraphy.
Biondi-Zoccai, G, Pinto, A, Versaci, F, Procaccini, E, Neri, G, Sesti, G, Uccioli, L, Vetere, M, Peruzzi, M, Nudi, F
Journal of cardiovascular pharmacology. 2016;(2):162-70
Abstract
BACKGROUND Hypoglycemic agents differ in mechanism, efficacy, and profile. However, there is uncertainty on their impact on myocardial perfusion. We thus aimed to investigate whether individuals with type 2 diabetes mellitus treated with different drug classes exhibit different perfusion patterns at myocardial perfusion scintigraphy (MPS). METHODS AND RESULTS We queried our administrative database for patients with diabetes mellitus without prior or recent myocardial infarction. The primary objective was to compare the severity and extent of ischemia at MPS, distinguishing patients according to management strategy. A total of 7592 patients were included [2336 (31%) on diet, 3611 (48%) on metformin, 749 (10%) on sulfonylureas, 449 (6%) on metformin plus sulfonylureas, 447 (6%) on metformin plus insulin]. Unadjusted analyses and analyses adjusting for baseline features suggested that sulfonylureas alone or in combination were associated with more severe ischemia than nonsulfonylurea regimens (P < 0.05), whereas combination regimens including metformin were associated with more extensive myocardial ischemia than the other regimens (P < 0.05 for both). However, no significant difference disfavoring either metformin or sulfonylurea regimens persisted after multivariable adjustment for baseline, stress, and angiographic characteristics (all P > 0.05). CONCLUSION Several significant differences in baseline, stress, and scintigraphic features appear evident in patients with diabetes mellitus receiving different hypoglycemic agents or regimens.
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Value of CACS compared with ETT and myocardial perfusion imaging for predicting long-term cardiac outcome in asymptomatic and symptomatic patients at low risk for coronary disease: clinical implications in a multimodality imaging world.
Chang, SM, Nabi, F, Xu, J, Pratt, CM, Mahmarian, AC, Frias, ME, Mahmarian, JJ
JACC. Cardiovascular imaging. 2015;(2):134-44
Abstract
OBJECTIVES This prospective, observational study in 988 asymptomatic or symptomatic low-risk patients without prior coronary artery disease was conducted to define the relative value of coronary artery calcium score (CACS), exercise treadmill testing (ETT), and stress myocardial perfusion single-photon emission computed tomography (SPECT) variables in predicting long-term risk stratification. BACKGROUND CACS, ETT, and stress myocardial perfusion SPECT results predict patients' outcome. There are currently no data comparing their relative value in long-term risk stratification. METHODS Patients were stratified by Framingham risk score (FRS), with a median follow-up of 6.9 years. Cardiac events were defined as a composite of cardiac death, nonfatal myocardial infarction, and the need for coronary revascularization. Most patients (87%) were considered appropriate candidates for functional testing as defined by current appropriate use criteria. RESULTS The long-term cardiac event rate was 11.2% (1.6% per year). Multivariate risk predictors in all patients and in the appropriate use cohort were abnormal SPECT (hazard ratio [HR]: 1.83 and 1.99), ETT ischemia (HR: 1.70 and 1.76), decreasing exercise capacity (HR: 1.11 and 1.17), decreasing Duke treadmill score (HR: 1.07 for both), and CACS severity (HR: 1.29 for both), respectively. Throughout the 10-year follow-up, CACS improved risk prediction, with event rates ranging from 0.6% per year (CACS ≤10) to 3.7% per year (CACS >400) (p < 0.0001). CACS also improved risk prediction in all patients, in the appropriate use cohort and among those with low-risk ETT and SPECT results (all, p < 0.001). Area under the receiver-operating characteristic curve was increased when CACS variables (from 0.63 to 0.70; p = 0.01) but not ETT variables (from 0.63 to 0.65) were added to FRS. Moreover, net reclassification improvement was significantly increased when CACS was added to FRS + functional variables in all patients and in the appropriate use cohort (both, p < 0.0001). CONCLUSIONS CACS significantly improved long-term risk stratification beyond FRS, ETT, and SPECT results across the spectrum of clinical risk and importantly even among those who are currently considered appropriate candidates for functional testing or have low-risk functional test results. Our findings support CACS as a first-line test over ETT or SPECT for accurately assessing long-term risk in such patients.
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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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Comparison between stress myocardial perfusion SPECT recorded with cadmium-zinc-telluride and Anger cameras in various study protocols.
Verger, A, Djaballah, W, Fourquet, N, Rouzet, F, Koehl, G, Imbert, L, Poussier, S, Fay, R, Roch, V, Le Guludec, D, et al
European journal of nuclear medicine and molecular imaging. 2013;(3):331-40
Abstract
PURPOSE The results of stress myocardial perfusion SPECT could be enhanced by new cadmium-zinc-telluride (CZT) cameras, although differences compared to the results with conventional Anger cameras remain poorly known for most study protocols. This study was aimed at comparing the results of CZT and Anger SPECT according to various study protocols while taking into account the influence of obesity. METHODS The study population, which was from three different institutions equipped with identical CZT cameras, comprised 276 patients referred for study using protocols involving (201)Tl (n = 120) or (99m)Tc-sestamibi injected at low dose at stress ((99m)Tc-Low; stress/rest 1-day protocol; n = 110) or at high dose at stress ((99m)Tc-High; rest/stress 1-day or 2-day protocol; n = 46). Each Anger SPECT scan was followed by a high-speed CZT SPECT scan (2 to 4 min). RESULTS Agreement rates between CZT and Anger SPECT were good irrespective of the study protocol (for abnormal SPECT, (201)Tl 92 %, (99m)Tc-Low 86 %, (99m)Tc-High 98 %), although quality scores were much higher for CZT SPECT with all study protocols. Overall correlations were high for the extent of myocardial infarction (r = 0.80) and a little lower for ischaemic areas (r = 0.72), the latter being larger on Anger SPECT (p < 0.001). This larger extent was mainly observed in 50 obese patients who were in the (201)Tl or (99m)Tc-Low group and in whom stress myocardial counts were particularly low with Anger SPECT (228 ± 101 kcounts) and dramatically enhanced with CZT SPECT (+279 ± 251 %). CONCLUSION Concordance between the results of CZT and Anger SPECT is good regardless of study protocol and especially when excluding obese patients who have low-count Anger SPECT and for whom myocardial counts are dramatically enhanced on CZT SPECT.
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Absolute quantification of left ventricular global and regional function at nuclear MPI using ultrafast CZT SPECT: initial validation versus cardiac MR.
Cochet, H, Bullier, E, Gerbaud, E, Durieux, M, Godbert, Y, Lederlin, M, Coste, P, Barat, JL, Laurent, F, Montaudon, M
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2013;(4):556-63
Abstract
UNLABELLED We sought to evaluate the accuracy of myocardial perfusion imaging (MPI) using cadmium-zinc-telluride (CZT) SPECT cameras for the measurement of left ventricular (LV) global and regional function, and the performance of absolute wall motion (WM) and wall thickness (WT) measurements for the detection of myocardial scarring, using cardiac MR as a reference. METHODS Sixty patients with known or suspected coronary artery disease underwent MPI using a CZT SPECT camera, as well as cine and delayed enhanced cardiac MR. Gated MPI data were processed using quantitative gated SPECT software. LV global function was assessed by measuring LV end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF). Regional function was assessed by quantifying segmental WM and WT according to the 17-segment model. Myocardial scarring was quantified on each segment using delayed enhanced cardiac MR. Agreement between SPECT and cardiac MR was assessed using Pearson correlation and Bland-Altman analyses. The influence of measurement magnitude on the agreement was analyzed using Spearman correlation coefficients between the mean and SD of measurements. The performance of WM and WT for the detection of segments with more than 25% scar transmurality was assessed using receiver-operating-characteristic analysis. RESULTS Correlation between methods was excellent for EF (R = 0.81, P < 0.0001) and ESV (R = 0.88, P < 0.0001) and was good for EDV (R = 0.71, P < 0.0001). Agreement was good for EF (bias, -2.7%; limits of agreement, -15.5 to +10.1) but was lower for EDV (bias, -29.7 mL; limits of agreement, -68.3 to +8.9) and ESV (bias, -9.9 mL; limits of agreement, -30.7 to +10.9). Correlation between methods was fair for WM (R = 0.49, P < 0.0001) and WT (R = 0.48, P < 0.0001). SPECT underestimated WT (bias, -41%; limits of agreement, -108 to +26), with an error depending on thickening magnitude (ρ = 0.70, P < 0.0001). The agreement in WM measurement was higher (bias, -1.4 mm; limits of agreement, -6.9 to +4) and independent of motion magnitude (ρ = 0.006, P = 0.86). WM and WT were equally able to identify scarred segments (area under the receiver-operating-characteristic curve, 0.74 ± 0.03 and 0.74 ± 0.03, respectively). CONCLUSION MPI using CZT SPECT cameras and quantitative gated SPECT analysis accurately quantifies EF but still underestimates LV volumes. WM shows a higher agreement with cardiac MR than does WT, with errors in WT measurement increasing at greater thicknesses. Absolute quantification of segmental WM and WT can equally be used to identify myocardial scarring.